Brain Disorders or Problems with Living? How Research on “Mental Illness” Went Awry

By the end of the 1970’s, psychiatry was facing a crisis of identity that threatened its very existence. Books such as The Myth of Mental Illness by Thomas Szasz and The Death of Psychiatry by E. Fuller Torrey argued that the very concept of mental illness was meaningless. The Rosenhan Experiment had convinced many that psychiatrists could not distinguish the sane from the insane. To many, the tired old dogmas of Herr Doktor Freud seemed about as scientific as astrology or tarot reading. The so-called “minor tranquilizers” such as Valium had been exposed as the dangerous and highly addictive drugs they were, while the major tranquilizers such as Thorazine were derided by patients who had been forced to take them as a form of torture. Other somatic interventions for mental illness, such as lobotomy and insulin coma, were as discredited as bloodletting.

About the only arrow psychiatry had left in its quiver was talk therapy, and while no doubt individual psychiatrists did some good in that capacity, there was a growing awareness among the public, and themselves, that the conditions they were treating were not really diseases, and what they were doing was not really practicing medicine. Third-party payers, both public and private, saw psychiatry as a bottomless pit of need, and were demanding accountability.

Moreover, psychiatrists were facing competition from lesser-paid professionals—counselors, clinical psychologists, social workers, etc.—as well as a growing army of lay therapists. Psychiatrists’ salaries were among the lowest of any medical specialty, and medical school graduates were avoiding psychiatry in droves.

Psychiatry was at a crossroads. Practicing psychiatrists could have concentrated their efforts on talk therapy, and accepted the salary of a clinical psychologist or a social worker. Medical schools could have begun shuttering residency programs in psychiatry, and the American Psychiatric Association could have merged with the other APA, the American Psychological Association.

In short, psychiatry could have begun the process of dismantling itself as a profession.

Of course that didn’t happen. Instead psychiatry embarked upon a vigorous re-branding campaign, as described by Robert Whitaker in his book Anatomy of an Epidemic, in order to convince the public (and themselves?) that these conditions called “mental illnesses” were real diseases, which psychiatrists by virtue of their medical training were uniquely qualified to treat. The public was assured that the biological bases of mental illnesses would be discovered, sometime really soon, and that psychiatry had (or soon would have) safe and effective treatments to correct the chemical imbalances that underlay these conditions—within “three to five years,” reporter Jon Franklin repeatedly assured us in a series of articles published in 1984 in the Evening Sun, for which he was awarded the Pulitzer Prize.

Not everyone was so sanguine about all this. In the 1977 ABC News documentary Madness and Medicine, psychiatrist Peter Breggin had this to say:

Mental illness is a myth. A fraud. A bad metaphor. An excuse. A rationalization. It’s a religious viewpoint held by psychiatrists which says that human troubles are somehow medical in origin and medical in their solution. Now just how poverty, unemployment, unhappiness, fights between husbands and wives, beatings of children, anxiety, alienation—just how all these problems with living relate to medicine and relate to illness is never stated.

Back then, Dr. Breggin was like a lone voice crying out in the wilderness. All of these words of caution fell upon deaf ears.

The linchpin of these efforts was the third iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), released in 1980 among promises that it would help put the field onto a more scientific footing, ushering in what historian Edward Shorter has called “the second biological psychiatry,” with an emphasis on diagnosis and symptom suppression, rather than on addressing the psychological and social roots of a patient’s problems. The stated intent of the authors was to narrow the range of problems treated by psychiatrists.

While the drug companies played no role in the creation of the DSM-III, the document proved a bonanza for them, creating hundreds of new billing categories for which they could develop new drugs (or repurpose old ones). The efforts of third-party payers to introduce some accountability into the system backfired in a big way, as spending on psychiatric drugs skyrocketed. Far from being narrowed, the range of problems treated by psychiatrists mushroomed, as each new iteration of the DSM expanded the scope of human experience to be labeled drug-treatable “illness.”

Efforts to medicalize seemingly every problem with living intensified with the Decade of the Brain, the Human Genome Project, and the National Institutes of Mental Health Research Domain Criteria. When linkage studies and candidate-gene studies failed to demonstrate the genetic basis of mental illness, billions of dollars were poured into genome-wide association studies involving tens or even hundreds of thousands of subjects, hoping to crack the code through sheer number-crunching power—a project one expert termed “unapologetic, high-tech p-hacking.” When brain imaging studies likewise failed, billions more were poured into “brain-wide association studies,” with the same end in mind.

In 2008, NIMH Director Thomas Insel declared:

The National Institute of Mental Health (NIMH) has just entered its seventh decade as the nation’s scientific leader in the fight against mental illness. The landscape of mental health research has changed considerably over these decades. A critical acceleration began in the 1970’s and 1980’s when researchers began making rapid strides towards understanding the science of human behavior and the ways medicines can be used to treat illnesses. In the 1990’s, the “Decade of the Brain” yielded insights into fundamental aspects of how the brain works including new ways of visualizing the brain with imaging technologies.

Dr. Insel added these words of caution:

Our success cannot be measured solely by our traditional “outputs”: the numbers of grants, papers, or discoveries supported. In addition, NIMH must measure success by “outcomes”: how well the research we support provides the evidence base for mental health providers to preempt illness for those at risk (including prevention targeted to those individuals most at risk), enhance recovery for those affected, serve diverse and previously under-served populations, and reduce premature mortality among persons with mental illnesses.

And how did all this work out for us? In fact, not one of the exuberant promises made by biological psychiatry and its boosters has been fulfilled. More than forty years after the publication of DSM-III, all the billions and billions of dollars spent on brain-based and gene-based research have yet to yield a single cure, or treatment, or even a diagnostic test for any of the so-called “functional disorders” commonly treated by psychiatrists.

Less than ten years after Dr. Insel vowed to “preempt illness,” “enhance recovery,” and “reduce premature mortality,” in an interview with Wired he took a considerably more somber tone:

I spent 13 years at NIMH really pushing on the neuroscience and genetics of mental disorders, and when I look back on that I realize that while I think I succeeded at getting lots of really cool papers published by cool scientists at fairly large costs—I think $20 billion—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.

In fact, Dr. Insel’s assertion that they had “not moved the needle” was overly optimistic. given that during this time the proportion of the population disabled by mental illness had soared. Depression is now the world’s leading cause of disability. The suicide rate has soared as well. The needle had moved—but in the wrong direction.

This is not what happens when treatments work.

Even before Dr. Insel issued his now-famous apologia, there had been ample evidence that psychiatric “medications” were making things worse. So-called “anxiolytics” cause worsening anxiety while so-called antidepressants cause worsening depression. The long-term prognoses for schizophrenia, depression, and bipolar disorder all had gotten worse as consumption of these drugs rose. Meanwhile, the MTA Study, far and away the largest and far and away the longest randomized controlled trial of stimulant drugs for children diagnosed with something called “ADHD,” followed up nearly six hundred kids for sixteen years—and the only long-term effect the researchers were able to document was that the drugs stunted the kids’ growth (and they didn’t “catch up”). Moreover ADHD, once a much-contested diagnostic label applied mainly to young boys who were fully expected to grow out of it, now is seen as a devastating condition requiring life-long drug treatment.

The outlook for biological psychiatry has not improved since then. Despite breathless reports that appear like clockwork in the popular press, no genes for mental illness have been found. The claimed effect sizes for genes associated with “mental illness” are absurdly tiny—one the order of one in a hundred (or less) for depression or ADHD, one in five hundred or less for schizophrenia. And, oddly, as the number of “schizophrenia-associated alleles” has soared, not only have their individual effect sizes diminished—their aggregate effect size has diminished as well.

Moreover, the effects of these genes do not map to existing diagnostic categories. Rather, many genes make tiny contributions to the risk of a variety of psychiatric diagnostic categories.

These genes are not disease genes. Rather, they are part of the normal range of human genetic variation.

The results from other fronts have been equally disappointing. Three years ago, a major review found no evidence for the supposed serotonin theory of depression, which had long been presented to the general public as established fact That same year, another major review concluded:

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.

Almost exactly half a century after the publication of his book The End of Psychiatry, psychiatrist E. Fuller Torrey reviewed the contribution of the Human Genome Project to our understanding of the etiology of schizophrenia and concluded:

Three decades later, NIMH’s genetic investment has yielded almost nothing clinically useful for those affected.

Could there ever be any clinical utility to phenomena whose very existence can be demonstrated only after spending billions of dollars and generating mountains of data—and sometimes not even then? At what point do we get to ask whether we want to keep pouring money down this seemingly bottomless pit? If not now, when?

While all this talk about brains and genes has yet to yield a single benefit to a single patient in any clinic anywhere in the world, it has tended to obscure the story of that other psychiatry, with its long and rich tradition of successfully treating those complaints that fall under the diagnostic rubric of “mental illness” with empathy and compassion. These efforts extend at least as far back as the middle of the eighteenth century, at Saint Luke’s Hospital in London, and continued with the Salpêtrière in Paris, the Retreat at York, and Charité Hospital in Berlin.

Psychiatrist David Healy and his colleagues scrutinized asylum records from north-west Wales for the year 1896 (before any of the modern-day psychiatric drugs were introduced) for patients who today likely would have been diagnosed with schizophrenia, bipolar disorder, or major depression, and compared them to those from 1996. They found that while the average length of a single hospital stay had decreased, the total number of admissions had skyrocketed, as had the total number of days per patient spent in hospital. Moreover, modern-day patients were far more likely to die as a direct result of their mental illness compared to their counterparts in 1896.

These are astonishing findings. In what other branch of medicine have outcomes gotten worse since the nineteenth century?

This tradition extended into the twentieth century with Frieda Fromm-Reichmann at Chestnut Lodge, Ronald Laing at Gartnavel Royal Mental Hospital in Glasgow, and Loren Mosher at Soteria House in San Francisco, and it continues to this day with the Open Dialogue Therapy which had its origin in Finland but which since has spread to a number of countries. The Soteria experiment treated first-time episodes of schizophrenia with lay therapists and minimal use of neuroleptic drugs, and obtained results as good or better than those achieved at a well-staffed state mental hospital, while the practitioners of Open Dialogue Therapy in Finland reported that this modality dramatically increased the number of first-time psychosis patients returning to full-time work or studies, and dramatically decreased the rate of death, disability, and hospital admissions. These benefits continued to manifest themselves some nineteen years or more down the road after initiation of therapy.

The efficacy of psychotherapy for treating those conditions called “mental illness” is beyond doubt. There have been so many studies establishing its efficacy, we now have meta-analyses of the meta-analyses. A meta-analysis of studies that compared outcomes for depressed subjects who received psychotherapy with those of wait-listed controls found an average effect size of 0.70—far outstripping reported effect sizes for antidepressant therapy. And a systematic review found that, for patients who had already been hospitalized for a previous suicide attempt, a short course of cognitive behavioral therapy cut the risk of subsequent suicide attempts in half. Surprisingly, effective psychotherapy need not cost more than drug therapy.

And yet, funding for psychotherapy research has lagged far behind that for biologically-based endeavors. A 2016 editorial in the British Journal of Psychiatry claimed that only fifteen percent of NIMH funding since 2012 had gone to non-HIV/AIDS services and interventions, with the remaining eighty-five percent allocated for basic and translational neuroscience research. Since then the picture has gotten even more dismal.

Along with some of my colleagues at the International Foundation for Ethical and Human Psychiatry and Psychology (ISEPP), it has been my privilege to assist with a survey of NIMH grant applications (click here and here) for the years 2012 and 2020. The results have been worrisome—although unfortunately not very surprising.

The lion’s share of research funding—seventy percent of the total—went to gene-based or brain-based studies. Only fifteen percent went to studies of treatment, and only a third of that—a mere five percent of the total—went to studies of psychotherapy. Even more disheartening, nearly half of those studies were devoted to looking for ways to do psychotherapy on the cheap (via telephone or internet).

The issue here is bigger than just a matter of this year’s funding or next year’s funding. It takes years and years to train a researcher. If the young researchers see that grant money is not flowing to psychotherapy research, they will not enter the field. As the practitioners in this field retire, no one will be left to take their place, and our capacity even to carry out this kind of investigation will disappear. We stand in danger of losing an entire field of practical knowledge.

Reading the abstracts of these proposals has been an eye-opening experience. Some of them propose to systematically terrorize rats or mice or monkeys in some unspecified fashion, and then use all sorts of gee-whiz technology to look at the effects on their brains or their DNA. This sort of thing seems preposterously self-refuting. In order to put the animal in a state the researchers think is comparable to “mental illness” in human beings, they have to systematically terrorize it. There was nothing wrong with its brain, or its DNA, before they began doing so. Why don’t we just assume that being systematically terrorized is a bad thing, and if rats or mice or monkeys or human beings are being systematically terrorized, put a stop to it?

One proposal abstract recommended using brain imaging to study children with tics. The abstract noted that half of the kids with tics have also been diagnosed with ADHD, but never mentioned that this diagnosis usually is followed by prescription for stimulant drugs, and that tics are a well-known toxic effect of these drugs.

Another proposed “to investigate the role of frontostriatal glutamatergic metabolism in medication-naive children with ADHD using proton magnetic resonance spectroscopy at 7.0 Tesla.” What is this supposed to tell us about how to teach a child to read? Or how to raise children to grow up to be strong, self-reliant adults? This is an industry that has lost all sight of what it means to be human.

It’s also an industry that continues to consume billions of taxpayer dollars without producing any results benefitting humanity in any measurable way. In February of this year Psychiatric Genetic Consortium announced the discovery of 308 genes “associated” with Major Depressive Disorder. These 308 genes, in aggregate, were said to account for 5.6% of the population liability for this condition, whose lifetime incidence is on the order of one percent. That means the average effect size for any one of these genes must be on the order of one in five hundred thousand.

This is madness. This is the twenty-first century equivalent of medieval scholastics debating how many angels can dance on the head of a pin.

Unless the authors are planning some kind of gigantic eugenics program to eliminate these faulty genes from the population (and I don’t believe they are), what on earth is the point of all this? Instead of focusing on the five percent of the population liability due to genetic variation (which we can’t change), why not focus on the remaining 95% which we can do something about?

The researchers have an answer to that question:

Together, these findings highlight the value of ancestrally diverse genetic studies to prioritize the study of pathophysiological processes in MD. The clearer association of genetic variants with altered gene expression and the enrichment of antidepressant targets provide confidence that genetic association findings will be relevant to the development, deployment, or repurposing of pharmacotherapies. Critically, these findings suggest genetic associations will point to new drug targets and more effective therapies that may reduce the considerable disability caused by depression.

No timeline was given as to when we may expect to see these wonderful benefits materialize. Nor did the authors mention that their professional colleagues have been making similar promises for over eighty years, without any of them ever being fulfilled.

A few years ago, an article authored by psychiatrists Calen Gardner and Arthur Kleinman appeared in the New England Journal of Medicine. Subtitled “The consequences of psychiatry’s identity crisis,” the piece recited a familiar litany of complaints—there are no biological tests for any of the so-called “functional disorders” treated by psychiatrists, no coherent theoretical understanding of what “mental illness” is, and an overreliance on overlapping symptom checklists and hurried “medication management” visits.

But psychiatry has been writing in the throes of this identity crisis for more than forty-five years now. Is it time to consider the possibility that the entire field is a failed enterprise, a wrong turn in human history?