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Perceptual Control Theory

In this post, I review a single excerpt from page 1 of the above book. The entire book is freely available online. On the basis of page 1, William T Powers’ ‘Perceptual Control Theory’ (PCT) cannot be correct. Dag Forssell explains the provenance of this piece as follows:

I have annotated the text to indicate my initial thoughts:

’10 Minutes’ from Forssell, 2016, p. 1.

I cannot believe William Powers could have been serious in writing these words. If so, he was a seriously deluded man. Note the following, manifestly untrue assertions:

It (PCT) explains why one organism cannot control another without physical violence. There is a long list of counter-examples: honey bees, murmuration, bird song, classroom teaching, coaching, managing, leadership, being a guru, altruism, pacifism, non-violent protest, laws, the justice system, social cohesion, sports such as cricket, tennis and baseball, international treaties, the European Union, etc.

It explains why people deprived of any minor part of their ability to control soon become disfunctional (sic), lose interest in life, pine away and die. Steven Hawking, people with sensory impairments, pw motor impairments, people living in torture or concentration camps, the vast majority of people living without enough food, water or money, patients with cancer or other fatal illnesses, patients infected with the SARS-CoV-2 pandemic, the list goes on and on.

It explains why it is so hard for groups of people to work together even on something they all agree is important. Another very long list of counter-examples: scientific discoveries, e.g. the Double Helix, the Curies – radiation, the war effort in WWI and WWII, space travel, the First Person on the Moon, July 20, 1969, the International Space Station, the production of SARS-CoV-2 vaccines in less than one year 2020-1, etc, etc.

What planet was William T Powers living on?

I had read the first couple of chapters of one Powers’ books on PCT a few decades ago and found it unconvincing.

Recently I received a recommendation from a proponent of the approach and had been looking forward to taking another look at PCT. Sadly, my initial reaction to page 1 is disappointment. Under normal circumstances, I would put this book down and never pick it up again. However I find the ‘guru’ status of Powers among his supporters somewhat intriguing. I note that many are engineers.

It is said that one must never judge a book by its cover. Never judge a book by what is says on page 1 either? Or what?

I will soldier on to see if Powers begins to make sense. Any graphologists out there might gain insights by looking at his handwriting.

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Science is Beautiful

Science is beautiful when it makes simple explanations of phenomena or connections between different observations. Examples include the double helix in biology and the fundamental equations of physics.

Steven Hawking

I have something beautiful to offer, not in Biology or in Physics, but in Psychology:

A General Theory of Behaviour”.

It’s got harmony, synchrony and zing, and it’s closely linked to the natural world. To be honest, it’s got me a little excited.

A General Theory of Behaviour is a whole new perspective on the Science of Psychology. The focus is psychological homeostasis, a seemingly ‘magical’ principle of revolutionary significance. This new focus has the potential to unify the disparate field of Psychological Science under a single umbrella. No theory did that before, which is why I’m a little excited.

Any theory that can make novel predictions that are confirmed by data is along the right lines. The original formulation of the theory includes 20 principles and 80 empirical propositions, all receiving strong empirical support (Marks, 2018). There is also huge potential to test many more novel predictions. That is rather beautiful! Independent commentators appear to agree:

Stevan Hobfoll, Rush University Medical Centre, himself a significant theorist, states:

“Marks brings exceptional insights and a driving logic to bear to navigate through many fragmented theories of behaviour that are by their nature partial and limited.  It is not that these more fragmented theories are not often important, but that we need the grander theory to hold disparate ideas together.  Marks does so convincingly and in a way that is testable, refutable, and often even entertaining.

Henderikus J. Stam, Professor of Psychology at the University of Calgary, Founder & Editor Emeritus of the leading journal, Theory & Psychology, wrote:

A General Theory of Behavior is an innovative and promising new theory that integrates the long tradition of investigations on homeostasis with contemporary research in such diverse areas as emotion, addiction and sleep. A truly original and wide-ranging study of human nature, this book will be foundational for anyone who considers the importance of theory for modern psychology.”

Amedeo D’Angiulli, Department of Neuroscience, Carleton University, Ottawa, Editor-in-Chief, of the main journal for studies on the human imagination, Imagination, Cognition and Personality, wrote:

Dear Professor Marks (David if I may) I re-read your paper on Brain Sciences I Am Conscious, Therefore, I Am: Imagery, Affect, Action, and a General Theory of Behavior, May 2019, Brain Sciences 9(5):107 and then I discovered your book on your General Theory through it, which I read just afterwards. Both are major contributions to psychology, but they also read like classics to me. They have a guiding vision forwardCongratulations.

Janine Crosbie, Psychology Lecturer, University of Salford, commented:

This inspiring book applies the seemingly simple biological concept of homeostasis to human behaviour.  There is beautiful historic detail about key researchers, whilst considering modern issues such as stress, lack of sleep and addiction. A compelling read, which feels like an engaging lecture, by a passionate and considered speaker.

David A Holmes, Senior Lecturer in Psychology, Founder of the Forensic Research Group, Manchester, wrote:

“In ‘A General Theory of Behaviour, David Marks has applied scientifically established theory to conceptualize disparate areas of Psychology in a manner that both unifies and brings greater insight, establishing this book as a milestone text of the 21st century.”

Scott Barry Kaufman, University of Pennsylvania, opined:

“The field of psychology has many theories, but no General Theory. The unifying theory David Marks presents, along with the 20 principles, provide rich soil for further testing and opens up exciting avenues for psychology.

The General Theory appears to these independent experts be an ‘inspiring milestone’ with ‘a guiding vision forward’. These comments are most encouraging and help to motivate me to persevere with the work. Thanks to all of the experts named above for your positive comments.

Life is short and there is a lot more work still to be done. I need many more hands on deck.

If you’d like to collaborate to help build the Homeostasis Project, please contact me at: dfmarksphd@gmail.com. I look forward to hearing from you.

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The British Psychological Society

This series of posts examines the current situation of crisis that exists within the British Psychological Society (BPS). The series is a collaboration with the team at BPSWatch. I am reposting here content originally published at BPSWatch. Readers may also be interested in the posts here, here and here.

How much does the future of the BPS actually matter to you?

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We began this blog and the associated Twitter feed because we were all extremely concerned about what we see as the misgoverance of an organisation that we gave our time and energy to over many years because we believed in what it stood for. What we have seen in recent years is an increasing distancing of those that run the BPS from its membership – as our posts and out tweets demonstrate. The recent expulsion of the President Elect exemplifies the parlous state of the BPS. 

We have had some feedback from people who are of a similar opinion to us, some of which has appeared here, and it’s helpful to know that our concerns are shared by others. We have also had many informal comments of support either applauding our efforts or telling us of similar experiences with this failing organisation. Disturbingly, we have been told of those who, after working hard on behalf of the Society, have left feeling betrayed and traumatised by their experiences. More evidence that change is needed urgently.

But, and it is a big but, we are retired from practice and at are a distance from active involvement in the BPS. Frankly, whether it survives or not will have little practical impact on our lives professionally although its demise would cause us great sadness. But its continued existence as a thriving, member-led organisation which represents the best of UK psychological thinking and practice matters, perhaps never more so than now. Over the half-century that we have been psychologists we have seen such enormous strides made in how psychological practice has grown in maturity and relevance. Psychologist of all sorts and conditions are listened to with respect and can speak with authority. When we started out it was psychiatry that was seen as the ‘go-to’ source of expertise in matters psychological – no more. Psychologists can be proud of the strides that it have made over the years. And that process is almost entirely due to those psychologists, members of the BPS by-and-large, who were willing to spend time and energy to build the discipline, the profession and the BPS. That psychology has got to where it is today is due almost entirely to the hard work – often against the odds – of those who cared deeply and passionately about their discipline. They were not professional, go-anywhere managers – they were psychologists who believed in what psychology could do.

So this is a plea to all those of you who want to be represented by an organisation of which you can be proud. An organisation that reflects and promotes psychology to the benefit of all and of which membership can be seen as badge of honour. The BPS can be this – it is clearly not this right now. Its future cannot depend on the likes of us old codgers alone. It must involve those of you who are still out there, working as psychologists, on whose future the health of a thriving BPS is dependent. It is your responsibility more than ours. 

This is a critical time for the BPS. The current ‘leadership’ is engaged in highly unprofessional actions for which they are not being held accountable. The BPS has no senior member-elected officers. The fact that the Charity Commission is heavily involved is a serious warning sign. There is a commitment of £6 million (yes, £6 million of your money) to an ill-specified and inadequately scrutinised change project. There is a £2 million loan (securitised against two BPS-owned properties) with no CFO or CEO in post to manage or oversee these vast financial commitments. 

This needs you (yes, you) to act now. Be prepared to be rebuffed and ignored or accused of harassment if you express you concerns to the current BPS officials. Write to the Charity Commission with your comments. Read and contribute to the blog. Email the blog – BPSWatch@btinternet.com. Read and forward the Tweets  – @psychsocwatchuk. Share your experience with others.

It’s your Society – and your responsibility to rescue it.

Peter Harvey2 CommentsEXPULSION OF PRESIDENT-ELECT

A challenge to the BPS narrative.

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From the BPSWatch Editorial Collective…..

Since the inception of this blog we have had intermittent contact with the now expelled President Elect around matters of concern regarding what we believed were clearly signs of organisational misgovernance, irregularities and toxic culture at the BPS. These had been separately signposted to us individually when we had dealings with senior staff about a range of policy issues. We had become increasingly alarmed by the way we were ignored, brushed off, rebuked, and, as one of the recent threads on @psychsocwatchuk https://twitter.com/psychsocwatchuk/status/1401165572436602884?s=20  demonstrated, we had our correspondence closed down with implications, explicit or veiled, that we were harassing or bullying staff. During our exchanges with Dr. MacLennan over months, he indicated his growing belief that he would never be allowed to become President and that there were moves afoot to prevent that. Latterly he told us he was sure he would be suspended or expelled for persisting with challenging the current governance process and practice. This was, of course, his stated reason for standing to be elected. Members gave him their backing.

His appeal against expulsion remains unheard and there is another legal matter that remains sub judice so he cannot yet speak out in his own defence, despite all that has been said in print and on a Youtube video that he is a “bully”, deserving only expulsion.

We can say, without hesitation, that in the contacts the three of us have separately had with Dr. MacLennan, we have detected no signs in his manner or his expressed attitudes that he is disrespectful, aggressive or demeaning. And despite all the slights and insults he has received, he remains passionate in his commitment to making the BPS a better organisation.  All three of us have had long careers as clinical psychologists, two of us with very significant forensic experience. We do not just take things at face value when there are conflicting views and narratives about individual behaviour.

Taken in that context, and with Dr. MacLennan unable to defend himself publicly at this stage, we are publishing verbatim a communication that we received from a friend and long-term colleague and collaborator of Dr. MacLennan. We have permission of the author who is happy to be named, and of Dr. MacLennan.

Good Morning,

I have recently been following your articles about Dr MacLennan on BPS Watch and feel your concerns.

I am not a member of the BPS and feel it would be inappropriate for me to pass comment on recent events, but I am a close friend of Nigel and have been horrified at his very public vilification because this is not the Nigel I recognise. While I have my own views, I recognise that there are two sides to every story and I only have one side, but I feel that I must tell you about my relationship with him and, in a sense, to defend him.

But first, a little bit about myself. I served for 30 years as a police officer with Surrey Police. Towards the end of my career I was seconded to the National Leadership Academy for Policing at Bramshill as a Programme Director to deliver programmes on the High Potential Development Scheme and the Senior Leadership Development Programme. While I have delivered all types of Leadership programmes and consultancy services across England, Wales and Northern Ireland (and to every public service) my core programmes were Managing Finance and Resources, Media Strategy (I developed the National Police Media Strategy in conjunction with the highly respected journalist Brian Morris), and Strategic Community Relations. I retired in 2005 and was retained as a consultant until 2015.

In 2012 I became the Honorary Secretary of the British Academy of Management Special Interest Group on Corporate Governance with a special interest in ethics and, in 2013, I became an Honorary Visiting Professor at London Metropolitan University Business School. This is when I met Nigel. With him, I have delivered talks to four Advances in Leadership Conferences, been a judge and Chairman of judges at national leadership awards, and have even delivered a talk at the last BPS conference. I have also worked with Nigel on a 9 month Leadership Development Programme for BAME officers in the Metropolitan Police Service. In my opinion, his skills and talents are without doubt.

As a former police officer, I tend to view people with suspicion until I can understand their motivations and I have never doubted Nigel’s motivations. As you are probably aware, he has had a glittering career working for blue chip companies and organisations such as the Chartered Management Institute and I have found his honesty and integrity beyond reproach. What I particularly liked about him was his assertiveness – he was not afraid to tell you how it is – and this is an in-demand skill for effective leaders. I have learnt many things from Nigel and have been quite happy when he has pointed out that I am wrong and, I hasten to add, vice versa.  In my experience he has never strayed into aggressiveness – forceful yes, aggressive no. However, like me, he does struggle with obfuscation, and this can become a barrier to communication with certain people.

In short, I have always found Nigel to be competent, conscientious, a supreme coach and, above all, honest.

Kindest regards.

Graham Buchanan, BSc(Hons), NdipM, PGCE, CMgr FCMI, FRSALeave a comment“THE PSYCHOLOGIST”BOARD OF TRUSTEESEXPULSION OF PRESIDENT-ELECTGOVERNANCE

The legitimation crisis and a membership denied answers

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David Pilgrim posts….

Today, the concept of a ‘legitimation crisis’ can be applied clearly to the BPS. Although explored at length in a book with that title by Habermas (1974), many other social and political scientists have returned to the theme. This is about leadership regimes, which may notionally still retain power, but their strained credibility reflects an imminent or current breakdown in their actual authority. The cabal currently at the centre of the BPS is still in power but its credibility is in rapid decline. It lacks what Eric Fromm, in his book The Sane Society, called ‘rational authority’ and, instead, exercises power on its own terms in order to ward off the stream of criticism warranted. For Fromm this would be an expression of ‘irrational authority’.

On this blog we have been reporting the character and history of this crisis in recent months and each entry, such as this one, is a new take on an unprecedented state of affairs for the Society. The occasional flurry of criticism of rogue celebrity researchers, such as Cyril Burt (Joynson, 1988) or Hans Eysenck (Marks, 2018), barely dented the reputation of the BPS. Similarly, the spat between the Maudsley methodological behaviourists and their scorned psychodynamic colleagues from north of the Thames, in a struggle to control the Medical Section and its journal, led to a temporary closure of its business in 1958 (Pilgrim and Treacher, 1991). These small eruptions of doubt, that all was well in the BPS, pale into insignificance today. We have never seen anything like this, either in living memory or in the literature on the history of British psychology. Those past examples, looked at in the current context, are like comparing a bar room brawl with a military coup. 

In meetings of the Board of Trustees today all of the Presidential triumvirate have gone, so it contains nobody elected from the general membership. Unelected Senior Management Team members now outnumber Trustees from the sub-systems. This trend is now amplified by the Board preventing members electing a replacement for the radically reforming President Elect, after expulsion from the Society, a cue for the next main point.

The public disparagement of Nigel MacLennan

The video released, vilifying the President Elect in advance of his appeal being submitted and heard, is a complete outrage. It offends our normal understanding of natural justice and leaves the Board of Trustees, who planned its production and dissemination on YouTube, open to the charge of unethical and possibly illegal activity. Are the Trustees so determined to crush this man’s reputation that they will simply ‘do anything that it takes’? 

It is officially the position of the BPS (according to its own website for all to read) not to investigate individual members. However, does that claim fail to apply only when it is politically expedient for the interests of the incumbent leadership? Are the members seriously expected to believe that this has been anything but a ‘stitch up’ from start to finish? Was the investigation panel hand-picked by the Board of Trustees or not? How many on that panel were truly independent and without their own vested interest in the current regime of power? Were membership funds used liberally by the Board to hire legal advice in order to justify the scapegoating of a reformer, turned whistle blower? The questions go on and on. Some of them ultimately may be resolved in court but what is clear already is that Nigel MacLennan has not been treated in a fair manner, if we use everyday criteria of common sense and decency.

If the stitch up hypothesis is in doubt, look at how Carol McGuinness, in a follow-up document to that unedifying and ill-advised video, made it quite clear that even if Nigel MacLennan were to be re-instated on appeal, as a member of the Society, he would still not be permitted back to his role as the President Elect. This nothing-left-to-chance approach, reflecting the persecutory intent of the Board, sticks out like a sore thumb in this planned and vindictive attack on a man whose career has now suffered immediate detriment. 

I can find no justification for this pre-emptive strike from McGuinness, on behalf the Board, within the Statutes and Rules. Does she offer no rule-based rationale in the script she is reading because one simply does not exist? This brings us back to Fromm’s notion of ‘irrational authority’. Those in power often do and say things, simply because they can. But do we have to believe this travesty of justice? And given that under Statute 20 of the Society, the Board should have been chaired on an interim basis by MacLennan not McGuinness, is there an Alice in Wonderland feel to this whole scenario? 

We know that such a surreal quality can indeed emerge from group think, especially when it leads to scapegoating in order to create an illusion of homeostasis and harmony (Baron, 2005; Leyens et al. 2000). The warring factions of the SMT and the Trustees could take temporary comfort in a common enemy to be eliminated, but the facts of the crisis are still there, with or without the removal of MacLennan. Facts do not disappear because they are ignored conveniently by displacement activity or an ostrich stance.

Keeping the membership in the dark

If a making-the-rules-up-as-you-go-along approach to governance now characterises the workings of the cabal, then another supportive tactic has been information control. Nowhere has this been more obvious than in the silence in the pages of The Psychologist. An exception has been the printing of the statement about the expulsion of MacLennan from McGuinness (giving the BPS a free noticeboard posting without editorial comment or analysis), as well as the link to her video. No right of reply was offered to MacLennan. If this were a normal magazine it would reflect the normal rules of journalism and both sides of a story would have been offered, or at least taken into account.

However, this is not a normal magazine. For example, the political turbulence in the Society, should have warranted some commentary but none has been evident. Its inside cover reminds us every month that it is ‘…the magazine of the British Psychological Society…’. If this means that it obeys the contingent expectations of those running the BPS, then this is actually a fair and valid description. However, maybe members of the Society have broader expectations (such as it being a forum for free debate about the current legitimation crisis). Such expectations are indeed raised, conveniently, by the subsequent cover description ‘…It provides a forum for communication, discussion and controversy among all members of the Society…’. Has there been any actual sign of the latter, in practice, in the past turbulent year? Why are ordinary members still playing catch up about the financial scandal in the Society, the fat file of complaints being held by the Charity Commission and the expensive legal shenanigans to expel Nigel MacLennan?

During the crisis, the monthly column of the Chief Executive Officer suddenly disappeared without editorial comment, and we slowly became aware that he was ‘not in his office’ and his function was then taken on by his Deputy, Diane Ashby. And before the President, Hazel McLoughlin, also disappeared from the pages because she had resigned, citing family reasons, the content of her column revealed nothing to the membership of the chaos and tensions, which led to the resignation of the Vice President David Murphy. He explained on Twitter that this was because of his concerns about both governance and finance.  

However, the role of this ‘magazine’ has not gone unquestioned. For example, here is a reply to Pat Harvey from the editor (12.12.20) responding to her criticism of The Psychologist failing to provide information of legitimate concern to the BPS membership:

We are not a ‘house journal’, we are a magazine. Our responsibility is not to speak for the Society or to align with any documents it might publish; it is to provide a forum for communication, discussion and controversy among members and beyond.

This restatement of the confusing and contradictory blurb, cited earlier from the inside cover of The Psychologist, does not cease to be confusing and contradictory simply because it is robotically restated. Does the membership deserve a better journalistic service, during the current legitimation crisis of the BPS, than this sort of vacuous rhetorical gambit? The supine post-it-board role offered by The Psychologist on behalf of the current BPS leadership, reminds us of one of many of Orwell’s dire warnings about democracy: ‘Journalism is printing what someone else does not want printed. Everything else is public relations.’

The exchange between Pat Harvey and the editor of The Psychologist, Jon Sutton, did not end with the above restated confusion. She also wrote to the Chair of the Editorial Advisory Committee, Richard Stephens, starting with a complaint about the narrow and prejudicial role of The Psychologist, when being biddable and posting the offensive video. She made other criticisms of the magazine as well. This was the response she received from Stephens:

Thanks for your letter and for raising these concerns. I plan to table these for discussion at the next meeting of the Psychologist and Digest Editorial Advisory Committee on 24th June. I felt that your first raised point warranted some urgency of response so I discussed it today with our editor, Jon Sutton. Jon’s view was that while the video featuring Professor Carol McGuinness as Interim Chair of the Board of Trustee has been widely disseminated among BPS members, it is unlisted on YouTube. Given that The Psychologist has a much wider audience, Jon reflected that it’s inclusion in the piece “‘The Society is at a crossroads’” was not appropriate. On that basis the video has been removed. I will feedback in due course following our meeting on the 24th

This is a small sign of good sense and fairness from Richard Stephens, although at the time of writing the video is still available on YouTube.  Will this be the start of a period of genuine honest reflection from the Advisory Committee? Would the video have been removed had it not been for these critical questions from Pat Harvey? In my view, it seems as though those below the cabal level in the Society are very slowly waking up to the serious challenges that the legitimation crisis is posing for freedom of expression and balanced and open journalism in the future pages of The Psychologist. Elsewhere on the blog I have addressed the matter of censorship in the Society.

The ethical and legal culpability of the Trustees

The Charity Commission continues to work with the Society to bring it into ‘regulatory compliance’. This raises questions about the role of the Trustees in the recent past. How many of them (other than Nigel MacLennan), out of public interest, took their concerns about poor governance and financial irregularities to the Charity Commission or the press? 

Many resignations have been evident in recent months, including the President and Vice President. Are they now prepared to offer a full and frank account to the membership of what happened in the Board, which went so badly wrong? This could be a starting point for the ‘root and branch’ reform now required, to reverse the demise of the organisation. 

Will they admit that the conflicts of interest inherent to the current definition of a Board (which date back to a lack of specificity in the Royal Charter arrangements in 1988) have been routinely out of sync with current expectations of properly independent trustees in charities today? The current Board of Trustees is a sham because its members all have conflicts of interest and there are no outsiders from the Society to offer impartial oversight. Given the legitimation crisis, should the current Trustees at least own up to this basic fact, resign and insist on a properly constituted Board in line with Charity Commission expectations?  

And if it turns out that the negligence, or worse, of some Trustees has cost the BPS dearly, will they be held liable for these costs, as Charity Commission regulations allow? Will BPS members now seek to hold Trustees liable for the seeming losses incurred to the Society, by their apparent lack of oversight? Will that liability also extend to those who resigned but were in place during that period of apparent lack of oversight (in legal terms this is called ‘legacy liability’)?

This particular legitimation crisis, like all others, never stops posing questions for democracy. We all (not just a few pushy malcontents) need to keep asking them. The passivity in our current zeitgeist about trying to influence events around us does not have to lead to fatalism. We can still challenge the cabal and the current shambles in the BPS, as this blog and Nigel MacLennan have already demonstrated. The more of us taking up this challenge, the less likely that victimisation will be seen and the more likely that the Society will be saved from its own self-inflicted wounds. 

Baron, R. (2005). So right it’s wrong: Groupthink and the ubiquitous nature of polarized group decision making. Advances in Experimental Social Psychology. 37: 35.

Habermas, J. (1974) Legitimation Crisis Boston: Beacon Press. 

Joynson, R. B. (1989). The Burt Affair. New York: Routledge

Leyens, J. Ph., Paladino, M. P., Rodriguez, R. T., Vaes, J., Demoulin, S., Rodriguez, A. P., & Gaunt, R. (2000) The emotional side of prejudice: The attribution of secondary emotions to ingroups and outgroups. Personality and Social Psychology Review. 4, 2, 186–97.

Marks,D.F  (2019) The Hans Eysenck affair: time to correct the scientific record Journal of Health Psychology 24, 4, 409–42.

Pilgrim, D. and Treacher, A. (1991) Clinical Psychology Observed London: Routledge.3 CommentsEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 3

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Was the evidence sound?

As psychologists, from our very earliest years as bright-eyed, bushy-tailed undergraduates, we are used to dealing with evidence. We learn how to evaluate it, how to contextualise data, how to look in detail at the hypotheses, the method, the analyses. We are used to defining behavioural referents for concepts. Professional researchers carry on and refine this whilst practitioners hone their evidence-gathering skills through the interview rather than controlled trial and have to remain alert to their own biases as well as to the inevitable and understandable one-person perspective of their client. Perhaps we could characterise all these approaches as one of benign scepticism, always open to correction the face of new data.  We are assured the BPS commissioned external investigations (presumably at the expense of member subscriptions – will the total cost of all this appear in the audited accounts?) into the allegations and their findings were a central part of the case against Dr MacLennan. All well and good and superficially follows due process. But it raises an important set of questions. As outlined in Part 2, we suggest that Dr MacLennan’s arrival may have heralded an unwelcome intrusion for some in the organisation. Perhaps they had already formed an opinion of him and his reformist zeal and put the shutters up in advance. They were, perhaps, primed to view him as the ‘enemy’. Perhaps Dr MacLennan’s enthusiasm and energy was seen as ‘over the top’. Perhaps he felt he had to be assertive in the face of what he saw, rightly or wrongly, as intransigence and unhelpfulness – and, of course, assertion is not the same as bullying.  We ourselves have been subject to veiled accusations of harassment and bullying, simply because we refused to stop asking questions when legitimate requests for information or clarification were denied (an experience not unique to us). So we would ask how many respondents in the data-gathering exercise actually used the word ‘bullying’? What overt, identifiable behaviours of ‘bullying’ did Dr MacLennan show? And, most importantly, what was the criterion used by any of those involved into what constituted ‘bullying’, especially as there are well-documented definitions available? These interactions presumably took place during the COVID epidemic and in many cases could not have involved an intimidating physical presence. How did the Panel account for the potentially distorting effects of conversations being mediated by technology?

Was the sanction proportionate?

The BPS is clear on the three sanctions available to the Responsible Person (and note here that in the long and highly detailed justification issued by the BPS it contradicts itself saying that the Panel recommended the sanction in one place and that the Responsible Person made the decision, acting on the evidence provided by the Panel in another passage – which was it BPS?). He chose the most serious of the three – immediate expulsion. We have no information as to how he reached that decision other than that it is stated that he was presented with the Panel’s findings – minus, of course, any input from Dr MacLennan. That last point raises the question as to whether, in the light of the possible consequences, he might have thought it advisable, at the very least, to check with Dr MacLennan that he had nothing to contribute. The relevant paragraph of the BPS statement is this

The member conduct process involved a careful review of sanctions applied in other similar cases and in relation to the conduct that might reasonably be expected of a member of this standing and experience.

We are in uncharted territory here as we, as mere members, don’t have access to any data about the outcome of any disciplinary process (which may or may not exist) since part of it was outsourced to the HCPC. In the days when the BPS did take this responsibility seriously, the outcome of investigations was published in The Psychologist. Looking at the statement above, we have no idea as to how many similar cases there have been and we have no idea of how many members have been expelled – and, of crucial importance, for what offences were they deprived of society membership. We have already noted the ‘proportionality’ of sanctions in the light of previous cases and we really do need to know what offences committed by (now ex-) members resulted in expulsion. We are left with the highly general and completely subjective judgement (made by one person) as to what he might reasonably expect of a member of standing. And as we have already noted, he is the Chair of a Standing Committee of the Board of Trustees.

We would also ask how he judged the possible consequences of his decisions on all those involved – particularly on the person who is most affected – Dr MacLennan. We understand that he runs his own business and is more dependent than many psychologists on being able to attract clients – they do pay his income quite directly. He has not only been deprived of his BPS membership – this action, compounded and magnified by the subsequent barrage of publicity will cause enormous reputational damage and may well cost him his livelihood. Did the RP take this into account at all?

In a final act of this grossly public humiliation, we are told by ‘the BPS’

If Professor MacLennan has his membership reinstated on appeal, he would not automatically reassume his role as trustee and President Elect, although he would be eligible for re-election to the Board in line with its usual procedures. The BPS constitution provides mechanisms for filling vacancies on the board and these must be followed. These procedures do not include an option for the board to choose to reinstate Professor MacLennan (as President or President Elect) if his appeal is successful.

This is saying that the BPS can overturn the democratic process ‘just because it can’ – and we are sure that many members would value a sight of the rules that allow this. Should Dr MacLennan be cleared of all charges, then how can the BPS justify not reinstating him to his democratically elected post? He has been expelled from membership the Society, the consequence of which is the loss of his position. Reinstatement of his membership should, therefore, mean being able to take up the post to which he is entitled. This looks very much like a small group within the BPS doing its absolute utmost to ensure that Dr MacLennan never becomes President.

Was the video absolutely necessary? 

Many of you, like us, will have been shocked by the lengths to which the BPS has gone to justify itself and to ensure the widest possible coverage of this unfortunate affair – before the appeal has even been heard. Five closely typed pages, one video (now on YouTube), all going into the grisly and hurtful accusations of a case that has yet to reach its lawful conclusion. This stands in complete contradistinction to the following; the fact that the CEO is out of his office about which the members have been told nothing (not even the fact of it); the police investigation about which the members have been told nothing (not even the fact of it); that the Charity Commission is engaged with the Society about which it needed a bunch of “malcontents” and the resignation of the Vice-President for the BPS to even acknowledge.  These are critical issues for the membership as a whole and could have easily been communicated to us in a way that did not prejudice any legal investigations. So what’s the difference, BPS? Why go in to the sort of supposed detail that is career-wrecking when a simple holding statement would have sufficed? Looks a lot like the actions of a bully to us.

Where from here?

We hope that our highlighting of the issues that we think to be of importance has, at the least, piqued your interest. Perhaps we could encourage you to look further into the workings of your Society – the minutes of the Board of Trustees is a good place to start as much for what it doesn’t say as to what it does. If you are a member of the Senate (a body, as far as we can tell, without Terms of Reference) or know one of the Trustees, perhaps you could ask some questions – and be prepared to fobbed off or accused of harassment. If you have social media links to other colleagues who care about our Society’s future then get involved by spreading the word.

We will do our best to keep you up to speed as far as we are able. 

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.1 CommentEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 2

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Were both sides heard fairly?

The statements from the BPS make the observation that Dr MacLennan declined to present evidence to support his case despite repeated requests. We are at a loss understand this as it is presented. We could speculate that Dr MacLennan might chose to distance himself from a process that he might believe to be illegitimate and be biased against him and that, by co-operating, he would add spurious validity to it. However, it is a surprise that, in view of the seriousness of the issue for him on a personal and professional level, it is implied that he made no efforts to defend himself robustly. We would ask, therefore, whether he was given due time to collect together all the evidence he might need? Was he able to access all available material that would be necessary, such as privileged communications to which he as an office-holder, would be entitled? What efforts were made by either the Panel or the Responsible Person to find our why he would choose to take this course of action? Was the RP able to satisfy himself that Dr MacLennan did not wish to defend himself in the dock?

Was it a level playing field from the outset?

We can have some idea of how the BPS views complaints from this extract from the Minutes of the Board of Trustees meeting in December 2020

“This year has seen a trend for the potential misuse of the complaints process, where it has been used to express a difference of opinion or dissatisfaction with a consultation outcome.The volume of complaints is a strategic risk for the Society and was considered at the Risk Committee.”

Clearly, complaints about the running of the Society are unwelcoming intrusions rather than a learning experience, a risk to be managed. Whilst is it easy to fob off the ordinary member with tactics such as simply not responding, not answering questions or crudely cutting off debate, when an elected officer, who will be an integral part of the organisation arrives, different tactics will be required.

It was very clear from his election statement that Dr MacLennan was a man on a mission – a mission to overhaul the BPS. His successful election (44% of votes cast) must have given him some confidence that he was doing the right thing. His experience, and that of others who he canvassed and supported him, was enough for him to believe that reform was an absolute necessity. We have no doubt that this energy translated into an enthusiasm and diligence to find out, in greater detail, about the mechanics of how the BPS worked (or, more importantly, how it didn’t work). We have no doubt that for some in the organisation this was a significant threat. We have already noted that the BPS had serious problems well before his election and that many people who were meant to have formal oversight of the organisation had – at the very least – taken their individual and collective eyes off the ball (including the Trustees). To support this assertion we can do no more than to quote part of the resignation tweet of Professor David Murphy, lately Vice-President (and therefore a Trustee during his period as President-Elect and President) which identified 

“…governance oversight, escalating expenditure and lack of openness and transparency…”

as one trigger for his leaving. And that of Past President, Professor Peter Kinderman

“…When I was President, I was routinely excluded from key decisions, was threatened with legal action over ‘fraud’ (I was completely exonerated, of course) and forced to resign (as Vice-President) for advocating for what is now effectively BPS policy…”

So we know, from two very senior past office holders, that there were significant problems well before Dr MacLennan was propelled into the scene. And remember that Professor Kinderman was in post for the two years 2015-2017 (until his forced resignation) and Professor Murphy for the years 2018 – 2021.  We also know, from the minutes of the Board of Trustees meeting in December 2020, that some Trustees themselves were anxious enough about the Society to support

“…a wider discussion in relation to a governance review and stressed the urgency of moving forward with this action…”

Bear in mind also that the Leicestershire police are investigating an allegation of a major financial fraud within the Society.  So we have a picture of an organisation that is clearly dysfunctional and under scrutiny and had been so for some considerable period of time. Is it any wonder that some within the organisation, both staff and volunteers, may have felt more than a twinge of anxiety at the arrival of an avowed new broom? We would suggest that in the light of all this, the BPS bureaucracy was on the defensive. This not only might have influenced the trigger for the investigation, it may have influenced its course.

The third and final post will appear tomorrow, Saturday 22 May 2021.

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.Leave a commentEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 1

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This is the first of three posts looking closely at the recent expulsion of the Present-Elect.  We will be asking a series of questions about both the process and outcome, identifying what we see as major deficiencies which highlight, in stark detail, the issues which we have been raising about the sorry state of our organisation. Much of this is speculation and informed guesswork, some generalising from our own experiences because, despite the mass of defensive information coming from the BPS there are many serious omissions and obfuscations.

So, to begin at the beginning.

Can we trust the overall process?

Before we get into the fine detail, let’s step back and cast an eye over the disciplinary process itself.  We would remind you that in the Complaints FAQs on the BPS website there is the following statement

The Society does not have a function to investigate complaints against its members…

This, of course, is in complete contradiction to the various statements in the Member Conduct Rules which do outline such a function. If it were sentient, the complaints process would be in a serious existential crisis. 

We must also remember that we have been told, by the Acting CEO, that the Society is undertaking a root-and-branch review of the whole of the complaints procedure. To put it at its mildest, this suggests that all is not well with the process, whether it actually exists or not.

In addition, we must also ask who actually made the decision to pursue this complaint against the President-Elect. Again, to remind you, the CEO is still ‘out of the office’; there is no CFO; the President has resigned; the Vice-President has also resigned citing failures of governance amongst his reasons for going; we have an “Interim Chair” of the Board of Trustees (presumably this same Board that is accused of the aforementioned governance failures); an acting CEO who is, presumably, involved in the issues raised by the President-Elect. So the question remains, who decided? Was it the full Board of Trustees or some select subgroup of the willing? Was the complete (if depleted, of course, due to resignations) Board given full and unredacted information about the reasons for this course of action and its possible consequences? Who chose the Panel members and the Responsible Person? Did the Board as a whole and unanimously sign all this off?

In view of the serious and unusual nature of this whole business – disciplining the only remaining elected senior officer of the Society must surely rate as out-of-the-ordinary – and the fact that this would be subject to more than the usual degree of scrutiny from the membership and the outside world, one might hope (perhaps, vainly, expect) that the BPS would go to some lengths to show that justice would not only be done, but would be seen to be done.  It should be a shining example of how to do things right. This takes on a particular relevance in the light of the current application to the Professional Standards Authority where matters of monitoring and managing professional standards (the clue is in the name) are paramount.

We argue and will, we hope, show that the whole process, from start to finish, is fatally flawed and itself brings the BPS into disrepute. 

How “independent” is independent?

The various self-exculpatory outpourings of the BPS make great play of the ‘independence’ of the investigation. What does that mean to you? To us it suggests – at the very least – that whoever is carrying out the investigation is as far removed from both the current and past history of the BPS as possible. This is not just a matter of not being a Trustee or a member of the SMT. Many of the problems and issues identified by us and by others pre-date the election of Dr MacLennan by many years. Indeed, as we will see later, at least one past President identified serious problems as did the now-resigned Vice-President who had been in post (President-Elect, President) for two years prior to his abandonment of the sinking ship. So any properly constituted investigatory panel should comprise people untainted by previous appointments as Trustees or as senior post-holders with the BPS. This seems to be particularly important in the light of the fact that this may be, to our knowledge, a unique event in BPS history.  Ideally, the panel should be made up of people from outside of the organisation completely. After all, the allegations against Dr MacLennan were of ‘bullying’ – this is a generic, non-organisation-specific behaviour. You don’t need to know about the arcane intricacies of the BPS to recognise bullying when you see it. Again, given the importance of being seen to do this correctly, it would be sensible to have someone who has considerable HR experience. Was this the case?  No, it was formed of some (number unstated) of ‘…our most senior experienced colleagues…’. The fact is, however worthy and experienced,  they are not independent of the BPS. This failure is also shown by asking the Chair of the Ethics Committee to act as the Responsible Person –  who is accountable to and appointed by the Board. As an officer holder of a Standing Committee of the Board of Trustees, he is neither independent of the Board nor of the BPS. We assume (again, lack of detail makes this suppositional on our part) that he was completely distant from the everyday work of the Panel for otherwise he would be unable evaluate the evidence presented with fresh and neutral eyes.

It is stated by the BPS that 

The process was also conducted throughout with the benefit of independent legal advice to give additional assurance that it was being carried out with propriety and fairness.

This could mean all manner of things. Given that the whole complaints process is muddled and inconsistent and would need an awful lot of (expensive) lawyers’ and consultants’ time to sort through and make sense of, we can only hope that the BPS see this is a good use of your subscriptions. But the point we are making is that even if the letter of law was followed to the last dotted i and crossed t this is not the same as ensuring that the overall process was seen to be just. In our view, it could not be.

We will continue to raise questions in Part 2, to be posted tomorrow (21 May 2021).

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.1 CommentBOARD OF TRUSTEESEXPULSION OF PRESIDENT-ELECTGOVERNANCE

The End of Membership Democracy in the BPS?

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The campaign in the self-serving bunker at the centre of the BPS continues unabated. Its main character, which we have documented in our posts in the past few months, includes a number of strands. Some reflect the tactics of evasion and secrecy. They include complaints being ignored, as well as concerns (that are not complaints) being turned into complaints and sent into a rabbit hole.  The complicit non-reporting of the crisis in ‘the magazine of the British Psychological Society’ has been a trusted management mechanism to keep members in the dark. Dictates have been sent out by ‘Trustees’ to Senate members to demand their silence in a comical pantomime of control freakery.

Other tactics have involved clear projection: a bullying and high-handed culture of management has accused its critics of being the bullies. The power asymmetry here between the parties is ignored but that acknowledgment would require a capacity for honest reflectiveness. Journalists just doing their job in a democracy have been threatened with legal action. By any standards of common sense and fair judgement, this precarious regime of power has had a probity bypass. 

The most egregious example of this has been the ‘investigation’ and subsequent expulsion of the President Elect. His sin was to be open from the beginning about reforming the governance arrangements in an organisation which, for years, had flouted the normal expectations of charity law and good practice guidelines offered by the Charity Commission.

What price membership democracy?

The literal price of being in the BPS is known to its membership. For now, some of those fees are maintaining the high salary of a CEO who is still ‘out of the office’, so remains unable to fulfil his duties. Those in the bunker have told us nothing, so members are left to speculate. 

In the few days that have elapsed since the expulsion of the President Elect was announced (in a scripted account – crafted by whom?), matters have deteriorated further. The unprecedented video from the ‘Interim Chair’ of the Board of Trustees was a callous public disparagement of the President Elect. Speaking from an office and role that, under Statute 20 of the Society, she still has no right to hold, her personalised career-threatening attack upon him remains on Youtube for the world to see.

This scandal now has worsened.  A rapid election is to be held to replace the summarily deposed President-Elect before his appeal has even been heard. From well before he took office there were overt intentions to obstruct him wherever possible. We believe that there is evidence to support this that will be made public. Like the ‘investigation’ of the allegations against him this is a travesty. History will judge those responsible for deposing him, so this faux process of justice will peter out to its discreditable conclusion.

In case members are getting too excited about choosing someone new and untainted by what has gone before, they need to be prepared for a disappointment. This is the score. Only candidates from the current Board of Trustees or Senate members will be permitted to stand. This is the very group under whose ‘oversight’ the Charity Commission has become involved on an ongoing basis. There is an active police investigation into an alleged major fraud (watch this space next month). The self-same group from which the Vice-President resigned,  citing issues about “…governance oversight, escalating expenditure and lack of openness and transparency…”, which he communicated to the Charity Commission.  Former President, Professor Peter Kinderman, informs us that several years ago “…When I was President, I was routinely excluded from key decisions, was threatened with legal action over ‘fraud’ (I was completely exonerated, of course) and forced to resign (as Vice-President) for advocating for what is now effectively BPS policy…” .

What sort of real choice are members now given?   

The candidate will be drawn from a pool of complicit individuals. They assume that everything in the garden is rosy and the much-vaunted £6 million Change Programme will supercharge the BPS, when the membership to date have been shown no substantive evidence to support this wishful thinking. 

Meanwhile, for now, any vestige of membership democracy has been placed on indefinite hold. We can only hope that needed legal proceedings, active media interest and decisive action from the Charity Commission will, between them, resolve this sinister and shameful demise of the public face of psychology in the UK once and for all. 

BPSWatch – Editorial CollectiveLeave a comment‘FALSE MEMORY SYNDROME’MEMORY AND THE LAW GROUP

On memories of abuse….

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The BBC websitethe Daily Telegraph and the Daily Mail are all reporting on the trial of an alleged sexual abuser, the widow of a former High Court judge. All quote the following statement by the prosecuting QC

“He tried to bury away the memories and not to think about them”.

As is her right, we have no doubt every effort will be put into her defence, perhaps even involving the British False Memory Society.

How will any witnesses for the prosecution or the barristers involved be able to rely on a balanced, empirically based set of guidelines to argue against any claims that the accuser’s memories may be ‘recovered or false’? The short answer is that they won’t because ‘The BPS’, in its wisdom, has given up on any pretence to take this matter with the seriousness that it deserves by abandoning the revision of its Memory and The Law guidelines (see here).

We can only hope that the court is able to hear from a balanced and fully informed range of expert witnesses. It is shameful than none of the psychologists who may be in that position will be able to call on the backing and support of their professional society.

The BPSWatch Editorial CollectiveLeave a commentGOVERNANCE

The BPS is unfit for purpose

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This was originally sent as a comment to our post ‘The Crisis deepens…’ We felt that it was important enough to stand on its own as a separate post.

TheBPSWatch Editorial Collective.

I am Professor David Marks, membership number 3829, a Chartered Member with FBPsS, currently a member of the Division of Health Psychology, previously a member of other groups and networks. I joined the BPS as a student in 1963. After completing a BSc and PhD I worked in universities in the UK and overseas carrying out teaching administration and research. I have practiced as a psychologist and worked as a consultant to multiple organisations within the NHS, industry and voluntary sectors. I served as Head of Department at two large Psychology Departments, firstly at Middlesex University, where I worked from 1986 to 2000, and then at City, University of London from 2000 to 2010. I founded two scholarly journals and, for 26 years, have served as Editor-in-Chief of the Journal of Health Psychology

Based on my research publications, I was appointed to a BPS Fellowship in 1984. In the early 1990s, I was elected chair of the BPS Health Psychology Section, which was taken into Special Group status and subsequently to a Division. I was actively involved in the BPS accreditation of the first MSc awards in health psychology and the first Stage 2/doctoral training provision in the UK. I sat on various BPS boards and represented the BPS on international bodies. Over many years multiple elected and unelected BPS officers were well known to me and I counted many as personal friends. 

It with sadness and regret that I believe that I must state my concerns about the Society, its organization, working practices and public outputs. 

I am writing this comment in support of the recent blog postings on ‘BPSWatch’. I do not know and have never met any of the three authors. However I have read their postings and find myself in total agreement with the points they have been making. Rather than resign from the Society, which has crossed my mind on numerous occasions, I had always hoped that change could come from within. Now, seeing the total chaos that reigns, and the complete lack of transparency, accountability and honesty with members, I am strongly doubtful.

I can summarise my current thoughts on the BPS in four sentences: 

1) The BPS is grossly failing the public good, its members, and the discipline of Psychology.
2) The current problems of the BPS cannot and will not be solved by tinkering with the system, as has been tried unsuccessfully on a frequent basis over several decades.
3) Only root-and-branch restructuring would be able to make the necessary changes to achieve the objects of its charter.
4) Sadly, I do not believe the BPS has the wherewithal to achieve the necessary structural reorganization that is called for.

The BPS website (https://www.bps.org.uk/about-us/who-we-are) states:
“The British Psychological Society is a registered charity responsible for the development, promotion and application of psychology for the public good.
Through our Royal Charter we are charged with overseeing psychology and psychologists in the UK, and we are governed by a number of democratically-elected boards and committees.”

My nearly 60-year long association with the BPS indicates to me that the BPS is woefully unfit for purpose. The BPS fails to meet its obligations as a registered charity. This fact is evidenced by the Society’s:

Ineffective governance
Lack of accountability
Lack of transparency
Institutional racism
Improper complaints procedures
Willful neglect of fraud and/or malpractice

In due course, unless I resign first, I will address each point on this and/or my own blog site at: https://davidfmarks.com/

David F Marks
5 May 20211 CommentBOARD OF TRUSTEESFINANCIAL ISSUESGOVERNANCE

Twenty Tough Questions for ‘the BPS’

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Questions are coming thick and fast from colleagues new to the story of the crisis in the BPS. Of course, they are new to it because, amongst other things, the Board of Trustees (BoT) and Senior Management Team (SMT) have been secretive about the facts. In the past year nothing has appeared in The Psychologist (relevant note: ‘the magazine of the British Psychological Society’) to give the slightest hint of any organisational problems. The CEO’s monthly homilies petered out with no editorial explanation. The President, who has recently resigned, made absolutely no mention of the troubled state of the organisation in her final ‘reports’.

This blog and an increasing number of reputable journalists are now bringing into public gaze the extent of organisational dysfunction in the Society. We have been trying our best to do what the BPS has palpably failed to do in relation to transparency. However, we are not private detectives or forensic accountants and nor do we have the investigatory powers of the Charity Commission. The latter is hovering nearby, but to date it has not fully disclosed its intentions in relation to its ongoing ‘engagement’ with the BoT. Given the very large file of complaints against the Society, we are left wondering what will be the tipping point for them to announce a Statutory Inquiry.

The 20 questions that require answers

Here we raise some questions crossing our minds and those put to us by perplexed colleagues. Ipso facto, we cannot answer them definitively but we can pose them in good faith on behalf of the membership.

  1. Why is the CEO still in post and being paid (from membership fees) but ‘not in his office’?

2. The Finance Director left the Society abruptly just before Christmas last – what were the circumstances surrounding that departure?

3. Was the expelled President Elect genuinely allowed to conduct his duties and was he given access to information appropriate for that task?

4. Was there a deliberate strategy on the part of the BoT and SMT to marginalise and disempower him, given his election pledges to rectify governance problems in the Society?

5. Was there a large fraud conducted in the Society that is still being investigated by the police? 

6. What recruitment checks were conducted on the person who was alleged to have committed the fraud?

7. Who appointed this person?

8. Was the arson attack on the Leicester office during this period of turmoil (unreported to the membership) linked in any way to the alleged fraud investigation?

9. Did the BPS report the arson to the Charity Commission, as it is supposed to do under their guidance?

10. Why did the SMT refuse to give the BoT access to critical information, about the £6 million ‘change programme’?

11. What oversight was the BoT providing of the SMT and how was the effectiveness or otherwise of that oversight assessed? 

12. Did the BoT consider that its culture of information restriction, which we have experienced directly ourselves, reasonable for a membership organisation professing a value of openness and transparency?

13. Why did the BoT make public the alleged grounds for the expulsion of the President Elect in advance of his appeal?

14. How can the President Elect have a fair appeal, when it appears to have been already prejudiced?

15. In light of answers to the above questions, has the President Elect been subjected to a ‘kangaroo court’ or ‘show trial’?

16. Was there a planned and wilful campaign to remove the President Elect by the BoT and SMT, as both a radical reformer and a whistle blower, as soon as he was elected?

17. Have journalists making legitimate enquiries, about all of the above matters, been threatened with legal action by the BPS?   

18. Had the Vice-President, who resigned citing concerns about finance and governance, already ensured that those concerns were reported fully to the Charity Commission?

19. The ACAS definition of bullying is this: “Offensive, intimidating, malicious or insulting behaviour, involving an abuse or misuse of power through means intended to undermine, humiliate, denigrate or injure the recipient.”  Accordingly, does the action of broadcasting a video denouncing the President Elect constitute bullying by the BPS? 

20. Finally, does the BoT now knowingly have a policy to ward off legitimate questions from members about governance matters, by alleging that the questioning, in of itself, constitutes bullying and harassment of BPS staff? 

The final question is rhetorical; as victims of this tactic we can vouch that the answer is in the affirmative. Some of the questions on the list relate to criminal matters and others to aspects of due diligence and common decency. Ordinary members not only pose them now on reasonable grounds, but they deserve reasonable answers. The BoT have warded off the inconvenient truth surrounding the questions, using a mixture of silence, glib evasions, bureaucratic obfuscation and legal threats. 

Is this how we expect a properly functioning learned organisation to operate, with its rhetorical adherence to the principle of openness and transparency? We ask readers to please send us any other questions that come to mind, which we might have missed from the above list. If we cannot answer them we can at least share them.

We will be posting some more detailed analyses of these questions over the course of the next couple of weeks.

The BPSWatch Editorial Collective

How much does the future of the BPS actually matter to you?

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We began this blog and the associated Twitter feed because we were all extremely concerned about what we see as the misgoverance of an organisation that we gave our time and energy to over many years because we believed in what it stood for. What we have seen in recent years is an increasing distancing of those that run the BPS from its membership – as our posts and out tweets demonstrate. The recent expulsion of the President Elect exemplifies the parlous state of the BPS. 

We have had some feedback from people who are of a similar opinion to us, some of which has appeared here, and it’s helpful to know that our concerns are shared by others. We have also had many informal comments of support either applauding our efforts or telling us of similar experiences with this failing organisation. Disturbingly, we have been told of those who, after working hard on behalf of the Society, have left feeling betrayed and traumatised by their experiences. More evidence that change is needed urgently.

But, and it is a big but, we are retired from practice and at are a distance from active involvement in the BPS. Frankly, whether it survives or not will have little practical impact on our lives professionally although its demise would cause us great sadness. But its continued existence as a thriving, member-led organisation which represents the best of UK psychological thinking and practice matters, perhaps never more so than now. Over the half-century that we have been psychologists we have seen such enormous strides made in how psychological practice has grown in maturity and relevance. Psychologist of all sorts and conditions are listened to with respect and can speak with authority. When we started out it was psychiatry that was seen as the ‘go-to’ source of expertise in matters psychological – no more. Psychologists can be proud of the strides that it have made over the years. And that process is almost entirely due to those psychologists, members of the BPS by-and-large, who were willing to spend time and energy to build the discipline, the profession and the BPS. That psychology has got to where it is today is due almost entirely to the hard work – often against the odds – of those who cared deeply and passionately about their discipline. They were not professional, go-anywhere managers – they were psychologists who believed in what psychology could do.

So this is a plea to all those of you who want to be represented by an organisation of which you can be proud. An organisation that reflects and promotes psychology to the benefit of all and of which membership can be seen as badge of honour. The BPS can be this – it is clearly not this right now. Its future cannot depend on the likes of us old codgers alone. It must involve those of you who are still out there, working as psychologists, on whose future the health of a thriving BPS is dependent. It is your responsibility more than ours. 

This is a critical time for the BPS. The current ‘leadership’ is engaged in highly unprofessional actions for which they are not being held accountable. The BPS has no senior member-elected officers. The fact that the Charity Commission is heavily involved is a serious warning sign. There is a commitment of £6 million (yes, £6 million of your money) to an ill-specified and inadequately scrutinised change project. There is a £2 million loan (securitised against two BPS-owned properties) with no CFO or CEO in post to manage or oversee these vast financial commitments. 

This needs you (yes, you) to act now. Be prepared to be rebuffed and ignored or accused of harassment if you express you concerns to the current BPS officials. Write to the Charity Commission with your comments. Read and contribute to the blog. Email the blog – BPSWatch@btinternet.com. Read and forward the Tweets  – @psychsocwatchuk. Share your experience with others.

It’s your Society – and your responsibility to rescue it.

Peter Harvey2 CommentsEXPULSION OF PRESIDENT-ELECT

A challenge to the BPS narrative.

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From the BPSWatch Editorial Collective…..

Since the inception of this blog we have had intermittent contact with the now expelled President Elect around matters of concern regarding what we believed were clearly signs of organisational misgovernance, irregularities and toxic culture at the BPS. These had been separately signposted to us individually when we had dealings with senior staff about a range of policy issues. We had become increasingly alarmed by the way we were ignored, brushed off, rebuked, and, as one of the recent threads on @psychsocwatchuk https://twitter.com/psychsocwatchuk/status/1401165572436602884?s=20  demonstrated, we had our correspondence closed down with implications, explicit or veiled, that we were harassing or bullying staff. During our exchanges with Dr. MacLennan over months, he indicated his growing belief that he would never be allowed to become President and that there were moves afoot to prevent that. Latterly he told us he was sure he would be suspended or expelled for persisting with challenging the current governance process and practice. This was, of course, his stated reason for standing to be elected. Members gave him their backing.

His appeal against expulsion remains unheard and there is another legal matter that remains sub judice so he cannot yet speak out in his own defence, despite all that has been said in print and on a Youtube video that he is a “bully”, deserving only expulsion.

We can say, without hesitation, that in the contacts the three of us have separately had with Dr. MacLennan, we have detected no signs in his manner or his expressed attitudes that he is disrespectful, aggressive or demeaning. And despite all the slights and insults he has received, he remains passionate in his commitment to making the BPS a better organisation.  All three of us have had long careers as clinical psychologists, two of us with very significant forensic experience. We do not just take things at face value when there are conflicting views and narratives about individual behaviour.

Taken in that context, and with Dr. MacLennan unable to defend himself publicly at this stage, we are publishing verbatim a communication that we received from a friend and long-term colleague and collaborator of Dr. MacLennan. We have permission of the author who is happy to be named, and of Dr. MacLennan.

Good Morning,

I have recently been following your articles about Dr MacLennan on BPS Watch and feel your concerns.

I am not a member of the BPS and feel it would be inappropriate for me to pass comment on recent events, but I am a close friend of Nigel and have been horrified at his very public vilification because this is not the Nigel I recognise. While I have my own views, I recognise that there are two sides to every story and I only have one side, but I feel that I must tell you about my relationship with him and, in a sense, to defend him.

But first, a little bit about myself. I served for 30 years as a police officer with Surrey Police. Towards the end of my career I was seconded to the National Leadership Academy for Policing at Bramshill as a Programme Director to deliver programmes on the High Potential Development Scheme and the Senior Leadership Development Programme. While I have delivered all types of Leadership programmes and consultancy services across England, Wales and Northern Ireland (and to every public service) my core programmes were Managing Finance and Resources, Media Strategy (I developed the National Police Media Strategy in conjunction with the highly respected journalist Brian Morris), and Strategic Community Relations. I retired in 2005 and was retained as a consultant until 2015.

In 2012 I became the Honorary Secretary of the British Academy of Management Special Interest Group on Corporate Governance with a special interest in ethics and, in 2013, I became an Honorary Visiting Professor at London Metropolitan University Business School. This is when I met Nigel. With him, I have delivered talks to four Advances in Leadership Conferences, been a judge and Chairman of judges at national leadership awards, and have even delivered a talk at the last BPS conference. I have also worked with Nigel on a 9 month Leadership Development Programme for BAME officers in the Metropolitan Police Service. In my opinion, his skills and talents are without doubt.

As a former police officer, I tend to view people with suspicion until I can understand their motivations and I have never doubted Nigel’s motivations. As you are probably aware, he has had a glittering career working for blue chip companies and organisations such as the Chartered Management Institute and I have found his honesty and integrity beyond reproach. What I particularly liked about him was his assertiveness – he was not afraid to tell you how it is – and this is an in-demand skill for effective leaders. I have learnt many things from Nigel and have been quite happy when he has pointed out that I am wrong and, I hasten to add, vice versa.  In my experience he has never strayed into aggressiveness – forceful yes, aggressive no. However, like me, he does struggle with obfuscation, and this can become a barrier to communication with certain people.

In short, I have always found Nigel to be competent, conscientious, a supreme coach and, above all, honest.

Kindest regards.

Graham Buchanan, BSc(Hons), NdipM, PGCE, CMgr FCMI, FRSALeave a comment“THE PSYCHOLOGIST”BOARD OF TRUSTEESEXPULSION OF PRESIDENT-ELECTGOVERNANCE

The legitimation crisis and a membership denied answers

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David Pilgrim posts….

Today, the concept of a ‘legitimation crisis’ can be applied clearly to the BPS. Although explored at length in a book with that title by Habermas (1974), many other social and political scientists have returned to the theme. This is about leadership regimes, which may notionally still retain power, but their strained credibility reflects an imminent or current breakdown in their actual authority. The cabal currently at the centre of the BPS is still in power but its credibility is in rapid decline. It lacks what Eric Fromm, in his book The Sane Society, called ‘rational authority’ and, instead, exercises power on its own terms in order to ward off the stream of criticism warranted. For Fromm this would be an expression of ‘irrational authority’.

On this blog we have been reporting the character and history of this crisis in recent months and each entry, such as this one, is a new take on an unprecedented state of affairs for the Society. The occasional flurry of criticism of rogue celebrity researchers, such as Cyril Burt (Joynson, 1988) or Hans Eysenck (Marks, 2018), barely dented the reputation of the BPS. Similarly, the spat between the Maudsley methodological behaviourists and their scorned psychodynamic colleagues from north of the Thames, in a struggle to control the Medical Section and its journal, led to a temporary closure of its business in 1958 (Pilgrim and Treacher, 1991). These small eruptions of doubt, that all was well in the BPS, pale into insignificance today. We have never seen anything like this, either in living memory or in the literature on the history of British psychology. Those past examples, looked at in the current context, are like comparing a bar room brawl with a military coup. 

In meetings of the Board of Trustees today all of the Presidential triumvirate have gone, so it contains nobody elected from the general membership. Unelected Senior Management Team members now outnumber Trustees from the sub-systems. This trend is now amplified by the Board preventing members electing a replacement for the radically reforming President Elect, after expulsion from the Society, a cue for the next main point.

The public disparagement of Nigel MacLennan

The video released, vilifying the President Elect in advance of his appeal being submitted and heard, is a complete outrage. It offends our normal understanding of natural justice and leaves the Board of Trustees, who planned its production and dissemination on YouTube, open to the charge of unethical and possibly illegal activity. Are the Trustees so determined to crush this man’s reputation that they will simply ‘do anything that it takes’? 

It is officially the position of the BPS (according to its own website for all to read) not to investigate individual members. However, does that claim fail to apply only when it is politically expedient for the interests of the incumbent leadership? Are the members seriously expected to believe that this has been anything but a ‘stitch up’ from start to finish? Was the investigation panel hand-picked by the Board of Trustees or not? How many on that panel were truly independent and without their own vested interest in the current regime of power? Were membership funds used liberally by the Board to hire legal advice in order to justify the scapegoating of a reformer, turned whistle blower? The questions go on and on. Some of them ultimately may be resolved in court but what is clear already is that Nigel MacLennan has not been treated in a fair manner, if we use everyday criteria of common sense and decency.

If the stitch up hypothesis is in doubt, look at how Carol McGuinness, in a follow-up document to that unedifying and ill-advised video, made it quite clear that even if Nigel MacLennan were to be re-instated on appeal, as a member of the Society, he would still not be permitted back to his role as the President Elect. This nothing-left-to-chance approach, reflecting the persecutory intent of the Board, sticks out like a sore thumb in this planned and vindictive attack on a man whose career has now suffered immediate detriment. 

I can find no justification for this pre-emptive strike from McGuinness, on behalf the Board, within the Statutes and Rules. Does she offer no rule-based rationale in the script she is reading because one simply does not exist? This brings us back to Fromm’s notion of ‘irrational authority’. Those in power often do and say things, simply because they can. But do we have to believe this travesty of justice? And given that under Statute 20 of the Society, the Board should have been chaired on an interim basis by MacLennan not McGuinness, is there an Alice in Wonderland feel to this whole scenario? 

We know that such a surreal quality can indeed emerge from group think, especially when it leads to scapegoating in order to create an illusion of homeostasis and harmony (Baron, 2005; Leyens et al. 2000). The warring factions of the SMT and the Trustees could take temporary comfort in a common enemy to be eliminated, but the facts of the crisis are still there, with or without the removal of MacLennan. Facts do not disappear because they are ignored conveniently by displacement activity or an ostrich stance.

Keeping the membership in the dark

If a making-the-rules-up-as-you-go-along approach to governance now characterises the workings of the cabal, then another supportive tactic has been information control. Nowhere has this been more obvious than in the silence in the pages of The Psychologist. An exception has been the printing of the statement about the expulsion of MacLennan from McGuinness (giving the BPS a free noticeboard posting without editorial comment or analysis), as well as the link to her video. No right of reply was offered to MacLennan. If this were a normal magazine it would reflect the normal rules of journalism and both sides of a story would have been offered, or at least taken into account.

However, this is not a normal magazine. For example, the political turbulence in the Society, should have warranted some commentary but none has been evident. Its inside cover reminds us every month that it is ‘…the magazine of the British Psychological Society…’. If this means that it obeys the contingent expectations of those running the BPS, then this is actually a fair and valid description. However, maybe members of the Society have broader expectations (such as it being a forum for free debate about the current legitimation crisis). Such expectations are indeed raised, conveniently, by the subsequent cover description ‘…It provides a forum for communication, discussion and controversy among all members of the Society…’. Has there been any actual sign of the latter, in practice, in the past turbulent year? Why are ordinary members still playing catch up about the financial scandal in the Society, the fat file of complaints being held by the Charity Commission and the expensive legal shenanigans to expel Nigel MacLennan?

During the crisis, the monthly column of the Chief Executive Officer suddenly disappeared without editorial comment, and we slowly became aware that he was ‘not in his office’ and his function was then taken on by his Deputy, Diane Ashby. And before the President, Hazel McLoughlin, also disappeared from the pages because she had resigned, citing family reasons, the content of her column revealed nothing to the membership of the chaos and tensions, which led to the resignation of the Vice President David Murphy. He explained on Twitter that this was because of his concerns about both governance and finance.  

However, the role of this ‘magazine’ has not gone unquestioned. For example, here is a reply to Pat Harvey from the editor (12.12.20) responding to her criticism of The Psychologist failing to provide information of legitimate concern to the BPS membership:

We are not a ‘house journal’, we are a magazine. Our responsibility is not to speak for the Society or to align with any documents it might publish; it is to provide a forum for communication, discussion and controversy among members and beyond.

This restatement of the confusing and contradictory blurb, cited earlier from the inside cover of The Psychologist, does not cease to be confusing and contradictory simply because it is robotically restated. Does the membership deserve a better journalistic service, during the current legitimation crisis of the BPS, than this sort of vacuous rhetorical gambit? The supine post-it-board role offered by The Psychologist on behalf of the current BPS leadership, reminds us of one of many of Orwell’s dire warnings about democracy: ‘Journalism is printing what someone else does not want printed. Everything else is public relations.’

The exchange between Pat Harvey and the editor of The Psychologist, Jon Sutton, did not end with the above restated confusion. She also wrote to the Chair of the Editorial Advisory Committee, Richard Stephens, starting with a complaint about the narrow and prejudicial role of The Psychologist, when being biddable and posting the offensive video. She made other criticisms of the magazine as well. This was the response she received from Stephens:

Thanks for your letter and for raising these concerns. I plan to table these for discussion at the next meeting of the Psychologist and Digest Editorial Advisory Committee on 24th June. I felt that your first raised point warranted some urgency of response so I discussed it today with our editor, Jon Sutton. Jon’s view was that while the video featuring Professor Carol McGuinness as Interim Chair of the Board of Trustee has been widely disseminated among BPS members, it is unlisted on YouTube. Given that The Psychologist has a much wider audience, Jon reflected that it’s inclusion in the piece “‘The Society is at a crossroads’” was not appropriate. On that basis the video has been removed. I will feedback in due course following our meeting on the 24th

This is a small sign of good sense and fairness from Richard Stephens, although at the time of writing the video is still available on YouTube.  Will this be the start of a period of genuine honest reflection from the Advisory Committee? Would the video have been removed had it not been for these critical questions from Pat Harvey? In my view, it seems as though those below the cabal level in the Society are very slowly waking up to the serious challenges that the legitimation crisis is posing for freedom of expression and balanced and open journalism in the future pages of The Psychologist. Elsewhere on the blog I have addressed the matter of censorship in the Society.

The ethical and legal culpability of the Trustees

The Charity Commission continues to work with the Society to bring it into ‘regulatory compliance’. This raises questions about the role of the Trustees in the recent past. How many of them (other than Nigel MacLennan), out of public interest, took their concerns about poor governance and financial irregularities to the Charity Commission or the press? 

Many resignations have been evident in recent months, including the President and Vice President. Are they now prepared to offer a full and frank account to the membership of what happened in the Board, which went so badly wrong? This could be a starting point for the ‘root and branch’ reform now required, to reverse the demise of the organisation. 

Will they admit that the conflicts of interest inherent to the current definition of a Board (which date back to a lack of specificity in the Royal Charter arrangements in 1988) have been routinely out of sync with current expectations of properly independent trustees in charities today? The current Board of Trustees is a sham because its members all have conflicts of interest and there are no outsiders from the Society to offer impartial oversight. Given the legitimation crisis, should the current Trustees at least own up to this basic fact, resign and insist on a properly constituted Board in line with Charity Commission expectations?  

And if it turns out that the negligence, or worse, of some Trustees has cost the BPS dearly, will they be held liable for these costs, as Charity Commission regulations allow? Will BPS members now seek to hold Trustees liable for the seeming losses incurred to the Society, by their apparent lack of oversight? Will that liability also extend to those who resigned but were in place during that period of apparent lack of oversight (in legal terms this is called ‘legacy liability’)?

This particular legitimation crisis, like all others, never stops posing questions for democracy. We all (not just a few pushy malcontents) need to keep asking them. The passivity in our current zeitgeist about trying to influence events around us does not have to lead to fatalism. We can still challenge the cabal and the current shambles in the BPS, as this blog and Nigel MacLennan have already demonstrated. The more of us taking up this challenge, the less likely that victimisation will be seen and the more likely that the Society will be saved from its own self-inflicted wounds. 

Baron, R. (2005). So right it’s wrong: Groupthink and the ubiquitous nature of polarized group decision making. Advances in Experimental Social Psychology. 37: 35.

Habermas, J. (1974) Legitimation Crisis Boston: Beacon Press. 

Joynson, R. B. (1989). The Burt Affair. New York: Routledge

Leyens, J. Ph., Paladino, M. P., Rodriguez, R. T., Vaes, J., Demoulin, S., Rodriguez, A. P., & Gaunt, R. (2000) The emotional side of prejudice: The attribution of secondary emotions to ingroups and outgroups. Personality and Social Psychology Review. 4, 2, 186–97.

Marks,D.F  (2019) The Hans Eysenck affair: time to correct the scientific record Journal of Health Psychology 24, 4, 409–42.

Pilgrim, D. and Treacher, A. (1991) Clinical Psychology Observed London: Routledge.3 CommentsEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 3

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Was the evidence sound?

As psychologists, from our very earliest years as bright-eyed, bushy-tailed undergraduates, we are used to dealing with evidence. We learn how to evaluate it, how to contextualise data, how to look in detail at the hypotheses, the method, the analyses. We are used to defining behavioural referents for concepts. Professional researchers carry on and refine this whilst practitioners hone their evidence-gathering skills through the interview rather than controlled trial and have to remain alert to their own biases as well as to the inevitable and understandable one-person perspective of their client. Perhaps we could characterise all these approaches as one of benign scepticism, always open to correction the face of new data.  We are assured the BPS commissioned external investigations (presumably at the expense of member subscriptions – will the total cost of all this appear in the audited accounts?) into the allegations and their findings were a central part of the case against Dr MacLennan. All well and good and superficially follows due process. But it raises an important set of questions. As outlined in Part 2, we suggest that Dr MacLennan’s arrival may have heralded an unwelcome intrusion for some in the organisation. Perhaps they had already formed an opinion of him and his reformist zeal and put the shutters up in advance. They were, perhaps, primed to view him as the ‘enemy’. Perhaps Dr MacLennan’s enthusiasm and energy was seen as ‘over the top’. Perhaps he felt he had to be assertive in the face of what he saw, rightly or wrongly, as intransigence and unhelpfulness – and, of course, assertion is not the same as bullying.  We ourselves have been subject to veiled accusations of harassment and bullying, simply because we refused to stop asking questions when legitimate requests for information or clarification were denied (an experience not unique to us). So we would ask how many respondents in the data-gathering exercise actually used the word ‘bullying’? What overt, identifiable behaviours of ‘bullying’ did Dr MacLennan show? And, most importantly, what was the criterion used by any of those involved into what constituted ‘bullying’, especially as there are well-documented definitions available? These interactions presumably took place during the COVID epidemic and in many cases could not have involved an intimidating physical presence. How did the Panel account for the potentially distorting effects of conversations being mediated by technology?

Was the sanction proportionate?

The BPS is clear on the three sanctions available to the Responsible Person (and note here that in the long and highly detailed justification issued by the BPS it contradicts itself saying that the Panel recommended the sanction in one place and that the Responsible Person made the decision, acting on the evidence provided by the Panel in another passage – which was it BPS?). He chose the most serious of the three – immediate expulsion. We have no information as to how he reached that decision other than that it is stated that he was presented with the Panel’s findings – minus, of course, any input from Dr MacLennan. That last point raises the question as to whether, in the light of the possible consequences, he might have thought it advisable, at the very least, to check with Dr MacLennan that he had nothing to contribute. The relevant paragraph of the BPS statement is this

The member conduct process involved a careful review of sanctions applied in other similar cases and in relation to the conduct that might reasonably be expected of a member of this standing and experience.

We are in uncharted territory here as we, as mere members, don’t have access to any data about the outcome of any disciplinary process (which may or may not exist) since part of it was outsourced to the HCPC. In the days when the BPS did take this responsibility seriously, the outcome of investigations was published in The Psychologist. Looking at the statement above, we have no idea as to how many similar cases there have been and we have no idea of how many members have been expelled – and, of crucial importance, for what offences were they deprived of society membership. We have already noted the ‘proportionality’ of sanctions in the light of previous cases and we really do need to know what offences committed by (now ex-) members resulted in expulsion. We are left with the highly general and completely subjective judgement (made by one person) as to what he might reasonably expect of a member of standing. And as we have already noted, he is the Chair of a Standing Committee of the Board of Trustees.

We would also ask how he judged the possible consequences of his decisions on all those involved – particularly on the person who is most affected – Dr MacLennan. We understand that he runs his own business and is more dependent than many psychologists on being able to attract clients – they do pay his income quite directly. He has not only been deprived of his BPS membership – this action, compounded and magnified by the subsequent barrage of publicity will cause enormous reputational damage and may well cost him his livelihood. Did the RP take this into account at all?

In a final act of this grossly public humiliation, we are told by ‘the BPS’

If Professor MacLennan has his membership reinstated on appeal, he would not automatically reassume his role as trustee and President Elect, although he would be eligible for re-election to the Board in line with its usual procedures. The BPS constitution provides mechanisms for filling vacancies on the board and these must be followed. These procedures do not include an option for the board to choose to reinstate Professor MacLennan (as President or President Elect) if his appeal is successful.

This is saying that the BPS can overturn the democratic process ‘just because it can’ – and we are sure that many members would value a sight of the rules that allow this. Should Dr MacLennan be cleared of all charges, then how can the BPS justify not reinstating him to his democratically elected post? He has been expelled from membership the Society, the consequence of which is the loss of his position. Reinstatement of his membership should, therefore, mean being able to take up the post to which he is entitled. This looks very much like a small group within the BPS doing its absolute utmost to ensure that Dr MacLennan never becomes President.

Was the video absolutely necessary? 

Many of you, like us, will have been shocked by the lengths to which the BPS has gone to justify itself and to ensure the widest possible coverage of this unfortunate affair – before the appeal has even been heard. Five closely typed pages, one video (now on YouTube), all going into the grisly and hurtful accusations of a case that has yet to reach its lawful conclusion. This stands in complete contradistinction to the following; the fact that the CEO is out of his office about which the members have been told nothing (not even the fact of it); the police investigation about which the members have been told nothing (not even the fact of it); that the Charity Commission is engaged with the Society about which it needed a bunch of “malcontents” and the resignation of the Vice-President for the BPS to even acknowledge.  These are critical issues for the membership as a whole and could have easily been communicated to us in a way that did not prejudice any legal investigations. So what’s the difference, BPS? Why go in to the sort of supposed detail that is career-wrecking when a simple holding statement would have sufficed? Looks a lot like the actions of a bully to us.

Where from here?

We hope that our highlighting of the issues that we think to be of importance has, at the least, piqued your interest. Perhaps we could encourage you to look further into the workings of your Society – the minutes of the Board of Trustees is a good place to start as much for what it doesn’t say as to what it does. If you are a member of the Senate (a body, as far as we can tell, without Terms of Reference) or know one of the Trustees, perhaps you could ask some questions – and be prepared to fobbed off or accused of harassment. If you have social media links to other colleagues who care about our Society’s future then get involved by spreading the word.

We will do our best to keep you up to speed as far as we are able. 

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.1 CommentEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 2

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Were both sides heard fairly?

The statements from the BPS make the observation that Dr MacLennan declined to present evidence to support his case despite repeated requests. We are at a loss understand this as it is presented. We could speculate that Dr MacLennan might chose to distance himself from a process that he might believe to be illegitimate and be biased against him and that, by co-operating, he would add spurious validity to it. However, it is a surprise that, in view of the seriousness of the issue for him on a personal and professional level, it is implied that he made no efforts to defend himself robustly. We would ask, therefore, whether he was given due time to collect together all the evidence he might need? Was he able to access all available material that would be necessary, such as privileged communications to which he as an office-holder, would be entitled? What efforts were made by either the Panel or the Responsible Person to find our why he would choose to take this course of action? Was the RP able to satisfy himself that Dr MacLennan did not wish to defend himself in the dock?

Was it a level playing field from the outset?

We can have some idea of how the BPS views complaints from this extract from the Minutes of the Board of Trustees meeting in December 2020

“This year has seen a trend for the potential misuse of the complaints process, where it has been used to express a difference of opinion or dissatisfaction with a consultation outcome.The volume of complaints is a strategic risk for the Society and was considered at the Risk Committee.”

Clearly, complaints about the running of the Society are unwelcoming intrusions rather than a learning experience, a risk to be managed. Whilst is it easy to fob off the ordinary member with tactics such as simply not responding, not answering questions or crudely cutting off debate, when an elected officer, who will be an integral part of the organisation arrives, different tactics will be required.

It was very clear from his election statement that Dr MacLennan was a man on a mission – a mission to overhaul the BPS. His successful election (44% of votes cast) must have given him some confidence that he was doing the right thing. His experience, and that of others who he canvassed and supported him, was enough for him to believe that reform was an absolute necessity. We have no doubt that this energy translated into an enthusiasm and diligence to find out, in greater detail, about the mechanics of how the BPS worked (or, more importantly, how it didn’t work). We have no doubt that for some in the organisation this was a significant threat. We have already noted that the BPS had serious problems well before his election and that many people who were meant to have formal oversight of the organisation had – at the very least – taken their individual and collective eyes off the ball (including the Trustees). To support this assertion we can do no more than to quote part of the resignation tweet of Professor David Murphy, lately Vice-President (and therefore a Trustee during his period as President-Elect and President) which identified 

“…governance oversight, escalating expenditure and lack of openness and transparency…”

as one trigger for his leaving. And that of Past President, Professor Peter Kinderman

“…When I was President, I was routinely excluded from key decisions, was threatened with legal action over ‘fraud’ (I was completely exonerated, of course) and forced to resign (as Vice-President) for advocating for what is now effectively BPS policy…”

So we know, from two very senior past office holders, that there were significant problems well before Dr MacLennan was propelled into the scene. And remember that Professor Kinderman was in post for the two years 2015-2017 (until his forced resignation) and Professor Murphy for the years 2018 – 2021.  We also know, from the minutes of the Board of Trustees meeting in December 2020, that some Trustees themselves were anxious enough about the Society to support

“…a wider discussion in relation to a governance review and stressed the urgency of moving forward with this action…”

Bear in mind also that the Leicestershire police are investigating an allegation of a major financial fraud within the Society.  So we have a picture of an organisation that is clearly dysfunctional and under scrutiny and had been so for some considerable period of time. Is it any wonder that some within the organisation, both staff and volunteers, may have felt more than a twinge of anxiety at the arrival of an avowed new broom? We would suggest that in the light of all this, the BPS bureaucracy was on the defensive. This not only might have influenced the trigger for the investigation, it may have influenced its course.

The third and final post will appear tomorrow, Saturday 22 May 2021.

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.Leave a commentEXPULSION OF PRESIDENT-ELECT

Questioning the Expulsion – Part 1

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This is the first of three posts looking closely at the recent expulsion of the Present-Elect.  We will be asking a series of questions about both the process and outcome, identifying what we see as major deficiencies which highlight, in stark detail, the issues which we have been raising about the sorry state of our organisation. Much of this is speculation and informed guesswork, some generalising from our own experiences because, despite the mass of defensive information coming from the BPS there are many serious omissions and obfuscations.

So, to begin at the beginning.

Can we trust the overall process?

Before we get into the fine detail, let’s step back and cast an eye over the disciplinary process itself.  We would remind you that in the Complaints FAQs on the BPS website there is the following statement

The Society does not have a function to investigate complaints against its members…

This, of course, is in complete contradiction to the various statements in the Member Conduct Rules which do outline such a function. If it were sentient, the complaints process would be in a serious existential crisis. 

We must also remember that we have been told, by the Acting CEO, that the Society is undertaking a root-and-branch review of the whole of the complaints procedure. To put it at its mildest, this suggests that all is not well with the process, whether it actually exists or not.

In addition, we must also ask who actually made the decision to pursue this complaint against the President-Elect. Again, to remind you, the CEO is still ‘out of the office’; there is no CFO; the President has resigned; the Vice-President has also resigned citing failures of governance amongst his reasons for going; we have an “Interim Chair” of the Board of Trustees (presumably this same Board that is accused of the aforementioned governance failures); an acting CEO who is, presumably, involved in the issues raised by the President-Elect. So the question remains, who decided? Was it the full Board of Trustees or some select subgroup of the willing? Was the complete (if depleted, of course, due to resignations) Board given full and unredacted information about the reasons for this course of action and its possible consequences? Who chose the Panel members and the Responsible Person? Did the Board as a whole and unanimously sign all this off?

In view of the serious and unusual nature of this whole business – disciplining the only remaining elected senior officer of the Society must surely rate as out-of-the-ordinary – and the fact that this would be subject to more than the usual degree of scrutiny from the membership and the outside world, one might hope (perhaps, vainly, expect) that the BPS would go to some lengths to show that justice would not only be done, but would be seen to be done.  It should be a shining example of how to do things right. This takes on a particular relevance in the light of the current application to the Professional Standards Authority where matters of monitoring and managing professional standards (the clue is in the name) are paramount.

We argue and will, we hope, show that the whole process, from start to finish, is fatally flawed and itself brings the BPS into disrepute. 

How “independent” is independent?

The various self-exculpatory outpourings of the BPS make great play of the ‘independence’ of the investigation. What does that mean to you? To us it suggests – at the very least – that whoever is carrying out the investigation is as far removed from both the current and past history of the BPS as possible. This is not just a matter of not being a Trustee or a member of the SMT. Many of the problems and issues identified by us and by others pre-date the election of Dr MacLennan by many years. Indeed, as we will see later, at least one past President identified serious problems as did the now-resigned Vice-President who had been in post (President-Elect, President) for two years prior to his abandonment of the sinking ship. So any properly constituted investigatory panel should comprise people untainted by previous appointments as Trustees or as senior post-holders with the BPS. This seems to be particularly important in the light of the fact that this may be, to our knowledge, a unique event in BPS history.  Ideally, the panel should be made up of people from outside of the organisation completely. After all, the allegations against Dr MacLennan were of ‘bullying’ – this is a generic, non-organisation-specific behaviour. You don’t need to know about the arcane intricacies of the BPS to recognise bullying when you see it. Again, given the importance of being seen to do this correctly, it would be sensible to have someone who has considerable HR experience. Was this the case?  No, it was formed of some (number unstated) of ‘…our most senior experienced colleagues…’. The fact is, however worthy and experienced,  they are not independent of the BPS. This failure is also shown by asking the Chair of the Ethics Committee to act as the Responsible Person –  who is accountable to and appointed by the Board. As an officer holder of a Standing Committee of the Board of Trustees, he is neither independent of the Board nor of the BPS. We assume (again, lack of detail makes this suppositional on our part) that he was completely distant from the everyday work of the Panel for otherwise he would be unable evaluate the evidence presented with fresh and neutral eyes.

It is stated by the BPS that 

The process was also conducted throughout with the benefit of independent legal advice to give additional assurance that it was being carried out with propriety and fairness.

This could mean all manner of things. Given that the whole complaints process is muddled and inconsistent and would need an awful lot of (expensive) lawyers’ and consultants’ time to sort through and make sense of, we can only hope that the BPS see this is a good use of your subscriptions. But the point we are making is that even if the letter of law was followed to the last dotted i and crossed t this is not the same as ensuring that the overall process was seen to be just. In our view, it could not be.

We will continue to raise questions in Part 2, to be posted tomorrow (21 May 2021).

Peter Harvey, Pat Harvey and David Pilgrim

BPSWatch Editorial Collective.1 CommentBOARD OF TRUSTEESEXPULSION OF PRESIDENT-ELECTGOVERNANCE

The End of Membership Democracy in the BPS?

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The campaign in the self-serving bunker at the centre of the BPS continues unabated. Its main character, which we have documented in our posts in the past few months, includes a number of strands. Some reflect the tactics of evasion and secrecy. They include complaints being ignored, as well as concerns (that are not complaints) being turned into complaints and sent into a rabbit hole.  The complicit non-reporting of the crisis in ‘the magazine of the British Psychological Society’ has been a trusted management mechanism to keep members in the dark. Dictates have been sent out by ‘Trustees’ to Senate members to demand their silence in a comical pantomime of control freakery.

Other tactics have involved clear projection: a bullying and high-handed culture of management has accused its critics of being the bullies. The power asymmetry here between the parties is ignored but that acknowledgment would require a capacity for honest reflectiveness. Journalists just doing their job in a democracy have been threatened with legal action. By any standards of common sense and fair judgement, this precarious regime of power has had a probity bypass. 

The most egregious example of this has been the ‘investigation’ and subsequent expulsion of the President Elect. His sin was to be open from the beginning about reforming the governance arrangements in an organisation which, for years, had flouted the normal expectations of charity law and good practice guidelines offered by the Charity Commission.

What price membership democracy?

The literal price of being in the BPS is known to its membership. For now, some of those fees are maintaining the high salary of a CEO who is still ‘out of the office’, so remains unable to fulfil his duties. Those in the bunker have told us nothing, so members are left to speculate. 

In the few days that have elapsed since the expulsion of the President Elect was announced (in a scripted account – crafted by whom?), matters have deteriorated further. The unprecedented video from the ‘Interim Chair’ of the Board of Trustees was a callous public disparagement of the President Elect. Speaking from an office and role that, under Statute 20 of the Society, she still has no right to hold, her personalised career-threatening attack upon him remains on Youtube for the world to see.

This scandal now has worsened.  A rapid election is to be held to replace the summarily deposed President-Elect before his appeal has even been heard. From well before he took office there were overt intentions to obstruct him wherever possible. We believe that there is evidence to support this that will be made public. Like the ‘investigation’ of the allegations against him this is a travesty. History will judge those responsible for deposing him, so this faux process of justice will peter out to its discreditable conclusion.

In case members are getting too excited about choosing someone new and untainted by what has gone before, they need to be prepared for a disappointment. This is the score. Only candidates from the current Board of Trustees or Senate members will be permitted to stand. This is the very group under whose ‘oversight’ the Charity Commission has become involved on an ongoing basis. There is an active police investigation into an alleged major fraud (watch this space next month). The self-same group from which the Vice-President resigned,  citing issues about “…governance oversight, escalating expenditure and lack of openness and transparency…”, which he communicated to the Charity Commission.  Former President, Professor Peter Kinderman, informs us that several years ago “…When I was President, I was routinely excluded from key decisions, was threatened with legal action over ‘fraud’ (I was completely exonerated, of course) and forced to resign (as Vice-President) for advocating for what is now effectively BPS policy…” .

What sort of real choice are members now given?   

The candidate will be drawn from a pool of complicit individuals. They assume that everything in the garden is rosy and the much-vaunted £6 million Change Programme will supercharge the BPS, when the membership to date have been shown no substantive evidence to support this wishful thinking. 

Meanwhile, for now, any vestige of membership democracy has been placed on indefinite hold. We can only hope that needed legal proceedings, active media interest and decisive action from the Charity Commission will, between them, resolve this sinister and shameful demise of the public face of psychology in the UK once and for all. 

BPSWatch – Editorial CollectiveLeave a comment‘FALSE MEMORY SYNDROME’MEMORY AND THE LAW GROUP

On memories of abuse….

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The BBC websitethe Daily Telegraph and the Daily Mail are all reporting on the trial of an alleged sexual abuser, the widow of a former High Court judge. All quote the following statement by the prosecuting QC

“He tried to bury away the memories and not to think about them”.

As is her right, we have no doubt every effort will be put into her defence, perhaps even involving the British False Memory Society.

How will any witnesses for the prosecution or the barristers involved be able to rely on a balanced, empirically based set of guidelines to argue against any claims that the accuser’s memories may be ‘recovered or false’? The short answer is that they won’t because ‘The BPS’, in its wisdom, has given up on any pretence to take this matter with the seriousness that it deserves by abandoning the revision of its Memory and The Law guidelines (see here).

We can only hope that the court is able to hear from a balanced and fully informed range of expert witnesses. It is shameful than none of the psychologists who may be in that position will be able to call on the backing and support of their professional society.

The BPSWatch Editorial CollectiveLeave a commentGOVERNANCE

The BPS is unfit for purpose

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This was originally sent as a comment to our post ‘The Crisis deepens…’ We felt that it was important enough to stand on its own as a separate post.

TheBPSWatch Editorial Collective.

I am Professor David Marks, membership number 3829, a Chartered Member with FBPsS, currently a member of the Division of Health Psychology, previously a member of other groups and networks. I joined the BPS as a student in 1963. After completing a BSc and PhD I worked in universities in the UK and overseas carrying out teaching administration and research. I have practiced as a psychologist and worked as a consultant to multiple organisations within the NHS, industry and voluntary sectors. I served as Head of Department at two large Psychology Departments, firstly at Middlesex University, where I worked from 1986 to 2000, and then at City, University of London from 2000 to 2010. I founded two scholarly journals and, for 26 years, have served as Editor-in-Chief of the Journal of Health Psychology

Based on my research publications, I was appointed to a BPS Fellowship in 1984. In the early 1990s, I was elected chair of the BPS Health Psychology Section, which was taken into Special Group status and subsequently to a Division. I was actively involved in the BPS accreditation of the first MSc awards in health psychology and the first Stage 2/doctoral training provision in the UK. I sat on various BPS boards and represented the BPS on international bodies. Over many years multiple elected and unelected BPS officers were well known to me and I counted many as personal friends. 

It with sadness and regret that I believe that I must state my concerns about the Society, its organization, working practices and public outputs. 

I am writing this comment in support of the recent blog postings on ‘BPSWatch’. I do not know and have never met any of the three authors. However I have read their postings and find myself in total agreement with the points they have been making. Rather than resign from the Society, which has crossed my mind on numerous occasions, I had always hoped that change could come from within. Now, seeing the total chaos that reigns, and the complete lack of transparency, accountability and honesty with members, I am strongly doubtful.

I can summarise my current thoughts on the BPS in four sentences: 

1) The BPS is grossly failing the public good, its members, and the discipline of Psychology.
2) The current problems of the BPS cannot and will not be solved by tinkering with the system, as has been tried unsuccessfully on a frequent basis over several decades.
3) Only root-and-branch restructuring would be able to make the necessary changes to achieve the objects of its charter.
4) Sadly, I do not believe the BPS has the wherewithal to achieve the necessary structural reorganization that is called for.

The BPS website (https://www.bps.org.uk/about-us/who-we-are) states:
“The British Psychological Society is a registered charity responsible for the development, promotion and application of psychology for the public good.
Through our Royal Charter we are charged with overseeing psychology and psychologists in the UK, and we are governed by a number of democratically-elected boards and committees.”

My nearly 60-year long association with the BPS indicates to me that the BPS is woefully unfit for purpose. The BPS fails to meet its obligations as a registered charity. This fact is evidenced by the Society’s:

Ineffective governance
Lack of accountability
Lack of transparency
Institutional racism
Improper complaints procedures
Willful neglect of fraud and/or malpractice

In due course, unless I resign first, I will address each point on this and/or my own blog site at: https://davidfmarks.com/

David F Marks
5 May 20211 CommentBOARD OF TRUSTEESFINANCIAL ISSUESGOVERNANCE

Twenty Tough Questions for ‘the BPS’

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Questions are coming thick and fast from colleagues new to the story of the crisis in the BPS. Of course, they are new to it because, amongst other things, the Board of Trustees (BoT) and Senior Management Team (SMT) have been secretive about the facts. In the past year nothing has appeared in The Psychologist (relevant note: ‘the magazine of the British Psychological Society’) to give the slightest hint of any organisational problems. The CEO’s monthly homilies petered out with no editorial explanation. The President, who has recently resigned, made absolutely no mention of the troubled state of the organisation in her final ‘reports’.

This blog and an increasing number of reputable journalists are now bringing into public gaze the extent of organisational dysfunction in the Society. We have been trying our best to do what the BPS has palpably failed to do in relation to transparency. However, we are not private detectives or forensic accountants and nor do we have the investigatory powers of the Charity Commission. The latter is hovering nearby, but to date it has not fully disclosed its intentions in relation to its ongoing ‘engagement’ with the BoT. Given the very large file of complaints against the Society, we are left wondering what will be the tipping point for them to announce a Statutory Inquiry.

The 20 questions that require answers

Here we raise some questions crossing our minds and those put to us by perplexed colleagues. Ipso facto, we cannot answer them definitively but we can pose them in good faith on behalf of the membership.

  1. Why is the CEO still in post and being paid (from membership fees) but ‘not in his office’?

2. The Finance Director left the Society abruptly just before Christmas last – what were the circumstances surrounding that departure?

3. Was the expelled President Elect genuinely allowed to conduct his duties and was he given access to information appropriate for that task?

4. Was there a deliberate strategy on the part of the BoT and SMT to marginalise and disempower him, given his election pledges to rectify governance problems in the Society?

5. Was there a large fraud conducted in the Society that is still being investigated by the police? 

6. What recruitment checks were conducted on the person who was alleged to have committed the fraud?

7. Who appointed this person?

8. Was the arson attack on the Leicester office during this period of turmoil (unreported to the membership) linked in any way to the alleged fraud investigation?

9. Did the BPS report the arson to the Charity Commission, as it is supposed to do under their guidance?

10. Why did the SMT refuse to give the BoT access to critical information, about the £6 million ‘change programme’?

11. What oversight was the BoT providing of the SMT and how was the effectiveness or otherwise of that oversight assessed? 

12. Did the BoT consider that its culture of information restriction, which we have experienced directly ourselves, reasonable for a membership organisation professing a value of openness and transparency?

13. Why did the BoT make public the alleged grounds for the expulsion of the President Elect in advance of his appeal?

14. How can the President Elect have a fair appeal, when it appears to have been already prejudiced?

15. In light of answers to the above questions, has the President Elect been subjected to a ‘kangaroo court’ or ‘show trial’?

16. Was there a planned and wilful campaign to remove the President Elect by the BoT and SMT, as both a radical reformer and a whistle blower, as soon as he was elected?

17. Have journalists making legitimate enquiries, about all of the above matters, been threatened with legal action by the BPS?   

18. Had the Vice-President, who resigned citing concerns about finance and governance, already ensured that those concerns were reported fully to the Charity Commission?

19. The ACAS definition of bullying is this: “Offensive, intimidating, malicious or insulting behaviour, involving an abuse or misuse of power through means intended to undermine, humiliate, denigrate or injure the recipient.”  Accordingly, does the action of broadcasting a video denouncing the President Elect constitute bullying by the BPS? 

20. Finally, does the BoT now knowingly have a policy to ward off legitimate questions from members about governance matters, by alleging that the questioning, in of itself, constitutes bullying and harassment of BPS staff? 

The final question is rhetorical; as victims of this tactic we can vouch that the answer is in the affirmative. Some of the questions on the list relate to criminal matters and others to aspects of due diligence and common decency. Ordinary members not only pose them now on reasonable grounds, but they deserve reasonable answers. The BoT have warded off the inconvenient truth surrounding the questions, using a mixture of silence, glib evasions, bureaucratic obfuscation and legal threats. 

Is this how we expect a properly functioning learned organisation to operate, with its rhetorical adherence to the principle of openness and transparency? We ask readers to please send us any other questions that come to mind, which we might have missed from the above list. If we cannot answer them we can at least share them.

We will be posting some more detailed analyses of these questions over the course of the next couple of weeks.

The BPSWatch Editorial Collective

Featured

Insights from ME/CFS May Help Unravel the Pathogenesis of Post-Acute COVID-19 Syndrome

New paper by:

Anthony L. Komaroff 1 and W. Ian Lipkin 2

1 Division of General Medicine, Department of Medicine, Brigham and Women’s
Hospital, Harvard Medical School, Boston, MA
2 Center for Infection and Immunity, Mailman School of Public Health, Columbia
University, New York, NY

Available here from 7 June 2021

Journal Pre-proof
DOI: https://doi.org/10.1016/j.molmed.2021.06.002

Citation: A.L. Komaroff and W.I. Lipkin, Insights from Myalgic
Encephalomyelitis/Chronic Fatigue Syndrome May Help Unravel the Pathogenesis of
Post-Acute COVID-19 Syndrome, Trends in Molecular Medicine (2021),

https://doi.org/10.1016/j.molmed.2021.06.002

Keywords: myalgic encephalomyelitis/chronic fatigue syndrome, SARS-CoV-2, COVID19, post-acute sequelae of SARS-CoV-2, post-COVID-19 syndrome, long COVID

Abstract


SARS-CoV-2 can cause chronic and acute disease. Post-Acute Sequelae of SARSCoV-2 infection (PASC) include injury to the lungs, heart, kidneys and brain, that may produce a variety of symptoms. PASC also includes a post-COVID-19 syndrome (“long COVID”) with features that can follow other acute infectious diseases as well as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of acute COVID-19, and speculate that
the pathogenesis of post-COVID-19 syndrome in some people may be similar to that of
ME/CFS. We propose molecular mechanisms that might explain the fatigue and related
symptoms in both illnesses, and suggest a research agenda for both ME/CFS and postCOVID-19 syndrome.

Highlights

In some people, the aftermath of acute COVID-19 is a lingering illness with fatigue and cognitive defects, known as post-COVID-19 syndrome or “long COVID”.

Post-COVID-19 syndrome is similar to post-infectious fatigue syndromes triggered by other infectious agents, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition that patients often report is preceded by an infectious-like illness.

ME/CFS is associated with underlying abnormalities of the central and autonomic nervous system, immune dysregulation, disordered energy metabolism and redox imbalance. It is currently unclear if the same abnormalities will be identified in post-COVID-19 syndrome.

The US and other developed nations have committed considerable support for research on post-COVID illnesses.

A.L. Komaroff and W.I. Lipkin, (2021)
Featured

The Rise and Fall of the Wessely School

New preprint available here

ABSTRACT

The Wessely School’s (WS) approach to medically unexplained symptoms, myalgic encephalomyelitis and chronic fatigue syndrome (MUS/MECFS) is critically reviewed using scientific criteria. Based on the ‘Biopsychosocial Model’, the WS proposes that patients’ dysfunctional beliefs, deconditioning and attentional biases cause illness, disrupt therapies, and lead to preventable deaths. The evidence reviewed here suggests that none of the WS hypotheses is empirically supported. The lack of robust supportive evidence, fallacious causal assumptions, inappropriate and harmful therapies, broken scientific principles, repeated methodological flaws and unwillingness to share data all give the appearance of cargo cult science. The WS approach needs to be replaced by an evidence-based, biologically-grounded, scientific approach to MUS/MECFS.

Featured

Psyche in Mythology and the British Psychological Society of Today

Psyche/ˈsʌɪki/the human soul, mind, or spirit

“their childhood made them want to understand the human psyche and to help others”

Similar: soul spirit(inner) self innermost self(inner) ego true being essential nature life force vital force inner man/woman persona identity personality individuality make-up subconscious mind intellect anima pneuma

Opposite: body

Wikipedia

the fountain of knowledge in the contemporary world, states :

Psyche (mythology)

Psyche (/ˈsaɪkiː/;[2]Greek: Ψυχή, romanizedPsukhḗ) is the Greek goddess of the soul. She was born a mortal woman, with beauty that rivaled Aphrodite. Psyche is known from the story called The Golden Ass, written by Lucius Apuleius in the 2nd century. See Cupid and Psyche.

The following text is extracted directly from Wikipedia and adapted to the world of the British Psychological Society, which uses Psyche as its figurehead and logo image. Readers can make their own comparisons to recent events within the Society, such as these may be discerned by interested parties.

Early life

Psyche was the youngest child of a Greek king and queen. She had two elder sisters. She was the most beautiful among her siblings and she looked like a goddess among mortals. She was so beautiful that people, including priests, compared her to Aphrodite, the Greek goddess of love and beauty. Many went to the extent of saying that she was even more beautiful than the goddess. When Aphrodite’s temples were deserted because people started worshiping Psyche, the goddess was outraged. As a punishment, she sent their son, Eros, to make Psyche fall in love with a vile and hideous person. However, Eros fell in love when he saw her and decided to spare her from his mother’s wrath.

Both of her elder sisters were jealous of her beauty. Her sisters eventually got married with kings and left to be with their partners. Nobody asked Psyche’s hand for marriage; people would rather admire her beauty. She was left alone. Desperate, her father decided to consult the oracle of Delphi to get answers.

Wikipedia

Marriage to Eros

The story continues:

[Psyche’s] father, the king, consulted the Oracle of Delphi for the solution of this problem. From inside the priestess, Apollo himself spoke. He said, “Despair, king. Your daughter will marry a beast even the gods fear. Dress her in funeral clothes and take her to the tallest rock spire in the kingdom. There, she shall meet her doom.” Hearing this, the king was heartbroken. But since he had got direct orders from Apollo, he did as he was ordered.

He took her in funeral clothes to the tallest rock spire in the kingdom. Psyche waited for the beast to come, but when it did not come, she took matters in her own hands. She jumped off the spire. Everyone in the kingdom thought she was dead.

[This is precisely how some members view recent events within the British Psychological Society.]

But Zephyrus the Greek lord of west wind, had saved her from death. He had taken her to Eros‘s palace where she waited until night for Eros to return. There, she saw that the palace was very large and each cupboard was filled with gold. When Eros returned, he said to Psyche in utter darkness that she must not see him. She must not try to see him and he can’t tell her his name or it would ruin everything. 

The first few weeks of Psyche’s life in the palace were great, but soon she heard her sisters calling out her name. Her two sisters convinced her to see her husband’s true form, in case he was tricking her.

Psyche eventually listened to what they told her. She snuck into her husband’s room with an oil lamp and a knife. Psyche shone the light on her husband’s face, and a small drop of hot oil fell onto his shoulder, awakening him and burning him.

Betrayed by his wife’s actions, Eros ran off to his mother, Aphrodite. After learning what she had done, Psyche was miserable and depressed.

Aphrodite found Psyche and made her face four trials. 

Wikipedia

Trial Number One

According to the myth, Psyche’s first trial was to sort a huge mount of seeds. With the help of an empathetic ant colony, Psyche completed this task.

Wikipedia

Translating ‘seeds’ as ‘data’ and ‘ants’ as ‘BPS members’ creates a simile for the current organisation of the British Psychological Society.

Let me explain.

Recently I contacted Neil Baker, the Society’s Diversity and Inclusion Manager seeking any existing sociodemographic data held by the Society on the diversity of the BPS membership and workforce including gender, ethnicity and age. Neil responded as follows:

“the BPS declaration on equality, diversity and inclusion has formed the basis of all work relating to EDI (Electronic Data Interchange) over the past five years, including our commitment to anti-racist practice and decolonising the curriculum. The declaration will be replaced later this year by a brand new 18 month strategy incorporating EDI outcomes...

“In terms of demographic data BPS has been working hard to ensure demographic and diversity data form a core part of all membership systems. This work will lead to roll out of a brand new CRM system for membership over the next six months…

Our commitment to capturing data is embedded in our core belief that membership data can help the society actively challenge prejudice and discrimination, while promoting equity, social mobility and inclusion. While at the same time, allowing us to explore potential gaps, barriers and/or concerns for members as they undertake their membership journey.”

In spite of all its professed, good intentions, the BPS is yet to collect any sociodemographic data on its membership and so does not have the foggiest idea about this issue.

It is notable that Neil Baker has neglected to provide any information on the socio-demographics of the BPS workforce. Surely the Society must have this information in its HR department but, seemingly, prefers not to reveal it. One can only imagine why this might be the case.

The Society’s official policy and its actual practice could not be more different. I can illustrate this fact with an account of a personal experience of what can happen when one attempts to “actively challenge prejudice and discrimination, while promoting equity, social mobility and inclusion.

[Health warning: expect to be insulted, attacked and canceled if you should ever have the audacity to attempt this.]

In July 2017, I tweeted about The Psychologist‘s penchant for ‘white’ people on its covers and in its content of its publications. Editor Sutton responded that I was being “shrill and condescending” and he would “continue the discussion today with others who might have more constructive stuff to say”.

Sutton later accused me of trolling him, something he (wisely) later retracted.

Jon Sutton states his mantra that his team believe they are “doing good things”.

Then comes a very curious statement: “over those four years we’ve repeatedly been criticised on here in the opposite direction…”

What could this possibly mean – that the Psychologist editor has been repeatedly criticised by BPS members for being too non-racist?

If so, that is extremely alarming. Because there has been an objective, racist bias within BPS publications over the entire history of the organisation aided and abetted by its appointed editors. There are multiple examples.

The Society’s deletion of members’ comments does not pass unnoticed:

So much for the ability of concerned members to challenge the Society’s publication practices and policies.

The BPS needs to establish an anti-racist policy which is supported by a statistical database of the sociodemographic diversity of its membership that can be tracked over time.

It is unacceptable in the third decade of the 21st century that the BPS is playing catch up on a process that has been standard in reputable institutions of higher learning for years.

Psyche, wake up from your slumbers. Wake up, or you will die.

Trial Number Two

[Psyche’s] next task was to gather wool from a notoriously dangerous sheep. Psyche was saddened but helped by a river god, who taught her to collect pieces of wool from bushes.

Let’s translate ‘wool’ as ‘criticism’ , ‘dangerous sheep’ as ‘critics’ and the ‘river god’ as the recently deposed President-Elect. The latter had been elected on an explicit platform to transform the Society’s out-dated and ineffective structure and governance.

It is current practice of the Society’s unelected officers to not respond to, cancel or delete all forms of criticism. Witness this example. I submitted the following (abbreviated) critical comment on The Psychologist website on 2nd June 2021. As predicted, it got deleted five days later, but not before it had been archived:

Pravda-esque

Permalink Submitted by David F Marks on Wed, 06/02/2021 – 10:25

If the issues affecting the BPS and its membership had never been more serious and dire, I would think this article on “Power Posing” must be an embarrassing joke…

Readers interested in how their membership fees are being squandered can get up to speed by reading “The legitimation crisis and a membership denied answers” available at: https://bpswatch.com/. You will not find any of the most essential information here in the Psychologist. It has all been embargoed by the unelected management.

Instead of doing a genuine job as a forum for “communication, discussion and controversy”, this magazine hides behind the coattails of senior management and drags its readers through the pseudoscientific depths of topics such as ‘power posing’.  

Contrary to its published statement to “provide a forum…among all members of the society” and “to promote the advancement and diffusion of a knowledge of psychology pure and applied”, the Psychologist’s editor, Jon Sutton, serves as a minion of the unelected officers of the BPS Psychologist. BPS members are treated with contempt by the Society and its magazine. This un-peer-reviewed magazine claims to promote advancement of knowledge; on the contrary it promotes a regress to the lowest common denominator of  content that aims to be ‘popular’. Unfortuntaely, ‘Pop Psychology’ tends to be ‘Pseudopsychology’, as Mr Loncar’s article demonstrates. 

The Psychologist fails to address the most relevant truth: the BPS has reached a nadir in its reputation as a professional society and has no credible governance. In parallel, a nadir has been reached by the Psychologist in the art of bullshitting as eloquently explained in the May issue by Emma Young: “people who bullshit more often in a bid to impress or persuade others are also more susceptible to bullshit themselves”. 

As the complaints mount up, the Charity Commission is investigating. One fears that the ending of the BPS story will not be a good one. 

The BPS needs to stop debarring, deposing, canceling and deleting those who are critical of its policies, practices and governance, start listening to its members and to radically transform at root-and-branch level its current processes of communication, governance and decision making. Or it will die.

Trial Number Three

[Psyche’s] next task was to collect water from the underworld. Psyche was now assisted by the eagle of Zeus, who collected the water for her.

Translate ‘water’ as ‘evidence’, the ‘underworld’ as ‘malpractice’, and the ‘eagle of Zeus’ as ‘ethics procedures’ and the simile is pertinent to the recent practice of the Society.

In my capacity as Editor of the Journal of Health Psychology, an independent, non-BPS journal, and as a BPS Fellow, I wrote an Open letter to the Chief Executive of the BPS about the malpractice of a major figure within British Psychology, the late Professor H J Eysenck:

Dear Mr Bajwa,

I am writing about a serious matter concerning the research integrity of a person who one can presume was a member of the British Psychological Society. In the interests of openness and transparency, this is an Open Letter. If left unresolved this is a matter that can be expected to produce potential harm to patients, to biomedicine and science, to your institution, to its members and students. Although Professor Hans Eysenck died in 1997, the issue of alleged falsified science committed by the late Professor remains current to the present day.

To give a few examples, the 2017 edition of Eysenck’s autobiography published by Springer, in relation to the causal link between smoking and cancer, states, ‘On a purely statistical basis the causal efficacy of smoking – if this can be deduced at all from a simple correlation – is very much less than that of psychosocial factors; about one-sixth in fact’ (Eysenck, 2017Rebel with a Cause. Kindle Locations 3759–3761). Is the claim that psychosocial factors are six times more important than smoking something that the British Psychological Society is content to endorse or is it a claim that the BPS would like to see corrected? Or consider where Eysenck describes the effectiveness of psychotherapy in preventing cancer: ‘The total number of deaths in the control group was 83 per cent, in the placebo group 81 per cent, and in the therapy group 32 per cent, again demonstrating the efficacy of the method in preventing death from cancer and coronary heart disease’ (Eysenck, 2017, Kindle Location 3804–3806). Or the section where Eysenck claims that ‘there is some evidence that behaviour therapy may be useful in prolonging life, as well as in preventing disease’ (Eysenck, 2017, Kindle Locations 3821–3822).

I hope that the Society will add its voice to those who are requesting that the relevant publishers and journals should correct or retract Eysenck’s publications wherever they can be shown to contain questionable data-sets or claims that are known to be false.

The case is fully documented in Dr. Anthony Pelosi’s peer-reviewed article: ‘Personality and fatal diseases: revisiting a scientific scandal’. As the Editor responsible for the peer review and publication of Dr. Pelosi’s article, I have every confidence that Dr. Pelosi’s evidence and conclusions are reliable and true. In light of the policies and statutes of the British Psychological Society concerning research integrity I bring this case to your attention for investigation. A full and thorough investigation would be good for Psychology, for the research integrity of the BPS as a professional society and for the welfare of patients and the general public.

I look forward to your response.

Kind regards, David F Marks BSc PhD CPsychol FBPsS
Editor, Journal of Health Psychology

The letter was sent two-and-a-half years ago (in October 2018) and no reply has ever been received. This lack of response is discourteous and unprofessional. Some might say plain rude.

The BPS needs to stop prevaricating, formulate a clear, unambiguous ethics policy and implement that policy without fear or favour. Or it will die.

Trial Number Four

The myth continues:

Psyche’s last task was the most difficult; she had to bring back some of Persephone’s beauty for Aphrodite. Persephone willingly gave Psyche some of her beauty. When she was near Olympus, Psyche opened the box of Persephone’s beauty, but the only thing inside was the essence of death.

Psyche died, but her husband, Eros, who had forgiven her, saved Psyche’s life and took her to Olympus.

Psyche was made the goddess of the soul.

Task four requires no translation.

Conclusion

What will be the fate of Psyche? Will she be saved, or will she forever remain a myth of a bygone age?

Featured

Can Long-Covid be Cured with the Mind: Expert Patient or Nutty Professor?

Guest authored by Dr. Keith Geraghty
I am a research fellow working from the University of Manchester Centre for Primary Care. A major focus of my work is on medically unexplained symptoms and illness. I promote evidence-based medicine and psychology, so like a detective, I spend a lot of my time discerning ‘good’ and ‘bad’ data and science, particularly in the field of health psychology. I am currently researching ‘Long-Covid’, the name giving to a syndrome of lingering symptoms post-Covid infection. The Office of National Statistics recently reported an alarming figure that 1.1 million people in the UK may be experiencing Long-Covid, with symptoms lasting anything from a few weeks to a year or more.

‘Weird as Hell’: From Near Death to Diving

Perhaps the most famous of all Long-Covid patients is Professor Paul Garner at Liverpool School of Tropical Medicine and a founding member of the Cochrane Collaboration, a group that seeks to provide credible answers to the many questions impacting modern medicine. Garner began blogging about his struggle with Covid that he contracted on the 19th March 2020 in the British Medical Journal website. His blogs continued through until January 2021, whereby he details his experience of suffering Long-Covid for 7 months. Garner has done considerable amounts of media engagements, an interview on BBC Newsnight, live interviews on BBC Breakfast, interviews for radio and TV in Australia, CNN, media in the US, Europe and beyond, newspaper articles, blogs and live zoom meetings with senior NHS clinicians, regaling of his personal story. Garner has done more media on his Covid experience than most academics might do over the course of their entire careers.

Garner’s story resonated with many doctors and health professionals suffering from Long-Covid, many of whom had to stop working due to lasting symptoms like extreme fatigue, pain, breathlessness and cognitive complaints. What a great story, a doctor and professor going out there telling the world that Long-Covid is real and that recovery takes time – only problem, my fact detector hit high alert when a patient sent me a picture of Professor Garner on a diving holiday in Grenada in November 2020 during the midst of the pandemic and around the time of the UK travel lockdown, and smack bang in the middle of his media stream.

Stepping into a ‘Parallel Universe’: From Near Death to Diving in Grenada

Wow I said: “what a remarkable recovery story, to go from near death’s door to diving in the Caribbean sea”? I had listened to the professor on BBC Breakfast in January 2021 and he made no mention of his trip abroad, and even more curiously, I had listened to a BBC Radio Leeds interview he gave on 5th of October 2020 where he stated he had ‘only started to feel a bit better in the last week or two’. Could someone with Long-Covid, who said they could hardly get out of bed for many months, go from that level of poor health to being able to dive in the Caribbean within the space of a month? I wanted to know more

Piecing the Garner story together required a notepad, a pen, and some of the type of head scratching you might see on an old episode of the Columbo detective show.

He Could Control His Brain, he said

I don’t doubt the veracity of Professor Garner’s Covid story, his symptom profile fits the classic presentation, but he does admit that he has never had an actual positive Covid test. This is not unusual – many Covid sufferers do not get tested or attend hospital. My interest in the Garner story peaked when I read a number of interviews with him where he said he put his recovery down to being able to ‘control his brain and stop fatigue and alarm signals to his body’. Essentially, Garner now claims that be cured his Long-Covid using the power of his mind. In his Sept 4, 2020 BMJ blog, Garner wrote:

“Has covid-19 gone?” My first thought every morning for six months. A few weeks ago, I was jubilant. The muscle aches had evaporated, my head was clear. I announced this to Rachael, a friend who knows chronic fatigue well. “Fantastic, Paul. You have found your baseline.” Crestfallen, I realised this was not the end; it was the end of the beginning.

Garner often uses metaphors to describe Long-Covid, such as ‘like a cricket bat that hits you over the head’ – an apt but perhaps ornate wording to use for a professor of infectious diseases who must have seen many hundreds of patients with similar post-infectious symptoms over the years. So, by early Sept 2020 Garner had a dramatic fall in symptoms but some lingering issues. Like detective Columbo, I noted the importance of the timeline.

He recounts doing a 10-minute bike ride prior and having some symptom flare. This is commonly known as post-exertional malaise and is often seen in post-infectious illnesses, such as chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS) – and illness I research. At this point, Garner talks about his illness resembling ME/CFS. His concern about this would be well-founded, many ME/CFS patients report that their illness started after an infection, and while some recover relatively quickly, a large percentage go on to suffer debilitating symptoms for years.

So, how does Garner go from Long-Covid and possible ME/CFS in September to full recovery in October and diving in November?

He Receives a ‘Magical’ Phone Call

The answer, according to Garner, lies in a mysterious phone call he received from a psychology coach in Norway, whom he claims helped him overcome his fear of exercise. He writes in one interview 12 March 2021:

Later, she asked what I most feared. I said payback and relapse from exercise, which was making me sad as I love exercise. So she suggested we both went for (separate) bike rides, and left the video call running then meeting back at the computer. She would help me deal with any side effects from the cycle ride. I went out on my bike, a gentle 20 minutes, and I was just overjoyed. I was suddenly out doing what I love which I’d stopped myself doing because of all this fear and there was absolutely no kickback. Then I used graded exercise therapy, which is often recommended for chronic fatigue. I started with 20 minutes a day for a week, then up to 30 minutes in the second week. After two weeks, I was back at my military fitness class in the park.

So, Garner’s symptoms had subsided in September and he was doing 10-minute bike rides and sometime in October he was able to have no symptoms after a 20-min bike ride and a magical phone call from his coach. Within 2 weeks he was back doing full military exercises in the park – a truly remarkable tale. Garner writes that he was a fitness fanatic pre-Covid infection, thus he was delighted to be back at his local park doing regular exercise.

Can the Conscious Mind Heal the Body?

Garner says in his January 2021 BMJ blog that,

I was asked, “are you open to the idea that you can have an impact on your symptoms with your conscious mind?” and that “This opened the door that led to my recovery”.

I returned to my notebook: Garner had written to an ME/CFS patient in early October 2020 stating that he did not have the classic ME/CFS symptom of orthostatic intolerance (difficulty standing) and that he was doing 5km walks daily, but was fearful of increasing the distance. In a TV interview Garner gave to Channel 5 news aired 23rd of September, Garner can be seen walking relatively long distances around Liverpool docklands and getting a local ferry, yet in the same interview Garner reported that he still felt ‘disabled by Long-Covid’. Garner’s perception of his disability is not in question, my only observation concerns the fact a person doing 5km walks daily would not generally meet any criteria for ME/CFS, as Garner claimed, and the physical improvements around Sept-Oct appear to have occurred prior to his meeting with the mysterious Norwegian psychology coach that led to his statements that he overcame Long-Covid using his mind.

Garner’s claims about the power of mind to heal illness are not new in my field of research; the only question is what evidence do we have for such claims. In this case, we have the personal account of one patient’s story, albeit a very influential and prominent patient who holds centre-stage in many media reports on Long-Covid and a doctor who seems to be at the epicentre of professional forums with NHS leaders about how best to treat Long-Covid patients. Garner has come out in favour of a controversial treatment called Graded Exercise Therapy (GET), a treatment that the National Institute of Health and Care Excellence (NICE) UK plans to drop as a recommended treatment for ME/CFS. Garner has been critical of this decision.

Healing over Time – Naturally

What is most remarkable to me as an evidence-based medicine and health psychology researcher is the fact a professor of infectious diseases and expert in evidence-based medicine, makes scant mention of the fact that the vast majority of Covid sufferers will recover in time, even those who suffer Long-Covid. Research by Kings College London suggests that around 10-15% will suffer lingering symptoms lasting longer than 6 weeks, but again by the end of year 1 this percentage will be vastly lower.

The human body takes time to recover from infections, people recover at different rates and humans experience illness and symptoms in different ways. Covid-19 is a novel human disease, and we do not fully understand how it impacts health, but early data suggest the majority of people will recover. However a significant but smaller percentage of patients may well continue to suffer longer term health complications. Eventually most people recover simply by the body’s own healing powers of homeostasis.

So, why does Garner put his recovery down to the power of his mind, rather than the power of his body and cells, which operate largely outside of his conscious control?

Believing the mind can cure Covid is perfectly fine as a belief, some people believe crystals can help heal illness, others believe in the power of prayer. I make no disparaging comment on anyone’s beliefs, but Professor Garner is not a lay person. Since his miraculous recovery he has sat on high-level medical meetings with NHS clinicians regarding the best way to manage patients with Long-Covid. Garner’s story and position carry weight – he is no ordinary patient, hence why media outlets chose his story above that of many other sufferers. Therefore the details of his personal case-study and beliefs are of importance.

Mistories

Garner, like all of us, is at the mercy of one of the strongest biases in everyday experience: ‘subjective validation’. The mind-body connection is a fascinating and complex research topic, but the brain is also part of ‘the body’ – such a distinction is often missed. Being ill causes anxiety, and a global pandemic that has killed many people impacts collective anxiety. Being struck down by a mysterious virus, must be a terrifying experience, many people will require medical and psychological support, but it’s important that personal anecdote does not become factual dogma – that is why ‘evidence-based medicine exists’.  

In Garner’s January blog he uses yet another metaphorical soundbite when he says he ‘stared down the barrel of ME/CFS and disarmed it’. Garner claims he met the Canadian Consensus Criteria for ME/CFS. This Criteria requires at least 6 months unexplained fatigue and 5 other symptoms that are not associated with an acute or linked illness. Garner was suffering from Covid, this explained his symptoms, and he recovered within 6-7 months, so he either never had ME/CFS or met the criteria for 1 month before full recovery. This point exemplifies the potential harm of taking one person’s story as ‘credible evidence’ – evidence-based medicine exists to overcome such bias. Yet, Garner continues to tell media outlets and health care officials that exercise is a good treatment for both ME/CFS and Long-Covid and he continues to promote his story of mind-over-matter. In a November interview Garner did with Swedish TV, a reporter asked him how get got out of bed to do military exercises in the park, he states he ‘Got up out of bed, relaxed, thought about nice things and jumped on my bicycle and went off to fittness class…and felt better that evening’

Symptoms ‘Evaporated’ Overnight

The implicit message Garner promotes is that others with ME/CFS and Long-Covid, many being health professionals like doctors and nurses who’ve been unable to recover fully since contracting Covid working on the frontline of the NHS, should just stop being afraid of exercise, relax and get outside. Such a narrative grossly distorts the reality of the diseases ME/CFS and Long-Covid, minimises the role of immune and other physiological dysfunction in these disorders, and stigmatises sufferers as anxious hypochondriacs – symptoms are real, but not related to anything biological. His underlying claim is that symptoms are manifestations of fearful thoughts that can be overcome with the mind. This is not a scientific explanation, it’s one man’s story, it won’t fit all patients, it may be dangerous for some patients to ignore symptoms and head to the park for exercise, it’s also insulting to many others, both ME/CFS and Long-Covid patients, doctors and health care staff, health care assistants in nursing homes and so on, who remain unwell after putting themselves in harms-way. Professor Garner states that he has the support of his employer during his months of convalescence, many Long-Covid sufferers aren’t so lucky and will suffer ongoing physical, mental and economic challenges.

Conclusions

Paul Garner’s recovery may have had very little to do with his mind, yet his mind now tells him it was the most important factor. That is perhaps the true power of the mind. The mind subjectively validates the stories one tells about oneself.

In his early media posts Garner said pacing helped, and also diet, sleep, rest, accommodating to the virus and setting up a self-help support group, all before the magical mind guru entered his Long-Covid tale.

This researcher wishes Professor Garner continued good health, but remains concerned that Long-Covid NHS care planning could be influenced by anecdotal stories; we must listen to all patients and be evidence-led.

text © Keith Geraghty, 2021

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Myalgic encephalomyelitis/ chronic fatigue syndrome as a breakdown of homeostasis

David F Marks published on 31 May 2021 here

Abstract

Homeostasis is a fundamental physiological principle that ensures equilibrium, stability and safety of the organism in a continuously changing and potentially life-threatening environment. This article introduces a new theory of the aetiology of ME/CFS that hypothesises that ME/CFS is caused by a breakdown of homeostasis that produces an aberrant state of disequilibrium with endocrinological and immunological changes.  The current hypothesis is that ME/CFS involves a changed set point such that homeostasis persistently pushes the organism towards a pathological dysfunctional state because the disequilibrium fails to reset. To use an analogy of a thermostat, if the ‘off switch’ of a thermostat stops working,  the house would become warmer and warmer without limit. Here I summarise the evidence in support of the theory. Clinical trials to investigate the role of suggested biological mediators such as thyrotropin-releasing hormone in ME/CFS would appear to be helpful.

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Neural mechanisms of social homeostasis

Annals of the New York Academy of Sciences

Gillian A. Matthews and Kay M. Tye First published: 15 March 2019 

https://doi.org/10.1111/nyas.14016

Originally published as a REVIEW

Open Access Article

This is an open access article distributed under the terms of the Creative Commons CC BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

You are not required to obtain permission to reuse this article.

Abstract

Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating “social homeostasis.” We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long‐term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

Introduction

The twenty‐first century has unleashed a tsunami of opportunities for social engagement and accelerated the flow of social information. Yet as our outlets for social sustenance proliferate, along with the global population,1 there is a paradoxical increase in social isolation within society.2 The proportion of the population who live alone has risen3 and an increasing number of people experience loneliness.45 Social isolation presents itself in multiple forms including social rejection, exclusion, ostracism, discrimination, social loss, or neglect—all of which have a significant negative impact on emotional state. Across the animal kingdom, social isolation can threaten survival—individuals lack protection from predators, assistance foraging, support raising offspring, opportunities for social play, and mating prospects. Similarly, in humans, deficits in objective quantity and/or subjective quality of social relationships can compromise longevity.6 Lower social integration (assessed by network size/participation, living arrangements, and frequency of close social contact) is predictive of elevated mortality,69 and even just the perception of isolation (colloquially referred to as loneliness) is associated with poor physical and mental health1011 and higher mortality rates.1213

However, beyond just constituting an unwelcome emotional side effect of social isolation, loneliness is theorized to represent an “adaptive predisposition” providing the motivational drive to maintain social contact and prevent the aversive consequences of isolation.1415 This adaptive response to deviation from an expected quantity/quality of social connections is reminiscent of negative feedback mechanisms triggered by challenges to physiological homeostasis, such as energy balance or thermoregulation.

In our review, we introduce the idea that coordinated adaptations across discrete neural circuits function to maintain “social homeostasis.” The term social homeostasis has previously been applied to the maintenance of stable organization within a large group of animals, typically social insects, such as ants, termites, and bees. This “supraorganismal” structure requires tight regulation to maintain stable social organization when met with changes in the environment or internal composition.1617 Here, we propose to extend this concept to the individual level in order to encourage a mechanistic understanding of how deficiencies in social connection are detected and evaluated, and how effector systems are activated to compensate for perturbations.

Social homeostasis: a widespread phenomenon

Homeostasis classically refers to physiological processes wherein stable states are maintained through compensatory mechanisms.18 Homeostatic systems are known to exist for a number of physiological needs essential to survival such as thermoregulation, energy balance, and osmoregulation. These rely upon detection of a deviation from a defined homeostatic “set point,” followed by central coordination of a response in a “control center,” and the recruitment of “effector systems” that interact with the environment to correct the deviation (Fig. 1). Challenges to physiological homeostasis can also elicit motivated behaviors associated with strong negative “drive” states, such as overheating, thirst, and hunger, designed to appropriately adapt/direct behavior.1921

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Figure 1Open in figure viewerPowerPointProposed model for social homeostasis. Based on Cannon’s classic model for homeostatic regulation,18 we propose that a social homeostatic system consists of a detector to sense a change in overall quantity/quality of social contact, a control center to compare this deviation to the individual’s set point, and effector systems to correct the change. (A) Detection of social signals (both their quantity and quality) would require social recognition in order to facilitate recall of previous social encounters and determine the expectation for interaction. Information relevant to the identity of the social agent (recognizing that individual as such) as well as estimation of their relative social rank would be required for appropriate evaluation of a deviation. Integration of this information may occur at the level of the detector (model A) or the control center (model B) stage of processing. Identity and rank information may be represented in an overlapping or nonoverlapping fashion (callout box). For a familiar animal, both these variables may be incorporated to set social expectation, but for an unfamiliar animal, only rank perception would be available. (B) Deviations from the set point would be evaluated within the control center by comparing the current social input to the homeostatic set point for quantity and/or quality of social contact. The social control center may integrate information pertinent to other homeostatic needs (e.g., energy balance, fluid balance, and thermoregulation) in a “hub and spoke” fashion (model A), or the social control center may be subservient to other homeostatic control systems (model B). Alternatively, integration of homeostatic needs may occur in a convergent arrangement onto shared effector systems (model C), with interconnections between control centers (model D). (C) If a deviation from set point is determined, effector systems may be engaged to correct the change. This process could include activation of “external” effectors to promote behavioral adaptation (e.g., social approach/avoidance) along with “internal” effectors to adjust internal/emotional state (model A). Alternatively, engagement of internal effector systems, and a change in emotional state, may itself promote behavioral adaptation (model B).

While a change in social connection may not appear to constitute an immediate challenge to internal stability, individuals on the social perimeter are vulnerable and becoming isolated can threaten survival. Even in controlled laboratory environments (where external threats to survival are absent), the presence of social contact is associated with increased life span across a range of social species including honeybees, ants, Drosophila melanogaster,2223 mice,2425 and rats,2628 as well as in free‐ranging groups of macaques29 and baboons.30 Therefore, an emerging social neuroscience model posits that evolutionarily conserved neurophysiological mechanisms underlie the adaptive, short‐term, self‐preservation mode triggered by a lack of social connections/mutual protection.1431 This model proposes that loneliness operates as an aversive signal designed to promote adaptation to the vulnerabilities of being alone and motivate reconnection.32 Thus, the long‐term disease states perpetuated by chronic loneliness may result from the prolonged engagement of neural systems that were intended for short‐term preservation.

To begin unraveling how the chronic state of loneliness emerges, it is necessary to first understand the neural response to social deficit. Conceptualizing this as the response of a homeostatic system would apply certain defined principles (Fig. 1). A social homeostatic system would be required to (1) monitor social conditions; (2) detect deviation from a homeostatic “set point” in control centers; and (3) activate effector systems to elicit an appropriate response (e.g., strategies to promote social contact). A deficit in social connections (whether perceived or actual) would be predicted to engage this system. In animals, one way to create a social deficit is to remove social contact entirely. While this only captures the objective component of social isolation, it offers controlled conditions for assessing rapid neurophysiological adaptations. Chronic social isolation, particularly in rodents, has been used as a developmental model of early life stress since many of the long‐term maladaptive changes resemble features of human neuropsychiatric disease.33 This rich body of work has been comprehensively reviewed elsewhere for both rodents3337 and nonhuman primates.3840

Alternatively, here we examine the response to acute social isolation (using under 1 week as an arbitrary operational definition of “acute” for the purpose of the review) in order to identify candidate neural circuits involved in the rapid response to social deficit. We focus primarily on experiments in social rodents, including laboratory mice (Mus musculus), rats (Rattus norvegicus), and prairie voles (Microtus ochrogaster), which are social species, adapted to group living, but with different styles of social behavior. The wild species of mice and rats from which laboratory strains were derived are promiscuous and territorial, but show greater social tolerance in high‐density living environments and adopt linear dominance hierarchies that promote group stability.41 In a laboratory setting, mice and rats prefer social company (even that of other males) over a solitary existence.4243 They show conditioned preference for regions previously associated with social contact,44 make nests in close proximity to conspecifics when partially separated,4345 and will actively work to obtain social contact.4647 Alternatively, prairie voles are socially monogamous and form an enduring, selective bond with their partner following mating. They show biparental care toward offspring, tend to live in extended families,4849 and are well utilized in the study of social bonding and isolation.

Here, we evaluate social isolation–induced adaptations in these rodents, in light of the phenotype of human loneliness, which may also represent a state of activation of “social homeostatic systems.” We have categorized the behavioral and neural adaptations into three broad themes: (1) hypervigilance/arousal; (2) social motivation; and (3) passive coping. We propose that parallel, overlapping circuits mediate the response to social deficit (the output of homeostatic “effector” systems) in an effort to heighten attention to environmental stimuli, motivate social reconnection, and limit emotional distress (Fig. 2). While we can only speculate as to the neural identity of the detector, control, and effector systems in a social homeostatic network, we anticipate that a cohesive understanding of the response to social deficit will help unmask candidate neural substrates.

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Figure 2Open in figure viewerPowerPointNeural circuit components implicated in the response to social deficit. Pathways, neuromodulators, neuropeptides, and receptors showing modifications following acute social isolation in rodents. Circuit components are colored based on their involvement in hypervigilance, social motivation, and passive coping. Other prominent projections/connections are shown in gray. Coordinated activity across these parallel, overlapping circuits may function to maintain social homeostasis by heightening attention to environmental stimuli, motivating social reconnection, and limiting emotional distress. 5‐HT, 5‐hydroxytryptamine (serotonin); ACTH, adrenocorticotropic hormone; AT1, angiotensin II receptor 1; BNST, bed nucleus of the stria terminalis; CeA, central amygdala; CRF, corticotropin‐releasing factor; CRFR1/2, corticotropin‐releasing factor receptor 1/2; DA, dopamine; D1/2, dopamine D1/2 receptor; DRN, dorsal raphe nucleus; Hp, hippocampus; KOR, ĸ‐opioid receptor; LC, locus coeruleus; MeA, medial amygdala; MOR, μ‐opioid receptor; NAc, nucleus accumbens; NE, norepinephrine; OT, oxytocin; PFC, prefrontal cortex; PVN, paraventricular hypothalamic nucleus; VMH, ventromedial hypothalamus; VTA, ventral tegmental area.

Homeostatic response to social deficit: promoting hypervigilance

An evolutionary perspective on the origins of loneliness proposes that the vulnerabilities of isolation promote hypervigilance to guard against potential threats.50 Lonely individuals often show high levels of anxiety,5152 and hypervigilant responses to negative social stimuli, suggesting heightened recruitment of attentional and self‐preservation mechanisms.53 In rodents, acute isolation can promote behaviors that indicate enhanced arousal and heightened vigilance. For example, adult rats show an increase in escape‐related behaviors over 1–7 days of isolation,54 along with a reduction in exploratory behavior and an increase in self‐grooming.5557 Targeted manipulations in rodents have unveiled that anxiety‐related behaviors arise from activity across distributed, interconnected corticolimbic circuitry, which interpret and evaluate incoming environmental stimuli (reviewed in Ref. 58). One major output system is the hypothalamic–pituitary–adrenocortical (HPA) axis, which regulates arousal, vigilance, and attention, in concert with central arousal circuits including the lateral hypothalamic (LH) orexin/hypocretin system, locus coeruleus (LC) noradrenergic neurons, basal forebrain cholinergic neurons, dorsal raphe nucleus (DRN) serotonergic neurons, and midbrain dopaminergic neurons.5960 Several of these neural circuits exhibit rapid adaptations following acute social isolation. Here, we briefly outline the nature of these changes and their potential role in the response of a social homeostatic system.

HPA axis

Glucocorticoid production is initiated by paraventricular hypothalamic nucleus (PVN) secretion of corticotropin‐releasing factor (CRF) into the hypophyseal portal system, triggering adrenocorticotropic hormone (ACTH) release by the anterior pituitary that in turn acts on the adrenal cortex to secrete glucocorticoids. The HPA axis is regulated by a negative feedback loop, wherein glucocorticoids bind to receptors in the pituitary and other brain regions including the hippocampus, which subsequently inhibits CRF and ACTH production. While acute activation of the HPA axis can be an adaptive physiological response to salient events, chronic activation of this system, particularly by continued psychosocial stressors, is implicated in the progression of multiple disease states and psychopathologies.61 Consistent with this, high self‐reported loneliness in humans has been associated with elevated daily cortisol output6266 and a flattening of diurnal cortisol rhythm,65 suggesting poor regulation of the HPA axis.67

Heightened HPA axis activity (evidenced by a robust increase in circulating corticosterone and ACTH) is observed after 1–5 days of social isolation in juvenile (3–5 weeks old)6869 or pair‐bonded adult7072 prairie voles. Peripheral corticosterone levels are also reportedly increased in male mice isolated for 12 h,73 and both pituitary ACTH and adrenal corticosterone are increased in male rats isolated for 24 h in a novel environment.7475 This recruitment of the HPA axis during acute periods of isolation may reflect the increased need for vigilance and attention to salient stimuli.

CRF signaling

CRF pathways are a prominent point of convergence for isolation‐induced adaptations. Aside from their role in initiating the neuroendocrine response to stress, PVN CRF neurons are pivotal in orchestrating the rapid, complex behavioral adaptations that occur following acute stress (potentially via glutamate coreleasing projections to neighboring hypothalamic regions).76 CRF‐producing neurons are also widely distributed in extrahypothalamic regions, including the bed nucleus of the stria terminalis (BNST), central amygdala (CeA), nucleus accumbens (NAc), and hippocampus,7779 which have, likewise, been implicated in the behavioral and physiological responses to stress. Isolation of preadolescent female (but not male) mice for <24 h decreased the excitability of PVN CRF neurons in a glucocorticoid‐dependent manner.80 This finding may reflect glucocorticoid feedback–induced suppression of CRF activity. Consistent with this interpretation, a 24‐h isolation of adult rats decreased CRF mRNA and protein in the PVN75 and decreased cortical CRF1 receptor levels.81 Moreover, these changes in CRF were accompanied by enhanced angiotensin II (ATII) AT1 receptor expression in the PVN.74 ATII is a circulating endocrine factor that can trigger CRF production in response to stress.82 This factor may be necessary for isolation‐induced adaptations within the hypothalamic CRF system, as the isolation‐induced decrease in CRF mRNA in male rats could be prevented by an AT1 receptor antagonist.75 Conversely, a shorter period (1 h) of social isolation in adult male and female prairie voles housed with same‐sex siblings, resulted in increased hypothalamic and hippocampal CRF mRNA.83 This discrepancy may reflect the shorter duration of isolation or the different species under study. However, it highlights the growing need for a thorough understanding of the timeline of adaptations following social isolation.

LC noradrenergic system

The LC is the sole source of noradrenergic innervation to the central nervous system, best known for its role in arousal and vigilance, but more broadly thought to be recruited to combat environmental challenges.8485 In adult rats, a 24‐h isolation increased tyrosine hydroxylase (TH; the rate‐limiting enzyme in catecholamine synthesis) mRNA in the LC, an effect that could be blocked by an AT1 receptor antagonist.81 Thus, the acute response to isolation involves coordination across both peripheral and central neuromodulatory systems.

Homeostatic response to social deficit: engaging social motivational systems

In humans, a deficit in social connections is conceptualized to engage the “social monitoring system”86 with the purpose of directing attention toward socially relevant information. Accordingly, individuals that either self‐identified as lonely or expected a lonely future showed enhanced sensitivity to social cues and increased socially affiliative motivation.8690 Enhanced social motivation is similarly evident in acutely isolated rodents: when given the opportunity, previously isolated (2‐ to 48‐h duration) juvenile and adult rodents spend more time engaged in social behaviors.9198 It is suggested that up to 7 days of isolation promotes affiliative social behavior and social interest in rats,5792 whereas in adult mice, a significant increase in aggressive behavior was observed after 48 h, but not 24 h of social isolation.99

For many social species, the inherently rewarding nature of social interactions is a major driving force for social contact. In rodents, one method to evaluate the positive reinforcing properties of social interaction is the social conditioned place preference (social CPP) assay—an adaptation of a test traditionally employed to measure the rewarding properties of drugs of abuse.44 In this task, animals typically demonstrate preference for a place previously paired with social housing over one paired with isolate housing (∼24‐h duration44). Notably, therefore, the conditioned approach to a socially conditioned context may be a product of both “social reward” and “isolation aversion.”44 Several neuromodulatory systems (including dopamine, oxytocin, and opioid circuits) are posited to underlie the motivation for social reward. These circuits are also prominent sites of rapid adaptation following social isolation, which we discuss below. The degree to which neural circuits for “social reward” and “isolation aversion” overlap and diverge remains to be determined.

Ventral tegmental area dopamine system

The midbrain dopamine system has a long‐standing role in reward processing100 and affiliative social behavior,101 and is frequently reported as a site of isolation‐induced adaptation. The ventral tegmental area (VTA) dopamine neurons project to multiple regions including the striatum, prefrontal cortex (PFC), and basolateral amygdala (BLA), with the VTA–NAc pathway being particularly well associated with social reward.102103 In juvenile rats, isolation‐induced social play was suppressed by D1‐ or D2‐receptor blockade in the NAc,104 while in adult rats, 24 h or 4 days of isolation decreased striatal D2‐receptor density105 and increased mesostriatal TH activity,106 respectively. Isolation‐induced changes do not appear to be limited to the mesostriatal pathway, however, as adolescent mice isolated for 1–7 days showed an increase in cortical dopamine metabolism.107 Additionally, in the PFC, decreased GABAA‐stimulated chloride influx was evident in a membrane preparation from 24‐h isolated rats108 along with reduced benzodiazepine binding,81 indicating a decrease in cortical GABAA expression and/or function. Given the functional diversity of dopamine input to striatal subregions109110 and dopamine’s divergent effects on cortical projector populations,111 further work is necessary to elucidate precisely how these rapid isolation‐induced changes to dopamine neurotransmission influence downstream activity.

DRN dopamine system

Another component of the midbrain dopamine system—the DRN dopamine neurons—also exhibits acute isolation‐induced adaptations. These dopamine neurons were historically considered a caudal extension of the VTA, but accumulating evidence has revealed distinct downstream projections and functional roles.112118 In adult male mice, 24‐h social isolation potentiated glutamatergic synapses onto DRN dopamine neurons, and also heightened their activity in vivo in response to a novel mouse.118 Artificially enhancing activity of DRN dopamine neurons with optogenetic stimulation was sufficient to increase social preference. However, in the absence of a social stimulus, mice chose to avoid receiving stimulation of DRN dopamine neurons (demonstrated by real‐time and conditioned place avoidance), which suggests the induction of a negative affective state.118 DRN dopamine neurons may, therefore, be recruited following acute isolation to elicit “negative drive”–induced social motivation, in a manner distinct from the reward‐related social motivation mediated by the VTA–NAc dopaminergic pathway.103 Consistent with this assertion, optogenetic inhibition of the DRN dopamine population had no effect on sociability in group‐housed animals, but it suppressed social preference following 24 h of isolation.118

The DRN dopamine neurons lie directly upstream of several regions, most notably the BNST and CeA.116118 While the explicit role of dopamine in these regions in social behavior remains to be determined, dopamine receptor signaling can modulate synaptic transmission and activity in both the BNST and CeA.115118120 Specifically, in the dorsolateral BNST blunting of long‐term potentiation (LTP) is evident after 24 h of social isolation in male mice.121 Given that dopamine in the BNST can facilitate glutamatergic transmission, via a CRF‐dependent process,119 it is tempting to speculate that increased dopamine neurotransmission following acute isolation may occlude LTP.

Interestingly, it was recently revealed that an intermediate duration of isolation in mice (2 weeks) is associated with upregulation of the neuropeptide tachykinin 2 (TAC2; also known as neurokinin B) in several regions including the anterodorsal BNST (adBNST), CeA, and dorsomedial hypothalamus (DMH), with levels gradually increasing from just 30 min post‐isolation.122 Behavioral changes observed following 2 weeks of isolation appeared to be mediated by TAC2 upregulation in discrete sites, as chemogenetic silencing of TAC2‐expressing neurons in the adBNST, CeA, or DMH selectively prevented persistent freezing, acute freezing, or aggression, respectively.122 Notably, ∼50% of TAC2‐expressing neurons in the adBNST and CeA co‐expressed CRF,122 which again highlights the involvement of CRF circuits in isolation‐induced adaptation. A substantial body of work supports a role for the BNST in mediating sustained responses, and the CeA in mediating rapid responses, to potential/unpredictable threats.123 This behavioral control is enabled by the far‐reaching connections of the BNST and CeA, particularly with hypothalamic and brainstem structures, which underlies their ability to influence autonomic and neuroendocrine functions.124125 These regions are therefore well positioned to drive isolation‐induced adaptive responses, under modulatory control from upstream regions, including the DRN dopamine neurons.

This collection of findings compels the hypothesis that dopaminergic signaling may be involved in the initial response to social isolation, but that downstream regions (including the BNST and CeA) might exhibit longer term remodeling/plasticity following chronic isolation. Indeed, there is considerable evidence to support a similar model for the stages of drug‐evoked plasticity in the mesocorticolimbic dopamine system. Specifically, a single dose of cocaine is sufficient to potentiate glutamatergic transmission onto VTA dopamine neurons after 24 hours.126 Synaptic strength returns to baseline levels within a week, however, this VTA plasticity is required for the persistent changes that occur downstream in the NAc following prolonged cocaine exposure127 (reviewed in Ref. 128). This permissive role of synaptic plasticity in VTA dopamine neurons could similarly be a feature of DRN dopamine neurons in the response to social isolation. Such a feature would predict that acute isolation‐induced synaptic changes in DRN dopamine neurons precede, and are necessary for, chronic isolation‐induced adaptations in downstream regions. In this way, the myriad of maladaptive behavioral changes associated with long‐term social isolation37 might result from chronic engagement of neural circuits mediating the acute response to social isolation and persistent remodeling in downstream regions.

Opioid system

The opioid system exerts a broad influence on neural activity through widespread expression of opioid peptides and receptors, most notably within regions connected to positive reinforcement (reviewed in Ref. 129). Opioid signaling plays well‐documented roles in regulating pain/analgesia,130 reward processing,129 and social bonding,131 and has also been implicated in isolation‐induced social behavior. In vivo autoradiography revealed changes to opioid receptor binding, with 7 days of isolation in juvenile rats associated with upregulation of opioid receptor number or affinity in the PFC.57 Additionally, isolation‐induced social play in juvenile rats was attenuated by systemic administration of a μ‐opioid receptor (MOR) antagonist97132 or a ĸ‐opioid receptor (KOR) agonist,132 but enhanced by administration of a MOR agonist.97 Furthermore, in the CeA, infusion of an ACTH analog suppressed isolation‐enhanced social interest in 7‐day isolated rats, but this was prevented by administration of naltrexone (a MOR and KOR antagonist).56133 Therefore, both opioid and dopamine receptor signaling may be necessary for the heightened sociability evoked by acute isolation.

Hypothalamic oxytocin system

Oxytocin‐producing neurons of the PVN, along with the closely related vasopressin (AVP) neurons, are intimately involved in the regulation of social affiliation134 and have been particularly well studied in the monogamous prairie vole, as they play a pivotal role in pair bonding.135 Oxytocin neurons project not only to the posterior pituitary where they release oxytocin into the bloodstream but also to distinct targets within the brain for direct modulation of neuronal activity. One important site for oxytocin action is the NAc, which is a critical hub for the integration of motivationally relevant information and relays information to elicit motor responses.136 In male prairie voles, 3 days of isolation from a bonded female partner, but not a male sibling, decreased oxytocin mRNA in the PVN and oxytocin receptor binding in the NAc shell.137 Notably, oxytocin signaling in the NAc is reportedly essential for the expression of social CPP in adult male mice.138 Specifically, it was elegantly demonstrated that social CPP required activation of oxytocin receptors on presynaptic terminals in the NAc arising from DRN serotonergic neurons—facilitating serotonin release.138 Social CPP was further shown to be dependent on the PVN oxytocin projection to the VTA.139 Either suppressing activity in the PVN–VTA pathway or VTA dopamine–specific knockout of oxytocin receptors prevented social CPP in male mice.139 Collectively, these findings illustrate the dynamic balancing of dopamine, oxytocin, and serotonin signaling that is required for the reinforcing properties of social interactions.

Acute isolation has also been demonstrated to disrupt social recognition memory.140 Rodents possess an innate tendency to investigate novel rather than familiar social stimuli and typically reduce their investigation of a familiar conspecific on repeated exposure.141 This effect is absent in mice isolated for 24 h or 7 days, who display equivalent investigation of a familiar juvenile compared with the first exposure.142143 This lack of social recognition memory is associated with a suppression of oxytocin‐dependent synaptic plasticity in the medial amygdala (MeA) following 7 days of isolation in rats.144 Impaired social recognition memory may also result from elevated hippocampal Rac1 (a small GTPase), which is evident in male mice isolated for 24 h or 7 days.145 Thus, isolation‐induced modifications to oxytocin signaling, in a pathway‐specific manner, may contribute to changes in both social motivation and social recognition memory.

Homeostatic response to social deficit: a self‐protective coping strategy?

Individuals that self‐identify as lonely frequently exhibit features of negative affective state or depression.1050146149 Furthermore, individuals swayed toward feelings of future loneliness (by receipt of false feedback following a questionnaire) show a reduction in physical pain sensitivity and emotional sensitivity.89 This suggests the adoption of self‐protective strategies to minimize further emotional distress. While we cannot directly measure emotional state in rodents, we can assay motivated behavior as a proxy.58150 In rodents, immobility in the forced swim and tail suspension tests is thought to reflect passive coping and/or behavioral despair151152 (but see Ref. 153). There is a general lack of agreement over whether acute isolation alters immobility in these assays in mice.5573154 However, more consistent results have been obtained in monogamous prairie voles, wherein females or males isolated from their bonded partner for 3–5 days show an increase in immobility time.7071137

There is also evidence for disruption of reward‐related behavior in acutely isolated rodents, specifically in the response to addictive drugs. In rats, a 24‐h social isolation increased preference for ethanol and opioid intake, which was reversed with social housing.155156 Reduced pain sensitivity has also been reported, with male mice and juvenile rats exhibiting higher thermal and mechanical pain thresholds following 2–7 days of social isolation.157158 The prominent role of dopamine and opioid signaling in mediating the effects of drugs of abuse159 and analgesia130160 makes them strong contenders for underlying these adaptations. In particular, chemogenetic activation of ventrolateral periaqueductal gray (vlPAG)/DRN dopamine neurons can promote antinociception,117 while lesion of these neurons suppresses both the antinociceptive161162 and rewarding163 properties of exogenous opioids. Furthermore, inhibition of VTA dopamine signaling in mice can induce depression‐related behaviors,164 while KOR antagonists are proposed to have antidepressive effects in rodents (see Refs. 165167). In this way, interaction between the dopamine and opioid systems may underlie isolation‐induced changes to reward processing, pain sensitivity, and emotional affect.

In addition to dopaminergic and opioidergic mechanisms, isolation‐induced depressive‐like behavior may result from changes in the balance of CRF and oxytocin neurotransmission. Specifically, the passive coping behavior observed in pair‐bonded prairie voles isolated for 3 days was prevented by NAc shell infusion of a CRF2 receptor antagonist, or oxytocin, throughout the period of isolation.137 Microdialysis experiments suggest a mechanism by which this effect is mediated via presynaptic CRF2 receptor activation on oxytocin terminals in the NAc, which serves to reduce oxytocin release.137 These findings point toward a confluence of isolation‐induced adaptations in the NAc. The NAc receives strong glutamatergic input from thalamic and cortical regions, enabling it to integrate motivationally relevant information from neuromodulatory nuclei with higher cognitive and sensory input.168 Thus, this region is aptly poised to adapt goal‐directed behavior in response to social deficit.

Proposed attributes of components within a social homeostatic system

Flexibility

Animals are frequently faced with conflicting signals in the environment, which can elicit competing motivational drives. To ensure survival, animals must appropriately weigh environmental cues and evaluate them in light of current homeostatic need state. Selecting the appropriate behavioral response under these conditions requires dynamic coordination of neural activity.169 Thus, a key requirement for a social homeostatic system is its capacity for flexibility. Specifically, a change in environmental conditions and/or need state (e.g., hunger and thirst) may require a shift in the “set point” for social contact in the control center (Figs. 1B and 3). This will be heavily influenced by dynamic factors, such as resource availability, predator threat, mating prospects, and the presence of offspring.

image
Figure 3Open in figure viewerPowerPointLong‐term integration of social experience within a homeostatic system. (A) Under normal conditions, appropriate functioning of a social homeostatic system would maintain social contact quantity/quantity within an acceptable dynamic range. Experienced social interactions may be assimilated and assessed (compared with set point) in a sliding window fashion across time (e.g., days/months). Social quality and quantity information might be weighted differently depending on the individual (traits) and current environmental conditions. The set point could be determined by a combination of factors including age, sex, species‐typical behavior, and past history of social encounters. (B) Failure of homeostatic system to correct deviations in social contact quantity/quality might result in a chronic deficit. This deficit (whether perceived or actual) may be associated with chronic engagement of homeostatic effector systems, and experienced as a state of loneliness. (C) Major life or environmental changes, such as moving away from home, or switching jobs, might provoke the need for a shift in set point. A stable shift in set point, and acceptance of a new expected quantity/quality for social contact, could represent an adaptive change. This shift may prevent social homeostatic effector systems from being chronically recruited and promote continued balance.

For example, in a state of hypernatremia (elevated plasma sodium, which is associated with the perception of thirst), rats exhibit greater social investigation of a novel intruder.170 This effect is proposed to have evolved to suppress anxiety in social situations, such as those encountered at a communal source of water, in order to promote social approach and allow drinking behavior.170 This observation suggests that social motivation can be altered by other physiological needs. Intriguingly, acute hypernatremia in rats is associated with increased plasma oxytocin, increased c‐Fos expression in magnocellular PVN oxytocin neurons, and suppression of ATII production.170 Given that ATII signaling can drive HPA axis activity, these data suggest that hypernatremia concomitantly suppresses activity within stress‐related circuitry, while promoting activity in social reward‐related oxytocin pathways, thereby inhibiting stress/anxiety‐related behavior and facilitating social interaction. This relationship illustrates overlap and coordination across homeostatic systems and also demonstrates the flexibility of effector systems.

The motivational state of hunger is another essential homeostatic drive that promotes rapid neural adaptations.171172 Specifically, the agouti‐related protein (AgRP) neurons in the arcuate nucleus of the hypothalamus are essential in the maintenance of energy balance, and increasing their activity can rapidly drive feeding behavior.173 Interestingly, in isolated mice, optical stimulation of AgRP neurons, or physiological hunger, provoked feeding, even in the presence of a novel male or female mouse.171 This finding suggests that AgRP activity in a state of hunger is sufficient to override a competing social motivational drive. Conceptually, it is possible that competing homeostatic drives are integrated into a social homeostatic system at the level of the control center in a “hub‐and‐spoke” fashion, or they may form an interconnected hierarchical arrangement that converges on effector systems (Fig. 1B). While it is possible that one homeostatic system may be subservient to another, an interconnected network would permit flexible control in a state of motivational need competition, prior to convergence on effector systems. Precisely how these homeostatic systems interface with one another remains to be elucidated.

Maintaining physiological variables, such as core body temperature and energy levels, within an appropriate dynamic range relies heavily upon a functioning immune system. Inflammation is theorized to be a unifying feature of homeostatic perturbation: providing a protective response to extreme deviations from the homeostatic set point.174175 Adverse conditions, including social isolation, can provoke a shift in immune function: enhancing expression of proinflammatory genes and reducing expression of antiviral/antibody‐related genes in circulating leukocytes.176 Social isolation may recruit this response to appropriately prepare an individual for the susceptibilities of being alone, which might include an increased need for a rapid inflammatory response to combat bacterial infections sustained through physical injury, but reduced need for protection against socially transmitted viral infections.15176 This immune response also appears to be recruited in a state of perceived isolation—humans with high self‐reported loneliness show enhanced proinflammatory activity but reduced antiviral response.66177179 Immune system changes can also predict subsequent loneliness, suggesting a reciprocal relationship between these two phenomena.64 Remarkably, classifying rhesus macaques as putatively high in loneliness (by sociability levels and social initiation attempts)180 revealed leukocyte gene expression changes similar to those observed in lonely human subjects.64 The recruitment of inflammatory processes under conditions of actual or perceived social isolation31 suggests that this state is recognized as a threat to an essential variable. As such, this supports the assertion that social contact may be regulated in a homeostatic manner.

Mixed selectivity

Considering the neural processing of “social homeostatic” information, one possibility is the existence of dedicated neural circuitry. An alternative model would feature overlap between neural systems governing social homeostasis and other highly conserved neural circuitry. This scenario would predict that certain nodes in a social homeostatic network display “mixed selectivity,” similar to neurons underlying other complex cognitive processes.181 In particular, this is conceivably a feature of “effector” regions in a homeostatic system. The disinhibition of VTA dopamine neurons, for example, has been shown to enhance motivation toward a variety of stimuli ranging from social stimuli to novel objects.182183 Furthermore, activation of BLA input to the ventral hippocampus or medial PFC (mPFC) not only induces robust anxiety‐like behavior in exploratory assays but also suppresses social investigation in the resident–intruder assay.184186 Perturbations in social behavior are often, but not always, co‐expressed with anxiety‐related behaviors, and there is significant overlap in their neural correlates, which suggests a tight relationship between these two forms of behavioral expression.58187

The DRN dopamine system is another prime example of overlapping circuit function. Monitoring fluorescent calcium activity in vivo revealed that these neurons are active in response to social stimuli, and this activity is heightened following acute isolation.118 However, these neurons are also responsive to other salient stimuli, including palatable food and unexpected foot shock, and show greater activity during wakefulness compared with sleep, suggesting an arousal‐promoting function.112115188 This diversity of sensitivities is consistent with the notion that neural circuits regulating social homeostasis may promote attention to a variety of salient stimuli, in an effort to scan the environment for potential threats or opportunities for social engagement. It was also recently reported that optogenetic or chemogenetic inhibition of DRN dopamine neurons during fear conditioning suppressed freezing in response to a footshock‐predictive cue, suggesting an additional role in aversive responding.115 Taken together, these findings illustrate the existence of multiple mechanisms through which DRN dopamine neurons may limit the vulnerabilities of being alone: increasing social motivation, promoting vigilance/arousal, and enhancing responsivity to aversive stimuli.

Considering the potential for mixed selectivity, the recent observation that activation of DRN dopamine neurons not only increases social preference118 but can promote antinociception117 could be reconciled in a number of ways. One possibility is that functional heterogeneity exists within this cell population. Another possibility is biological convergence in the representation of emotional pain and nociceptive pain in DRN dopamine neurons. In accordance with this notion, an emerging hypothesis posits that social pain and physical pain are processed by overlapping neural circuitry.189 This is supported by human imaging studies revealing that social disconnection engages brain regions including the dorsal anterior cingulate cortex and anterior insula cortex,190 which also process the affective component of physical pain.191 This dual role of DRN dopamine neurons also points toward a potential mechanism through which acute isolation reduces pain perception.157158 It is also interesting to note that inflammatory pain is suppressed by activation of AgRP neurons, suggesting a general reduction of chronic pain perception by strong motivational drive states.192 Mixed selectivity may, therefore, be a common feature within neural circuits regulating homeostatic needs, and cross talk between these systems might facilitate the activation or suppression of appropriate “effector” systems (Fig. 1).

Subjective nature of social experience

A third element in conceptualizing a social homeostatic system is the integration of subjective experience. There is mounting support for the notion that subjective or “perceived” isolation (the quality of social relationships) is a stronger predictor of poor health and emotional state in humans than objective isolation (the number/frequency of social contacts).1162146 Consistent with this, loneliness—independent of social network size—is associated with higher mortality13193 increased blood pressure,11194 higher rate of diabetes, hypertension, arthritis, emphysema,195 and Alzheimer’s disease,196 along with poor health habits stemming from a lack of self‐control.197198 Thus, in evaluating social needs, a homeostatic system would need to incorporate a subjective assessment of social experience, in addition to its overall objective nature), which may be heavily influenced by interoceptive signals and internal state (Figs. 1 and 3).

There is an ongoing debate as to whether animals experience emotions in the same way as humans.150199 However, it has been reasoned that emotions constitute an internal state, encoded by specific neural circuits, which can give rise to externally observable behaviors.150 These internal brain states may be subjectively perceived as feelings by the individual.150 Although the traditional concept of homeostasis refers to a purely automatic physiological control system, motivational drive states (guided by “homeostatic feelings”) play a significant role in maintaining homeostasis.200 Homeostatic feelings act as “informative regulatory interfaces”—providing means for an animal to sense its physiological state and guaranteeing attention to relevant stimuli.200 While this process can be adaptive and introduces greater flexibility into homeostatic regulation, it also passes an element of control to the individual, taking homeostatic regulation beyond purely automatic mechanisms.200

In order to understand the neural mechanisms of social homeostasis, a major hurdle lies in the ability to infer subjective social experience in animals.14 Although we can never truly know the emotional experience of a rodent, one method of differentiating between individuals is by exploiting the natural variability introduced by social hierarchy. Grouped living can lead to the establishment of social hierarchies in multiple species including fish, birds, rodents, and primates.201204 Hierarchies create a scenario in which grouped individuals might have divergent perceptions of their social experience. Social rank can influence access to essential resources including food, territory, and mates,205 and thus a more dominant rank is often a coveted position associated with higher quality of life. Although subordination in animal societies is not always directly related to low social connectedness or unmet social needs, social rank bestows variability in subjective social experience without removing support structure for safety, warmth and other nonsocial benefits of a group.

Strikingly, studies on social hierarchy in mice and rats have revealed underlying neural correlates in the same circuits implicated in the response to social deficit (Fig. 2). These findings include differences between subordinates and dominants in CRF expression in the BNST, CeA, MeA, and medial preoptic area;206 mitochondrial function and dopamine signaling in the NAc;207208 and glutamatergic synaptic strength in the mPFC.209 The mPFC, in particular, is frequently implicated in the representation of social rank. Most recently, “winning”‐induced plasticity in the tube test was localized to a mediodorsal thalamic (MDT) projection to the dorsomedial PFC (dmPFC), as phasic optogenetic stimulation of the dmPFC, or the MDT–dmPFC projection, immediately induced winning against a previously dominant cagemate.210 Notably, social rank also predicted the magnitude of behavioral effects elicited upon DRN dopamine manipulations in mice.118 Optogenetic activation of these neurons promoted social preference and real‐time place avoidance, whereas inhibition reduced isolation‐induced social preference. However, the behavioral change observed in these assays was greater in dominant animals relative to subordinates.118 This observation suggests that prior social experience may influence the ability of the DRN dopamine neurons to modulate behavior. Collectively, these findings illustrate that rank‐related information may be integrated into multiple neural circuits that respond to social deficit (Fig. 1A). This organization would permit flexible control over homeostatic regulation and adjustment of goal‐directed behavior depending on the social opportunities available.

Moving forward, several questions remain in elucidating how social information might be processed through a homeostatic system. For example, is the individual’s “expectation” for social contact encoded upstream in detector regions, or at the level of the control center? And how are different categories of social contact represented? To speculate on this last point, one possibility is that a social homeostatic system is category blind. Another potential arrangement would involve separate processing streams for the regulation of different social relationships, such as same‐sex, opposite sex, mother–offspring, or unfamiliar conspecifics. Indeed, specialized circuits, within discrete hypothalamic nuclei, underlie the expression of parental behavior,211 aggression,212 male intruder–specific behavior,213 opposite‐sex approach,214 and mating.212 If we conceptualize these as discrete “effector systems,” then this raises the possibility that decentralized processing of different social “needs” may occur in separable nodes.215 However, the precise organization of social homeostatic elements remains a topic of conjecture.

Valence of motivational drive

A fourth consideration is the valence of motivational drives that direct social interaction.216 Motivated behaviors regulating food intake are often distinguished as homeostatic (essential for maintaining energy balance and survival) or hedonic (driven by sensory perception or pleasure in the absence of a need state).217 Feeding behavior, therefore, is directed by motivational drives of opposing valence: the negative sensation of hunger and the positive hedonic value of palatable food. In extrapolating to social behavior, equivalent opposing motivational drives may promote social interaction: the aversive state of isolation and the hedonic value of social reward. However, while mechanistic differences exist, the neural systems mediating homeostatic and hedonic feeding are proposed to be intertwined, and highly overlapping with reward circuitry.217218 Similarly, social reward circuitry is heavily recruited in isolated animals. Engagement of reward circuitry in situations of social deficit may enhance the rewarding value of social contact—potentially similar to how food deprivation enhances the rewarding properties of food.219222 In support of this concept, functional magnetic resonance imaging (fMRI) in humans has revealed that more lonely individuals show greater activation of the ventral striatum in response to familiar social cues,223 but contrastingly reduced activation in response to unfamiliar social cues.224 Similarly, ventral striatal activity is initially high in response to palatable food but diminishes as individuals consume beyond satiety.225

The coordination of social behavior to meet homeostatic needs may, therefore, recruit both positive and negative motivational processes. The DRN dopamine system might be one source of negative motivational drive in response to social deficit.118 Recruitment of this system aligns with the “drive reduction” hypothesis, in which internal state elicits goal‐directed behaviors in order to reduce the intensity of an aversive/negative motivational drive (e.g., hunger and thirst)226 (Fig. 1C). A potentially similar function has been described for arcuate nucleus AgRP neurons and nitric oxide synthase 1 (NOS1) neurons in the subfornical organ (SFO). These neurons show heightened activity during hunger (AgRP) and thirst (NOS1), their activity elicits an aversive state (place avoidance), and they are essential for driving feeding and drinking behaviors, respectively.21227

However, the role of valence processing in homeostatic feeding behavior is complex. AgRP neurons are activated in a state of energy deficit,228 and their optical stimulation can voraciously promote food consumption, but also elicits real‐time place avoidance (indicative of an aversive state) in the absence of food.173227229 However, AgRP activity is rapidly suppressed on sensory detection of food,227228230 which, surprisingly, suggests that ongoing AgRP activity is dispensable for food consumption. This paradox is potentially reconciled by the observation that brief optical stimulation, as little as 1 min, prior to food availability was sufficient to promote robust, sustained feeding in well‐fed mice once food was made available.231 Furthermore, mice performed operant responses to stimulate AgRP neurons in the presence, but not the absence of food, suggesting that AgRP activity can be positively reinforcing.231 Therefore, an alternative hypothesis proposes that AgRP activity provides a sustained positive valence signal that potentiates the incentive value of food, and supports transition from foraging to feeding behavior via persistent changes in downstream circuitry.231 Intriguingly, this is not a feature of SFO NOS1 neurons, as prestimulation was insufficient to drive drinking behavior when water was subsequently made available.231 Therefore, the relationship between neuronal activity and behavioral regulation may depend on the specific homeostatic need.

While the precise role of DRN dopamine activity in social motivation and valence processing remains to be fully elucidated, drawing insight from other neural circuits that participate in maintaining homeostatic balance provides mechanistic clues into their mode of operation. However, an important consideration for social behavior is that (unlike food detection) initial social contact does not necessarily guarantee a rewarding social experience. Therefore, immediate suppression of neural activity on social contact may be inappropriate for DRN dopamine neurons, and activity might persist until a stable relationship has been achieved. Moving forward, it will be important to determine the temporal dynamics of activity within and across neural circuits during the response to social deficit and to understand how valence is represented in these systems.

Outlook

Moving forward, we propose that improving the evaluation of subjective social experience, and standardizing parameters used in studies of social behavior (Table 1), will accelerate the assembly of a cohesive model for social homeostasis. Studies in rodents are continuing to move toward approaches that capture larger, more naturalistic group living,206 and the incorporation of automated tracking is permitting a deeper longitudinal analysis of complex social interaction dynamics.232 Great promise has arisen from detailed behavioral observations on groups of nonhuman primates, facilitating classification of social relationship quality in females chacma baboons30 and putative loneliness in male rhesus macaques.180 Across the animal kingdom, we may see conservation in neuromodulatory systems for social behavior all the way to invertebrate systems, as recent groundbreaking work in the octopus demonstrates.233Table 1. Experimental conditions to report in the methodology of studies on social behavior and/or social isolation to facilitate informative interpretation and reproducibility

Grouped/Control AnimalsIsolated Animals
Housing conditions
Number of cage matesPrior number of cage mates
Cage mate relationship (siblings/age‐matched etc.)Cage mate relationship (siblings/age‐matched etc.)
Sexual experienceSexual experience
Age at isolation
Duration of isolation
Extent of experimenter handlingExtent of experimenter handling
Housing type (size, bedding material etc.)Housing type (size, bedding material etc.)
Social rank (if known)Social rank (if known)
Environmental enrichmentEnvironmental enrichment
Proximity of other animals
Normal or reverse light/dark cycleNormal or reverse light/dark cycle
Measurement of behavioral/neurophysiological parameters
Time of testing
Age at testing
Conditions of behavioral assays
Stress exposure
Food/water restriction
Timeline of conducted experiments

Current technological approaches in rodents now provide unprecedented temporal and spatial resolution with which to scrutinize neural circuits and have already yielded fascinating results identifying discrete systems mediating specific social behaviors including parental behavior,211 social reward,103138139 and social observational learning.234 The new millennium has brought with it a rapid rise in opportunities for social nourishment together with a growing prevalence of loneliness and social isolation. Given the protective effects of social contact on a vast array of physical and mental health measures, there has never been a more important time to understand the neural mechanisms underlying the need for social connection.

Acknowledgments

This article was prepared by invitation of the New York Academy of Sciences for publication in a special issue of Ann. N.Y. Acad. Sci. presenting work from winners and finalists of the Innovators in Science Award; K.M.T. was an Early‐Career Scientist finalist in 2017. Takeda Pharmaceutical Company Limited sponsors the Innovators in Science Award, as well as open access of this paper.

We thank Gwendolyn G. Calhoon and Ruihan Zhang for comments on the manuscript and all members of the Tye Lab for helpful discussion. K.M.T. is a New York Stem Cell Foundation–Robertson Investigator and McKnight Scholar and supported by funding from the JPB Foundation, the Picower Institute Innovation Fund (PIIF), the Picower Neurological Disorder Research Grant, the Picower Junior Faculty Development Program, the Alfred P. Sloan Foundation, the New York Stem Cell Foundation, the McKnight Foundation, and by the following Grants from the National Institutes of Health: NIMH R01‐MH102441‐01, NIMH R01‐MH115920, NIA RF1‐AG047661‐01, the NIH Director’s New Innovator Award DP2‐DK‐102256‐01 (NIDDK), and the NIH Director’s Pioneer Award DP1‐AT009925 (NCCIH). G.A.M. was supported by a fellowship from the Charles A. King Trust Postdoctoral Research Fellowship Program, Bank of America, N.A., cotrustees.

Competing interests

The authors declare no competing interests.

Featured

Consciousness as a Delusion

In Chasing the Rainbow: The Non-conscious Nature of Being, David Oakley and Peter Halligan (2017) present the theory that consciousness is a delusion.

At the time of publication, the paper in Frontiers has received 107,012 views.

According to their theory, consciousness is a specially engineered delusion; let’s call it the ‘CAD theory’. Because, to them at least, consciousness is only a delusion, O&H place the word inside scare quotes, as ‘consciousness’. Here, I leave the word as it should be left: consciousness it is and consciousness it stays.

According to the CAD theory, the ‘epiphenomenon’ of consciousness evolved to provide humans a false belief that they are actors with agency. In reality, so O&H claim, all psychologically meaningful and functional processes occur within an unconscious ‘Central Executive Structure’ (CES).

The CES is an amazing cortical device that craftily creates a fake experience of consciousness to deceive naïve humans into the false belief that they have the power to voluntarily control their individual destinies with agency and selfhood. All other psychological products are manifested in Personal Awareness a brief ‘Libet’ unit of time after their production by the CES. Consciousness does not control any behavior. It serves a passive, narrative function as an excrescence. Humans are simply automatons. In 1999, the editor of an American Psychologist special issue entitled “Behavior— It’s Involuntary” wrote: “We perceive ourselves to have far more control over our everyday behavior than we actually do. . . . [T]he source of behavioral control comes not from active awareness but from . . . mental activations of which we are unaware and environmental cues to which we are not consciously attending that have a profound effect on our behavior (Park, 1999, p. 461). The CAD theory is illustrated in Figure 1.

The CAD Theory

Figure 1. The Oakley-Halligan CAD model. The schematic diagram shows all current CES functions and other psychological activities as non-conscious processes and their products. The most task-relevant of these psychological products are selected by a Central Executive Structure (CES) to create an ongoing personal narrative via the process of Internal Broadcasting. This personal narrative is passively accompanied by personal awareness – a by-product of Internal Broadcasting. Some components of this narrative are selected by the CES for further transmission (External Broadcasting) via spoken or written language, music, and art to other individuals. The recipients in turn transmit (internally then externally) their own narrative information, which may contain, or be influenced by, the narrative information they have received. The CES also selects some contents of the current personal narrative for storage in autobiographical memory. The contents of external broadcasts contribute (via Cultural Broadcasting) to an autonomous pool of images, ideas, facts, customs, and beliefs contained in folklore, books, artworks, and electronic storage systems (identified as “Culture” in the Figure) that is accessible to others in the extended social group but is not necessarily dependent on direct interpersonal contact. The availability of culturally based resources is a major adaptive advantage to the social group and ultimately to the species as a whole. The CES has access to self- and other-generated externally broadcast content as well as to cultural information and resources, all of which have the potential to provide information that supports the adaptedness of the individual and to be reflected in the contents of their personal narrative. As a passive phenomenon, personal awareness exerts no influence over the CES, the contents of the personal narrative or on the processes of External and Cultural Broadcasting. In the Figure non-conscious process are identified in green and personal awareness (subjective experience) in blue. (From Oakley & Halligan, Front. Psychol., 14 November 2017).

The simplistic automaton of the epiphenomenonalist view, in this reviewer’s opinion, is an inadequate and flawed scientific theory, which, ultimately, offers a false doctrine. Alternative positions that warrant more serious consideration include the emergence theory that views phenomenal ‘consciousness’ as a naturally emergent feature of life and complex brains (e.g. Sperry, 1990; Feinberg & Mallatt, 2020). IMHO, in spite of its rhetorical merits, this interesting and provocative paper does not ‘unmask consciousness’ but manages to conceal and obscure its true nature in obfuscation.

Merits and Demerits of the CAD Theory


Overall, the paper provides a clear statement of a well-known epiphenomenonalist view of consciousness, namely that consciousness is a superfluous carbuncle in the scientific analysis of behavior. The paper is concise and mainly internally consistent but it presents a highly incomplete and misleading analysis of consciousness and the associated cortical structures.

If it is to be given serious attention as a scientific theory, the authors need to specify not only (A), the axiomatic assumptions and ancillary propositions of the theory, but also (B), refutable and novel predictions evaluated with robust empirical evidence. However, to date they have only succeeded in producing A, the ‘pudding’, but there is no B, ‘proof of the pudding’. Unless refutable predictions can be added, this paper and theory will remain a flight of fancy about what might be so that is lacking any defined empirical tests to assess its veracity one way or the other. The current iteration of the theory, crafted and polished over several decades, remains a scientifically weak, descriptive theory of consciousness.


Unless the claims sketched out by O&H can be substantiated with hard evidence, the theory will remain a quaint ‘straw man’ on the hinterlands of the scientific study of consciousness. To be fair, the authors do mention in passing a few speculative hypotheses about brain mechanisms but they are vague (e.g. Figure 3) and I can find no substantive hypotheses that can be tested in non-brain-damaged subjects. The Casarotto et al. (2016) study described by the authors appears to this reviewer to have questionable relevance and should perhaps be removed.

There have already been several criticisms of the CAD paper. How are these known criticisms to be rebutted? What new research will follow from the claim that consciousness is a delusion? Does the CAD claim not have a stultifying impact on new investigation if there is nothing worth discovering about the consciousness delusion?

There are some well-known limitations and shortcomings of the CAD theory that need to be addressed.

Consciousness as an Unnecessary Epiphenomenon

As the authors must be aware, there are established objections to their type of epiphenomenalist account of consciousness that they have not addressed. For example, Meese (2018) raises the first technical objection with these words: “…the simple fact is, we can talk about consciousness. This is not trivial; it means the thing we call consciousness can influence the underlying system (by causing it to speak), and in philosophy of mind, epiphenomena do not have causal feedback (e.g., Megill, 2013), so consciousness cannot be epiphenomenal (Blackmore, 2004; Bailey, 2006; Robinson, 2015)”. So how do O&H answer this objection? To date, they have given no answer.


O&H believe that consciousness is not required. Yet, they write about consciousness throughout the article as (a) process(es) that they and readers all perfectly understand as universally available phenomenal consciousness. However, different people often mean different ‘things’ when they talk about consiousness. Also following Meese (2018): “we can envisage a machine that is programmed to store only some of its internal operations in memory, and call that a personal narrative, but it does not follow that this will imbue the machine with consciousness.”


A significant point overlooked in O&H’s manuscript is the fact that, in one or more of its different states, consciousness has demonstrable adaptive value. Consciousness convincingly delivers selfhood to ‘actors’ who set global, behavioral priorities and goals, life choices, career, country and region of residence, sexual preferences, gender assignment and choice of mate, beliefs, values, opinions, and significant communication, social, artistic and cultural functions. According to O&H’s theory, these ‘choices’ are all delusory products of an unconscious CES. Yet, in delegating all of developmental, personal, social and behavioral adaptations to the CES with a stroke of the pen, gaping holes are evident, straining the theory with severe limitations.


First Missing-Link: Motivation


According to O&H’s theory, the unconscious CES is responsible for the ‘what’ and ‘when’ of behavior – thinking, choosing, planning, remembering, problem solving, acting – in their entirety. However, the all-important ‘how’ and ‘why’ and associated ‘feelings’, emotions, drives and cravings that underly behavior are in another department of unconscious processing not considered relevant in the theory. Motivation, needs, wants are nowhere to be found. If ‘free will’ really is a delusion, then surely it remains necessary to formulate how and why the CES decides which actions are momentarily beneficial to survival and need to be prioritized? The authors do not say. Perhaps O&H could consider the following sources:

Maslow (1943): “”Thus man is a perpetually wanting animal.” Thwarting, actual or imminent, of these basic needs provides a psychological threat that leads to psychopathy”;

Rogers (2008): “The directional tendency in every living organism of maintaining, enhancing, and reproducing itself is seen as fundamental to the question of motivation. This “actualizing” tendency involves development toward autonomy and away from heteronomy, or control by external forces”;

Fanselow (2018):”Fear has the ability to overwhelm consciousness so that that nothing but phylogenetically selected action occurs. By filling consciousness fear prevents flexible behaviors and that is one reason why anxiety disorders can be so debilitating. Anxiety, fear and panic are states within the emotion that correspond to different levels of threat.”

If consciousness as a delusion is overwhelmed by fear, then the feeling of fear itself must be a delusion. Yet this ‘fear delusion’ is necessary for survival. In which case, consciousness is necessary for survival. QED.


Second Missing Link: Arousal, the Waking State, and Sleep


The well-known circadian alterations in consciousness that fall under the ‘arousal’ umbrella range from the fully awake state through intermediate states of inattention and drowsiness to sleep are all missing from O&H’s theory of consciousness. Self-evidently, these dramatically different, scientifically well-established states of conscious awareness are not delusory, nor are they figments of the CES ‘broadcasting station’. They exist. They are real. They are universal across many species apart from humans.


Third Missing Link: Mental Imagery/Imagination


Another notable absentee from the CAD theory is mental imagery/imagination. In this respect, O&H differ from Jorion (1999), who equated the alleged ‘consciousness delusion’ with ‘imagination’. O&H talk instead about ‘internal broadcasting’, the scripted narrative provided by the CES, serving the function of keeping the deluded and unconsciously controlled human content with their little lot by listening to especially scripted messages broadcast by an all-powerful inner structure. Thus, the internal broadcasting is like a ‘mental radio station’. O&H appear to have missed a trick here. They could just as easily have inserted a ‘multi-channel mental TV’ into the CES which could include fantasy fiction, travel, series, horror, thrillers, erotica/’adult’ material for instant replay whenever required by waking daydreams, dreams and nightmares, and even a ‘playstation’ for hypnotic and hypnagogic mental games such as counting sheep as people are drifting off to sleep. This ‘modernisation’ of the CES would make it immensely more powerful by enabling ‘broadcasting’ of a vast range of imaginative material into what the lay person calls the ‘mind’s eye’ unavailable on steam radio. Other sensory modalities could be added to the broadcasting of the CES to bring it into line with the quasi-perceptual qualities of taste, olfaction, touch, somatic sensations and synaesthesia. The current version allows only narratives ‘propaganda’ conjured up for innocents who believe the delusion that they are fully conscious with agency, selfhood, integrity, and a moral compass.

Figure 2 mentions the right cortex having ‘visuo-spatial ability’ so a rudimentary ‘mind’s eye’ is present in the theory but needs to be elaborated if the full range of known ‘internal broadcasting’ is to be captured by the theory. A more minor point: Figure 2 suggests a division of the two cortical hemispheres (‘verbal’ vs ‘visuo-spatial ability) in line with 1960s and 1970s neuropsychology with ‘sequential’ processing on the left side and ‘simultaneous’ processing on the right side. Is this classification still viable? Also, the arrow at the top of Figure 2 labelled “suppresses” requires clarification.


Fourth Missing Link: Adaptive Benefits of Consciousness


O&H’s proposition that consciousness should be abolished from science would gain more credence if there did not exist multiple, well-established, demonstrable evolutionary benefits of consciousness. Evidence of biologically adaptive benefits of consciousness has been reviewed in several articles (e.g. see Earl, 2014, 2019; Feinberg & Mallatt, 2020).

Consider these 12 categories of evidence :


1) The complexity and enormous range of altered states of consciousness need to be explained. O&H lump all of the processes and states of consciousness together as a single entity yet this is manifestly incorrect, viz. sleep, dreams, hypnagogic/hypnopompic state, hypnotic state, hypnotic analgesia, meditation, trance, trance logic, dissociative states, etc. Why do these empirically identifiable ASCs all exist and why are they necessary? Are these states all delusional? Do none have beneficial advantages to survival? Why does sleep and/or dream deprivation have such strongly detrimental effects on wellbeing? Lacking any consideration or acknowledgement of the complexity of consciousness, the O&H theory falls at the first post.


2) It is known that ancillary systems have evolved in association with consciousness, e.g. two perceptual systems, two memory systems, explicit vs implicit memory. In each case, why would two systems be necessary? Are both systems delusory – in spite of decades of supportive empirical evidence that they have functional relevance?


3) Whenever one is actively involved with events, one experiences representations of them, which aids selection of pleasurable vs non-pleasurable stimuli. If consciousness had no effect on behaviour, then it could indicate something quite different to what was actually happening, and it wouldn’t actually matter because, according to the theory, the CES would still control all human actions, so ‘consciousness’ must be adaptive.


4) Clearly, pleasure and pain are not delusory, yet they are an essential part of conscious experience. Consciousness ranks sensed stimuli by importance, enabling decisions on how to respond (Cabanac, 1996).


5) Self-related information, very relevant to survival, is treated differently from non-self-related information. This consciously experienced ‘personal self’ appears to be anything but a delusion. The selfhood/identity of a person is associated with a unique life history, kith and kin relationships, legal identity and set of morals, values and beliefs. The sense of selfhood is palpable and real.Self-protective behaviors in the face of danger trigger near-instantaneous “freeze, flight, fight, or fright” (4 F’s) behaviors with millisecond rapidity. A dog walks towards me barking aggressively. I freeze before moving away rapidly. It is me the dog approaches not the person on the other side of the road. I take preventive action accordingly. No internal broadcast here, just an instantaneous physiological and conscious choice.


6) Consciousness can directly influence behavior. Feelings and perceptions re-direct one from one activity to another without any significant delay. One can make immediate ‘changes of mind’ with fast adjustments to new stimuli. The few 2-300ms delay suggested by Libet’s contentious work is neither here nor there in the bigger picture of adapting to life’s slings and arrows.


7) Consciousness includes qualia, which convey information at a subjective level from a particular point of view. Why would qualia have evolved without adaptive purpose? The use of qualia increases with experience in specialized tasks, e.g. sommelier training for wine tasting. “An experienced taster obtains an initial, visual impression, potentially signals unappealing smells, and decides whether the eyes were right, indeterminate, or wrong. He/she then decides whether the wine is a good exemplar of the premium quality category or not. Taste representations may only provide confirmation, in combination with the representations available from the other senses (e.g., taste balance)” (Caissie, A. F., Riquier, L., De Revel, G., & Tempere, S. (2021). Representational and sensory cues as drivers of individual differences in expert quality assessment of red wines. Food Quality and Preference, 87, 104032.) Without qualia, such fine distinctions among trained experts would be impossible. The CES alone is not sufficient to explain human sensory discrimination ability. Chefs, composers, conductors, designers, engineers, surgeons, and artists rely on qualia in their creative work, which would be poorer in their absence.


8) Consciousness perceives and organizes sensory information into a detailed, unified simulation of the world, so that a person can choose the most efficacious and desirable responses based on simulations and conscious mental maps. Geographical space serves as a mental framework for an individual’s experiences of the world. Immensely significant life choices do not happen using only the unconscious CES. They require the entirety of the conscious imagination in communication with connected others. Consider migration: “Quintessential human migration occurs when people deliberately abandon one home in favor of a distant and unseen goal. In the nineteenth century many Europeans left their homes for remote parts of the world of which they had no direct experience. They did not go blindly: the move was a calculated risk. They had images of their new homes based on hearsay, letters from relatives, and immigration literature. Indeed these attractive images were a cause of their desire to move.” (Tuan, 1975).


9) Memories and thoughts are triggered by consciously experienced feelings, a process that is utilized beneficially in multiple kinds of psychotherapy and in nostalgic episodes when recalling earlier experiences, childhood memories and occasions. The conscious ‘reliving’ of life experiences with nostalgia provides joy for the self and affirms social identity (Sedikedes et al., 2015). The CES cannot achieve the positive outcomes achieved by memory work without the beneficial outcomes of conscious recall.


10) O&H insist that scientific psychology rests exclusively on a third-person perspective. However a complete science of psychology requires the first-person perspective also. One cannot be reduced to the other. Neither has priority in a proper science of ‘consciousness’. In accordance with Velmans (1991b): “information processing models which view humans only from a third-person perspective are incomplete…first-person and third-person accounts are complementary, and mutually irreducible. A complete psychology requires both.”


11) Again, following Velmans (1991b), from a third-person perspective, consciousness does not enhance adaptive functioning. Rather, the brain functions, in part, to produce experience. From a first-person perspective, the difference this makes is obvious. Without consciousness there would be no experienced world.”


12) In the domain of health-related behavior, people often act in non-optimal ways. Individuals would like to quit smoking, eat healthily, get enough sleep, and exercise, but they do not engage in these behaviors as often as they wish. Individuals also engage in risky behaviors such as drinking too much, unprotected sex, and the like, that can compromise health, either acutely or over the long-term. Issues of this type often result from failures to transcend the moment in the service of long-term goals. Impulsive tendencies (controlled by the CES in O&H’s theory) tend to favor behaviors, such as eating fatty food, that provide immediate pleasures, but can be problematic if repeated. Something like an ‘ego centre’ for control based in consciousness is needed to represent long-term goals of restraint to align current behaviors with courses of action that tend to be health-promoting (de Ridder & de Wit, 2006). See also point 3 above.


Conclusion


The CAD theory fails on a number of counts. Major revision is necessary to rebut the criticisms and to fill the void left by the numerous gaps identified above. Perhaps O&H will claim points 1-12 above are all, like consciousness itself, delusional. Owing to the flaws inherent in the approach, it seems doubtful that a rebuttal can be successfully achieved.

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“Doctors can commit scientific fraud and financial fraud and not be punished”

Press Release by Dr Myhill concerning Dr Myhill’s Virtual Hearing 22 MARCH 2021 – vs ICO & GMC

Doctors can commit scientific fraud and financial fraud and not be punished. This is the conclusion of Dr Sarah Myhill following her recent hearing vs the ICO and GMC.

Dr Sarah Myhill tells us “That is official General Medical Council policy”.

The PACE study of 2011, which concluded that patients with CFS and ME could be effectively treated with graded exercise and cognitive behaviour therapy, has been proven to be scientifically fraudulent. This fraud is so profound that PACE recommendations have been dropped by NICE. We now know that graded exercise makes patients with CFS, ME and Long Covid much worse. CBT is of little benefit, only as a supportive measure.


In response to this fraudulent study, Dr Myhill reported the authors of PACE, and its directors, to the General Medical Council in January 2018. The GMC has a duty, and is empowered by Parliament, to regulate doctors and this includes research misconduct. Despite taking six months to consider Dr Myhill’s request, the GMC refused to investigate. Dr Myhill supplied extensive scientific proofs but in its refusal the GMC failed to supply its scientific defence.


So, Dr Myhill, through FoI legislation, asked that the GMC supply her with the scientific references on which it relied in coming to its decision not to investigate the PACE authors. The GMC refused. It gave no reasons whatsoever.


Consequently, Dr Myhill reported the GMC to the Information Commissioner who in a ruling of 30 September 2019 agreed with her. The ICO informed the GMC that it must supply her with the scientific references on which it relied in deciding not to investigate the PACE authors. This was because Dr Myhill was asking simply for scientific references already in the public area. This was only fair to the thousands of patients who have been damaged by graded exercise and who have a right to a proper explanation as to why.


At this point you would think the GMC had to comply. However, it is suspected that the GMC refusal arose for reasons of cronyism – it did not want ex-Presidents of Royal Societies up in
front of the GMC and the Police. It did not want to admit that actually it held NO scientific evidence, and it had no good reason to proceed as it did.


So, the GMC had to think up some sort of legal argument for refusal. Hitherto it had no argument – simply blunt refusal. The GMC consulted with its legal beavers within and outside the GMC and came up with the argument that to comply with the ICO demands would infringe the personal privacy of the PACE authors. What a nonsense! Dr Myhill has no interest in the personal data of the PACE authors. She simply requested scientific references which should all be in the public arena!


This was the subject of the ICO Hearing on 22 March 2021: Myhill vs GMC and ICO.


The outcome was a split decision. It boiled down to the Public Interest test. Tribunal member Mr Malcolm Clarke agreed with Dr Myhill. He stated:


“I conclude that Dr Myhill’s legitimate interest in seeking this information, if it exists, as a practising doctor with patients, who has a deep professional interest in ensuring that national recommended treatments in this area of medicine are evidence-based, is a very strong one …Dr Myhill’s legitimate interest in knowing whether the information she requests is held by the GMC is a very strong one. I therefore conclude that ……Dr Myhill’s legitimate interests are not overridden by the rights and freedoms of the data subjects.”

Ref paragraphs 42-47,EA-2020-0018 Myhill v IC & GMC


Luckily for the GMC, the Judge Hazel Oliver and Panel member Gareth Jones disagreed. They decided the other way round.


This Ruling sends a very clear message to doctors who commit scientific fraud – it is easy to get away with it, you can easily hide behind Data Protection issues and the General Medical Council will assist. Cronyism works.


………and so now to round 4. Dr Myhill will not give up.


See https://www.drmyhill.co.uk/wiki/My_Complaint_to_the_GMC_about_the_PACE_authors for more detail

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Towards a comprehensive theory of obesity and a healthy diet: The causal role of oxidative stress in food addiction and obesity

Review published in Behavioural Brain Research

Volume 384, 20 April 2020, 112560

written by: Tobore Onojighofia Tobore

Independent Scholar, San Diego 92110, United States

ShareCite https://doi.org/10.1016/j.bbr.2020.112560

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Abstract

Background

Obesity is a major public health problem whose prevalence has been rapidly increasing in the United States (U.S), and globally. It is one of the leading causes of preventable deaths globally and contributes to the development of many diseases.

Methods

The search was limited to studies published in English and other languages involving both animal and human subjects. Articles selected included preclinical studies, randomized clinical trials RCTs, observational studies, meta-analyses, narrative and systemic reviews providing primary quantitative data with a measure of obesity or food addiction as an outcome. Over 5000 articles were found in the first round of search which was filtered to 506 articles.

Results

Oxidative stress plays a critical role in food addiction and is both a cause and mediator of obesity. Reactive oxygen species play a direct role in adipogenesis and oxidative stress modulates all factors involved in obesity including genetics, sleep, gut microbiome, insulin, ghrelin, inflammation, adipokines, leptin, stress, HPA axis, and the hypothalamus.

Conclusions

The idea of thinking of combating obesity from the lens of calorie count, low carbohydrate, high or low-fat, vegetarian, vegan, plant-based, or animal-based diet is fundamentally wrong. The best way to look at obesity is through the framework of systemic redox homeostasis. Since redox homeostasis is tilted towards increased reactive oxygen species production, and excessive antioxidant intake can result in oxidative stress, an antioxidant and prooxidant food ratio of 2:3 per meal is the ideal nutritional ratio for good health and ideal weight. A ratio of 3:4 is ideal for obese individuals because of their state of chronic oxidative stress and inflammation. Physical activity, sleep quality, psychological stress, maternal prenatal diet and oxidative stress promoting disease conditions are important modulators of oxidative stress and obesity.

Illustration from: Savini I., Gasperi V., Catani M.V. (2016) Oxidative Stress and Obesity. In: Ahmad S., Imam S. (eds) Obesity. Springer, Cham. https://doi.org/10.1007/978-3-319-19821-7_6

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How is obesity associated with happiness? Evidence from China

Abstract

Yiwei LiuLing XuAaron Hagedorn

First Published October 11, 2020 

Research Articlehttps://doi.org/10.1177/1359105320962268

Liu Y, Xu L, Hagedorn A. How is obesity associated with happiness? Evidence from China. Journal of Health Psychology. October 2020. doi:10.1177/1359105320962268rticle information 
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Abstract

Happiness is a universal goal that people pursue. Studies of the relationship between obesity and happiness have shown mixed findings. It is uncertain whether an optimum BMI level exists and at what level obesity interferes or interacts with happiness. Guided by the Circle of Discontent Theory, we examined the relationship between obesity and happiness among Chinese residents using the 2014 China Family Panel Studies data. The results reveal an inverted U-shaped relationship between BMI and happiness, with obesity associated with happiness through physical appearance, health, and income. The socioeconomic conditions for the appropriate weight to achieve happiness are discussed.

Keywords Chinacircle of discontent theoryhappinesshealthincomeobesityphysical appearance

Figure 2. Relationship between BMI and happiness.

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Body mass index trajectories during mid to late life and risks of mortality and cardiovascular outcomes: Results from four prospective cohorts

Yun-JiuChengab1 Zhen-GuangChenc1 Su-HuaWuab1 Wei-YiMeiab Feng-JuanYaod MingZhange Dong-LingLuof

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Citation: Cheng, Y. J., Chen, Z. G., Wu, S. H., Mei, W. Y., Yao, F. J., Zhang, M., & Luo, D. L. (2021). Body mass index trajectories during mid to late life and risks of mortality and cardiovascular outcomes: Results from four prospective cohorts. EClinicalMedicine33, 100790.

Note: This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.

open access

Abstract

Background

Our understanding of the weight-outcome association mainly comes from single-time body mass index (BMI) measurement. However, data on long-term trajectories of within-person changes in BMI on diverse study outcomes are sparse. Therefore, this study is to determine the associations of individual BMI trajectories and cardiovascular outcomes.

Methods

The present analysis was based on data from 4 large prospective cohorts and restricted to participants aged ≥45 years with at least two BMI measurements. Hazard ratios (HR) and 95% confidence intervals(95%CI) for each outcome according to different BMI trajectories were calculated in Cox regression models.

Findings

The final sample comprised 29,311 individuals (mean age 58.31 years, and 77.31% were white), with a median 4 BMI measurements used in this study. During a median follow-up of 21.16 years, there were a total of 10,192 major adverse cardiovascular events (MACE) and 11,589 deaths. A U-shaped relation was seen with all study outcomes. Compared with maintaining stable weight, the multivariate adjusted HR for MACE were 1.53 (95%CI 1.40–1.66), 1.26 (95%CI 1.16–1.37) and 1.08 (95%CI 1.02–1.15) respectively for rapid, moderate and slow weight loss; 1.01 (95%CI 0.95–1.07), 1.13 (95%CI 1.05–1.21) and 1.29 (95%CI 1.20–1.40) respectively for slow, moderate and rapid weight gain. Identical patterns of association were observed for all other outcomes. The development of BMI differed markedly between the outcome-free individuals and those who went on to experience adverse events, generally beginning to diverge 10 years before the occurrence of the events.

Interpretation

Our findings may signal an underlying high-risk population and inspire future studies on weight management.

Funding

National Natural Science Foundation of China, Guangdong Natural Science Foundation.

Keywords

Trajectories Body mass index Cardiovascular events Mortality Mid-to-late life

Research in context

Evidence before this study

We searched Pubmed for articles published in English assessing risk of cardiovascular disease and all-cause mortality in relation to BMI and BMI trajectories, using the search terms “BMI”, “change in BMI”, “BMI trajectories”, “cardiovascular diseases”, “major adverse cardiovascular events”, “death”, “mortality”, “coronary heart disease”, “stroke”, “heart failure”, “myocardial infarction” and “risk”, from the inception to December 15, 2020. We found numerous studies discussing the associations of single time BMI measurements and cardiovascular risks, but few of them explored the associations of individual change trajectories and adverse outcomes.

Added value of this study

In this large population-based study, a U-shaped relation was observed between BMI trajectories and subsequent risk of different health outcomes. Both weight gain and weight loss conferred increased risks for cardiovascular events and all-cause mortality. In addition, we found for the first time that falling off the BMI trajectory could be a warning sign for future occurrence of adverse events.

Implications of all the available evidence

Our findings may signal an underlying high-risk population and underscore the importance of maintaining body weight over the middle to late adulthood.

1. Introduction

In light of the obesity epidemic [1,2], it is imperative to understand the relationship of weight to the risks of mortality and cardiovascular diseases (CVD). Although this relation is well documented in previous researches, most of them were based on single-time assessment of body weight (or body mass index, BMI) [3][4][5][6][7][8]. As noted, the relation of single-time BMI measurement to adverse outcomes changed during the observation period [9]. Specifically, the magnitude of this association weakens among middle-aged and elderly populations [10,11].

Further, using single-time BMI may fail to recognize the effect of weight change on the associated risks. Weight changes are highly variable over the life course [12][13][14][15]. Both weight loss and gain in middle-aged adults rendered increased risk of all-cause and CVD mortality [4,[16][17][18][19]]. However, the patterns of BMI change may differ among individuals; thus, a life-course perspective is essential. Mapping the longitudinal trajectory of BMI may directly capture the within-person change in BMI, and better characterize the associated risks.

Although increasing number of studies have investigated the relationship of BMI trajectories and cardiovascular outcomes, most were assuming the population lies within a mixture of latent groups, using either growth curve model or group-based latent model [11,[20][21][22][23][24][25][26][27][28][29]]. These models are largely based on subgroup means over a specific period of time and might be imprecise. Till now, there are at least 2 to 6 different BMI trajectory patterns being reported [11,[20][21][22][23][24][25][26][27][28][29][30]], even using the same dataset [20,26].

Therefore, in order to obtain a more precise association between BMI trajectory and cardiovascular outcomes, we here used the original BMI slope from each individual to represent individual BMI change trajectory. As far as we know, less than ten papers have reported the value of BMI slope in cardiovascular system [13,14,[31][32][33][34][35][36][37]]. Most of them investigated the association of BMI slope and change in cardiovascular risk factors [14,31,[33][34][35][36]]. Only two researches illustrated its association with cardiovascular outcomes [13,32]. However, models were not fully adjusted and differences on weight change direction were not taken into consideration.

Therefore, in our current study, we separated weight gain and weight loss by different degrees of change to comprehensively illustrate the relation of individual BMI trajectory to diverse study outcomes. As a second aim, we explored and characterized the developmental paths of BMI prior to individual outcomes.

…..

Model 1, adjusted for age, gender and race; Model 2, adjusted for age, gender, race, smoking status, current alcoholic use, education level, marital status, income, physical activity, consumption of fruits and vegetables, history of hypertension, diabetes, HF, CHD, cancer, COPD and stroke, baseline BMI, serum level of glucose, total cholesterol, LDLCHDLC and triglyceride.

Abbreviation: MACE, major adverse cardiovascular events; MI, myocardial infarction; CHF, chronic heart failure; CVD, cardiovascular disease; Non-CVD, non-cardiovascular disease; CHD, coronary heart disease.

3.2.1. Primary outcomes

Compared with maintaining stable weight, the multivariate adjusted HRs for MACE were 1.53 (95%CI 1.40–1.66), 1.26 (95%CI 1.16–1.37) and 1.08 (95%CI 1.02–1.15) respectively for rapid, moderate and slow weight loss; 1.01 (95%CI 0.95–1.07), 1.13 (95%CI 1.05–1.21) and 1.29 (95%CI 1.20–1.40) respectively for slow, moderate and rapid weight gain. Models examining the associations with outcomes of MI and CHF yielded similar results as MACE. While for stroke, the hazard was significantly increased in participants with moderate-to-rapid weight loss and moderate weight gain, but for slow weight loss or slow weight gain, the association was insignificant (Table 2). Consistently, Fig. 1-A shows a U-shaped relation of the entire range of annual BMI change to individual cardiovascular outcomes in the cubic spline models.

Fig 1

3.2.2. Secondary outcomes

Similarly, the HRs for all-cause mortality were 1.98 (95%CI 1.83–2.13), 1.38 (95%CI 1.28–1.49) and 1.18 (95%CI 1.12–1.25) respectively for rapid, moderate and slow weight loss; 0.99 (95%CI 0.93–1.04), 1.08 (95%CI 1.01–1.15) and 1.29 (95%CI 1.20–1.38) respectively for slow, moderate and rapid weight gain, when compared to maintaining stable weight. Identical patterns of association were observed for CVD, non-CVD and CHD death (Table 2). Likewise, in the restricted cubic spline models, we detected a U-shaped relationship between annual BMI change and mortality risk, with a nadir around 0 kg/m2/year (Fig. 1-B).

3.3. BMI trajectories prior to different outcomes

Fig. 2 is an illustrative drawing to represent the general developmental patterns of BMI prior to different outcomes. We found that the development of BMI differed markedly between the outcome-free individuals and those who went on to experience adverse events. Trajectories appeared similar for the outcomes of MACE, all-cause, CVD and non-CVD death. The outcome-free participants followed a trajectory where the average BMI levels rise initially, remain stable or steadily decreased throughout follow-up. Those who went on to experience events generally showed lower baseline levels of BMI, steeper rise initially and faster fall before the occurrence of the events. With regards to MI and CHD death, the average BMI level was comparable in participants with or without the outcomes, but an accelerated decline was observed in those who died or experienced the events. Interestingly, although the developmental trend was identical among participants with and without CHF, those who experienced CHF had a generally higher BMI level during their life. With respect to the outcome of stroke, the BMI trajectories were less distinctive between groups.

Fig 2

3.4. Additional information and stratified analysis

We repeated the primary analyses in a series of sensitivity analyses. Excluding participants with missing values on baseline covariates (supplementary Table 3 in Appendix 3), with preexisting illnesses at baseline (supplementary Table 4 in Appendix 3), or with highest weight variability during follow-up (supplementary Table 5 in Appendix 3) did not appreciably change the results. In terms of percent change of BMI, the association patterns for cardiovascular outcomes were identical to our primary analysis (supplementary Table 6 in Appendix 3). But for the death outcomes, we only found significant increased risk in weight loss quintiles (quintile 1 and 2). When separating the primary analysis by individual cohort, consistent findings were observed (supplementary Table 7 in Appendix 3).

As depicted in Fig. 3, the associations of BMI trajectories and MACE were generally consistent in stratified analyses by sex, race and smoking status. It should be noted that the BMI-MACE association was significantly modified by age and borderline by baseline BMI. The hazards for MACE were significantly higher in those younger than 60 years, but lower in those who were initially with obesity. For all-cause mortality, the associations with BMI trajectories were generally consistent in white or non-white population and significantly modified by age, sex, and smoking status. It’s revealed that male and individuals younger than 60 years had higher hazards for death. But surprisingly, the hazards were lower in the smoker subgroups. Similar to the MACE outcome, the hazards for death were lower in subgroup with obesity, but the modification effect by baseline BMI was insignificant. The association of BMI trajectories and other outcomes across the predefined subgroups are provided in supplementary Table 8 and Table 9 (Appendix 3).

4. Discussion

In our analyses of the overall cohort of 29,311 participants, a U-shaped relation was observed between BMI trajectories and subsequent risk of cardiovascular events and all-cause mortality. Significant increase of risks for MACE and all-cause death were noted for people assigned in weight loss or weight gain categories. The hazard risks for adverse outcomes were consistently lowest among individuals maintaining their body weight. Although effect modification was observed in several subgroups, our findings were generally robust in a number of sensitivity analysis. Furthermore, our study for the first time delineates the characteristics of BMI trajectories prior to different health outcomes, showing an accelerated decline in BMI almost ten years before the occurrence of the events.

More than 38.9% of US adults have obesity [1]; however, much of our understanding of the BMI-mortality association comes from single-time BMI measurement, without considering within-person variation over the long term. Since weight change is highly variable across adulthood, more studies are now focusing on BMI trajectories and different health outcomes [11,13,[20][21][22][23][24][25][26][27][28][29][30],32]. However, most of these studies were grouping people using growth curve model or group-based latent model [11,[20][21][22][23][24][25][26][27][28][29]]. Using the above models, one can identify individuals with distinct BMI trajectories from the available data [25,48]. However, class membership is not determined with certainty for each individual since it relies on the selected models (linear, curvilinear, cubic and other forms) and probability of belonging [20,49]. Thus, misclassification is possible and the associated risk of adverse outcomes could be invalid. In articles published by Zeng H.et al. and Zajacova et al., the authors used the same data but identified different patterns of BMI trajectory [20,26]. As of now, at least two to six patterns of BMI trajectories have been reported in the general population and majority of them were depicting an ascending trend or paralleling with each other [21,26,28,[50][51][52]]. It is unrealistic that all participants were going the same way over the life course. There must be some groups of individuals experiencing gradual weight loss or even rapid loss in their weight. Furthermore, most of the existing studies differentiate the curves by studying changes in pre-defined BMI categories: defining a change within normal weight as “normal-stable” [28], or a change from overweight category to category with obesity as “overweight obesity” trajectory [26]. This crude categorization of BMI trajectories would probably yield over- or under-deterministic results. It should be noted that a variety of changes could occur within the same categories; even a small change in BMI would pose a significant deleterious effect on health [26]. Furthermore, the rate of change, the direction of change, or the slope of the trajectory was all likely to make a difference in the negative outcomes [13,53].

Thus, from the current study, we derived an overall BMI trajectory (annul change in BMI or BMI slope) for each individual, giving further support to the associations of long term trajectories and diverse health outcomes. In our study, the slope of BMI throughout middle and older age, either positive or negative, rendered increased risks of MACE and mortality: the larger the changes the greater the risk. More specifically, BMI falling faster than 0.1 kg/m2 per year resulted in at least 8% higher risks of MACE and 18% of death. On the other hand, increasing BMI by 0.3 kg/m2 per year was associated with at least 13% higher hazards for MACE and 8% for death. Although several prior studies were conducted with a similar method, findings were mixed and inconsistent. As demonstrated in Framingham Heart Study, BMI slopes were inversely associated with the outcome of total mortality and morbidity due to CHD [13]. On the contrary, in the study of Chicago Western Electric Company, weight loss slope was significantly associated with total and cardiovascular mortality, while the weight gain slope showed nonsignificant increased risk of each endpoint for 25-year follow-up [32]. These inconsistencies may result from inadequate adjustment for potential cofounders and not considering the weight change direction.

Identical pattern of association was noted in subgroups of the population, after stratification for age, sex, race, smoking status and baseline BMI. However, effect modification of these stratification variables varied with respect to different outcomes. Generally, the hazardous effects of weight change and adverse outcomes were more pronounced in male participants and at younger age (<60 years). Two additional results should be noted. First, although previous studies have suggested that smoking status is a crucial modifier on the association of BMI and cardiovascular risks, we reveal that the hazards of cardiovascular outcomes were generally consistent in the three categories of smoking status. While for all-cause and non-CVD death, the association with weight loss were inconclusively modified by smoking status. The inconsistent observed relation could be the result of diverse weight change patterns associated with smoking or accounted for the unmeasured confounders [12,33]. Second, decreased weight in individuals with higher BMI (overweight or with obesity) may result in a better outcome when compared to those with normal weight at baseline, which could partially explain the phenomenon of “obesity paradox” [54]. The risk differences for weight gain among normal, overweight or individuals with obesity were less obvious.

In this study, we not only captured the characteristics of individual BMI change trajectory, but also directly evaluated the average BMI trajectories for those with and without specific outcomes. We found for the first time that patterns of change in BMI prior to different outcomes were different. Overall, the BMI trajectories appeared similar for most of the study outcomes: the outcome-free participants followed a trajectory where the average BMI levels remained relatively stable, while for those who went on to experience adverse events, the trajectories began to fall 10 years before the event. Although it’s unclear whether the observed weight loss was the antecedent cause or the consequence of the outcome, these findings may signal an underlying high-risk population and underscore the importance of maintaining body weight over the middle to late adulthood.

The major strengths of this study include the availability of multiple BMI measurements within identical time interval and using the linear mixed model, which entails a more accurate assessment of individual BMI trajectory. Furthermore, although distinguishing intentional and unintentional weight loss is challenging, we try to separate them by using weight variability, in which the highest variability subgroup represents intentional weight loss subcategory. As a result, in weight loss participants with high weight variability, moderate and rapid weight loss was not significantly correlated with increased risk of cardiovascular events. But likewise, we did not observe a beneficial effect in this group of population. One possible explanation for this is that weight rebound following intentional weight loss may offset the positive effect brought by losing weight [55]. Therefore, for weight loss individuals, it is imperative to first examine the reasons for weight loss: intentional or unintentional. If someone is losing weight intentionally, avoiding weight regain or achieving sustained weight loss may be the cornerstone of the accrued benefits brought by losing weight from a high BMI.

Despite of the strengths provided above, several limitations should be noted. Firstly, our findings relate solely to changes in BMI while the changes of fat mass, muscle mass and the general change of the body composition were unknown. In addition, since majority of the study participants were white US people, the results could not be generalized to more heterogeneous populations. Secondly, although we are trying to distinguish whether weight loss was intentional or unintentional in our sensitivity analysis, data on the causes of weight loss were unavailable in the current study. And thus, we could not confirm the above speculation and further studies are warranted.

In this large population-based study, a U-shaped relation was observed between BMI trajectories and subsequent risk of different health outcomes. Both weight gain and weight loss conferred increased risks for cardiovascular events and all-cause mortality. In addition, we found for the first time that patterns of change in BMI prior to different outcomes were different. Falling off the BMI trajectory could be a warning sign for future occurrence of adverse events; thus, maintaining body weight during the middle to late adulthood may be essential. Despite the observational nature of the current study, the trajectories and risk patterns identified here may inspire future studies on the cause and potentially weight management guidelines.

The ARIC, CHS, MESA and FHS studies are carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts. The study was also financially supported by the grants from National Natural Science Foundation of China (81600260), Guangdong Natural Science Foundation (2016A030313210), the Science and Technology Planning Project of Guangdong Province (2017A020215174), the Fundamental Research Funds for the Central Universities in Sun Yat-Sen University (18ykpy08), and the project of Kelin new star of the First Affiliated Hospital of Sun Yat-Sen University (Y50186).

Declaration of Competing Interest

We declare no competing interests.

Contributors

All authors contributed to the study concept and design. YC, CZ and WS contributed equally to this work. DL and YC are senior and corresponding authors who also contributed equally to this study. DL, YC, CZ and WS have full access to all the data in this study and take full responsibility as guarantors for the integrity of the data and the accuracy of the data analysis. CY, LD, CZ and WS contributed to the study design. CZ and WS contributed to analysis and data interpretation. CY and LD drafted the manuscript and contributed to the final approval of the manuscript. MW, YF and ZM contributed to critical revision of the manuscript for important intellectual content.

Data sharing statement

The cohort data sets were obtained from the NIH Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) and could be applied to the corresponding author upon reasonable request.

Appendix. Supplementary materials

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These authors contributed equally to the work.View Abstract© 2021 The Authors. Published by Elsevier Ltd.

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Total Wake: Natural, Pathological, and Experimental Limits to Sleep Reduction

New Mini Review Article in Frontiers in Neuroscience by:

Yuri Panchin1,2 and Vladimir M. Kovalzon1,3*

  • 1Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow, Russia
  • 2Department of Mathematical Methods in Biology, Belozersky Institute, Lomonosov Moscow State University, Moscow, Russia
  • 3Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, Moscow, Russia

Front. Neurosci., 07 April 2021 | https://doi.org/10.3389/fnins.2021.643496

Abstract

Sleep is not considered a pathological state, but it consumes a third of conscious human life. This share is much more than most optimistic life extension forecasts that biotechnologies or experimental and medical interventions can offer. Are there insurmountable physical or biological limitations to reducing the duration of sleep? How far can it be avoided without fatal consequences? What means can reduce the length of sleep? It is widely accepted that sleep is necessary for long-term survival. Here we review the limited yet intriguing evidence that is not consistent with this notion. We concentrate on clinical cases of complete and partial loss of sleep and on human mutations that result in a short sleep phenotype. These observations are supported by new animal studies and are discussed from the perspective of sleep evolution. Two separate hypotheses suggest distinct approaches for remodeling our sleep machinery. If sleep serves an unidentified vital physiological function, this indispensable function has to be identified before “sleep prosthesis” (technical, biological, or chemical) can be developed. If sleep has no vital function, but rather represents a timing mechanism for adaptive inactivity, sleep could be reduced by forging the sleep generation system itself, with no adverse effects.

 Dedicated to Michel Valentin Marcel Jouvet (1925–2017)

www.frontiersin.org
Michel Jouvet, 2005 (Photo by Vera Nezgovorova)

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Another dollar, another day, another set of slides for Swiss Re

Research requires funds and universities have overhead costs. The contributions of the Wessely School to research on ME/CFS are described in earlier posts. Here I start a series of posts on the funding sources of the universities involved.

Professor Sir Simon Wessely is the Regius Professor of Psychiatry, Director of King’s Centre for Military Health Research and, until recently, President, Royal Society of Medicine, 2017-2020.

Sir Simon Wessely is an eclectic presenter who taps effortlessly into a large store of knowledge from science, literature and the arts. He is a strategic thinker, who chooses his words carefully and deliberately. On this occasion, his topic is: “Everything you always wanted to know about mental health but were afraid to ask”.

Sir Simon is on home turf, an easy wicket on which to play smooth, well-timed strokes, with plenty of panache. No beating around the bush, Sir Simon’s first slide goes straight to the point: his competing interests. Here I quote directly from Sir Simon’s Swiss Re slide:

Competing interests


• Lots of funding from UK Research Councils, Wellcome, medical, military and veterans charities, UK Ministry of Defence and US Departments of Defense.


• Never had a penny from Pharma

• But frankly, my university will take money from anyone provided it comes with overheads.

Really? Can this be true?

Well, erm, yes, it is. In a later post, I will list a few specific funding sources.

A Significant Figure

In case it had escaped our attention, Sir Simon’s next slide shows a glimpse of the high circles he moves in.

A photo of a meeting with Mrs Theresa May, UK Prime Minister 2016-19.

Global Burden of Disease

The following slide turns to the meat of the presentation, mental health, and the huge global burden of disease, especially neuropsychiatric disease:

Medical Unexplained Symptoms

Curiously absent from Sir Simon’s slide is the category of Medical Unexplained Symptoms. According to the Royal Society of Psychiatrists:

  • About 1 in 4 people who see their GP have such symptoms. 
  • In a neurological outpatient setting, it is 1 in 3 patients or more

Stress is mentioned, insecurity, smoking, drinking, drugs, self-harm, internet abuse, almost everything to do with mental health, but nothing about MUS.

Skipping over 30 slides, available here – until they are taken down – Sir Simon finishes as he started, with humour and panache. Slide 34:

WHY I NEVER GIVE ADVICE

Then, slide 35:

BUT IF I DID…


• Never neglect the co morbidities
• Please don’t encourage anything that gives us more labels/diagnoses

• Be careful with your language – it can influence for good and ill

Sir Simon draws to a close with slide 36’s

Poetic Ending

“Who in the rainbow can draw the line where the violet tint ends and the orange tint begins? Distinctly we see the difference of the colors, but where exactly does the one first blendingly enter into the other? So with sanity and insanity. In pronounced cases there is no question about them. But in some supposed cases, in various degrees supposedly less pronounced, to draw the exact line of demarcation few will
undertake tho’ for a fee some professional experts will. There is nothing namable but that some men will undertake to do it for pay.”


“Billy Budd”, Herman Melville. 1888

I will return to this interesting conclusion later.

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Dog whistle medicine and disability denial

Here I review the corporate connections of the Wessely School with the insurance industry. The picture featured above shows the cover of a book edited by Peter Halligan and Mansel Alyward alongside a similar cover from the UnumProvident annual report of 2002.

Imaginary conversation

Imagine the conversation, which must have gone something like this:

Unum executive: Hi, how are you Mansel?

Aylward: Nor bad, thank you, I think I’ve got my ducks in a row with the university and the department.

Unum exec: Oh, great, your funding applications are being given serious attention.

Aylward: That’s wonderful, is there anything more I can do in return?

Unum exec: Well, yes, please keep plugging that biopsychosocial model thingy. Would be very good for our customers and, umm, well, yes, the profit margins of the company.

Aylward: Well, yes, sure, that’s exactly what we’re doing. We’re full steam ahead on it at the DWP also. We’ve got a new book about it coming out very soon.

Unum exec: Great. How about the book cover? Can you make it the same as our 2002 annual report?

Aylward: Well, yes, I’ll have to check with the publisher, of course, but I’m sure we can manage something quite similar.

Unum: This is why I like working with you guys, you are so cooperative.

Aylward: The feeling is mutual. Did you say the cheque’s in the post?

2002 Report by UnumProvident (on left} and book edited by Halligan and Aylward

———————————————————

Dogwhistle medicine

There’s nothing like a cartoon to get your point across. Here’s one chosen by Sir Mansel.

This picture is a favourite slide of inner circle member, Mansel Alyward, in a talk about disability medicine.

Another of Sir Mansell’s slides suggests the existence of strong scientific evidence that “we could reduce sickness absence due to common health problems by 30-50%, reduce number going on to chronic incapacity by 30-50% and, in principle, by much more” (Aylward, 2005).  

In Aylward’s own words lies the policy agenda for Unum, DWP, and the Wessely School all rolled into one:

‘Get people on sickness benefits back to work as quickly as possible’.

And if you can’t get them back to work, make sure their diagnosis is mental health not physical health.”

That’s the Holy Grail, a quick sharp shock (no pun intented) of GET and CBT, or no insurance payments for the rest of your unemployed life.

Under the imprint of the Royal Society of Medicine, Waddell and Aylward (2009) applied this approach in a comprehensive analysis of sickness and disability in common health problems, e.g. back pain and CFS.

Basically, it’s all about blaming the victim.

Dog whistles everywhere

Blaming-the-victim attitudes are contagious. They may be strong in Britain but in the popularist world they are spreading absolutely everywhere. Especially in disability medicine.

The European Union of Medicine in Assurance and Social Security EUMASS met in September, 2019. Its Vice President, Dr Gert Lindenger, gave a presentation entitled: How can social security/insurance better benefit from Cochrane Reviews?

One of Lindenger’s first slides reproduces the cartoon above. The joke sends a message. The audience smirks and smiles.

Nice to see Sir Mansel’s handiwork disseminating across Europe. The sophistication of the science may not bowl one over but, hey, nobody’s perfect. Look at this piece of epidemiological wisdom:

I bet you didn’t know that!? It’s got nothing to do with the government or Brexit or COVID-19. Dr Lindenger’s arrow is arriving near you.

More seriously, another of Dr Lindenger’s slides shows the sick leave figures from across Europe, 1987-2018.

The dog whistles are becoming a little shrill, perhaps, especially for the disability medics in Norway. But three cheers, for Sir Mansel and Sir Simon, the UK is up to speed and currently producing some of the lowest numbers of sick leavers right across Europe.

Another of Dr Lindenger’s slides asks: What is the essence of a work disability claim? he gives some straightforward answers:


• Very few medical conditions will with certainty lead to a completely reduced work ability.

• An assessment of work ability often involves interpretations which includes evaluations of where the limit is drawn for what strains and pressures that should normally be tolerated – what is reasonable for asking a claimant to contribute to his/hers own support?

Just an aside, from Unum’s perspective, a third related point, does the claimant perhaps have a work-related insurance policy that can’t pay out? If so, lovely jubbly!

Insurance Companies’ Involvement

Mansel Aylward, with most other members of the Wessely School, formed strong connections with the insurance industry and with UnumProvident and Swiss Re in particular. Here I discuss the profile of Unum.

In 2005 the California Department of Insurance investigations into Unum and found “widespread fraud”, prompting California Insurance Commissioner John Garamendi to describe Unum as an “outlaw company.”

In 2012 legal website LawyersandSettlements.com reported, “Unum continues to suffer from a global reputation that it denies, delays or discontinues benefits in an alleged attempt to wear down policyholders in their pursuit of legitimate benefits.”

The Unum/Provident Scandal

Unum provides the largest share of private sickness unemployment insurance in the US and UK. It isn’t all good news for Unum however. A Unum class action lawsuit in the US has been called “The Unum/Provident Scandal.

Unum (known then as Unum/Provident) was alleged to have denied or terminated thousands of legitimate disability claims starting in the 1990s and continuing until 2002.

The Unum class action lawsuit came about after an investigation by the US Department of Labor that put the long history of Unum claim denial under the microscope. The investigation also looked into Unum’s subsidiary companies, which at the time were Unum Life Insurance Company, Paul Revere Life Insurance Company, and Provident Life and Accident Insurance Company.

The Department of Labor found the company was acting “unfair and unjust” by deliberately resorting to fraudulent tactics of claim denial as a cost control measure. The claims involved employee group disability policies. In an investigation that involved insurance regulators from 48 states, lawsuits against Unum were granted class action status for violation of ERISA laws.

Under court order, Unum was directed to reopen more than 200,000 denied claims, and to reevaluate the claims based on their merit. Unum was charged with overhauling the methods by which they evaluate and process claims. Unum was also ordered to pay a fine of $15 million to several states.

Lesson Not Learned

After such legal actions and repercussions, Unum should have learned a lesson and learned to play by the rules. Not so.

According to the American Association for Justice in a document entitled: “The Ten Worst Insurance Companies in America“, where Unum is honoured with 2nd place, by 2007 Unum confessed that only 10 percent of the claims earmarked for reopening under the terms of the previous legal settlements had been reviewed.

New cases are ongoing

See this:

The Wessely School sure did choose some fine bedfellows.

Sir Mansel is now at a different Welsh university. Did something go wrong at Cardiff? Or is Swansea just nicer than Cardiff?

Probably.

Personal footnote

Oblivious to the context, I contributed by invitation a chapter to Halligan and Aylward’s book on The Power of Belief. My chapter about ‘subjective validation’ concerns a process that happens when one’s beliefs are confirmed by ambiguous or contrary evidence. It is especially prevalent in the field of the anomalous experiences e.g. the paranormal. I had already critiqued the biopsychosocial model in a co-authored textbook on Health Psychology, currently in its 6th edition. Awareness of the abuse of the BPSM in disability denial deepened this critique significantly.

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Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie ME/CFS

HYPOTHESIS AND THEORY ARTICLE

Front. Med., 28 January 2021 | https://doi.org/10.3389/fmed.2021.62802

Dominic StanculescuLars Larsson and Jonas Bergquist

Under a Creative Commons license open access

Here Dominic Stanculescu et al. advance the hypothesis that ‘maladaptive mechanisms’ that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland’s pulsatile secretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.

Introduction

Critical illness refers to the physiological response to virtually any severe injury or infection, such as sepsis, liver disease, HIV infection, head injury, pancreatitis, burns, cardiac surgery, etc. (1). Researchers make a distinction between the acute phase of critical illness—in the first hours or days following severe trauma or infection; and the chronic or prolonged phase—in the case of patients that survive the acute phase but for unknown reasons do not start recovering and continue to require intensive care (i.e., “chronic ICU patients”). Independent of the nature of the critical illness, the acute phase is associated with an excessive response of pro-inflammatory cytokines (2) and is characterized by a uniform dysregulation of the endocrine axes (3). In prolonged critical illness, this dysregulation is maintained even once the initial inflammatory surge has settled (4). Regardless of the initial injury or infection, patients that suffer from prolonged critical illness experience profound muscular weakness, cognitive impairment, loss of lean body mass, pain, increased vulnerability to infection, skin breakdown, etc. (156). Whereas, the acute phase is considered to be an adaptive response to the severe stress of injury or infection (shifting energy and resources to essential organs and repair), the physiological mechanisms in the prolonged phase are now increasingly considered to be maladaptive responses to the stress of severe injury or infection, hindering recovery (710). Some have also suggested that the non-recovery from endocrine disturbances could explain the development of “post-intensive care syndrome” (PICS) (11); i.e., “the cognitive, psychiatric and/or physical disability after treatment in ICUs” (1213).

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating, multi-system disease of unclear etiology (1415). The most common peri-onset events reported by patients are infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%) (16). “Impaired function, post-exertional malaise (an exacerbation of some or all of an individual’s ME/CFS symptoms after physical or cognitive exertion, or orthostatic stress that leads to a reduction in functional ability), and unrefreshing sleep” are considered to be core symptoms (14). The severity of the symptoms varies: “very severely affected patients experience profound weakness, almost constant pain, severe limitations to physical and mental activity, sensory hypersensitivity (light, touch, sound, smell, and certain foods), and hypersensitivity to medications” (17). We have listed a few hall mark symptoms that are often found in critically ill patients in chronic intensive care (ICU) patients and ME/CFS patients (Table 1).TABLE 1

Table 1. Comparison of the typical clinical picture of ICU patients and patients with ME/CFS.

Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some ICU patients also underlie ME/CFS. Specifically, these mechanisms are: (a) suppression of the pituitary gland’s pulsatile secretion of tropic hormones, and (b) a “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. These mechanisms characterize prolonged critical illness regardless of the nature of the initial severe injury or infection (3810); similarly, we propose that these mechanisms could underlie the perpetuation of illness in ME/CFS regardless of the nature of the peri-onset event (i.e., infection, stressful incident, exposure to environmental toxins, or other). We provide an overview of these mechanisms in ICU patients and discuss their relevance for understanding ME/CFS. We also bring findings from fibromyalgia into the discussion here because ME/CFS and fibromyalgia are often jointly considered in the literature (2021); fibromyalgia is similarly a syndrome that is medically unexplained, often comorbid with ME/CFS, and “shares the core symptoms of fatigue, sleep problems and cognitive difficulties” (22). Additional research projects are required to investigate the validity of this hypothesis building on the findings from critical illness and ME/CFS summarized here.

This hypothesis may be particularly relevant in light of the current COVID-19 pandemic. Many COVID-19 patients continue to experience a variety of debilitating symptoms despite successfully defeating the virus—termed “post COVID-19 syndrome” or “long COVID-19”—that resemble ME/CFS (2326).

Suppression of Pulsatile Pituitary Secretions

Endocrine patterns observed during the initial acute phase of critical illness (in the first few hours or days) differ markedly from those observed during prolonged critical illness (after a few days) (2728). Indeed, the acute phase is characterized by increased release of pituitary hormones; the prolonged phase is characterized by suppression of the release of pituitary hormones. Simultaneously, hormone half-life and hormone up-take by the peripheral tissues differ markedly between these two phases (429). This biphasic pattern of the endocrine system during critical illness, however, is not readily observable in single or average measurements of circulating tropic and non-tropic hormone concentrations—which are a function of both hormone release and elimination from the blood stream. This pattern was thus only discovered in the early 1990s with measurements of the frequency and amplitude of pituitary secretions (i.e., pulsatility) performed as often as every 10 min over 24 h on ICU patients (29). The pulsatility of tropic hormone secretion is part of the signaling to the peripheral glands and thus considered a determining factor of hormone function (i.e., impact on target glands or tissues), in addition to overall volume of hormone release (3031). The finding that pulsatile pituitary secretions are suppressed during prolonged critical illness was critical in understanding the physiology of the syndrome and the curious failure of patients to recover (32). We describe the biphasic endocrine patterns during acute and prolonged critical illness for each of the main endocrine axes in further detail below, as well as the implications for the autonomic nervous system, metabolism and the immune system. We also provide evidence suggesting that the endocrine patterns observed in prolonged critical illness also underlie ME/CFS.

The Adreno-Cortical Axis (HPA Axis)

The adreno-cortical axis—also called hypothalamic-pituitary-adrenal (HPA) axis—is the body’s primary stress management system. The HPA axis responds to physical and mental challenges in part by controlling the body’s glucocorticoids levels, notably cortisol (33). Cortisol in turn modulates inflammation response, cardiovascular function and glucose metabolism (34). An inability to deal with stress, proneness to exaggerated immune responses and weight loss are associated with hypocortolism or poor HPA axis function (3538). The HPA axis also regulates mineralocorticoids that, in turn, regulate water and electrolyte balance (i.e., blood pressure). Low blood pressure and dizziness upon standing up are associated with a compromised HPA axis (35). Finally, the HPA axis (in addition to the gonadotropic axis not covered here) also contributes to the production of androgens, notably DHEA and testosterone, which are steroids that impact muscle mass, fat storage, pain, brain function and many other physiological traits. Low androgens are associated with muscle fatigue, joint pain, and noise intolerance (3942).

In normal conditions, the adrenal gland secretes cortisol during the day in pulses, with the highest amounts in the early morning hours and lower amounts at night. The hypothalamus signals to the pituitary with corticotrophin-releasing hormone (CRH), and to a lesser extent, arginine vasopressin (AVP), to produce adrenocorticotropic hormone (ACTH). This is in turn signals the adrenals to release cortisol and other hormones. Most cortisol circulating in the blood is bound to carrier molecules (2943). Production of cortisol is regulated by an inhibitory feedback loop. When free circulating cortisol attaches to glucocorticoid receptors on the hypothalamus and pituitary, these glands reduce production of CRH and AVP, and ACTH, respectively. The number and affinity of glucocorticoid receptors is thus considered one of the most important determining factors in the regulation of the HPA axis (43)

In Critical Illness

During the acute phase of critical illness, plasma cortisol concentrations rise rapidly. Increased cortisol availability is considered a vital response that allows for fluid retention, increased cardiac output and blood pressure, and induces an appropriate immune response while protecting against excessive inflammation (294445). Until recently believed to be the result of increased cortisol production by the adrenals, it is now known that high cortisol availability during this phase of critical illness is in fact largely driven by two peripheral mechanisms: a decrease in the abundance and affinity of the cortisol carrier molecules in circulation, and a slowing of cortisol breakdown in the liver and kidney (2934444647). Via inhibitory feedback loops, these higher cortisol concentrations suppress the HPA axis at the central level: the secretions of CRH and AVP by the hypothalamus and of ACTH by the pituitary fall, leading to an eventual drop in plasma cortisol levels (48).

Whereas, in critically ill patients that begin to recover, the HPA axis essentially normalizes within 28 days of illness, in cases of prolonged critical illness ACTH levels (surprisingly) continue to be depressed despite dropping cortisol levels (4950). Why and how this central suppression of ACTH is maintained is not clear and continues to be debated. Pro-inflammatory cytokines and O&NS likely play a leading role. Cytokines can mediate tissue-specific changes in the abundance and affinity of glucocorticoid receptors—which are major factors determining the activity of the HPA axis (244). Specifically, the cytokine IL-1β is known to modulate CRH release by the hypothalamus; TNF-α is known to impair ACTH release by the pituitary; and TNF-α is also known to impair cortisol production by the adrenal glands (2).

Without sufficient pulsatile stimulation by the tropic hormone ACTH, adrenal glands begin to atrophy and lose zonational structure. This is evidenced in the post-mortem dissection of patients that had been critically ill for a few weeks, but not in the patients that quickly died from their illness or trauma (3451). The weakening of adrenal glands not only compromises patients’ ability to cope with external stressors but also permits excessive inflammatory responses. In sum, the initial beneficial increase in cortisol availability induced by peripheral mechanisms during the acute phase of critical illness leads to a suppression of the HPA axis at the central-level from which a subset of patients appears unable to escape (Figure 1).FIGURE 1

Figure 1. The adreno-cortical axis (HPA axis) during normal conditions and prolonged critical illness.

In ME/CFS

Dysfunction of the HPA axis has been documented extensively in ME/CFS patients since the early 1980s (5263). Researchers have observed decreased baseline cortisol levels, blunted HPA axis responses to physical and psychological stressors, reduced HPA axis responsivity to provocation tests (such as CRH and ACTH administration), and a heightened inhibitory feedback loop (consistent with a higher abundance and affinity of glucocorticoid receptors at the level of the pituitary and hypothalamus). Strikingly, the magnitude of HPA axis dysfunction becomes more pronounced with illness duration and is associated with symptom severity (4364). Very few have studied pulsatility of ACTH release: one study of 36 study-pairs found no statistically significant differences in ACTH pulsatility between ME/CFS and matched controls (65), while another found a differential pattern of ACTH release over 24-h periods (66). Variations in the study-participants’ severity of illness—and methods used to control for these—may explain these apparently contradictory findings. Several studies have found the morning peak of ACTH is missing or weak in ME/CFS patients (43). A recent study assessing secretory events of cortisol found that CFS/ME patients have the same number of secretory events but secrete lower quantities in early morning hours (67). Significantly, a group of ME/CFS patients were found to have 50% smaller adrenals than controls (68), resembling adrenal atrophy in prolonged critical illness.

ME/CFS researchers have also proposed models to explain the persistence of a suppressed HPA axis (336970). Essentially, a short stress (i.e., a burst of cortisol) will produce a small perturbation in the glucocorticoid receptor concentration on the central glands that quickly returns to normal levels. However, long, repeated stress—from which the system doesn’t have time to recover—leads to a persistent high glucocorticoid receptor concentration, forcing the HPA axis to an alternate steady state. More recent models of the HPA axis have also included non-genomic feedback-controls (71), the endogenous effects of circadian rhythm (72), and interactions with the gonadotropic axis and the immune system (7374) to explain how HPA axis suppression is maintained even after the initial stress is gone.

HPA axis dysfunction is also present in the majority of fibromyalgia patients (7577). Various mechanisms have been suggested, including depressed secretion of CRH by the hypothalamus, a deficiency of CRH receptors on the pituitary, and adrenal atrophy due to chronic under-stimulation by reduced ACTH levels (78).

Moreover, the dysfunction of the HPA axis in ME/CFS and fibromyalgia has also been associated with pro-inflammatory cytokines and O&NS (43557980). A recent paper considering the bidirectional relationship between the function of the HPA axis and inflammation finds that immune-inflammatory and O&NS pathways induce HPA axis dysfunction in ME/CFS (81); the direction of causality is analogous to inflammatory pathways inducing endocrine dysfunctions in critical illness. Others have similarly theorized that local inflammation in the hypothalamus leads to a disturbed HPA axis in ME/CFS (82).

In sum, the HPA axis dysfunctions in ME/CFS are not unlike the dysfunctions in prolonged critical illness. However, to our knowledge a comprehensive study of the pituitary pulsatile secretions of ACTH in ME/CFS patients—which proved revelatory in understanding prolonged critical illness—does not yet exist. The relationship between the pituitary’s pulsatile ACTH secretions, severity of illness, the integrity and function of adrenal glands and resulting physiological alterations in ME/CFS thus remains largely unexplored.

The Somatotropic Axis (HPS Axis)

The somatotropic axis—also called hypothalamic-pituitary-somatotropic (HPS) axis—plays important roles in growth and development of children, but also contributes to a variety of physiological pathways in adults, including balancing catabolic (i.e., the break-down of molecules and tissues) and anabolic activities (i.e., the building of molecules and tissue) (4). An HPS axis dysfunction is known to cause loss of muscle and bone mass, induces weakness (29), and impacts gut mucosa integrity as well as glucose and fat metabolism (83). Low energy, exhaustion, mental fatigue, weak muscle strength as well as poor recovery after physical activity are associated with an inhibited HPS axis function (428485).

Uniquely, in the case of the HPS axis, the hypothalamus sends both stimulating (+) and inhibiting (-) signals to the pituitary for the production of growth hormone (GH): these are, respectively, the GH-releasing hormone (GHRH) and the GH-inhibiting hormone (GHIH, also called somatostatin) (4). In addition, ghrelin, mostly produced by the gut, also stimulates GH production by the pituitary. In normal conditions, GH is released by the pituitary in a pulsatile fashion under the control of these three signals, with peaks of GH levels alternating with virtually undetectable valleys in 3- to 5-h intervals over the course of the day (29). GH in turn has direct effects on some tissues and also stimulates the production of insulin-like growth hormone-1 (IGF-1), mostly by the liver. Nearly all of the IGF-1 hormones in the plasma are bound to IGF-binding proteins (IGFBP). IGF-1 and GH exert inhibitory feedback on the hypothalamus and the pituitary to maintain homeostasis. The half-life of GH is only 10 to 20 min, whereas the half-life of IGF-1 is more than 12 h. Thus, IGF-1 plasma concentrations are regularly used as proxies for GH secretion in clinical settings. This, however, overlooks the function of the pulsatile secretion of GH on the balance of anabolic and catabolic activities in the body (4).

In Critical Illness

In the acute phase of critical illness, the pituitary produces more GH: higher peaks, lower valleys and increased pulse frequencies (86). The rapid onset of two main peripheral mechanisms explain this finding: First, under the influence of cytokines, the liver expresses fewer GH receptors (i.e., becomes resistant to GH) and thus produces less IGF-1. Second, alterations in IGF binding proteins results in IGF-1 being cleared out faster from the system (i.e., IGF-1 has a shorter half-life) (87). The lower IGF-1 concentrations resulting from these two peripheral mechanisms will—via the feedback loop inherent to the axis—spur more GH production (29). The resulting increase in catabolic activity during the acute phase of critical illness serves to mobilize amino acids derived from the breakdown of peripheral tissues, such as skeletal muscle and bone, for use by the central organs (4).

However, if a critically ill patient fails to recover within a few days, GH secretion becomes erratic and almost non-pulsatile. Experiments have demonstrated that this is largely due to a lack of stimulation of the hypothalamus and pituitary by the hormone ghrelin. There is also evidence for changes in the relative amounts of GHIH and GHRH signals from the hypothalamus (4). As for the peripheral hormone, IGF-1, its levels are low or normal in prolonged critical illness. The liver’s resistance to GH (which previously suppressed IGF-1 production during the acute phase of critical illness) does not persist during prolonged critical illness (2987). However, without a concomitant pulsatile release of GH, the anabolic function of IGF-1 becomes inhibited (4).

In sum, although the increase in catabolic activity during the acute phase of critical illness may initially be beneficial because it serves to mobilize amino acids, the perpetuation of the imbalance in catabolic vs. anabolic activity (due in part to the loss of the pulsatile function of GH) during prolonged critical illness may be considered maladaptive (Figure 2). The imbalance in catabolic relative to anabolic activity in prolonged critical illness leads to protein break-down in skeletal muscle, liver, kidney and heart, reducing their cell mass and leading to impaired function (7). These processes are ultimately reflected in muscle and bone wasting typically present in prolonged critical illness (8889).FIGURE 2

Figure 2. The somatotropic axis (HPS axis) during normal conditions and prolonged critical illness.

In ME/CFS

GH regulation in ME/CFS has been studied since the 1990s. The findings are mixed, but almost none addresses the question of the pulsatility of GH release. Some described low nocturnal GH secretion (9091), while others have found normal levels of 24-h urinary GH excretion (92). Some have found reduced response to induced hypoglycemia (9091), while others describe normal GH responses to stimulation (93). One study describes unaffected diurnal patterns of GH release in ME/CFS, but it focused on assessing basal levels rather than the nature of secretory patterns (i.e., pulsatile vs. erratic) and may not have accounted for variations in the severity of illness of patients (66). In terms of IGF-1, there are no consistent differences between ME/CFS patients and controls (9394), which is consistent with findings from prolonged critical illness.

Studies in fibromyalgia show relative GH deficiency (76789599) and low or low-normal IGF-1 levels (9596100). Interestingly, some studies showed that fibromyalgia patients “failed to exhibit a GH response to exercise” (97101), consistent with a loss in pulsatility of GH release.

In sum, endocrine observations in ME/CFS are not unlike HPS axis dysfunctions found in prolonged critical illness. To our knowledge the pituitary pulsatile secretions of GH in ME/CFS patients has not been comprehensively studied. The relationship between the pituitary’s pulsatile GH secretions, severity of illness and the balance between catabolic and anabolic activities in ME/CFS thus remains largely undiscovered.

The Thyrotropic Axis (HPT Axis)

The thyrotropic axis—also called hypothalamic-pituitary-thyroid (HPT) axis—regulates the basal rate of our metabolism. Dysfunctions of the HPT axis are associated with tiredness, stiffness, constipation, dry skin and weight gain, among a myriad of other hypothyroid-like symptoms (3542).

In normal conditions, an inhibitory feedback loop works to maintain stable circulating thyroid hormone concentrations according to a daily rhythm (102). When unbound circulating thyroid hormone concentrations dip below a certain threshold, the hypothalamus produces thyrotropin-releasing hormones (TRH) in order to signal the pituitary to produce thyroid stimulating hormone (TSH), which in turn signals the thyroid gland to produce more thyroid hormones.

In Critical Illness

Dysfunctions of the HPT axis during critical illness have been studied extensively. Starting in the early 1970s, clinicians working in ICUs observed that patients with a wide range of critical conditions had low plasma concentrations of the active form of thyroid hormones (T3) relative to plasma concentrations of inactivated thyroid hormones reverse T3 (rT3) (103105). They gave this condition the name “non-thyroidal illness syndrome” (NTIS), also called “euthyroid sick syndrome” or “low T3 syndrome.” While NTIS was initially considered to be beneficial in critical illness—i.e., a state of “protective” down-regulation of metabolism during times of duress (106) —it is increasingly seen as maladaptive and hampering the recovery of patients in the case of prolonged critical illness (91029103104107108).

During acute and early stages of critical illness, peripheral mechanisms involving cytokines (notably IL-1β, IL-6, TNF-α) lead to the quick depression of thyroid hormone activity (104105109111) to help conserve energy resources (48104). The mechanisms include the alterations in the amount and affinity of thyroid hormone binding globulines in the blood (112114); modifications in the expression of the transporters that carry the thyroid hormone into the cells (115116); the down- and up-regulation of deiodinase enzymes that convert the thyroid hormone into active and inactive forms, respectively (113117); and the variation in the quantity and isoforms of cellular thyroid hormone receptors present (notably in the liver, adipose tissue and muscle) (118120). An alteration in any of these steps—which determine thyroid hormone function—can lead to large time- and tissue-specific adjustments in cellular metabolism (121122)—even without, or with only minor, changes in the blood concentrations of thyroid hormones (121123124).

During prolonged critical illness these peripheral mechanisms are supplemented by central mechanisms that also depress thyroid hormone function (125126). Cytokines (notably IL-12 and IL-18), in association with other signaling factors (including leptin, glucocorticoids, etc.), are believed to up-regulate the deiodinase enzymes D1 and D2 in the hypothalamus resulting in higher local levels of T3 that inhibit TRH release irrespective of circulating thyroid hormone concentrations (10127128). Moreover, cytokines (notably IL-1b and TNF-α) also suppress the release of TSH by the pituitary (129130). Finally, by reducing iodine uptake and thyroid hormone excretion, cytokines (notably IL-1) also impact the activity of the thyroid gland itself (103113). Together, these mechanisms can alter the inhibitory feedback mechanisms of the HPT axis (i.e., its “set-point”) during prolonged critical illness. Single measurements of circulating TSH, however, are ineffective in revealing such alterations in the set-point of the HPT axis.

In sum, an initial beneficial alteration of thyroid hormone activity in the periphery during acute critical illness is followed by a cytokine-mediated central suppression of the HPT axis resulting in a virtual complete loss of pulsatile TSH secretion (29). Peripheral mechanisms (notably variations in the conversion and transport of thyroid hormones) may further modulate thyroid hormone function in time- and tissue-specific ways resulting in complex physiological alterations in these patients (Figure 3) —not readily observable in blood concentrations of thyroid hormones. How these alterations of the HPT axis persist as well as their broader implications on metabolism and the immune system are further described below (see section A “Vicious Circle” Perpetuating Illness).FIGURE 3

Figure 3. The thyrotropic axis (HPT axis) during normal conditions and prolonged critical illness.

In ME/CFS

Dysfunctions of the HPT axis have long been suspected to play a role in ME/CFS (77131134) and fibromyalgia (135140). A recent study showed that ME/CFS patients had similar TSH levels as controls, but lower Free T3, Total T4, and Total T3, which the authors suggest resembles NTIS (141)—the typical feature of critically ill patients in ICUs described above.

In sum, alterations of the HPT axis in ME/CFS resemble dysfunctions found in prolonged critical illness. However, there does not to our knowledge exist a thorough study of the pulsatility of pituitary TSH secretion events in ME/CFS patients, nor a study of the tissue-specific alterations in thyroid hormone function—which proved revelatory in understanding prolonged critical illness. The relationship between the TSH axis dysfunctions, severity of illness, hypometabolic state and organ/tissue specific symptoms in ME/CFS thus remains largely unexplored.

Intermediate Conclusions

The endocrine axes control many of the most fundamental physiological processes; their suppression is associated with a myriad of symptoms (see Table 2). Essentially, the suppression of pulsatile pituitary secretions of ACTH, GH, and TSH are central to prolonged critical illness. Inflammatory pathways play a role in inducing and maintaining this suppression irrespective of the nature of the original illness or trauma (see Table 3). The resulting endocrine patterns may be considered maladaptive and have wide ranging implications, including dysfunction of the balance between anabolic and catabolic processes, metabolism, and the regulation of the immune system. The physiological parallels between ME/CFS and prolonged critical illness would suggest that the suppression of pulsatile pituitary secretions of these tropic hormones might also underlie ME/CFS, and that the severity of ME/CFS might be a function of the strength of the mechanism; this however remains largely unstudied. In the next section we provide an overview of a model from critical illness that explains the perpetuation of these endocrine dysfunctions and we describe the relevance of the model for understanding ME/CFS.TABLE 2

Table 2. Summary of endocrine axes and function of the main hormones in adults.TABLE 3

Table 3. Summary of endocrine dysfunctions and mechanisms in critical illness and ME/CFS.

A “Vicious Circle” Perpetuating Illness

Based on nearly five decades of research, critical illness researchers have proposed a model that describes how NTIS is maintained by reciprocal relationships between inflammation (notably pro-inflammatory cytokines), O&NS and reduced thyroid hormone function, forming a “vicious circle” (910) (Figure 4). This model can help to explain the perplexing failure to recover of some critically ill patients in ICUs that survive their initial severe illness or injury. We describe the main elements of this model in a simplified manner below, as well as the implications for metabolism and the immune system. We also provide evidence suggesting that the “vicious circle” observed in prolonged critical illness also underlies ME/CFS.FIGURE 4

Figure 4. Simplified model to explain the perpetuation of prolonged critical illness: a “vicious circle”.

In Prolonged Critical Illness

The key elements of the suggested “vicious circle” in prolonged critical illness include the following mechanisms:

(a) Cytokines depress thyroid hormone function: As described above [see section The thyrotropic axis (HPT Axis) In Critical Illness], in acute and early stages of critical illness, various peripheral mechanisms involving cytokines lead to the quick depression of thyroid hormone activity in tissue-specific ways. In prolonged critical illness, cytokines in association with other signaling factors targeting the hypothalamus, as well as the pituitary and the thyroid glands, also inhibit thyroid hormone production. The relative sequence and importance of these various mechanisms in depressing the HPT axis and thyroid hormone function in different tissues and phases of critical illness are the subject of most NTIS publications (10104105). Notwithstanding the effect of other mechanisms, alterations in the activity of the deiodinase enzymes lead to a decrease in T3 and an increase in rT3 and thus a reduction in thyroid hormone function in peripheral tissues during prolonged critical illness [based on biopsies on ICU patients who died (142) and studies on mice (143144)]. Circulating thyroid hormone concentrations, however, only reveal the “tip of the iceberg” of the alterations occurring at the tissue level (141145), which thus are often missed altogether in clinical settings (146).

(b) Low thyroid hormone function contributes to oxidative and nitrosative stress: The relationship between thyroid hormone function and O&NS is complex, and both hyperthyroidism and hypothyroidism have been associated with oxidative stress (147). Nonetheless, it seems clear that depressed thyroid hormone function hinders tissue cells from maintaining a healthy O&NS balance. Mechanisms include alterations to the lipid concentration of the cell membranes that maintain the cell’s O&NS balance (148), and reduced function of two proteins (Uncoupling Proteins-2 and -3) with anti-oxidant properties (149). Moreover, in low thyroid hormone function conditions, mitochondria damaged by O&NS are not cleared out of cells (9). In turn, it appears that oxidative stress depletes the glutathione required by the abovementioned deiodinase enzymes for the conversion of T4 into T3 (104). Similarly, competition for, and the resulting depletion of the trace mineral selenium—a component of both the deiodinase and the anti-oxidant enzymes (150) —may amplify the self-perpetuating link between increased oxidative stress and low thyroid hormone function.

(c) Oxidative and nitrosative stress stimulate the production of pro-inflammatory cytokines: The final mechanism which completes the “vicious circle” in prolonged critical illness is the link between O&NS and inflammation. O&NS stimulates the production of pro-inflammatory cytokines, notably leptin, resistin, TNF-α and IL-6 (151). In turn, pro-inflammatory cytokines (notably IL-6) further increase O&NS by triggering the production of superoxide radicals (104152). There is thus a tendency for O&NS and pro-inflammatory cytokines to perpetuate each other as well.

In sum, according to a model proposed by critical illness researchers, a “vicious circle” involving O&NS, pro-inflammatory cytokines, and low thyroid hormone function—as well as reciprocal relationships across these elements—can perpetuate a hypometabolic and inflammatory state, and thus help to explain why some critically ill patients fail to recover.

In ME/CFS

Similar patterns of O&NS, cytokines, and low thyroid hormone function have recently been documented in ME/CFS patients providing the elements for a similar “vicious circle.” We briefly summarize the findings from ME/CFS research relevant to each of these elements.

Reduced thyroid hormone function: An immune-mediated loss of thyroid hormone function in ME/CFS has long been suspected (132). As mentioned above [see section: The thyrotropic axis (HPT Axis) In ME/CFS], a recent study confirmed that CFS patients have lower circulating levels of Free T3, Total T4, and Total T3 than controls (141). Moreover, this study found a significantly higher ratio of rT3 to T3 hormones. These findings imply a depressed thyroid hormone function resembling NTIS. Given the possible tissue-specific alterations in thyroid hormone activity resulting from peripheral mechanisms, the authors suggest these circulating levels only reflect the “tip of the iceberg” of genuine T3 deficits in target tissues.

Oxidative & nitrosative stress: Numerous studies have found increased O&NS in ME/CFS and identified this as a factor in the observed metabolic dysfunction (153154). Indeed, Pall proposed a model that describes a “vicious circle” involving oxidative stress and cytokines in ME/CFS a decade ago (cf. the “NO/ONOO-Cycle”) (155). Researchers also suggest that high lactate and low glutathione levels found in the brains of ME/CFS patients likely derive from similar mechanisms involving oxidative stress (156). A recent study described the relationship between O&NS and immune-inflammatory pathways in ME/CFS (80).

Pro-inflammatory cytokines: Neuro-inflammation is central to ME/CFS, and many researchers have tried to develop diagnostic biomarkers for ME/CFS based on cytokine profiles of patients (157158). Montoya et al. found that some 17 cytokines were positively correlated with the severity of ME/CFS, of which 13 are pro-inflammatory. Similarly, circulatory levels of pro-inflammatory cytokines are altered in fibromyalgia patients (159). However, others have argued that given the innumerable sources of potential variance in the measurement of cytokines, it is “unlikely that a consistent and replicable diagnostic cytokine profile will ever be discovered” for ME/CFS (160). It may therefore be ineffectual to compare the cytokine profiles of ME/CFS and prolonged critical illness patients.

In sum, given the presence of reduced thyroid hormone function, O&NS and pro-inflammatory cytokines in ME/CFS, the “vicious circle” model proposed by critical illness researchers to explain prolonged critical illness may also help to understand why ME/CFS patients fail to recover.

Implications of the “Vicious Circle” and Its Elements

Reduced thyroid hormone function, increased O&NS and pro-inflammatory cytokines discovered in prolonged critical illness as well as in ME/CFS have important implications notably on metabolism, organ function, immune responses and the endocrine system. These are further described below:

Reduced thyroid hormone function: The prolonged down-regulation of thyroid hormone activity certainly has implications for the immune system. Authors describe the profound effects of circulating thyroid hormone levels on the activity of monocytes, lymphocytes macrophages, neutrophils, dendritic cells and natural killer cells; as well as cytokines (161170). Notably, depressed thyroid levels appear to depress the activity of natural killer cells (171)—a signature finding in ME/CFS (172). Such immune dysfunctions might explain other pathologies, such as viral reactivation observed in ICU patients (173175) and suspected in ME/CFS patients (176177). Experimenting on rats, researchers have shown that depressed thyroid hormone levels occur in a specific sequence, manifesting (from first to last) in the liver, kidney, brain, heart and adipose tissues (145). An implication of a tissue-specific down-regulation of thyroid hormone activity is differential impact on organ function. Some ME/CFS practitioners have argued that tissue-specific modulation of T3 can help explain the disparate and evolving symptoms in ME/CFS and fibromyalgia (133134138140). In aggregate, depressed thyroid hormone function would engender a general hypometabolic state. Finally, thyroid hormone function also impacts other endocrine axes as well (178179)—notably the HPA axis—setting the stage for further complex interactions between the various endocrine axes and the immune system.

Oxidative & nitrosative stress: The implications of chronic oxidative stress in the body are widely documented. In addition to inducing inflammation, oxidative stress causes cell damage and disrupts normal cellular transcription and signaling mechanisms (9). O&NS has been shown to cause mitochondrial damage during critical illness (180) and ME/CFS (153).

Pro-inflammatory cytokines: Researchers are finding that the more than 100 different cytokines play a part in determining the function of hormones through both central and peripheral mechanisms (32). As described in the previous section, cytokines are likely culprits in the central (i.e., hypothalamic and pituitary) suppression of the HPA, HPS and HPT axes in prolonged critical illness (29). Pro-inflammatory cytokines and inflammation also hinder normal mitochondrial function during critical illness (181). The alterations in cytokines found in critical illness likely have many further implications that have yet to be fully understood (182) which is also the case for ME/CFS (183).

Intermediate Conclusions

In sum, critical illness researchers have proposed that the self-perpetuating relationships between inflammation (notably pro-inflammatory cytokines), O&NS and low thyroid hormone function explains the maintenance of illness in some ICU patients following severe injury or infection. Given that the same elements of such a “vicious circle” have also been documented in ME/CFS, we suggest that the model can also explain the failure of ME/CFS patients to recover. Moreover, these elements have been shown to have profound implications on metabolism, as well as on the function of the immune and endocrine systems—which in in turn could explain the myriad of symptoms in prolonged critical illness and ME/CFS.

Relationship to Other Hypotheses of ME/CFS Pathogenesis

Our hypothesis that maladaptive mechanisms which prevent recovery in prolonged critical illness also underlie ME/CFS complements several other hypotheses of ME/CFS pathogenesis. In this section we provide an initial and non-exhaustive discussion of some of these complementarities.

Allostatic overload: Some researchers consider ME/CFS to be a maladaptive response to physical, infectious, and/or emotional stressors. They describe an “allostatic overload” (i.e., the cumulative effect of stressful situations exceeding a person’s ability to cope) or a “‘crash’ in the stress system” (184185). Our hypothesis fits into this theoretical framework and offers an explanation for the possible underlying physiological mechanisms by drawing on the research from critical care medicine.

Hypothalamic endocrine suppression: Researchers have suggested that hypothalamic endocrine suppression could explain ME/CFS (132186) and fibromyalgia (187189). Our thesis upholds this hypothesis and seeks to strengthen it by suggesting that the controversy around the existence of central endocrine suppression in ME/CFS may be resolved by studying the pulsatile secretions of the pituitary—rather than single or average measurements of circulating tropic and non-tropic hormone concentrations, which can fail to discern the dysfunctions of the endocrine axes.

Anomalies in thyroid hormone function: Numerous clinical practitioners and researchers believe that anomalies in thyroid hormone function—including changes in the conversion of thyroid hormones, a resistance of thyroid hormone receptors at cellular level, etc. —contribute to ME/CFS and fibromyalgia (133141). Indeed, practitioners have written about their successes in treating ME/CFS patients with thyroid hormone supplements (4277188190194); and patients have published books on their experiences (195197). Our hypothesis complements this reasoning: we propose that both the central and peripheral mechanisms altering thyroid hormone function during critical illness (c.f. NTIS, euthyroid sick syndrome or “low T3 syndrome”) also occur in ME/CFS. Moreover, by applying a model from critical illness, we suggest that low thyroid hormone function is one element of a “vicious circle” perpetuating illness in ME/CFS.

Viral Reactivation: It has long been suggested that viral reactivation plays a role in ME/CFS, particularly reactivation of Epstein-Barr virus (EBV) and cytomegalovirus (CMV) (176177). Similarly, high incidences of viral reactivation have also been observed in ICU patients, notably in patients with sepsis and prolonged critical illness. ICU researchers propose that this viral reactivation is a result of immune suppression occurring during critical illness (173175). Thus, critical illness research would suggest that viral reactivation is a secondary pathology in ME/CFS—except in cases in which the viral infection was the onset event.

Viral infection: Viral infection is recognized to be a leading onset event of ME/CFS (16198201). This is particularly concerning in the context of the COVID-19 pandemic. Many COVID-19 patients continue to experience a variety of debilitating symptoms after defeating the virus that resemble ME/CFS. Building on our hypothesis, we would suggest that post COVID-19 syndrome is evidence of a maladaptive response to the stress of infection akin to that experienced in prolonged critical illness and ME/CFS.

Chronic inflammation: Researchers have found that chronic inflammation—auto-immune, allergic or bacterial/viral—underlies ME/CFS (194202203). Others also ascribe the perpetuation of ME/CFS to the relationship between inflammation and O&NS (80155). Our hypothesis is largely complementary to these findings and associated theories. Indeed, following a cytokine surge during the acute phase of critical illness, inflammation is believed to persist in the case of prolonged critical illness (4). Moreover, pro-inflammatory cytokines and O&NS are elements in the “vicious circle” model of prolonged critical illness, which we propose also serves to understand the perpetuation of illness in ME/CFS patients.

Neuroinflammation of the brain: ME/CFS is associated with inflammation of the brain (hence the name myalgic encephalomyelitis) (204205). Some have specifically proposed that inflammation of the hypothalamus underlies ME/CFS (8182). Similarly, alterations of the endocrine axes through mechanisms mediated by pro-inflammatory cytokines which impact the hypothalamus and pituitary are central to prolonged critical illness (see section Suppression of Pulsatile Pituitary Secretions).

Energy metabolic defect: Researchers have found impairment in energy production (205206), reduced mitochondrial activity (207209) and irregularities in the metabolites of ME/CFS patients (210211) —suggesting that they experience a hypometabolic or “dauer” state (212). Our hypothesis is compatible with analyses that emphasize metabolic defects in ME/CFS. Indeed, the suppression of pituitary secretions, depressed thyroid hormone function, O&NS and immune system dysfunction—hallmarks of prolonged critical illness—have severe impacts on metabolism, including on glucose utilization and mitochondrial activity (see section A “Vicious Circle” Perpetuating Illness). Certainly, prolonged critical illness resembles a hypometabolic “dauer” state as well.

Genetic predisposition: Research also suggests there may a genetic element in the pathogenesis of ME/CFS (213216). Our hypothesis is compatible with a possible genetic predisposition for ME/CFS. Indeed, it is not known why some critically ill patients succumb to prolonged critical illness while others begin recovery (217218); genetics may play a role. The findings from the field of ME/CFS in the area of genetics might inform the field of critical illness in this regard.

In sum, our hypothesis is largely complementary to hypotheses that emphasize metabolic, hormonal and/or immune dysfunctions in the pathogenesis of ME/CFS. Our hypothesis—drawing from research on critical illness—integrates these dysfunctions into a single framework and provides arguments for the direction of causality between them.

Conclusion

Decades of research in the field of critical medicine have demonstrated that in response to the stress of severe infection or injury, endocrine axes experience profound alterations. An assessment of the pituitary’s pulsatile secretions reveals that in the subset of patients which survive their severe infection or injury but do not begin recovery (i.e., prolonged critically ill patients), the suppression of endocrine axes is maintained irrespective of the initial severe infection or injury. Recent pathological models propose that mechanisms involving pro-inflammatory cytokines, O&NS and low thyroid hormone function explain the perpetuation of these endocrine dysfunctions (i.e., a “vicious circle”).

The symptoms, physiological abnormalities and endocrine patterns observed in severe ME/CFS are not unlike those of prolonged critical illness. Moreover, the same elements of a “vicious circle” also exist in ME/CFS. However, unlike in critical illness, the pituitary’s pulsatile secretion and its relationships to metabolic and immune functions remain largely unstudied in ME/CFS.

Without excluding possible predisposing genetic or environmental factors, we propose the hypothesis that the maladaptive mechanisms that prevent recovery of prolonged critically ill patients also underlie ME/CFS. The severity of ME/CFS illness may be a function of the strength of these mechanisms; very severe ME/CFS most resembles prolonged critical illness. We further argue that this hypothesis should be investigated through collaborative research projects building on the findings from critical illness and ME/CFS. If this hypothesis is validated, past trials to break the “vicious circle” that perpetuates critical illness, and the early successes to reactivate the pulsatile secretion of the pituitary in ICU patients, may provide avenues for a cure for ME/CFS—including cases onset by infections. Certainly, given the similarities described above, active collaboration between critical illness and ME/CFS researchers could lead to improved outcomes for both conditions.

Finally, we suggest that immediate collaborative efforts should be sought among the researcher community in order to conduct longitudinal studies with the aim of identifying similarities and differences across prolonged critical illness, post-ICU syndrome, ME/CFS, fibromyalgia and long-COVID in relation to the hormonal axes, O&NS and pro-inflammatory response with the objective of discovering diagnostic and therapeutic targets mitigating the functional disability that these conditions induce.

Abbreviations

ACTH, Adrenocorticotropic hormone; ARV, Arginine vasopressin; CRH, Corticotrophin-releasing hormone; DHEA, Dehydroepiandrosterone; GH, Growth hormone; GHIH, Growth hormone inhibiting hormone; GHRH, Growth hormone releasing hormone; HPA, hypothalamus-pituitary-adrenal axis: “Adreno-cortical axis”; HPS, Hypothalamic-pituitary-somatotropic axis: “Somatropic axis”; HPT, Hypothalamic-pituitary-thyroid: “Thyrotropic axis”; ICU, Intensive Care Unit; IGF-1, Insulin like growth hormone-1; IGFBP, Insulin like growth hormone binding proteins; ME/CFS, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome; NTIS, Non-thyroidal illness syndrome; O&NS, oxidative and nitrosative stress; PICS, Post-intensive care syndrome; POTS, Postural Orthostatic Tachycardia Syndrome; TRH, Thyrotropin-releasing hormone; TSH, Thyroid stimulating hormone.

Featured

MECFS: evidence for an autoimmune disease

Autoimmunity Reviews

Volume 17, Issue 6, June 2018, Pages 601-609

Autoimmunity Reviews

Review: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease

Franziska Sotzny et al., on behalf of the European Network on ME/CFS (EUROMEN)

https://doi.org/10.1016/j.autrev.2018.01.009

Under a Creative Commons license open access

Highlights

The pathogenesis of ME/CFS is multifactorial, and immunological and environmental factors play a role.•

Autoimmune mechanisms can be linked with ME/CFS at least in a subset of patients.•

Autoantibodies mostly against nuclear and neurotransmitter receptors are found in a subset of ME/CFS patients.•

Immunomodulatory therapeutic strategies targeting autoantibodies may be beneficial and should be pursued.

Abstract

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MECFS) is a frequent and severe chronic disease drastically impairing life quality. The underlying pathomechanism is incompletely understood yet but there is convincing evidence that in at least a subset of patients MECFS has an autoimmune etiology. In this review, we will discuss current autoimmune aspects for MECFS. Immune dysregulation in MECFS has been frequently described including changes in cytokine profiles and immunoglobulin levelsT- and B-cell phenotype and a decrease of natural killer cell cytotoxicity. Moreover, autoantibodies against various antigens including neurotransmitter receptors have been recently identified in MECFS individuals by several groups. Consistently, clinical trials from Norway have shown that B-cell depletion with rituximab results in clinical benefits in about half of MECFS patients. Furthermore, recent studies have provided evidence for severe metabolic disturbances presumably mediated by serum autoantibodies in MECFS. Therefore, further efforts are required to delineate the role of autoantibodies in the onset and pathomechanisms of MECFS in order to better understand and properly treat this disease.

Featured

ME/CFS and autoimmunity

The Emerging Role of Autoimmunity in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/cfs)

Molecular Neurobiology volume 49, pages741–756(2014) Cite this article

Abstract

The World Health Organization classifies myalgic encephalomyelitis/chronic fatigue syndrome (ME/cfs) as a nervous system disease. Together with other diseases under the G93 heading, ME/cfs shares a triad of abnormalities involving elevated oxidative and nitrosative stress (O&NS), activation of immuno-inflammatory pathways, and mitochondrial dysfunctions with depleted levels of adenosine triphosphate (ATP) synthesis. There is also abundant evidence that many patients with ME/cfs (up to around 60 %) may suffer from autoimmune responses. A wide range of reported abnormalities in ME/cfs are highly pertinent to the generation of autoimmunity. Here we review the potential sources of autoimmunity which are observed in people with ME/cfs. The increased levels of pro-inflammatory cytokines, e.g., interleukin-1 and tumor necrosis factor-α, and increased levels of nuclear factor-κB predispose to an autoimmune environment. Many cytokine abnormalities conspire to produce a predominance of effector B cells and autoreactive T cells. The common observation of reduced natural killer cell function in ME/cfs is a source of disrupted homeostasis and prolonged effector T cell survival. B cells may be pathogenic by playing a role in autoimmunity independent of their ability to produce antibodies. The chronic or recurrent viral infections seen in many patients with ME/cfs can induce autoimmunity by mechanisms involving molecular mimicry and bystander activation. Increased bacterial translocation, as observed in ME/cfs, is known to induce chronic inflammation and autoimmunity. Low ATP production and mitochondrial dysfunction is a source of autoimmunity by inhibiting apoptosis and stimulating necrotic cell death. Self-epitopes may be damaged by exposure to prolonged O&NS, altering their immunogenic profile and become a target for the host’s immune system. Nitric oxide may induce many faces of autoimmunity stemming from elevated mitochondrial membrane hyperpolarization and blockade of the methionine cycle with subsequent hypomethylation of DNA. Here we also outline options for treatment involving rituximab and endotherapia.

Featured

ME/CFS and homeostatic drive

A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome

PLEASE NOTE: THIS VERSION OF THE ARTICLE CONTAINS THE FOLLOWING CORRECTIONS:

16 Jun 2014: The PLOS ONE Staff (2014) Correction: A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome. PLOS ONE 9(6): e100355. https://doi.org/10.1371/journal.pone.0100355 View correction

3 Apr 2014: The PLOS ONE Staff (2014) Correction: A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome. PLOS ONE 9(4): e94161. https://doi.org/10.1371/journal.pone.0094161 View correction

Introduction

The hypothalamic-pituitary-adrenal (HPA) axis, a key component in the body’s stress response, serves to articulate changes in a broad range of homeostatic regulators as a function of environmental cues. Such cues can consist of both physical stressors (injury, infection, thermal exposure) and psycho-emotional stressors (frustration, fear, fight or flight decisions). Instantiation of this survival program is accomplished through controlled modulation of the neuroendocrine and immune systems, as well as the sympathetic nervous systems [1][3]. Considering its function as a broad-reaching integrator of major physiological systems, it is no surprise that numerous chronic conditions have been associated with abnormal regulation of the HPA axis, including major depressive disorder (MDD) [4][5], post-traumatic stress disorder (PTSD) [6][8], Alzheimer’s disease [9], Gulf War Illness (GWI) [10][12], and chronic fatigue syndrome (CFS) [13][15]. When compared to non-deployed veterans, Golier et al. [10] found that symptomatic Gulf War veterans without psychiatric illness, as well as veterans with PTSD alone, showed significantly greater cortisol suppression to dexamethasone (DEX) suggesting markedly enhanced negative feedback along the HPA axis. Further study by these same investigators indicated that this might be due to a significantly attenuated ACTH response by the pituitary in veterans with GWI without PTSD [11][12]. A similar suppression of cortisol response to DEX was found in CFS subjects by Van Den Eede et al. [13] with this being further exacerbated by oestrogen intake. With regard to HPA circadian dynamics, CFS subjects were found to exhibit significantly increased adrenal sensitivity to ACTH and marginally increased inhibitory feedback during the nocturnal period when compared with control subjects and CFS subjects comorbid with fibromyalgia (FM) [14][15]. Conversely the pain-dominant CFS-FM subjects showed significantly blunted cortisol inhibitory feedback. While evidence such as this implicates abnormal regulation of HPA function leading to chronic hypocortisolic and hypercortisolic states in these illnesses, the genesis of this dysregulation is unclear.

Previously we investigated the possibility that some of these pathological states may coincide with naturally occurring alternate homeostatic stable states [16]. These “backup programs” would offer a way of maintaining homeostatic control in crisis situations at the cost of reduced function. The existence of such multiple stable states is characteristic of systems that incorporate feed-forward and feedback mechanisms. Feed-forward loops in biology play the crucial role of driving rapid acute responses, while feedback loops will generally limit the extent of a response. Both will also drive complex dynamic behavior, including differentiation and periodicity [17]. While small perturbations may force temporary departures, these systems return to their original resting states once these perturbations are removed. If however, the perturbation is of significant strength and duration, the system may be incapable of returning to its normal operating regime and instead may assume a new alternate resting state. Knowledge of the system dynamics can allow us to map these different stable states and several mathematical models of the HPA exist [16][18][22]. So far, only one such model is known to accommodate multi-stability in the dynamic behavior of the HPA axis. It does so via the addition of a feed-forward mechanism involving dimerization of the glucocorticoid receptor (GR) complex [22] (Figure 1). In this process glucocorticoid (GC) bound GRs form homodimers that translocate into the cell nucleus to bind DNA, up-regulating GR synthesis and producing a positive feedback loop. However, this model and the majority of other models do not extend beyond the physiological boundaries of the HPA axis itself and thus are limited in their predictive capabilities. As discussed in the following sections, HPA activity is intertwined with the behavior of the hypothalamic-pituitary-gonadal (HPG) axis and the immune system, among others, and this interplay should not be ignored when considering the number and nature of stationary states available to the overarching system. Our hypothesis is that these alternate regulatory regimes may facilitate the persistence of complex chronic illnesses like GWI and CFS. To evaluate the role of alternate homeostatic attractors in these illnesses we constructed a computational model of regulatory control linking the HPA, HPG and immune systems.

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Figure 1. Standard and extended HPA models.

(A) Standard HPA model. (B) HPA-GR model of Gupta et al. [22]. Integrated models (C) HPA-GR-Immune-HPGa for males, and (D) HPA-GR-Immune-HPGb, (E) HPA-GR-Immune-HPGc, (F) HPA-GR-Immune-HPGd, and (G) HPA-GR-Immune-HPGe for females. For (C) – (G) connections between the sex steroid EST and the HPG and HPA components change between stimulatory and inhibitory to capture the effects of the menstrual cycle.

https://doi.org/10.1371/journal.pone.0084839.g001

There is a substantial body of physiological and biochemical data for many biological systems describing the connectivity between molecular and cellular elements, the presence of recurring structural motifs and functional modules. For example, negative autoregulation, in which a transcription factor represses its own transcription, is a simple network motif observed in many transcription networks. While, numerous motifs have been found in biological networks (negative/positive autoregulation, coherent/incoherent and multi-output feed-forward loops, single-input modules and dense overlapping regulons) [17], data regarding the precise stoichiometry and kinetics within and between these multiple systems in humans is extremely limited. Obtaining many of these parameters in humans currently presents significant challenges associated with invasive sampling. As such, many existing models rely heavily on animal data as a source of kinetic parameters, or adopt general order of magnitude estimates when this data is unavailable. Using such estimates allows Ordinary Differential Equation (ODE) based models to provide detailed descriptions of transitory behavior, albeit for well-characterized systems. To broaden this scope and draw on the rich body of known molecular and cellular interactions in physiological and biochemistry, we have adopted the discrete logical network methodology proposed originally by Thomas et al. [23][24] and developed further by Mendoza and Xenarios [25]. By applying logic rules to a network of known interactions it is possible to identify the number of stable resting states, their type as well as their molecular and cellular description, without detailed knowledge of the response dynamics. Here detailed kinetic data is not required as working with connectivity alone allows useful qualitative insights regarding the stability of these systems. In this work we use this method to extend our previous analysis of human HPA axis dynamics by including its regulatory interactions with the neighboring HPG axis and immune system. This resulting mathematical model better represents the complexity of endocrine-immune interactions by supporting the detection and identification of alternate resting modes of the HPA-HPG-immune axis. Based on connectivity information alone, we show that multi-stability is easily obtained from these interacting systems. Moreover, we show that experimental data from our on-going studies of GWI and CFS show better alignment with these alternate resting modes than with the typical healthy homeostatic stable state. Ultimately, knowledge of such homeostatic modes could be used to identify promising applications of pharmaceutical, hormone and/or immune therapy that exploit the body’s natural dynamics to reinforce treatment effects.

Methods

Ethics Statement

All subjects signed an informed consent approved by the Institutional Review Board of the University of Miami. Ethics review and approval for data analysis was also obtained by the IRB of the University of Alberta.

An Integrative Multi-systems Model of the HPA-HPG-Immune System

There is a substantial amount of physiological data describing the HPA, HPG and immune systems as stand-alone entities. To a much lesser degree there also exists evidence for the mutual interactions between these systems. The following sections describe the experimental evidence used to infer the topology of an overarching HPA-HPG-immune interaction network (Figure 1).

The HPA Axis.

Activation of the HPA axis begins at the paraventricular nucleus (PVN) of the hypothalamus. Specifically, afferents transmitting stress related information in the brain converge on the medial parvocellular neurons of the PVN inducing the release of several peptides, including corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), into the pituitary hypophysial-portal circulation. The unique vascular system allows very small quantities of these hypothalamic hormones to act directly on their targets in the anterior pituitary without dilution by systemic circulation. CRH and AVP act in conjunction on membrane bound CRH-R1 receptors in the anterior pituitary to stimulate adrenocorticotropic hormone (ACTH) synthesis, and its rapid release into peripheral circulation. ACTH circulates to the adrenal cortex where it acts on the membrane bound MC2-R receptor to simulate the release of GCs (corticosterone in the rat, and cortisol (CORT) in humans and nonhuman primates). To regulate the stress response, GCs exert negative feedback at the hypothalamus and pituitary to inhibit further synthesis and release of CRH and ACTH, respectively [26]. This is the standard view of the HPA axis utilized in the majority of models (Figure 1 A). However, as noted by Gupta et al. [22] circulating glucocorticoids act via cytostolic GRs, which, unlike membrane bound receptors, dimerize (GRD) and translocate into the cell nucleus upon activation to up-regulate GR synthesis and interact with other relevant transcription factors, or GC-sensitive genes (Figure 1 B). Gupta et al. included this GR expression feed-forward loop at the pituitary, as it is a main driver of the HPA axis, and found a resulting bistability in the HPA system [22]. However, all nucleated cells possess GRs, as GCs influence practically every system in the body, suggesting this feed-forward loop may be important in other tissues beyond the HPA axis. As described below major systems affected by GCs include the HPG axis and the immune system.

The HPG Axis.

GCs have an inhibitory effect on the HPG axis, a central regulator of the reproductive system, at all levels [27][31]. Activation of the HPG starts from brain generated pulsatile signals that stimulate the preoptic area of the hypothalamus to produce gonadotropin-releasing hormone (GnRH). GnRH is secreted into the pituitary hypophysial portal bloodstream, which carries it to the pituitary gland, where it activates membrane bound GnRH-R receptors, resulting in the synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) into circulation. These gonadotropins flow to the gonads where they work synergistically to promote the secretion of the sex steroids. In males, LH binds to receptors on Leydig cells in the testes to stimulate the synthesis and secretion of testosterone (TEST). In females, LH activates receptors on Theca interna cells in the ovaries to stimulate the release of androstenedione, which is aromatized by granulosa cells to produce estradiol (EST), and progesterone (PROG). TEST negatively feeds back on the HPG to inhibit GnRH, FSH and LH secretion and synthesis [27]. This feedback mechanism is somewhat more complex in females where, depending on the phase of the female menstrual cycle, EST and PROG can exert either positive or negative feedback on the production and release of GnRH and the gonadotropins [30][32][33].

A lesser-known aspect is that several components of the HPG axis exert reciprocal effects on the HPA axis [27][28][30]. Testosterone exhibits an inhibitory effect on all levels of the HPA [27] (Figure 1 C), whereas EST and PROG can serve to stimulate or inhibit the HPA axis depending on menstrual cycle phase, or phase of life [28]. These affects may be mediated through changes in adrenocorticoid synthesis, stress-induced ACTH and GC release, and CRH and AVP synthesis in the PVN, by direct activation of oestrogen and androgen receptors along the HPA or via interaction between GRs and sex steroid receptors to regulate transcription [27][28][30]. Thus, an interactive functional crosstalk exists between the HPA and HPG axes, which cannot be ignored when investigating HPA axis regulation and dysfunction. Mutual inhibition between the HPA and HPG (Figure 1 C) was considered standard for males. However, as it is not clear whether the EST and PROG inhibition/stimulation of the HPA occurs in coordination with the inhibition/stimulation of the HPG, these cases were explored for females alone as separate alternative models of the HPA-HPG interaction (Figure 1 D–G) in addition to the model considered for males.

A Simple Model of the Immune System.

While not typically considered part of the neuroendocrine system, the immune system plays a very important role in regulating the HPA axis. Here we base our simplified immune system upon our previous work detailing the communication network of the immune response [34]. Cells of the innate immune response (ICells), including mononuclear phagocytes, such as macrophages, and dendritic cells, natural-killer (NK) cells, endothelial cells and mucosal epithelial cells, communicate via the release of numerous cytokines. Cytokines that regulate the innate immune response (IIR) include interleukin (IL) -1, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α), and can also include IL-12, a primary mediator of early innate immunity. Primarily, these signals serve to activate and recruit other ICells, which in turn produce more cytokines. IL-15, which stimulates proliferation of NK cells and effector T-lymphocytes, can also be considered as part of the IIR as well as IL-23, an important inflammatory signal contributing to the Th17 response against infection.

IIR signals can also serve to prime helper T cells towards a Th1 type adaptive immune response (T1Cell). This response produces Th1 proinflammatory cytokines (T1Cyt) including IL-2, interferon-gamma (IFN-γ), and tumor necrosis factor beta (TNF-β), which further activate ICells, while suppressing the Th2 adaptive immune response (T2Cell). The T2Cell is responsible for the production of the Th2 anti-inflammatory cytokines (T2Cyt) IL-4, IL-5, IL-10 and IL-13, which have important anti-inflammatory and immunosuppressive activities, and serve to inhibit the activity of T1Cell and ICells.

Cytokines can also serve as mediators between the immune and endocrine systems. Between the HPA and the immune network there exists a mutual crosstalk [35][37] (Figure 1 C–G). The IIR and T1Cell cytokines selected here serve to stimulate the HPA axis at all levels [35][37]. CORT, in turn, acts to suppress the activity of ICells (specifically NK cells [38], and DC cells [39]), and the T1Cell [40] causing a shift from the inflammatory to the anti-inflammatory response [35][36][41]. The interaction between the HPG and the immune system is complex and sexually dimorphic, and is still an active field of research. However, at a general coarse level of description TEST serves to stimulate the development of the Th1 response [42] (Figure 1 C), whereas EST inhibits the Th1 response causing a shift towards the Th2 anti-inflammatory response [42][43]. The reciprocal crosstalk from the immune system to the HPG is equally intricate. In broad terms this conversation is communicated via T1Cyt. Receptors for TNF-α and IFN-γ are expressed in testicular Leydig cells and there is evidence that these cytokines can directly inhibit testosterone production [44]. TNFα also decreases the release of GnRH in the hypothalamus and LH in the pituitary gland in both males [44] and females [45] eventually leading to a decrease in sex steroid levels. As such, we model the T1Cyt as inhibiting GnRH and LH/FSH in both male and female models.

A Discrete State Representation

Following the methods of Thomas et al. [23][24], and more recently Mendoza and Xenarios [25], the neuroendocrine-immune system was represented as a connectivity model consisting of interconnected molecular and cellular variables with three discrete states: −1 (inhibited), 0 (nominal) and 1 (activated). According to this type of model the current state of all variables in a system is described by a state vector , such that:(1)where  is the state of the ith variable of the N variable system at time t. The image vector  describes the preferred state towards which the system evolves in the next time increment. The state value of the image vector for the ith variable is determined from its current state and a set of balanced ternary logic statements based on the current value of variable and the mode of action (i.e. activate or inhibit) of the neighboring input variables. These logic statements are expressed as follows (Eq. 2):

(2)where the ∇, ∨, and ¬ symbols are ternary HIGH/LOW PASS, OR and NOT operators,  is the state of the ith variable’s jth activator, is the state of the ith variable’s kth inhibitor. The ternary operators given in Equation (2) are described in further detail in Table 1Table 2Table 3. The first entry in Equation (2) is used when the variable possesses activators and inhibitors, the middle when the variable has only activators and last when the activator has only inhibitors.

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Table 1. Ternary HIGH/LOW PASS operator.

https://doi.org/10.1371/journal.pone.0084839.t001

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Table 2. Ternary OR operator.

https://doi.org/10.1371/journal.pone.0084839.t002

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Table 3. Ternary NOT operator.

https://doi.org/10.1371/journal.pone.0084839.t003

Applying Equation (2) to each variable in the model for the mth state of the system, , defines the image vector  for that state. With  defined, the system may be updated asynchronously (allowing only one variable to change at a time) following the generalized logical analysis of Thomas et al. [23][24]. According to this method the ith variable of the mth state vector  is moved one step towards its preferred image  (e.g. If   = −1 and   = 1, then  is set to 0). Thus, for each current state of the system there are potentially several subsequent states towards which it may asynchronously evolve.

The number of states, and the values they can be assigned, determine the total number of states available to the model system. With the ternary logic used here, a model of N variables possesses 3N states. As a result, the number of states increases rapidly as new variables are added. By analyzing all possible states of the system a temporal sequence of states may be discerned. To interpret the results, each state of the system can be represented as an element in a graph. The evolution from one state to a subsequent state can be represented as a directed edge between the two states in this graph. Representation of the state trajectories in this fashion makes it possible to draw on the concepts and tools of graph theory for analysis of the system dynamics. Steady states are defined as those states for which the image vector is the same as the current state vector; in other words the state possesses an out degree of 0.

Experimental Data

Experimental data obtained as part of a larger on-going study investigating changes in cytokines and hormones in GWI and CFS groups was used as a basis for comparison with the predicted resting states. Previous work with the CFS datasets by Broderick et al. presents full repeatability statistics on the cytokine panels using n = 9 CFS, and n = 12 controls [46]. Significant changes in correlation patterns linking immune gene sets in CFS with n = 39 CFS and n = 35 controls) [47]. Similarly in GWI we observed significant changes in association patterns (mutual information) for n = 9 GWI and n = 11 controls across 3 points in time [48] for salivary cortisol and plasma, serum or culture supernatants expression of neuropeptide Y (NPY), IL-1a, IL-5, IL-6, IL-10, TNF-α, IFN-γ and soluble CD26 (sCD26). Larger sample sizes are used in this work to further improve the statistical power and resolution in identifying characteristic differences between subject groups.

GWI.

Cytokine profiles and endocrine measures were obtained for 27 GWI and 29 HC subjects recruited from the Miami Veterans Administration Medical Center. Subjects were male with an average age of 43 years and BMI of 28. Inclusion criteria was derived from Fukuda et al. [49], and consisted in identifying veterans deployed to the theater of operations between August 8, 1990 and July 31, 1991, with one or more symptoms present after 6 months from at least 2 of the following: fatigue; mood and cognitive complaints; and musculoskeletal complaints. Subjects were in good health prior to 1990, and had no current exclusionary diagnoses [50]. Collins et al. [51] supports the use of the Fukuda definition in GWI. Control subjects consisted of gulf war era sedentary veterans and were matched to GWI subjects by age, body mass index (BMI) and ethnicity. Additional details regarding this cohort and the laboratory assays performed are available in Broderick et al. [48]. Data will be made freely available upon request.

CFS.

Levels of cortisol (CORT) and estradiol (EST) measured in peripheral blood were obtained from the Wichita Clinical dataset [52] for a group of 39 female CFS subjects and 37 Healthy controls (HCs) with an average age of 52 years and an average body mass index (BMI) of 29. Additional details of this cohort and the laboratory assays performed may be found in work previously reported by our group [53][54]. Multiplex cytokine profiles were obtained in plasma from a separate but demographically comparable cohort of 40 female CFS subjects and a group of 59 healthy female matched control subjects studied by our group at the University of Miami [55]. Average age in this cohort was 53 years with an average BMI of 26. Profiling of cytokine concentrations was performed in morning blood plasma samples using an enzyme-linked immuno-absorbent assay (ELISA)-based assay. Details of this protocol and results of a comparative analysis of cytokine expression patterns are available in Broderick et al. [55]. In both studies a diagnosis of CFS was made using the International Case Definition [50][56]. Exclusion criteria for CFS included all of those listed in the current Centers for Disease Control (CDC) CFS case definition, as well as psychiatric exclusions, as clarified in the International CFS Working Group [56]. Data will be made freely available upon request.

Statistical Analysis

Brown’s theoretical approximation [57] of Fisher’s statistics was used to calculate the significance of alignment between experimental data and a given model predicted state. Fisher’s method, a meta-analysis technique, combines probabilities to obtain the overall significance P of a set of p-values obtained from independent tests of the same null hypothesis. The combined χ2 statistic,(3)where N is the number of measureable variables and pi is the corresponding p-values under the null hypothesis, has a χ2 distribution with 2N degrees of freedom assuming that the performed tests are independent. As the molecular variables of the endocrine and immune system interact with one another, as evidenced by the above connectivity diagrams, they are not independent. As a result, direct application of this test statistic is invalid, since the assumption of independence is violated. Brown [57] suggested a method for combining non-independent tests. If the tests are not independent, then the statistic T0 has mean m = 2N and variance (σ2) given as,(4)where pi and pj are the p-values for each test and the covariance (cov) is calculated as,(5)with ρij being the unadulterated correlation between variable i and variable j. Finally, the overall significance P of a set of non-independent tests is calculated using the statistic T which under the null hypothesis follows the central χ2 distribution, where T = T0/c with 2N/c degrees of freedom and c = σ2/4N.

Here, we test if each experimental measure aligns with a given model predicted state. Our null hypothesis is that the experimental measures do not align. p-values for individual variables, pi, are calculated using two-sample t-tests between ill subjects and healthy controls. Where model predictions give a variable as high (+1), ‘right-handed’ one-tailed test are used, whereas a ‘left-handed’ test was used when model predictions are low (−1), to give the probability of obtaining the predicted value when the null hypothesis is true. For the case where the model predicts normal behavior for a variable (0) a two-tailed t-test is used. However, the p-value from the two-tailed test, ptwo-tail, gives the probability that there is an observable difference between illness and control, which is the null hypothesis. To rectify this, when comparing to a model predicted variable of 0 we take the p-value to be pi = 1 − ptwo-tail, giving the probability of obtaining the predicted value when the null hypothesis is true.

All cohort data was normalized using a Log2 transformation before T-tests and correlation calculations were performed. The unadulterated correlation values ρij between two variables i and j were calculated in healthy subjects as the pairwise Pearson’s linear correlation coefficient between variables. The above-mentioned experimental data was compared against model predictions based on the five measureable variables, namely TEST/EST, CORT, IIR, T1Cyt, and T2Cyt. Where model variables represent an aggregate set of markers each experimentally measured constituent marker was compared individually to the model predicted value. For example, T1Cyt is composed of IL-2, IFNγ and TNFβ, therefore 3 individual p-values were calculated based on the predicted value of T1Cyt.

These significances of alignment are best visualized with a Sammon projection of the aggregated P value as distances between the clinical data and the predicted model values. Non-metric multidimensional scaling using Sammon’s nonlinear mapping criterion was used to project the P value distances onto a 2 dimensional plot. The aggregate P values between predicted model states were determined via Brown’s method above. Where values between predicted states were found to disagree p-values for individual variables, pi, were taken as 1. Where values between predicted states were found to agree, pi was assigned a standard minimum value for significance of 0.05 to avoid numerical instability in the calculation of T0.

Results

Stable States in the HPA Models

Application of the discrete state representation to the basic stand-alone HPA model (Figure 1 A) generated 27 system states, and failed to produce multiple stable resting states (Figure 2). The only stable state found consisted of baseline values (SS0) for all state variables. This result is consistent with previous ordinary differential equation models based on this minimal representation of the HPA axis that produce solutions converging to a single fixed state [18].

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Figure 2. Steady states of standard and extended HPA models.

White – nominal state (0); Green – high state (1); Red – low state (−1); Grey – N/A to the model.

https://doi.org/10.1371/journal.pone.0084839.g002

Discrete state representation of the HPA-GR model (Figure 1 B) generated 243 system states. Of these, 2 system states possessed no outbound edges and were stable attractor steady states (Figure 2). In the first steady state all state variables assumed nominal values (SS0) whereas the second steady state corresponded to activation of state variables GRD and GR with suppression of ACTH and CORT (SS1). This hypocortisolic solution is consistent with that obtained by analysis of the ordinary differential equation model of the HPA-GR system proposed by Gupta et al. [22] and Ben Zvi et al. [16]. Further models by Walker and colleagues, based on Gupta et al. [22], have shown natural oscillatory rhythms in the HPA axis [19][21]. While these models make the significant association between delayed feedback and ultradian rhythms, the oscillations around baseline are small and consistent, representing a single resting behavior. As our discrete state representation considers normal resting values as 0, with −1 and 1 representing significant perturbations, minor deviations are not captured and therefore such small oscillatory behavior can be considered similar to our nominal steady state (SS0). This lower resolution allows for a greater breadth of study, accommodating the inclusion of multiple systems of interest, which previously have not been considered in modeling studies.

Combining the HPA-GR axis with the HPG axis and immune system (Figure 1 B–G) altogether produced 4,782,969 system states. For the male HPG (model a) (Figure 1 C), and three of the four female HPG models (models b, d and e) (Figure 1 D, E, G) five steady states were identified (Figure 2). One stable state is characterized by nominal values for all variables (SS0), which corresponds to the typically normal resting state of the system. The first alternate state (SS1) displays low ACTH with high GRD and GR, while the second (SS2) has inhibited innate and Th1 immune responses (low ICell, IIR, T1Cell, and T1Cyt), with increased Th2 activity (high T2Cell and T2Cyt). The third stable state (SS3) appears to be a combination of SS1 and SS2 with low ACTH, ICell, IIR, T1Cell and T1Cyt, and high GRD, GR, T2Cell and T2Cyt. The final state (SS4) presents with hypercortisolism, suppressed TEST and a shift towards the Th1 immune response (low T2Cell, T2Cyt, GnRH, LH/FSH and TEST/EST, and high CORT, GRD, GR, T1Cyt and T1Cell). The persistently low CORT state seen in the previous stand-alone HPA models of Gupta et al. [22] and Ben Zvi et al. [16] was not recovered here. Instead, CORT was expressed at a nominal or high value for all predicted states. SS1 most closely resembles the results of Gupta et al. [22], and Ben Zvi et al. [16], however these previous models only considered a single regulator of CORT, namely ACTH. The lack of a predicted hypocortisolic state in SS1 here can be attributed to the interplay of multiple regulators of CORT (ACTH, IIR, TEST/EST, and T1Cyt). Inclusion of additional regulators is not expected to further alter this state.

In the final female HPG model (model c) (Figure 1 F), corresponding to the ovulation phase, these same five states were recovered along with six new additional states (Figure 2). In the first three additional states the HPA axis and innate immune response are suppressed with low CRH, ACTH, CORT, ICell and IIR, while the HPG and anti-inflammatory response are raised with high T2Cell, T2Cyt, GnRH, LH/FSH and EST. The difference between the three states is noted in the level of glucocorticoid receptor response, GR and GRD, which together take values of low (SS5), nominal (SS6) and high (SS7). The remaining three additional states all give suppressed HPA (CRH, ACTH, and CORT) and lowered T1Cell activity, with high HPG activity (GnRH, LH/FSH and EST), and are again differentiated by their glucocorticoid receptor levels (GR, GRD): low (SS8), nominal (SS9) and high (SS10).

Overall, inclusion of the simplified immune system and the HPG works to regulate CORT levels in the HPA axis. The male HPG (HPG model a), and the majority of female HPG configurations (HPG models b, d and e), serve to produce either nominal values of CORT, with the potential of a shift towards Th2 activation (SS2 and SS3), or a hypercortisolic state with low TEST/EST and a shift towards Th1 (SS4). Only connections associated with the female gender (HPG model c) were responsible for the emergence of a natural hypocortisolic state (SS5 – SS10). This hypocortisolic state comes with high EST and may have a shift towards Th2 activation in the immune system.

Comparison of GWI and CFS to Predicted States

Application of Brown’s meta-analysis method allowed for the calculation of a combined P-value comparing the experimental data with the predicted stable states, allowing for the alignment between different predicted stable states to be ranked. As experimental measures allowed for comparison with only five variables (TEST/EST, CORT, IIR, T1Cyt, and T2Cyt) several of the predicted stable states resulted in the same experimental profile and resulting combined P-value despite being distinct states (e.g. SS0 and SS1 both show nominal values for the five measureable variables).

To compare to our model the difference between steroid and cytokine levels recorded in male Gulf War veterans with GWI and HCs were compared to the steady state values predicted by the male variant of the HPA-GR-Immune-HPG model (model a). Comparison to the nominal states (SS0/SS1) showed poor alignment, PSS0/SS1 = 0.82, suggesting that the GWI profile cannot be considered the same as nominal behavior. Alignment with states presenting a shift towards Th2 immune activation (SS2/SS3) showed better alignment, PSS2/SS3 = 0.38, although with low significance. The final state, displaying hypercortisolism, low TEST and a shift towards Th1 immune activation (SS4), yielded the best alignment, PSS4 = 0.30, again however, with a low overall significance. These alignments are illustrated via the Sammon plot shown in Figure 3A.

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Figure 3. Sammon projection of illness and model predicted states.

Axes represent arbitrary units such that the relative Euclidean distance between points approximates the significance of alignment P-value between states, as shown by connecting lines. (A) Male GWI. (B) Female CFS.

https://doi.org/10.1371/journal.pone.0084839.g003

The difference between steroid and cytokine levels of female CFS subjects and HCs were compared to the steady state values predicted by the female variants of the HPA-GR-Immune-HPG models (model b-e). Again, alignment with states presenting nominal changes in measureable variables (SS0/SS1) was poor, PSS0/SS1 = 0.83, supporting that CFS is distinctly different from normal behavior. The Th2 shifted immune profile states (SS2/SS3) showed a significant alignment, PSS2/SS3 = 0.04, suggesting Th2 activation in CFS. This is further supported by low alignment with the Th1 immune activated state, with hypercortisolism, and low EST (SS4), PSS4 = 0.28. Improved alignment is seen in states with a shift towards Th2, coupled with hypocortisolism, and high EST (SS5/SS6/SS7), PSS5/SS6/SS7 = 0.02, suggesting that these features contribute to the CFS profile. This is also supported by low alignment with states only presenting hypocortisolism and high EST with no immune activation (SS8/SS9/SS10), PSS8/SS9/SS10 = 0.60. These alignments are visualized in Figure 3B.

Discussion

The existence of multiple stable states is a prime characteristic of systems incorporating feed-forward and feedback mechanisms, and plays a critical part in guiding the complex dynamics observed in biology. These alternate stable regulatory regimes occur due to the feed-forward and feedback mechanisms within the system and may allow escape routes for survival of an insult and provide support in the medium or long-term to what is equivalent to an uneasy cease-fire or adaptive compromise. Examples of such compromises in functional status in exchange for survival include vasovagal response to decreased blood pressure and syncope (“fainting”) [58]. From an evolutionary perspective it would be advantageous for a pathogen to establish an adaptive relationship with the host. As naturally occurring alternate states of homeostasis are inherently stable, exploiting these regimes could be an advantageous way for a pathogen to establish long-term chronic infection, in essence using the body’s own homeostatic drive to maintain the status quo. Deviations of persistent illness profiles from normal homeostatic states argue in favor of the continued presence of an initial aggravating factor or of lasting alterations to the regulatory circuitry imparted by the initial insult [59][60]. The latter would essentially modify the solution landscape resulting in new natural attractors. To explore this hypothesis, we constructed a simple but integrated model incorporating three of the body’s major regulatory axes: the HPA, the HPG and the immune system. Modeling the dynamic properties of these complex systems presents a significant challenge, as much of the detailed information describing in vivo kinetics in humans is unavailable. However, there is a very significant body of connectivity data describing the interactions between the molecular and cellular elements of these biological systems. To make use of this wealth of information we have applied a discrete state representation to the neuroendocrine immune system based solely on the biological connectivity found in the literature and a set of ternary logical rules. Using a discrete logic methodology proposed by Thomas [24], we demonstrated that the inclusion of feed-forward/feedback loops leads to multiple stable states. Indeed, addition of the positive feedback loop regulating glucocorticoid receptor dimerization (GR-GRD) to a basic model of the HPA axis generated an alternate homeostatic state characterized by high receptor expression and low circulating cortisol levels, a result found previously by Gupta et al. [22] and Ben Zvi et al. [16] using differential equation based models. So dependent is the natural emergence of these states on the regulatory wiring that inclusion of this receptor dimerization in a more complex HPA-Immune-HPG models resulted in the disappearance of this alternate hypocortisolic state through compensatory effects of these axes. Only when all three interacting axes were included was an alternate hypocortisolic condition recovered. Therefore while simple models require the inclusion of positive receptor feedback dynamics to produce multistability, these effects become inherent in more coarse, but comprehensive regulatory circuits, and receptor-level feedback becomes less of a contributor in the support of multiple attractor states. Coarse-grained but comprehensive models may suffice therefore in capturing physiologically relevant and clinically verifiable response dynamics.

Our analysis of these coarse grained models spanning across multiple regulatory axes highlighted the important role of gender in supporting a persistent hypocortisolic condition. Due to the suppressive actions of the male gonadal system in regulating itself and the HPA axis, a low cortisol steady state is never available to the male, at least theoretically at this level of detail. In women however, the combined effect of EST and PROG on the HPA still remains somewhat inconsistent [28][61] owing to the varying effects of these hormones during and after the menstrual cycle. EST is generally believed to stimulate the HPA axis during the menstrual cycle [61][63], however evidence indicates that in perimenopausal, menopausal or ovariectomized women the HPA axis response is inversely correlated with plasma EST levels suggesting an inhibitory effect [63][64]. This suggests that sex hormone regulation may change in feedback polarity and act as both inhibitor and activator of the HPA axis. For this reason HPA-HPG interaction in women will in theory readily support the presence of a stable hypocortisolic condition when HPG axis regulation inhibits the HPA axis while stimulating itself.

In addition to sex hormone regulation, interaction with the immune system also appears to play a significant role in determining abnormal cortisol levels. In our coarse-grain models, cortisol exerts a suppressive action on the innate immune system and the Th1 adaptive immune response. Conversely, positive feedback by certain components of the immune system promotes increases in cortisol levels, which support a hypercortisolic steady state. While, inclusion of the glucocorticoid receptor dimerization (GR-GRD) in these models yielded additional steady states, it did not result in any significant changes to the profile in regards to cortisol levels. Combining the actions of HPA, HPG and immune regulation supported the existence of a stable hypercortisolic state in all models of men and women while a persistent hypocortisolic state was available only in women and only under certain modes of HPG regulation. Once again, while the inclusion of the GR-GRD receptor dimerization in this overarching model yielded additional steady states, it did not result in any significant changes to the homeostatic profiles.

These findings suggest that abnormally high levels of cortisol and adaptive immune activation, in this case Th1, may be perpetuated under certain conditions by the system’s own homeostatic drive. This prediction of persistent and stable Th1 activation is consistent with evidence of anomalies in immune signaling in GWI [48][65][66]. Skowera et al. measured intracellular production of cytokines in peripheral blood and found ongoing Th1-type immune activation in symptomatic Gulf War Veterans compared to healthy counterparts [65]. More recent work confirmed this finding while also suggesting that this may occur in the more complex context of a mixed Th1:Th2 response [48], something not captured by the simple immune model used here. Though we were unable to find documented reports of lower testosterone levels in GWI beyond the experimental data presented here, a large study of gulf war veterans in the UK found increased risk of fertility problems in this population [67], suggesting a possible relation.

In much the same way, conditions involving hypocortisolism and a Th2 shift may also be perpetuated at least in part by the natural homeostatic regulatory programming. In this case the homeostatic program may be driven by sex steroid suppression of the HPA axis and promotion of HPG function coupled with the mutual inhibition between the Th1 response and function of the gonadal axis, a configuration seemingly available only to female subjects in our models. This would suggest that the hypocortisolism seen in diseases, such as CFS [68][70], could be a result of the complexity afforded by the interaction between the HPA, immune and HPG axes in female subjects. Indeed model predictions describing such an alternate homeostatic state in women aligned with our experimental results from CFS subjects, and is consistent with previous findings of Th2 activation in CFS [55][71][73]. This alignment with a naturally occurring homeostatic conditions may explain, at least in part, the biased prevalence of such persistent diseases in women [74][79]. Indeed, these authors report that approximately 70% of observed CFS patients are women. Additionally, the prevalence of CFS in the 40–49-year-old age range [79], and the higher prevalence of gynecological conditions and gynecological surgeries in women with CFS [80] supports the evidence that HPA suppression by estradiol appears more likely in perimenopausal, menopausal or ovariectomized women [63][64]. Interestingly, as many as 1 in 3 CFS subjects have reported symptom relief during pregnancy [81]. The normal trend in pregnancy towards increased cortisol levels, especially in the third trimester, might be a contributing factor that would support the key involvement of sex hormone regulation proposed by our analysis [82]. While, in normal pregnancy this increase in cortisol typically coincides with an increase in cortisol-binding globulin (CBG) maintaining the level of free cortisol, CBG genetic variants in CFS have the potential to alter normal CBG function [83][84].

While certainly more comprehensive than their predecessors, these models remain relatively coarse representations of the interplay between the endocrine and immune systems.

This is particularly true of immune model granularity, especially when one considers the complex signaling network supported by immune cells as well as other immune-sensitive cells [85]. The important role of key neurotransmitters linking the central nervous system with the HPA axis and the immune system was also under-represented in this first generation of models. For example, norepinephrine and epinephrine stimulate the β2-adrenoreceptor-cAMP-protein kinase A pathway inhibiting the production of Th1/proinflammatory cytokines and stimulating the production of Th2/anti-inflammatory cytokines causing a selective shift from cellular to humoral immunity [86][87]. Additionally, lymphocytes express most of the cholinergic components found in the nervous system. Lymphocytes may be stimulated by, or release, acetylcholine thus constituting an immune regulating cholinergic system secondary to the nervous system [88]. Another neurotransmitter, neuropeptide Y (NPY), also serves as a powerful immune modulator [89] and has recently been shown to play a role in CFS [90]. These components are without question important, however based on our initial observations from this piecewise analysis we expect that increased detail will lead to the emergence of additional response programs rather than the elimination of attractors found here.

As these models are based on currently documented knowledge of human physiology and regulatory biochemistry they are necessarily incomplete. Nonetheless the simple models presented here illustrate the importance of an integrative approach to understanding complex illnesses. Further refinement of the model to include more detailed description of interactions within and between the HPA, HPG and immune systems could extend its applicability to other illnesses as would the incorporation of other key systems such as the brain and central nervous systems. Yet, even with the coarse-grained co-regulation networks investigated we found numerous stable resting states that differ significantly from normal and were indicative of complex and persistent regulatory imbalances. Findings such as this support the use of an alternate model for disease, one which is not necessarily associated with failure of individual components, but rather with a shift in their coordinated actions away from normal regulatory behavior. Response to exercise and other stressors has the potential to be very different in these new regulatory regimes. This is something that we have observed firsthand in our work with human GWI and CFS subjects [91].

Finally, when considering alignment with the experimental data presented here for CFS and GWI, it is important to remember that it was never our hypothesis that these illnesses resulted solely from the actions of homeostatic drive. Instead we proposed that homeostatic drive might be a significant contributor to the persistence of illness mechanisms. Because these naturally occurring regimes, once instantiated, provide an alternate stable homeostasis resistant to change, it may offer fertile ground in support of many chronic pathological processes. The alignment of several immune and endocrine markers modeled here with experimental data from CFS and GWI, two chronic conditions, would support at least partial involvement of the body’s own homeostatic drive in facilitating the perpetuation of these conditions. Correlation between these illness conditions and predicted stable states does not imply causation. These results do not suggest that homeostatic drive is the root cause of GWI or CFS, only that it might serve to sustain these chronic illnesses. This may promote resistance to therapy and the natural regulatory barrier to change, even positive change, should at least be considered in the design of robust treatment avenues. Knowledge of the basins of attraction identified by the modeling methods presented here can provide a comprehensive overview of multisystem dysregulation. This knowledge may be used to identify multiple therapeutic targets to be treated in conjunction to correct overall system imbalance. This opens the possibility of discrete interventions targeting multiple systems where treatment could eventually be discontinued, leaving normal regulatory drive to return the system to the correct resting state. This is very different from conventional long-term administration of a drug regimen, whereby the system is held artificially in a more desirable, but unstable state through continued intervention.

Acknowledgments

This research was conducted in collaboration with Dr. Joel Zysman, Director of High Performance Computing, using the Pegasus platform at the University of Miami Center for Computational Science (CCS) (http://ccs.miami.edu). This research was also enabled by the use of computing resources provided by WestGrid and Compute/Calcul Canada.

Author Contributions

Conceived and designed the experiments: TJAC DBM GB. Performed the experiments: TJAC PF MAR RMDR GB. Analyzed the data: TJAC PF DBM GB. Contributed reagents/materials/analysis tools: MAF NGK. Wrote the paper: TJAC DBM GB.

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Citation: Craddock TJA, Fritsch P, Rice MA Jr, del Rosario RM, Miller DB, Fletcher MA, et al. (2014) A Role for Homeostatic Drive in the Perpetuation of Complex Chronic Illness: Gulf War Illness and Chronic Fatigue Syndrome. PLoS ONE 9(1): e84839. https://doi.org/10.1371/journal.pone.0084839

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ME/CFS: A natural history

HYPOTHESIS AND THEORY ARTICLE

Front. Neurol., 11 August 2020 | https://doi.org/10.3389/fneur.2020.00826

How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS

Luis Nacul1,2Shennae O’Boyle1*Luigi Palla3,4Flavio E. Nacul5Kathleen Mudie1Caroline C. Kingdon1Jacqueline M. Cliff6Taane G. Clark6Hazel M. Dockrell6 and Eliana M. Lacerda1

  • 1Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
  • 2B.C. Women’s Hospital and Health Centre, Vancouver, BC, Canada
  • 3Department of Medical Statistics, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom
  • 4Department of Global Health, School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan
  • 5Pro-Cardiaco Hospital and Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
  • 6Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom

Originally publication:

Nacul, L., O’Boyle, S., Palla, L., Nacul, F. E., Mudie, K., Kingdon, C. C., … & Lacerda, E. M. (2020). How Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Progresses: The Natural History of ME/CFS. Frontiers in neurology11, 826.

Abstract

We propose a framework for understanding and interpreting the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) that considers wider determinants of health and long-term temporal variation in pathophysiological features and disease phenotype throughout the natural history of the disease. As in other chronic diseases, ME/CFS evolves through different stages, from asymptomatic predisposition, progressing to a prodromal stage, and then to symptomatic disease. Disease incidence depends on genetic makeup and environment factors, the exposure to singular or repeated insults, and the nature of the host response. In people who develop ME/CFS, normal homeostatic processes in response to adverse insults may be replaced by aberrant responses leading to dysfunctional states. Thus, the predominantly neuro-immune manifestations, underlined by a hyper-metabolic state, that characterize early disease, may be followed by various processes leading to multi-systemic abnormalities and related symptoms. This abnormal state and the effects of a range of mediators such as products of oxidative and nitrosamine stress, may lead to progressive cell and metabolic dysfunction culminating in a hypometabolic state with low energy production. These processes do not seem to happen uniformly; although a spiraling of progressive inter-related and self-sustaining abnormalities may ensue, reversion to states of milder abnormalities is possible if the host is able to restate responses to improve homeostatic equilibrium. With time variation in disease presentation, no single ME/CFS case description, set of diagnostic criteria, or molecular feature is currently representative of all patients at different disease stages. While acknowledging its limitations due to the incomplete research evidence, we suggest the proposed framework may support future research design and health care interventions for people with ME/CFS.

Introduction

The lack of progress in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) research has been attributed to a range of factors, including the paucity of large, high quality, hypothesis-driven studies, and controversy around diagnosis. Without recognized and validated biomarkers or diagnostic tests, there is an over-reliance on patient history for diagnosis, which is based on criteria with limited sensitivity and specificity (1) and which ignore disease sub-groups. Furthermore, the lack of consistency in the choice and application of research case definition has led to problems with reliability and comparability of research findings (2). An additional factor complicating diagnosis and case definition for research studies is the time-related variation in phenotype both in the short- (34) and long-term (5), which has seldom been considered in research studies.

In addition to often marked variability in disease presentation, severity, progression, and duration among different individuals, the way disease manifests in each individual may change with time. Inter- and intra-individual phenotypic variations lend toward the categorization of different subtype trajectories of ME/CFS that may differ in pathogenesis and prognosis. In some studies, female sex, increased age (68), and lower socio-economic status (9) have been found to predict poor prognosis; however, the variable nature of both population sampling and diagnostic criteria has led to ambiguous results and has reinforced the need for ongoing research in this area (10). Further subtypes have been defined on the basis of “minor” symptoms i.e., musculoskeletal, infectious, or neurological (11), through genetic studies (1213), metabolomics studies (14), and, duration of disease studies (5), highlighting the multitude of possible ways ME/CFS patients can be categorized. Other studies have identified variations in symptom profiles as disease progresses; however, such results are often limited by cross-sectional study design (15), and/or recall bias (16). The breadth of subtype studies available follow a similar model of looking for patterns across patient groups at single time-points; far fewer consider longitudinal subtyping and disease progression of a single patient cohort over time.

The concept of the natural history of disease is well-understood in public health and medicine: many, if not all, diseases are framed using this construct to formulate how they progress from a pre-illness stage to a final disease outcome, which may vary from full recovery to death. A good understanding of the disease course is vital not only for the design of preventative and intervention studies (17), but also to assess the timing and type of intervention that minimizes disease risk or optimizes prognosis. Although there is some understanding of the natural history of ME/CFS, this has been limited by problems in case definition (as above) as well as by the paucity of longitudinal studies, and in particular those that follow up individuals’ pre-illness. A review of studies on CFS prognosis (8) suggested recovery rates under 10% in adults, and an improvement rate over 40% for people with fatigue lasting <6 months. The prognosis was worse: when more stringent case definitions were used; in older people; in cases with more sev