The Lack of Strong Links Between Mental Illness and Brain States

The recent paper "Examining the Long-Term Impacts of Psychotropic Drugs and Considerations for People Discontinuing Treatment" is by Timothy Wand, PhD and a registered nurse. It can be read here. Below is a quote:

"Multiple studies have now cast doubt over any clear or direct neurobiological or genetic cause or association with mental illness (Border et al., Citation2019; Borsboom et al., Citation2018; Curtis, Citation2021; Marsman et al., Citation2020; Nour et al., Citation2022; Winter et al., Citation2024). For example, Nour et al. (Citation2022) surmise that despite three decades of intense neuroimaging research, there is no neurobiological account for any psychiatric condition. Torrey (Citation2024) concludes that not one gene has been found that can be causally linked to ‘schizophrenia’, and despite many studies and variety of techniques used, Parlatini et al. (Citation2024) confirm that no promising biomarkers have been identified for ‘Attention Deficit Hyperactivity Disorder (ADHD)’. The chemical imbalance theory of mental illness and the serotonin hypothesis of depression have been refuted (Ang et al., Citation2022; Healy, Citation2015; Hengartner & Plöderl, Citation2023; Moncrieff et al., Citation2022, Citation2023).

While genetics and biology have a role to play in all aspects of the human condition, the degree to which genetics and biology influence mental health and well-being remains a matter of conjecture. What is known without question, is that mental health challenges are predominantly associated with socio-economic disadvantage, as well as trauma, adversity, violence, abuse, neglect, oppression and discrimination (World Health Organization & the United Nations [WHO & UN], Citation2023).

The fact is, there is no pathophysiology, disease process or one identifiable biomarker associated with any psychiatric diagnosis. They are highly heterogeneous labels of questionable scientific validity (Kajanoja & Valtonen, Citation2024)." 

Below are two relevant quotes by scientists:

• "In contrast, the major mental illnesses...bipolar disorder, anxiety disorders, anorexia nervosa and depression have proved remarkably resistant to similar developments. Unfortunately, it is still not possible to cite a single neuroscience or genetic finding that has been of use to the practicing psychiatrist in managing these illnesses despite attempts to suggest the contrary." -- David Kingdon, Emeritus Professor of Mental Health Care Delivery. "Why Hasn't Neuroscience Delivered for Psychiatry?"
• "Despite three decades of intense neuroimaging research, we still lack a neurobiological account for any psychiatric condition. Likewise, functional neuroimaging plays no role in clinical decision making....It remains difficult to refute a critique that psychiatry’s most fundamental characteristic is its ignorance. . . . Casting a cold eye on the psychiatric neuroimaging literature invites a conclusion that despite 30 years of intense research and considerable technological advances, this enterprise has not delivered a neurobiological account (i.e., a mechanistic explanation) for any psychiatric disorder, nor has it provided a credible imaging-based biomarker of clinical utility."  -- Neuroscientist Raymond Dolan and two other scientists (link). 

Erroneous "brains make minds" ideas can lead to bad psychiatry. A psychiatrist may see mind and mood and behavior problems as being all due to brain causes, ignoring economic causes and bad parenting  causes and social injustice causes and societal causes and poor education causes and life history causes and trauma causes.  And sometimes what is called a mental illness may be mainly an example of nonconformity or human mental diversity, something a healthy society should tolerate under a policy of "let a hundred types of flowers bloom." 

Undark.org has published some good articles questioning some of the legends and boasts of science professors. But it recently had a poor article trying to sell us on the idea of "psychiatric brain surgery." The principle evidence it provides for such a thing is very weak from a standpoint of decent evidence. We hear some testimony from an anonymous person who 16 months ago underwent tissue-destructive brain surgery to try to prevent him from thought patterns that had been classified as "obsessive compulsive disorder." The man seems pleased with the results, although we should suspect that what is going on is a mere placebo effect, something that would have achieved the same results if a mere sham surgery (with no real surgery) had been done. The man says he is "still aware of his repeating thoughts after surgery" and he may wonder whether his problem may recur. The author confesses, "Given the small number of operations performed each year, the field lacks large-scale trial data on its effectiveness."  So why has she written  some article trying to boost this dubious approach to mental health? 

During the 19th century there was endless testimony about the high medical effectiveness of hypnotism, which previously had names such as artificial somnambulism and mesmerism. But the medical mainstream refused to listen, largely because hypnotism was strongly associated with reports of mysterious psychic powers such as clairvoyance.  The promise of hypnotism was immense, as shown by the success of the physician James Esdaile in supervising many hundreds of tumor removal operations in India, in which patients undergoing severe surgeries with no anesthesia reported no pain, because they had been hypnotized to think they would feel no pain. This route was taken because anesthesia had not yet been invented. On pages 27-28 of a book by Dr. James Esdaile he lists a host of dramatic painless surgeries he performed without using anesthesia, but only hypnosis on patients. The list includes about 20 amputations, and 200 removals of scrotal tumors ranging from 10 pounds in weight to more than 100 pounds in weight. A book on this topic by Esdaile can be read here. 

Medicine has largely failed to take advantage of hypnotism, because of medical personnel being stuck on "brains make minds" errors. And so we had disasters such as the opioid epidemic, in which more than 700,000 Americans died from overdoses of opioid pills that were overprescribed by physicians looking for quick and easy ways to do profitable high-volume patient processing, rather than slower methods such as hypnotism.   Astonishingly, most people in the US still have blind faith in people in white coats, ignoring how the greed and haste of white coat guys led to 700,000 US deaths. Shouldn't a toll like that make you think: maybe these guys can sometimes be seriously wrong about things? 

And speaking of the fellows in white coats making very bad mistakes, a recent NBC News story suggested that more than 2% of all cancers are caused by CT scans suggested by people in white coats, which are used too frequently, and often with too high radiation. We read this:

"About 93 million CT scans are performed every year in the United States, according to IMV, a medical market research company that tracks imaging. More than half of those scans are for people 60 and older. Yet there is scant regulation of radiation levels as the machines scan organs and structures inside bodies. Dosages are erratic, varying widely from one clinic to another, and are too often unnecessarily high, Smith-Bindman and other critics say.

'It’s unfathomable,' Smith-Bindman said. 'We keep doing more and more CTs, and the doses keep going up.'

One CT scan can expose a patient to 10 or 15 times as much radiation as another, Smith-Bindman said. 'There is very large variation,' she said, 'and the doses vary by an order of magnitude — tenfold, not 10% different — for patients seen for the same clinical problem.'  In outlier institutions, the variation is even higher, according to research she and a team of international collaborators have published.

She and other researchers estimated in 2009 that high doses could be responsible for 2% of cancers. Ongoing research shows it’s probably higher, since far more scans are performed today."

There are about 600,000 US cancer deaths per year. If we assume 2% of these were caused by unnecessary or too-strong CT scans per year, then maybe 240,000 were killed by such scans over the past 20 years. That's in addition to huge amounts of unnecessary suffering caused by non-fatal cancers.  Then there is also the very large number of neuroscience research subjects who may have been needlessly imperiled by the use of gadolinium contrast agents (discussed here), a technique that may have seriously endangered a much larger number of people who took them after doctors suggested taking them to make the doctor's analysis of MRI scans easier and faster. 

Besides such examples of guys in white coats blundering, there is an additional reason for suspecting that millions of others may have died in this decade because of guys in white coats blundering.  It seems that those in white coats can often make big mistakes. 

 

Most of those in white coats are good people. But don't assume a claim is very probably true merely because it comes from someone in a white coat. 

They Stored and Studied Thousands of Brains, But Still Failed to Show Mental Illness Comes From Sick Brains

In 2019 the Washington Post had a long article entitled "Dissecting brains to find the biological answers to the mysteries of mental disorders."  We hear about a Lieber Institute of Brain Development that is engaged in the strange business of requesting brains from the relatives of those who very recently died, and then studying such brains.  But we read nothing substantial in the Post story about any progress made in understanding mental illness by studying brains.   We are told, "Since opening in 2011, the institute has amassed more than 3,000 of these post-mortem brains that they are studying to better understand the biological mechanisms behind such neuropsychiatric disorders as schizophrenia, major depression, substance abuse, bipolar disorder and post-traumatic stress disorder."  

We are told of a guy working for that institute who has the job of calling the families of people who just died (often from suicide), asking them to donate the brain of the dead person. We are told such pleas must occur very quickly. The article says this guy "has a small window of time in which to get that consent — just one to three hours." We can only imagine how many families have been bothered in their worst hour of grief by such requests. Later the Post story makes it sound like some of the brains gathered are not that fresh, saying, "Researchers try to obtain brains within 24 to 36 hours." We are told the brains are "flash frozen." A 2019 annual report of the Lieber Institute tells us, "After consent, we obtain a detailed clinical history via interviews with the family." I can only imagine what a burden that would be on family members with a recently deceased relative. 

A page of the Lieber Institute brags that it now has a collection of 4000 brains. Another of its pages calls this collection "the largest collection of brains in the world that’s devoted to enhancing science’s understanding of psychiatric disorders" (which doesn't seem accurate, since the Dutch collection described below, existing for the same purpose, is twice as large). A page of the Lieber Institute entitled "Important Breakthroughs" mentions nothing very substantial about finding a link between brain structure and mental illness. 

The site has a link to a "10-Year Anniversary Report" that fails to report much of any real progress in finding a link between mental illness and brains. We have in the report a page with a big headline of "KEY PUBLICATIONS."  The first publication listed in this report has a title of "Electrophysiological measures from human iPSC-derived neurons are associated with schizophrenia clinical status and predict individual cognitive performance." It's a Questionable Research Practices study that used a sample size of only 13 subjects.  We read in the study, "The sample sizes were small and, because there were no similar prior studies, we could not reasonably estimate expected effect sizes or error rates." The study says, "Due to the small sample sizes and the number of tests performed, some of the associations observed may be spurious, so replication studies with larger samples are necessary to confirm and extend these findings." And this is what the Lieber Institute is offering as the first example of its work in their 10-year progress report?  The other three studies mentioned on the page only talk about claims of genetic differences. 

The 10-year report has this not-very-wise comment on suicide:

"There is certainly a genetic component to suicide, meaning that it can run in families. Twin studies, however, have shown there is more to it. Scientists believe epigenetics—the interaction of genes and the environment—is at play. Perhaps early trauma or illness can turn on specific genes, increasing a person’s risk of suicide. Until we unravel the biological mechanisms underlying suicide, it’s hard to fully understand, treat, or prevent it."

The idea of suicide being caused by genes is nonsensical, as are all ideas of some idea or behavior being caused by genes. Genes merely specify low-level chemical information such as the amino acid sequence of proteins, not any tendencies to think or act in a particular way.  A gene may help make possible some physical action, but is never the cause of such an action. The idea of a genetic basis for suicide is nonsensical according to the assumptions of Darwinism. According to such assumptions, if there were any gene tending to cause suicide, natural selection would tend to weed out such a gene, reducing its occurrence of such a gene in the gene pool of humans. But suicide is still a widespread phenomenon, and it is estimated that 1.7 percent of people in the US die by suicide.  The person claiming a genetic basis for suicide is as misguided as a person claiming a genetic basis for homosexuality. It's the same situation in regard to homosexuality: if there were a genetic basis for it, we would expect (according to Darwinian assumptions) for homosexuality to be very rare or nonexistent. Instead it is estimated that 5% or more of the population is homosexual. 

Ignoring socioeconomic causal factors

The 10-year Lieber Institute report says, "Lieber scientists ask what happens in the brain that makes some people take their own lives." That's a question making an implausible assumption, and what we should be asking is: what goes on in the mind or what occurs in a person's life history or current life situation that might make him suicidal?  There is no evidence that something occurring in a brain causes people to commit suicide. 

The 10-year Lieber Institute report has a link to a paper entitled, "Genetics and Brain Transcriptomics of Completed Suicide." The "Brain Transcriptomics" part involves the ridiculous procedure of trying to analyze rates of gene transcription activity in the brains of people who have already died, using brains frozen 12 to 24 hours after death.  Gene transcription is greatly altered by death, and rapidly trails off in the hours after death. The idea that you can shed some light on what was happening in either the minds or brains of people when they killed themselves or beforehand by studying gene transcription rates in brains frozen 12 to 24 hours after they died seems likes nonsense. 

A paper like this should not be taken seriously by anyone unless the authors followed a careful blinding protocol so that those analyzing the brains did not know whether any particular brain came from someone who committed suicide. We read of no such thing. There is merely a single sentence saying, "All diagnoses and decisions about manner of suicide were determined blind to any of the molecular data." That does not mean that people studying the brains were blind to whether suicide occurred. 

Very ridiculously, the 10-year Lieber Institute report has a line saying, "Lieber researchers are looking at these biological snapshots of what occurred in the brain at the moment of suicide completion to determine what's different about these brains."  The brain of a dead person frozen 12 to 24 hours after he died is not a biological snapshot of what occurred in the brain at the moment of suicide. 

The publications page of the Lieber Institute lists their top papers for the past nine years. We seem to find no mention of a discovery linking brain states and mental illness. Most of the papers mention only claims about genes. None of the papers listed uses the word "replication." What the Lieber Institute mainly seems to have in its research is gene analysis, particularly the weak borderline type of gene analysis called transcriptomics. Transcriptomics is some not-very-solid-seeming branch of inquiry that tries to analyze what genes were being used at particular times.  The idea of trying to use transcriptomics to study dissected dead brains is laughable. Gene transcription is greatly changed by death, and trails off not long after death. 

What do you do when you can't find differences in brain size or brain structure to explain mental differences? Maybe you look for differences in genomes. But the genes in genomes merely specify low-level chemical information such as the amino acid makeup of proteins,  and have basically nothing to do with mental states. What do you do if you cannot find differences in genomes to explain mental differences? Then maybe as a last resort you do some studies on the will-of-the-wisp, ever-changing kind of thing called "transcriptomic profiles." Since transcriptomic profiles are ever-changing, and it is possible to get a separate  "transcriptomic profile" for any of 20,000+ genes, you will have some very noisy data allowing you to see pretty much anything that you want to see. 

Apparently no drugs or treatment for mental illness have yet resulted from all this studying of 4000 brains.  On a page of the Lieber Institute we read this

 "Seven years of operations, we have made considerable progress in identifying and developing a promising set of novel therapeutic targets including two that could be in clinical trials within two to three years. In addition, we have four promising leads that could introduce two new drugs into Phase II clinical trials by 2021."

That isn't a report mentioning that any drug had yet been developed by such brain studies. We hear of four drugs "out-licensed for further development," but we don't hear of any drug that has been federally approved. Apparently all this annoying the families of just-deceased people for a brain donation isn't getting much of anywhere in establishing a link between brain states and mental illness. 

The Lieber Institute publishes a free online magazine called neuroDEVELOPMENTS. In the March 2019 edition we have the very untrue claim that "the genome guides construction of the brain." The human genome (DNA and the genes in it) do not guide or specify the construction of either any human organ or any human cell. The claim that DNA is a blueprint telling how to make a body or any of its organs or cells is a grotesque lie that materialist scientists have been telling for 70 years.  For a long list of quotes by scientists and doctors saying that DNA is not a blueprint, program or recipe for building a body, see my post here. 

Elsewhere in the world is an even bigger collection of brains, one that also has failed to substantially support claims of a brain basis for mental illness. The Japan Times tells us this:

" Countless shelves line the walls of a basement at Denmark's University of Odense, holding what is thought to be the world's largest collection of brains. There are 9,479 of the organs, all removed from the corpses of mental health patients over the course of four decades until the 1980s. Preserved in formalin in large white buckets labeled with numbers, the collection was the life's work of prominent Danish psychiatrist Erik Stromgren...The brains were collected after autopsies had been conducted on the bodies of people committed to psychiatric institutes across Denmark. Neither the deceased nor their families were ever asked permission."

We hear not one word about any discovery that came from studying these brains. A CNN story on the basement filled with brains tells us this:

"A 2012 study found that roughly 40% of Danish women and 30% of Danish men had received treatment for a mental health disorder in their lifetimes – though Werge estimated that number would 'almost certainly' be higher if the same study was done today. (By comparison, that same year, less than 15% of US adults received mental health services.) 

I don't think Danes are any more prone to mental illness than Americans, but it seems from the numbers above that Danish authorities have some great enthusiasm for diagnosing people with mental illness, particularly women. We may only wonder how many of the brains in the Danish collection were taken without permission from women who were wrongly put in mental hospitals. The CNN article also fails to tell us of any progress in understanding the cause of mental illness from studying such brains. A web page of the University of Odense describes the collection of brains, but fails to mention any progress that has come from studying the brains.  There is no link to any papers that were produced using such brains. 

There is another brain collection called the Human Brain Collection Core (HBCC). The collection is described here. The collection seems to consist of about 1000 brains, 700 from people who were diagnosed with mental illness. 300 of the brains are from normal people. We seem to have the same kind of method as used by the Lieber Institute. The families of people who recently died are asked to donate the brain of a family member, with a time pressure element of "we must act fast." We are told "there is no direct benefit to the family for allowing the donation." I guess such "grab the brains without paying a cent for them" stinginess is what we might expect from research neuroscientists, who nowadays pay meager  "chump change" wages to volunteers for scanning their brains in medically unnecessary brain scans that might expose them to health risks (as discussed here). 

Related to this collection is a "Selected Publications" page, apparently listing the best results obtained from studying these brains. None of the papers listed have impressive-sounding titles making it sound like any brain structure or brain condition has been found explaining mental illness. Most of the papers merely refer to obscure claims about genetics and genetic transcription.  

Of about 46 papers listed, the paper that sounds the most like something reporting a link between brain structure and mental illness is a paper entitled "Accelerated hippocampal biological aging in bipolar disorder." The paper does not report any differences in the hippocampus size or structure for those with bipolar disorder. The authors tried to look for some epigenetic difference, and initially found "Groups did not differ for epigenetic aging acceleration when considering the entire sample." After using the old "slice the study group into a smaller group, looking for statistical significance" trick, the authors were able to report a very marginal  statistical significance of just barely better than the minimum of p < .05, something that smells like p-hacking.  We can't tell how large the sample size is, because the authors haven't listed it in the abstract, and the paper is behind a paywall. This does not at all qualify as any brain difference explanation for bipolar disorder.  

The Lack of Correlation Between Most Mental Illness and Brain States

In a 1920 book by Carl August Wickland there is a discussion of the lack of correlation between brain states and mental illness. We read this:

"Dr. W. M. L. Coplin, Director of the Bureau of Health and Charities, Philadelphia, Pennsylvania, said 'Insanity, in most cases, is unaccompanied by any perceptible change in the brain structure. The brain of the patient, when examined under a microscope, shows absolutely nothing which differs in any way from the appearance of the brain of the perfectly sane person. It is therefore evident that the insanity might be due to toxemia, the effect of some subtle organism in the nature of bacilla.... Something causes insanity but what it is, we do not yet know.'

Dr. Britton D. Evans, Superintendent of the Morris Plains, New Jersey, Insane Asylum, stated: 'Brain tumor or brain fever may not affect the mind.... A man may have trouble of the brain and still have a normal mind.'

Dr. Th. Ziehen, a noted German alienist, and an authority on hysteria, wrote: 'For many functional neuroses there is as yet no accurate limitation and definition. As pathological anatomy does not aid us, no uniform and exclusive cause for hysteria can be demonstrated.'

Dr. William Hanna Thomson, physician to the Roosevelt Hospital and Professor of the Practice of Medicine and Diseases of the Nervous System, New York University Medical College, in referring to Tuke's Dictionary of Psychological Medicine, asserted that:  'The contributors to this great encyclopedia are from the most eminent professors, experts, and superintendents of insane asylums in Great Britain, the United States, France, Germany, Hungary, Belgium, Denmark, Switzerland and Russia. In the articles by the writers on kleptomania, dipsomania, chronic mania, etc., there is not a word about the pathological anatomy, (because none can be found). Just so it is in the article on melancholia, puerperal insanity, katatonia, circular insanity, homicidal insanity or epileptic insanity; in none of these is there a word about pathological anatomy, for the sufficient reason that not one of these forms of insanity shows any pathological or diseased condition in the brain different from the sound brain of a healthy man killed in an accident.'

He also said: 'It is high time that we now look in the direction of toxemia (or blood poisoning) for the explanation of the insanities which produce no changes whatever in the brain.' ”

The quotes above date from about 100 years ago. For a modern take on these questions, we can look at some of the chapters of the free online psychiatry textbook "Critical Psychiatry Textbook" by Peter C. Gøtzsche, MD. In Chapter 3 Gøtzsche states this: "Despite 15 years of intense studying, I have been unable to find any important contribution of biological psychiatry to our understanding of the causes of psychiatric disorders and how they should best be treated."  

Gøtzsche cites psychiatry textbooks that attempt to link small brain differences with mental illness. He gives many examples indicating that such textbooks routinely make untrue claims based on weak evidence. He points out that many of these textbooks are citing unreliable studies with too-small sample sizes. He also raises an important point that casts doubt on the unreliability of all such claims: the fact that nowadays people suffering from mental illness are massively prescribed brain drugs, and many think that such drugs themselves may produce changes in brain states, including shrinkage of brain tissue. If drugs may change some part of the brain, and the mentally ill people being studied have been long taking such drugs, then any difference in their brains may be caused by the drugs themselves, rather than such changes being the cause of their mental illness. 

He states this about brain imaging studies (often used to try to back up claims of a physical basis for mental illness):

"This whole area is a mess of highly unreliable research. A 2009 meta-analysis found that the false positive rate in neuroimaging studies is between 10% and 40%.  And a 2012 report written for the American Psychiatric Association about neuroimaging biomarkers concluded that 'no studies have been published in journals indexed by the National Library of Medicine examining the predictive ability of neuroimaging for psychiatric disorders for either adults or children.' 

One good research paper can sometimes make hundreds of poor studies redundant. This is the case for a 2012 systematic review by Joshua Carp that surveyed the methodological state of the art in a random sample of 241 fMRI studies. Carp found that many of the studies didn’t report on critical methodological details about experimental design, data acquisition, or analysis, and many studies were underpowered. Data collection and analysis methods were highly flexible. The researchers had used 32 unique software packages, and there were nearly as many unique analysis pipelines as there were studies. Carp concluded that because the rate of false positive results increases with the flexibility of the design, the field of functional neuroimaging may be particularly vulnerable to false positives. Fewer than half of the studies reported the number of people rejected from analysis and the reasons for rejection, and the median sample size per group was only 15, which generates an enormous risk of selective publication of those results that happened to agree with the investigators’ prejudice."

The doctor includes many additional paragraphs challenging the reliability of brain imaging techniques. He points out people analyzing brain scans have an almost infinite variety of possible "analysis pipelines" they can choose from, each of which is a different way of analyzing the data. He suggests that you can show almost anything you want from brain scan data, simply by fiddling around with different analysis pipelines until one such analysis pipeline shows what you are trying to show.  He then states this:

"The experience of the Editor-in-Chief of Molecular Brain is also relevant to consider when assessing the merits of brain scanning studies in psychiatry. In 2020, he described what happened when he requested to see the raw data in 41 of the 180 manuscripts he had handled. Upon his requests, 21 of the 41 manuscripts were withdrawn by the authors, and he rejected a further 19 'because of insufficient raw data,' which suggested that the raw data might not exist, at least for some of the cases. Thus, only 1 of 41 papers (2%) passed his reasonable test."

A 2016 paper ("Finding the Elusive Psychiatric 'Lesion' With 21st-Century Neuroanatomy: A Note of Caution") has this abstract:

"The widespread use of MRI has led to a wealth of structural and functional anatomical findings in patients with diverse psychiatric disorders that may represent insights into pathobiology. However, recent technical reports indicate that data from popular MRI research-particularly structural MRI, resting--state functional MRI, and diffusion tensor imaging--are highly sensitive to common artifacts (e.g., head motion and breathing effects) that may dominate the results. Because these and other important confounders of MRI data (e.g., smoking, body weight, metabolic variations, medical comorbidities, psychoactive drugs, alcohol use, mental state) tend to vary systematically between patient and control groups, the evidence that findings are neurobiologically meaningful is inconclusive and may represent artifacts or epiphenomena of uncertain value. The authors caution that uncritically accepting from study to study findings that may represent fallacies of all sorts carries the risk of misinforming practitioners and patients about biological abnormalities underlying psychiatric illness."

Referring to major depressive disorder, a 2019 paper published in Nature states this: "MRI scans cannot be used to aid in the diagnosis or treatment planning of patients with MDD." A 2019 scientific paper states this: "Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent."  The frequent "nonreplications" are apparently studies that fail to show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). The paper very weakly concludes that "subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD."  Given such frequent nonreplications, we may be skeptical about the "subtle differences" claimed. Gøtzsche  states, "The fact is that ADHD is a social construct and that no reliable studies have shown any biological origin for this construct, or that the brains of people with this diagnosis are different to the brains of other people."

A 2021 study is entitled "Systematic Review of Functional MRI Applications for Psychiatric Disease Subtyping." Hinting at a lack of good quality evidence that brain scans can be useful for psychiatric diagnosis, the paper says that "this subfield is at an incipient exploratory stage, and all retrieved studies were mostly proofs of principle where further validation and increased sample sizes are craved for," noting that "results for all explored diseases are inconsistent." Another 2021 study states this about MRI brain scan studies: "In a reflection on the history and future use of MRI in psychiatry, Etkin commented on the lack of reproducible, diagnosis-specific neuroimaging findings." A 2019 paper says that MRI brain imaging "still has only a minor role in the clinical assessment of patients at early stages of psychosis and whether it should be implemented as routine screening instrument in psychotic patients has continued to generate debate." Another paper says brain lesions of causal relevance occur in only 6% to 10% of schizophrenia patients, and then says that only 3% of secondary schizophrenia arises in the presence of systemic physical illness. The actual numbers are probably less, as estimates of this type (made by neuroscientists who love to suggest neural causes) are typically overestimates. 

In an illuminating article by Bruce E. Levine, we read the following:

"Published in the journal Neuron in 2022, Raymond Dolan—considered one of the most influential neuroscientists in the world—co-authored 'Functional Neuroimaging in Psychiatry and the Case for Failing Better,' concluding, 'Despite three decades of intense neuroimaging research, we still lack a neurobiological account for any psychiatric condition.'  Reflecting on the more than 16,000 neuroimaging articles published during the last 30 years, Dolan and his co-authors concluded: 'It remains difficult to refute a critique that psychiatry’s most fundamental characteristic is its ignorance. . . . Casting a cold eye on the psychiatric neuroimaging literature invites a conclusion that despite 30 years of intense research and considerable technological advances, this enterprise has not delivered a neurobiological account (i.e., a mechanistic explanation) for any psychiatric disorder, nor has it provided a credible imaging-based biomarker of clinical utility.' ”

Below is a recent quote from Allan Levinthal, PhD:

"In stark contrast to the discoveries by medical researchers of biological causation for many physical illnesses, psychiatric researchers have failed to find physiological or genetic causation for the most diagnosed mental disorders—the anxiety disorders and depression—negating the rationale for the prescription of these drugs. This failure has occurred despite (a) the expenditure by the NIMH of tens of billions of research dollars over this same more than century-long time span in a fruitless search for physical causation of these mental disorders and (b) patients spending tens of billions of dollars annually on these prescriptions."

"Brain Chemical Imbalance" Theory Is Fading Out as an Explanation for Mental Illness

An interesting exercise is to try the following Google query:

What causes mental illness?

Let us look at the extremely diverse results that come up on the first  page of search results that appear when we do such a Google query. Strangely, the first result is an article that does not make any attempt at all to suggest any explanation for a cause of mental illness. The second search result is a page from a small organization that states this:

"Most psychiatric survivors reject the term 'mental illness' altogether, as it supports what is considered the 'medical model' of mental health. The medical model is based on the idea that there is a physiological impairment creating a neurochemical imbalance in a person’s brain, resulting in a mental illness. Despite this popular perspective, it is based on flawed science."

The third result is a page that does not make any attempt at all to suggest any explanation for a cause of mental illness. The fourth result is a page that attempts to explain mental illness by first mentioning genetics. The page suggest that there might one day be some kind of genetic or epigenetic way of reducing suicide.  The page suggests that "macrophages" and "inflammation" somehow contribute to mental illness. 

The fifth search result is a page from a leading medical clinic, the Mayo Clinic. In a section entitled "Causes," the page lists three causes for mental illness:  "Inherited traits," "Environmental exposures before birth," and "Brain chemistry." What the page suggests under "brain chemistry" is basically the same idea that is rejected by the second search result (on this page). 

(I may note that after years in which the medical community kept telling us that mental illness is caused by imbalances of brain chemicals, we now have many authorities who are denying such claims. Such authorities sometimes claim that the medical establishment never taught that mental illness is caused by imbalances of brain chemicals. But the doctrine of mental illness being caused by brain chemical imbalances still is taught very widely by many medical authorities, and evidence of the massive teaching of the doctrine by the medical and neuroscience establishment can effortlessly be found very abundantly by searching for the past statements of such authorities.) 

The sixth search result is a page entitled "What causes mental illness?" The answers suggested (from first to last) are genetics, environment, childhood trauma, stressful events, negative thoughts, unhealthy habits, drugs and alchohol, and brain chemistry. The page tells us this: "Mental illness involves an imbalance of natural chemicals in your brain and your body."  This is the "chemical imbalance" theory of mental illness that numerous authorities are now saying is not true, and which some authorities are claiming was never taught. It very obviously was taught and continues to be taught by leading authorities. 

The seventh search result is a page from the widely read WebMD site. The page suggests the "chemical imbalance" theory of mental illness, along with a widely spread "bad wiring" theory. The page also suggests causes of genetics, infections, brain defects or injury, and substance abuse.  The page also mentions "stressor" events such as death or divorce, changing jobs, feelings of inadequacy and a dysfunctional family life.  The page kind of goes "all over the map" in trying to explain the causes of mental illness. 

The eighth search result is a 2012 page on the site of the American Psychological Association, one entitled "The Roots of Mental Illness." At first the page starts out by pitching purely biological causes of mental illness. We read this:

"Eric Kandel, MD, a Nobel Prize laureate and professor of brain science at Columbia University, believes it's all about biology. 'All mental processes are brain processes, and therefore all disorders of mental functioning are biological diseases,' he says. 'The brain is the organ of the mind. Where else could [mental illness] be if not in the brain?' "

We certainly do not know that all or even most mental processes are brain processes, and there are very strong reasons (discussed on this blog) for rejecting claims that all or most mental processes are brain processes, a claim which is dogma, not fact. As for the "where else" reasoning of Kandel, it is a type of rhetorical question sophistry that can sound convincing only because of the lack of imagination in the person hearing it.  The same type of fallacious reasoning was long used about DNA. People would say that DNA must contain some blueprint for making a human, arguing, "Where else could such a blueprint be?" The fact is no such blueprint has ever been discovered in DNA, which contains only low-level chemical information, not high-level structural information.  We can reasonably answer Kandel's question like this: mental illness (along with most other mental phenomena such as memory) could be in some non-material reality of a human (such as a soul) that is something different from the brain. 

Next on the 2012 "Roots of Mental Illness" page of the American Psychological Society, we read this: "That viewpoint is quickly gaining supporters, thanks in part to Thomas R. Insel, MD, director of the National Institute of Mental Health, who has championed a biological perspective during his tenure at the agency."  But a mental health expert claimed in a recent interview that Insel's "13 years in charge of the nation’s mental health research produced such uniformly dismal results."  The expert stated this, quoting Insel:

"When Insel stepped down as director of NIMH in 2015 he gave an interview about his accomplishments, after spending by his estimate $20 billion. 'I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that … I don’t think we moved the needle in reducing suicide, reducing hospitalizations, improving recovery for the tens of millions of people who have mental illness.' ”

Indeed, in its second part the 2012 "Roots of Mental Illness" page of the American Psychological Society shifts gears, giving us this quote:

"That complexity is one reason that experts such as Jerome Wakefield, PhD, DSW, a professor of social work and psychiatry at New York University, believe that too much emphasis is being placed on the biology of mental illness at this point in our understanding of the brain. Decades of effort to understand the biology of mental disorders have uncovered clues, but those clues haven't translated to improvements in diagnosis or treatment, he believes. 'We've thrown tens of billions of dollars into trying to identify biomarkers and biological substrates for mental disorders,' Wakefield says. 'The fact is we've gotten very little out of all of that.' "

The ninth search result gives another "all over the map" smorgasbord of reasons for mental illness. In a similar vein, the tenth search result is a page of the Center for Disease Control. Under a heading of "What Causes Mental Illness?" we read the following:

"There is no single cause for mental illness. A number of factors can contribute to risk for mental illness, such as

• Early adverse life experiences, such as trauma or a history of abuse (for example, child abuse, sexual assault, witnessing violence, etc.)
• Experiences related to other ongoing (chronic) medical conditions, such as cancer or diabetes
• Biological factors or chemical imbalances in the brain
• Use of alcohol or drugs
• Having feelings of loneliness or isolation"

The eleventh search result is a page that offers an extremely wide range of things that can affect mental health:

"

• childhood abuse, trauma, or neglect
• social isolation or loneliness
• experiencing discrimination and stigma, including racism
• social disadvantage, poverty or debt
• bereavement (losing someone close to you)
• severe or long-term stress
• having a long-term physical health condition
• unemployment or losing your job
• homelessness or poor housing
• being a long-term carer for someone
• drug and alcohol misuse
• domestic violence, bullying or other abuse as an adult
• significant trauma as an adult, such as military combat, being involved in a serious incident in which you feared for your life, or being the victim of a violent crime
• physical causes – for example, a head injury or a neurological condition such as epilepsy can have an impact on your behaviour and mood. (It's important to rule out potential physical causes before seeking further treatment for a mental health problem)."

The page rejects the "brain chemistry imbalance" so often advanced around the turn of the century, stating the following:

"The human brain is extremely complicated. Some research suggests that mental health problems may be linked to a variation in certain brain chemicals (such as serotonin and dopamine), but no one really understands how or why. Arguments that someone's brain chemistry is the cause of mental health problems are very weak. But even though there's no strong evidence to say that any mental health problems are caused by a chemical imbalance in our brains, you might find some people still use brain chemistry to explain them."

The 12th search result also suggests a wide range of causes for mental illness. The 13th search result is a World Health Organization page that does not attempt to describe the causes of mental illness. The 14th search result is a National Institute of Mental Health page that also does not attempt to describe the causes of mental illness.

From these results it seems we can draw three conclusions:

(1) The claim that mental illness is caused by brain chemical imbalances is a claim that is still being pushed here and there by various authorities.

(2) Such a claim is now disputed by many other authorities on mental illness, who say that there is no robust evidence for such a claim that mental illness is caused by chemical imbalances in the brain.

(3) The most common answer given regarding the cause of mental illness is a multi-factor answer that mentions a wide variety of possible causes, many of which include things other than brain states.

There was never any good evidence for the theory that mental illnesses are caused by brain chemical imbalances. The theory was popular largely because it was pushed by pharmaceutical companies. Neuroscientists often sounded supportive of the theory partially because many of them are financially entangled with  pharmaceutical companies.

A recent article on the Psychology Today web site is an illuminating expose of how doctors, professors and pharmaceutical companies long pushed an unwarranted theory that depression is caused by a chemical imbalance, an imbalance of the chemical serotonin. The article tells us that the theory was so widely spread by authorities that more than 80% of the public believed it, according to polls. We read this:

"A major new review of the research—the first of its kind exhaustively reviewing the evidence, published today in the journal Molecular Psychiatry—reaches a strikingly similar conclusion. In 'The Serotonin Theory of Depression: A Systematic Umbrella Review of the Evidence,' University College London Psychiatry Professor Joanna Moncrieff and a team of five other top European researchers found 'there is no evidence of a connection between reduced serotonin levels or activity and depression.' ...The researchers also looked at studies where serotonin levels had been 'artificially lowered in hundreds of people' (by depriving their diets of the necessary amino acid that makes serotonin) and found that 'lowering serotonin in this way did not produce depression in hundreds of healthy volunteers,' according to a 2007 meta-analysis and several recent studies. Numerous other reviews on re-examination were found to provide weak, inconsistent, or nonexistent evidence of a connection between serotonin and depression."

It was the same thing going on in regard to the serotonin theory of depression and the theory that the brain is the source of the human mind and the storage place of memories:

• In both cases a community of experts became a belief community with the goal of propagating some dubious explanation.
• In both cases an overconfident community of experts "jumped the gun" by claiming to understand things beyond its understanding. 
• In both cases the community of experts developed speech customs that were not based on sound scientific evidence, and were contrary to many observations.
• In both cases the story line being told served the vested interests of the experts, by helping to make them look like great lords of explanation who understood deep mysteries of the mind. 

Just as our professors and psychiatrists misled us for so long with unfounded theories of mental illness being caused by chemical imbalances, professors and psychiatrists and neuroscientists have misled us for so long by advancing unfounded claims that human minds comes from brains and that brains are the storage place of memories. The social construction of the serotonin theory of depression is a sociology story very similar to the sociology story of the social construction of claims that brains make minds and store memories. To understand how and why such folklore began to be told, use a rule of "follow the money" and ask this again and again: "Who was it benefited by the telling of such stories, and in what ways did they benefit?" And also ask again and again: "In what ways did the tellers of such stories break the rules of proper scientific inquiry, in a way that led to their own benefit?"

When the oppressed are sad largely because they have been oppressed, it is very convenient to tell such people that they are sad because of some problem in their brain that can be fixed if they buy pills, rather than because of all of the things that society has done to oppress them. Part of this oppression comes from academia itself, but explaining how that works would require a separate post.

And speaking of errors about brains, today's Health page on Google News has a link to an article entitled "Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives."

Postscript: The post here documents how leading authorities long pushed the serotonin theory of depression, and how some of them are backtracking, changing their web sites and claiming they never really believed such a thing (often in contrast to their previous statements).  At this page we read of a psychiatry professor who has been trying to stop using "anti-depression" SSRIs, through a very gradual reduction lasting years. We get the impression of some great hazard in suddenly stopping their use. But in the TV shows we never hear a psychiatrist say, "I'm going to put you on this pill, but it's pretty addictive." Claims that the serotonin theory of depression was a mere "urban legend" not taught by psychiatrists and neuroscientists are debunked in a scientific paper entitled "Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the scientific literature." That paper documents that very many psychiatrists and neuroscientists taught such a theory for decades, before beginning to backtrack around 2022.