Reports on Genetics in Psychiatry

Nothing new.

These posts examine modern psychiatry from a critical point of view. Unfortunately, mainstream psychiatrists usually react badly to any sort of critical analysis of their activities, labelling critics as “anti-psychiatry,” whatever that is. Regardless, criticism is an integral part of any scientific field and psychiatry is no different. As it emerges, there is a lot to be critical about.

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A couple of articles in this week’s Psychiatric Times emphasise the deep-seated contradictions at the heart of modern psychiatry. The first one talks about how drug development in psychiatry has gone through three phases. The first, starting 75 years ago, was when psychoactive drugs were discovered by chance. The original drugs called antidepressants and antipsychotics were found during research on antihistamines. It was known that antihistamines were sedating, so as a screening test, they were fed to rats, then the rats were given an electric shock through their feet. Rats have very sensitive feet so after the shock, they would turn and attack the nearest rat. The drugs dampened this aggressive response so it didn’t take long for psychiatrists to start giving them to patients. They found that the patients became passive and largely unreactive to the world around them, similar to the effects of leucotomy (lobotomy). One of the first, chlorpromazine was named Largactil because of its large list of effects, mostly unpleasant.

The second phase, starting in the 1980s, was to find out which part of a drug was causing side effects and modify the chemical by removing that bit. That still involved a great deal of blind poking and doing ugly things to rats but it led to one of the great explosions in human drug intake, the SSRIs. Drug companies have been laughing ever since but that phase has run out of steam, all that group are now off patent and there’s nothing new coming through the system. That leads to what is called phase three of psychiatric drug research, trying to find unique chemicals that will selectively block or stimulate specific bits of the brain (they call them circuits but they actually mean bits). So far, the results have been underwhelming but the money involved says it will keep going. Somewhat surprisingly, the article didn’t mention AI because one thing it’s good at is taking the sorts of vast databases drug companies have built up over decades and analysing them for linkages. The biggest handicap is that, for all their excited chatter about new drugs, psychiatrists don’t know what all the so-called brain circuits do or how they interact with each other. That doesn’t bother them because they’re all totally convinced that studying the brain will tell us all we need to know about humans.

This “brave new world” approach is seen in the second article, on drugs in schizophrenia, but it gives a handy little summary of half a dozen research lines that have been tried over the years, all to no avail. What they don’t reveal is that in each case the research is not theory-driven, as it should be, it just follows each new technology. Drug research is opportunistic and technology-driven. Years ago, they studied blood and urine, because that’s all they could do, then cerebrospinal fluid (CSF), then cerebral angiography and pneumoencephalography (replacing most of the CSF with air, which left patients with a fiendish headache for several days); then CTs arrived and oh boy, the excitement! As scans improved, so researchers found more subtle and diverse changes in the brain but that went nowhere. PET scans arrived, functional MRI, and now it’s all genes.

When the human genome was published nearly 25yrs ago, biological psychiatrists were beside themselves. At last they would find the key to mental disorder, especially schizophrenia ... correct that, bigger studies are needed, then bigger and bigger. The search for a genetic basis for mental disorder is pushed by an organisation called the Psychiatric Genomic Consortium, (PGC). It has about 1,800 members around the world, everybody who is anybody in the world of genes and psychiatry. They publish massive combined studies on different mental disorders (check this one for its astounding list of authors).

The amount of money being spent on this type of research is unbelievable; the results are very believable because there aren’t any. A major review published in Nature two years ago [1] leaves no doubt about that but, of course, the failure is dressed up in clever jargon designed to mislead. For example, the Psych Times article says: “Schizophrenia is simultaneously a neurodevelopmental and neurodegenerative disorder ...” What does that mean? What does ‘neurodevelopmental’ actually mean? A major report on ADHD, published recently in the UK, says it means:

... strongly genetically influenced and present from early life (exec. Summary) ... differences in how the brain and nervous system develop that are present from early life, although not always apparent immediately and shape enduring patterns of cognition, attention, communication, behaviour and learning.

OK, let’s assume schizophrenia is “strongly genetically influenced,” what has the PGC come up with? According to the Nature review, nothing remotely convincing. They’ve found over 300 genetic variants associated with the diagnosis, but (a) no person with the diagnosis has all of them or even more than a couple, (b) lots of people with the diagnosis don’t have any, and (c) lots of “neurotypicals” also have them but show no symptoms. The only definitive statement they made was this:

Taken together, these results suggest unexpected complexity in the mechanisms that drive schizophrenia, pointing to the involvement of ensembles of genes (polygenicity) rather than single-gene causation.

So it’s “strongly genetically influenced,” except nobody has found a genetic influence: billions of dollars to tell us what we’ve known for a hundred years. “Present from early life”: what does that mean? One thing is clear: symptoms of psychosis are not present from early life, that’s what the old term dementia praecox means, the dementia (mental disorder) starting in adolescence. The rest of that definition from the UK is just pseudoscience, they would be far better off to say: “We really don’t know the cause of this dire condition.” But they can’t say that because they believe fervently that it’s all biological.

The Psych Times article concludes by mentioning some of the other factors “associated” with schizophrenia: male sex (we can’t do much about that one); immigrant or refugee status; a history of head injury or cerebral affliction of some kind such as infections, epilepsy etc; drugs and alcohol of course; a history of educational difficulties and/or failure; conflict with law; a history of childhood abuse and neglect, esp. sexual abuse [2]. Each of these amounts to a weak contribution because they’re all very common in the community but the more you have, the more likely you are to break down. How should they be treated? An integrative model of mind and body would be a good start but the article concludes:

We have much to learn about the pathophysiology and novel treatments for the brain disorder that we call schizophrenia. Its current complex biography is a small telltale of the larger story of the remaining mysteries awaiting to be discovered about the structure and function of the healthy human brain.

Problem is, they’re all convinced they can unravel those “mysteries” by peering at scanners and gene studies. If you try and tell any of these people it won’t work, that their lack of results is not due to lack of technology but to lack of insight, they become incensed and walk away. The idea of a self-critical attitude is alien to them. Years ago, I suggested to the organiser of a psychiatric conference that they should devote a session to criticism but he snorted that it wasn’t necessary and stamped off.

The whole point of the discipline of philosophy of science is to make sure this sort of echo chamber doesn’t happen. It was developed to make sure that people understood that good intentions aren’t enough, that all researchers understand their duty to push ahead on the one hand, and to maintain a self-critical attitude on the other. Only psychiatrists locked in their groupthink believe they’re immune to critical analysis, which is why they spend huge sums of money rediscovering what Emil Kraepelin (1856-1926) described in his textbook about 140 years ago. Plus ça change, plus c’est la même chose.

PS In this week’s Mad in America, psychologist Richard Sears does the heavy work in looking at how the drug industry exerts a malign influence over psychiatric practice. Definitely worth reading.

References:

1. Sullivan PF, Yao S, Hjerling-Leffler J (2024) Schizophrenia genomics: genetic complexity and functional insights. nature reviews neuroscience 25(9):611-624. https://doi.org/10.1038/s41583-024-00837-7

2. Kisely S et al (2024). Admissions for psychosis following agency-notified child maltreatment at 40-year-follow-up: Results from the Childhood Adversity and Lifetime Morbidity (CALM) cohort. Schizophrenia Research 267 (2024) 247–253. https://doi.org/10.1016/j.schres.2024.03.040

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My critical works are best approached in this order:

The case against mainstream psychiatry:

McLaren N (2024). Theories in Psychiatry: building a post-positivist psychiatry. Ann Arbor, MI: Future Psychiatry Press. (this also covers a range of modern philosophers, showing that their work cannot be extended to account for mental disorder).

Development and justification of the biocognitive model:

McLaren N (2021): Natural Dualism and Mental Disorder: The biocognitive model for psychiatry. London, Routledge

Clinical application of the biocognitive model:

McLaren N (2018). Anxiety: The Inside Story. Ann Arbor, MI: Future Psychiatry Press.

Testing the biocognitive model in an unrelated field:

McLaren N (2023): Narcisso-Fascism: The psychopathology of right wing extremism. Ann Arbor, MI: Future Psychiatry Press.

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