More on the Biological Evidence for “Mental Illness”

On January 10, 2017, I put up a post titled The Biological Evidence for “Mental Illness”.  It was published simultaneously on Mad in America.  The post was a response to an earlier comment from Carolina Partners in Mental Healthcare PLLC, which included the assertion “mental illnesses have a long history of biological evidence.”  In my January 10 article, I challenged this assertion and pointed out that no such evidence existed.  The article generated some comments, most of which were favorable.  There was one comment, however, from Michael, who asserted:

“Your rebuttal that there are no scientific studies to these cases can be dismissed with a quick google search.”

In my response to Michael, I asked him to cite me some references to support this assertion.  On  January 15, Michael wrote back citing three studies:  the first on the neurobiology of depression; the second on the neurobiology of “schizophrenia”; and the third on the neurobiology of “bipolar disorder”.

I examined these studies, and started to draft a response to Michael, but as I was writing, I realized that the subject matter warranted a wider audience and needed to be put up as a post.  This is not because the studies cited are particularly compelling.  As we shall see below, they are not. But rather, because what has happened here is something that occurs routinely in these debates.  Psychiatry proponents claim there is evidence to support their position that “mental illnesses” are caused by biological malfunctions – but when pressed for references, they either don’t respond at all, or they dish up the kind of references cited by Michael.

All three papers are literature reviews.


Maletic V, Robinson M, et al, Neurobiology of depression: an integrated view of key findings, Int J Clin Pract, 2007 Dec; 61(12): 2030–2040.

From the point of view of Carolina Partners and  Michael’s original assertion, this study is particularly easy to rebut.  In fact, the authors do it for us.  Here’s the conclusion:

“Major depressive disorder is an illness with significant neurobiological consequences involving structural, functional and molecular alterations in several areas of the brain. Antidepressant pharmacotherapy is associated with restoration of the underlying physiology. Clinicians are advised to intervene with MDD using an early, comprehensive treatment approach that has remission as the goal.” [Emphasis added]

Note that the authors are stating clearly that the structural, functional, and molecular neurobiological alterations are consequences of depression, not causes.

. . . . . . . . . . . . . . . .

But the article has many additional points of interest.  Here are some quotes:

“Although much information still needs to be attained, imaging and other methods have begun to elucidate the neurobiological abnormalities associated with MDD. In particular, several prefrontal and limbic structures and their interconnected circuits have been implicated in affective regulation (Figure 2). These neuroanatomical areas include the ventromedial prefrontal cortex (VMPFC), lateral orbital prefrontal cortex (LOPFC), dorsolateral prefrontal cortex (DLPFC), anterior cingulated cortex (ACC), ventral striatum (including nucleus accumbens), amygdala and the hippocampus. Abnormalities in these areas have been shown in patients with MDD compared with healthy controls and thus suggest a foundation for the symptomatic expression of MDD (24, 25). However, these deviations may be obscured or not present at the individual patient level and thus, these findings cannot necessarily be considered pathognomonic.” [Emphasis added]

Note the admissions that:

“…much information still needs to be attained…”
“…imaging and other methods have begun to elucidate…” [Emphasis added]
“…implicated in affective regular…” [implicated in is not synonymous with causative of]
“…suggest a foundation…” [Emphasis added]
“…deviations may be obscured or not present at the individual patient level…” [Emphasis added]

This doesn’t sound very definitive or convincing.

. . . . . . . . . . . . . . . .

“Combining the evidence from these genetic, cross-sectional, and clinical treatment studies suggests that morphological differences in the hippocampus may be a predisposing factor in MDD, but changes can also accumulate in the course of the disease and thereby create an obstacle to full recovery.”

Again, note the vagueness:

“Combining the evidence…suggests…” [Emphasis added]
“…differences in the hippocampus may…” [Emphasis added]
“…be a predisposing factor in MDD…”

The ever-present predisposing factor – not quite the same thing as a cause – but good enough to convey the impression of causality.

But look at the last phrase in the quote:

“…changes can also accumulate in the course of the disease and thereby create an obstacle to full recovery.”

What the authors are suggesting here is that depression  causes neurological pathology “in the course of the diseases” and that this pathology could create an obstacle to full recovery.  Of course the drugs and hi-voltage electric shocks to the brain that psychiatrists routinely use to “treat” depression also cause neurological pathology.

And lest it be feared that I’m cherry-picking quotes that are particularly vague and unconvincing, the word “may” occurs 21 times in the paper, e.g. “this abnormal activity pattern may be responsible for the manifestations of symptoms associated with MDD”; “Symptomatically, disruptions as a result of proinflammatory cytokines may be experienced as fatigue, loss of appetite and libido as well as hypersensitivity to pain.”  The word “could” occurs three times and the word “suggest(s)” ten times.

Here’s the final sentence of the study:

“Once remission is attained, maintenance of effect may become the more appropriate term, rather than relapse prevention, to emphasise the necessity for an ongoing collaboration between patient and physician in order to maintain neurobiological homeostasis.”

And what do you think is going to happen in this “…ongoing collaboration between patient and physician…”?

Here’s a clue:

Vladimir Maletic has served on the Speaker’s Bureau or has been a consultant for Eli Lilly and Company and Cephalon.  He did not receive any financial compensation for his work on this manuscript. His co-authors are each employees and/or shareholders of Eli Lilly and Company”

And incidentally, according to Dollars for Docs, Dr. Maletic received $841,342 from pharmaceutical companies between August 2013 and December 2015.  In 2015 alone, he received 460 payments from pharma companies for a range of activities including promotional speaking, honoraria, consulting, education, food and lodging, etc.  According to his biography on Global Medical Education, he is a Professor of Neuropsychiatry and Behavioral Science at the University of South Carolina School of Medicine.


Ross CA, Margolis RL, et al, Neurobiology of Schizophrenia,  Neuron, October 5, 2006, 52, 139–153

Here again, the authors themselves have provided the rebuttal of Michael’s assertion.  The final section of the paper is Conclusions and Possibilities for Future Research.  Here are the first two sentences.

“In conclusion, we now believe that the molecular genetics of schizophrenia are sufficiently advanced such that etiology-based studies of the neurobiology of schizophrenia are both justified and feasible. The field is still in its infancy, and we must struggle to integrate our rudimentary knowledge of schizophrenia genetics with our scarcely better developed understanding of normal human brain function.”

So, etiology-based studies of the neurobiology of “schizophrenia” are justified and feasible.  Which, of course, is a clear admission that the evidence is not to hand.

Later in the same section there’s this gem:

“The genes associated with schizophrenia may have a spectrum of different pathogenic effects, altering neuronal development, neuronal plasticity, and signal transduction. While undoubtedly a great oversimplification, it may be of heuristic value to postulate that variations in particular genes can affect particular neurobiological processes (Figure 6), in turn causing specific phenotypes.” [Emphasis added]

So the genes associated with “schizophrenia” may have a spectrum of different pathogenic effects.  This is very vague.  The use of the word “may” clearly implies that they also may not have such effects.  But in any event, the evidence for such effects is not adduced in the paper.

And the assertion “…it may be of heuristic value to postulate that variations in particular genes can affect particular neurobiological processes…in turn causing specific phenotypes”, simply means that the hypothesis that genetic variations affect neurobiological processes, which in turn cause psychiatric “symptoms” may have value in encouraging us to explore and learn, which isn’t particularly profound.  Any hypothesis can act as a stimulus to explore and learn.

Here are three more quotes from the section headed Neuropathology:

“Neuropathological investigations of schizophrenia…have not found any evidence of the usual features of neurodegenerative diseases, such as inclusion bodies, dystrophic neuritis, or reactive gliosis.  There is intriguing, though not always consistent, evidence of subtle cytoarchitectural anomalies in entorhinal gray matter…and in other corticolimbic regions, and an abnormally high frequency of aberrant neurons in the white matter underlying prefrontal cortex…temporal, and parahippocampal regions…While these findings remain open to various interpretations…together they provide suggestive evidence for subtle abnormalities in neurodevelopment in schizophrenia, such as disordered cortical neuronal migration, consistent with the observation of subtle behavioral, neurological, and morphologic abnormalities.” [Emphasis added]

“Gene expression array studies have compared the expression profiles, in a number of different brain regions, of schizophrenias and controls…These studies have yielded inconsistent results and still need to overcome the difficulties inherent in the usage of postmortem brain tissue.” [Emphasis added]

“These studies may allow us to reconceptualize our definitions of the psychiatric disorders, including schizophrenia, based on a better understanding of etiology and pathogenesis.”

They may indeed – but clearly the authors are not saying that the evidence is in.  In fact, in the Introduction to the article, they stated that:

“We argue in this review that a definitive study of the neurobiology of schizophrenia is now possible.”

The definitive study is “now possible”!  This paper is dated October 2006, more than ten years ago.  Why haven’t we seen the definitive study yet?  Could it be, could it possibly be, that psychiatry, driven by its own self-centered considerations, is barking up the wrong tree?

Under the ACKNOWLEDGEMENT heading, the paper states:

“NARSAD, Stanley Medical research institute, NIMH, NINDS, and Johns Hopkins Psychiatry provided support.”


The word suggests(s) occurs 26 times; may, 57 times; can, 28 times; might twice; and could seven times.


Muneer A, The Neurobiology of Bipolar Disorder: An Integrated Approach, Chonnam Med J., 2016 Jan; 52(1):18-37

Once again, let’s start with the author’s own assessment of his paper.  The Conclusion section begins:

“A broad assessment of the current literature was done to bring to light the underpinnings of mood disorders in general and BD in particular. These are stress-related conditions with overt expression in individuals with an underlying genetic vulnerability. Modern neuroscience is utilizing animal models and conducting human research with increasingly sophisticated methods to unravel their pathophysiology. Significant strides have been made in understanding the neurobiology of affective illnesses, and in this regard new targets and biomarkers have been identified. Diverse biological systems act in concert in perpetuating the disorders. While obstacles in research remain in the basic scientific and clinical domains, there is no doubt that a representation is emerging that is providing a consolidated view regarding the development of these intractable conditions. It is hoped that new knowledge will translate into novel therapeutic measures that have both preventive and curative value for patients with bipolar spectrum disorders.”


“Modern neuroscience is [working]… to unravel their pathophysiology.”  The clear implication is that they haven’t unraveled it yet.

“Significant strides have been made in understanding the neurobiology of affective illnesses,”.  This is not what researchers say when they’ve made the great discovery.  They say Eureka!

“… new targets and biomarkers have been identified.”

Biomarkers sounds pretty good.  After all, it is widely claimed by psychiatry proponents that the identification of the elusive biomarkers is just around the corner.  It is widely promoted that the biomarkers, when discovered, will clinch the biological pathology issue once and for all.  So is that what the author is saying here?  Well, no.

It is clear from the text that what this author means by “biomarkers” is simply a biological factor that correlates to varying degrees with the bipolar label.  The author presents a few examples, but for illustrative purposes, let’s examine just one:  cortisol levels in the blood stream.

“Early in the trajectory of BD, episodes occur secondary to stress but there is blighted psychobiological resilience and defective coping that increase vulnerability to recurrent affective exacerbations with illness advancement.12  This impairment is principally provoked by the hypothalamic-pituitary-adrenal (HPA) axis, which does not function properly in patients with BD.13 Patients with BD have a hyperactive HPA axis, high levels of systemic cortisol, and nonsuppression of its circulating levels in the dexamethasone suppression test or the dexamethasone/corticotrophin-releasing hormone (DEX/CRF) test.14

This is a bit technical, but here’s the translation:

  1. In the early stages of those behaviors, thoughts, and feelings that psychiatrists label bipolar disorder, episodes of mania and depression occur in response to stress.
  1. But, as more episodes occur, there also occurs blighted psychobiological resilience, which presumably means reduced psychological resilience coupled with impairment in general health. These deteriorations are provoked by the HPA axis, “which does not function properly in patients with BD”.  Note the term provoked, which isn’t quite the same as caused.  Also note the cautious wording in the final clause:  “does not function properly in patients with BD”.  At first glance, this seems to be saying that the malfunctions cause the “BD”.  But when read more carefully, no such causal connection is stated or even implied.  All that’s being asserted is that HPA malfunction and being labeled BP are correlated.  The causation, if it exists at all, could go either way.
  1. People labeled BP have high cortisol levels as measured by the two tests mentioned.

From all of this, the author concludes:

“From this perspective, HPA axis irregularities seem to be a genetic attribute endowing vulnerability to mood disorders.”

Note the vagueness:  “seems to be” and “vulnerability”.  Not quite the same as cause.

But there’s more.  The evidence for the HPA “irregularities” is the elevated cortisol level, which, incidentally, is just an average figure.  In the study cited, several of the BD “patients” had cortisol levels in the same range as the controls.  But more importantly, it’s been common knowledge since the 50’s that high alcohol consumption is associated with high cortisol levels, and, according to DSM-IV:

“As the Manic Episode develops, there is often a substantial increase in the use of alcohol or stimulants which may exacerbate or prolong the episode.” (p 330)

This is echoed in DSM-5, which notes a

“…tendency for individuals with bipolar 1 disorder to overuse substances during an episode.” (p 131)

So the elevated cortisol may reflect nothing more than frequent heavy drinking.

. . . . . . . . . . . . . . . .

 In general, Dr. Muneer makes no claim that a biological cause to “BD” has been established.  Indeed, the paper is characterized by caution and guardedness in this matter.  For instance:

“…it is probable that most of the cortisol-GR [glucocorticoid receptor]-related mechanisms alluded to above are a sign of the putative genetic underpinning.” [Emphasis added]

Putative means assumed or believed to be the case.

“Given that the mechanisms of HPA axis dysregulation are incompletely known at present, as is its role in dictating the risk of the disease in vulnerable subjects, current work is beginning to unravel the molecular targets of illness development and progression in BD.” [Emphasis added]

“In bipolar patients, major mood episodes of either polarity result in an inflammatory response that has been convincingly shown in several studies.” [Emphasis added]

So the “episodes” cause the biological malfunction rather than the other way round.

Under the heading LIMITATIONS, the author states:

“The following caveats should be kept in mind while deducing any inferences with respect to the neurobiology of BD:
1) Not all predisposed individuals are afflicted by BD, which underscore the issues of genetic epistasis and hitherto little known mechanisms that mediate resiliency.
2) There are large gaps in knowledge due to the absence of good animal models replicating BD.
3) Technological advances are needed to reproduce findings from animal research in human samples.”

Note the truly exquisite optimism in item 1 above.  Not all the people who have the biological correlate in question go on to develop the thoughts, feelings, and actions which psychiatry labels BD.  So these individuals must have some as yet unknown “mechanisms” that confer resilience.  But the alternative perspective, that this is simply not a fruitful line of inquiry, isn’t even addressed.


None of the three studies put forward by Michael as evidence that “mental illness” is biologically caused come even close to establishing this premise.  Indeed, in each case, the authors are quite clear that the evidence for this premise is not to hand.  The articles are essentially discussion papers which discuss the implications of previous research, and express the hope that more definitive findings will be available some time in the future.

Meanwhile, psychiatrists and their supporters continue to claim that “mental illnesses” are real illnesses caused by brain pathology, that need to be corrected by drugs and/or high voltage electric shocks.  These assertions remain unsubstantiated despite decades of highly motivated and lavishly funded research.  For these assertions to acquire even a semblance of validity, psychiatry needs to demonstrate convincingly that all (or at last the great majority) of the individuals “diagnosed” with a particular “mental illness” have a clear and identifiable neural pathology, and that the causation runs from the pathology to the problems of thinking, feeling, and/or behaving in question.  Weak correlations to neurophysiological processes or genetic variations are irrelevant, as I showed in the original article.

And while psychiatrists, for self-serving reasons, continue their inane efforts to “unravel” the neurobiological causes of these so-called illnesses, more obvious natural causes are studiously ignored and neglected.  Tampering irresponsibly with a person’s brain because he is depressed, while ignoring  those features of his lifestyle and recent history that have been known from time immemorial to precipitate depression, is reckless folly.

  • Sweet63

    Let’s give the researchers the benefit of the doubt, that they earnestly think they can find a mechanism, something they can switch on and off, to make the job easier.

    Unfortunately these dubious studies are routinely cited by politicians and nonprofit hucksters who want more and more taxpayer funded “mental health” services in your town. Build it and they will come!

  • Olmy Olm

    I don’t know, I just don’t see eye to eye. These are, after all, the *experts* that we expect to get things right. So if they are saying something and pushing a certain narrative that they are committed to, then theirs is the lion’s share of the responsibility. It is not surprising that *non-experts* would believe them. After all, we live in a society where the scientists are the new “priesthood”. They darn better get it right then.

  • Echo

    More and more I start to think that these problems people call mental illnesses (especially the more common ones) are a result of people not learning or not using appropriate skills to deal with life. For example, one way to deal with conflict is to communicate assertively, another is to become submissive to appease the other person (as one option). If you face a failure you can decide to learn from it or try again or you can become relentlessly perfectionistic to ‘make up for it’ and so on and so forth. Which of these coping strategies will lead to feelings of anxiety or depression?
    It is not someone’s fault if they have not been given the opportunity to learn healthy ways of dealing with these things, but they can learn over time. Psychiatry says they can’t. I’m just thinking out loud here (figuratively speaking).
    Thanks again for writing Phil!

  • Echo

    Well, this is the problem. Scientism. Have you ever read Animal Farm by George Orwell? There’s a good passage in there where one of the pigs, justifying to the other animals why the pigs deserve better food than the others even though it is supposed to be an egalitarian utopia. It goes like this: “Milk and apples (this has been proven by Science comrades) contain substances absolutely necessary to the wellbeing of a pig. We pigs are brainworkers. The whole management and organization of this farm depend on us. Day and night we are watching over your welfare. It is for YOUR sake that we drink that milk and eat those apples.”
    The capitalisation of Science is deliberate. Even in 1945 Orwell could see how The Science is used to spread dubious ideas, control people and silence questioning.

  • Olmy Olm

    Fascinating. I haven’t read Animal Farm yet but it’s definitely on my list.

  • Phil_Hickey


    Good thinking! I think that what you’re saying is right on. Psychiatry takes ordinary problems that people have been dealing with in natural ways with help/support from family and friends, and arbitrarily turns them into brain illnesses that need to be treated with drugs. Of course, if one takes the drugs for extended periods, then one does indeed have brain problems – for which psychiatry prescribes more drugs.

    Best wishes.

  • Cledwyn B’Stard

    It’s a shame more isn’t done on this side of the divide to question the arbitrary division of society into the “sane” and the “insane”, and the subsumption of humanity under these two heads.

    The line separating the two runs through the human mind; insanity is a part of our common inheritance. A man is born a lunatic and he dies a lunatic.

    The average definition in the average dictionary – which some people invoke as if it was holy writ (thus committing the fallacy of the argumentum ad dictionarium) – connotes that rationality on the one hand and normalcy/popularity are mutual entailing, thus allowing us to use the latter as a yardstick.

    This has nothing to do with the facts, but can largely be traced to the simple fact that men are eternally biased in the direction of anything that confirms them in their asinine vanity, save the terminally self-loathing, who exhibit a prepossession of like strength in favor of anything that confirms them in their self-loathing

    The subsumption of men under these two heads – that is, the “sane” and the “insane” – is an injustice that persists largely because of the rich harvest this affords to some people’s pleasurable feelings, omitting mention of countless other reasons.

    Hobbes once said that all mental pleasure stems from the favorable comparison, actual or imaginary, between ourselves and others. This is one reason injustice and inequality are necessary, and why all attempts to root them out have and always will fail, why ideologies that elevate us at the expense of others are so eagerly and uncritically embraced, why a world in which men existed and related to each other on an equal footing, in which all were truly equal, is a world no-one really wants to live in.

    “A man is as inseparable from his vanities as a dog from its fleas.”

    H.L. Mencken

  • Cledwyn Spreadin MHD awareness

    Of course, one of the chief symptoms of the madness of the mob – Mad Herd’s Disease – is the belief in “mental illnesses”, which, spreading like a murrain among cattle, sweeping all sanity before it, and trampling all but a tiny pocket of resistance to dust, is impossible to be controlled, save by the expedient of a mass cull.

    (My apologies to any cattle of delicate sensitivities that might be reading this. I can assure you I wasn’t trying to hijack your experience.)

    Mad Herd’s Disease is a terrible and devastating brain disease, specifically afflicting the lateral orbitofrontal cortex of the brain.

    The person suffering from this disease cannot think rationally, about anything. His mental horizons are narrow to the point of neophobia. Any irregularity in his environment, any innovation of expression, be it in speech, dress, or a work of art, reduces him to a giggling imbecile, to bellowing like a donkey, or to gawping like an idiot; in severe cases, it incites him to violence. He is so small-minded, it’s a miracle that he can manage to fit more than one idea in the disproportionately large head in which his tiny mind is housed.

    The sufferer of MHD is a drooling fanatic, and displays a superstitious reverence for the customs, laws, and received stupidity of his society. There isn’t a belief that takes up residence in his diseased head that isn’t the profoundest nonsense.

    There are some opportunists out there who indulge the victims of this disease in their madness, telling them they are sane, and thus stopping them from getting the help they need.

    Epidemiologists say that as many as 6 and a half billion suffer from MHD.

  • Cledwyn B’Stard

    That should be “6 and a half billion people suffer…”

  • Cledwyn, where did you learn to write like this? I love your poetic style of writing. If you are open to it please, email me… bpdtransformation (at) gmail (dot) com… I have something else I’d like to ask you.

  • Cledwyn B’Stard

    People who are depressed aren’t mad, but in an advanced state of lucidity, terminal lucidity.

    Life is like a drug yielding ever-diminishing returns. When one is young, when one’s bottom is still in the full bloom of youth, before one’s illusions wither and die in the shadow cast by the memory of the bitter awakenings that still lie ahead, then life can be pretty good; but as lambs frolicking to the slaughterhouse are we in that age of fabled innocence.

    We spend our whole lives struggling and striving, all to keep ourselves afloat in this ocean of shit we call life, gasping for pure, unsullied air, when in truth we should just let the ocean swallow us up, and hurl ourselves off the nearest bridge, assuming there are no psychiatrists about, or other saboteurs of the suicide.

    Only madness propels us into the frenzy of becoming, and what is it that we become? Nothing. Our faculties and functions in free fall, we grow old and infirmed, end up in an old people’s home, thus taking our place in the vegetable kingdom to wait out the conclusion of our miserable existence, like prospective corpses in a morgue waiting room, with about as much reason to go on breathing as a cow in an abattoir antechamber, which is scarcely more reason than we had before. Until death providentially intervenes and takes our asses out of circulation. Or, of course, we drop dead before the onset of old age.

    As Balzac said, the extent of our fall is in direct ratio to the heights we scale. With this is in mind, why bother trying to become anything? A chronically depressed person’s claim – or at least some of us – to superior sanity (and such judgements can only ever be relative, since no man can be absolutely sane) consists principally in the fact that he possesses the foresight to see what all our efforts ultimately amount to, and, turning the insights thus gained to good account, withdraws from life.

    Why bother? Everything, as Sebald said of buildings, casts before it the shadow of its destruction.

    Including our achievements, which only rarely fall outside of the common run and thus surpass mediocrity, even though men will strain themselves to the limit to do so, and always against the odds, for the chances of achieving real distinction in any field of endeavor verge on the statistically impossible.