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Review Essay: Robert Plomin, Blueprint: How DNA Makes Us Who We Are. Cambridge: MIT Press, 2018

The primary paradigm for psychiatry at the moment is founded on the premise that mental disorders are largely a result of genetic, biologic causes, and therefore treatment rationales and understanding of mental illness are firmly rooted in this paradigm. Genetic research purports to demonstrate the truth of its premise.

This research however, is beginning to show some serious cracks, with genome wide association studies providing endless correlations for behavioral geneticists to chew on, but little of substance after two decades of time and expense.

If the recent book Blueprint by Robert Plomin is any indication, researchers are desperately trying to repackage genome wide associations studies (GWAS) under the auspices of “polygenic scores,” effectively doubling down on the GWAS failure as Plomin defiantly claims, “DNA is the only thing that makes a substantial systematic difference… related to psychological traits.”  He goes on to make even more dubious assertions in the book, suggesting that, “Genetics offers a causal basis for predicting disorders, rather than waiting for symptoms to appear,” and that elite schools should admit students based on their polygenic score for intelligence. This kind of dystopian science fiction is, thankfully, fiction. Like their GWAS parent, polygenic score hype is already beginning to crumble.

I can only assume that Plomin is part of a collective denial of the fact that the end is nigh. These heavily funded studies have not produced the hoped-for results. The endless rationalizations for that have run their course. They’ve spent two decades trying to spin these failures into seeming successes. It is time to acknowledge that they were barking up the wrong tree. They simply aren’t going to find genetic causes for mental disorders, personality traits or intelligence. Hopefully, this will be a wake-up call to psychiatry. It should be an interesting and awkward time for the field. This might seem upsetting to some, but it is, in my view, the basis for optimism and a chance to get back to our roots. The prospect is, frankly, exciting to me. As a recently retired psychiatrist, it might seem like I’m jumping on the last life boat on the Titanic with a smiling wave to those still on the ship, but here I am, hoping to witness exactly this collapse. Let me explain.

I started Psychiatry Residency training in the mid-1990s. While I found much of medical school disappointing, I was drawn to the field of psychiatry, which was the one specialty that inspired me to read books for my own interest, rather than clinical requirements. It seemed far more intellectually stimulating and thought-provoking than the algorithmic nature of most of the traditional medical specialties. I imagined that any professional psychiatric setting would include philosophical discussion and debate about the nature of mental illnesses, with attention paid to the unconscious and essential aspects of our human experiences, “Jungians” arguing with “Freudians,” etc. There was some of that but, for the most part, the field was on the verge of ideological and economic overhaul led by the pharmaceutical industry and “managed care” insurance companies. As the bank robber Willie Sutton said when asked why he robbed banks, “That’s where the money is.”

This ushered in a draconian, mental health-for-profit system, where psychiatrists earned revenue for the health care entity and salary for themselves, by juggling as many patient/customers as possible and cranking out drug prescriptions. The idea of working within a psychoanalytic model, that is, perceiving a human being as a complex, interdependent person and attempting to get to the root of a predicament or malady, was effectively abandoned by the profession. By the time I completed my psychiatric residency, I was left with unsatisfying, albeit well paying, job options.

Of course, such a consequential shift in the field needs some additional scientific justification beyond just a better financial model. A large part of that justification comes from genetic research related to mental disorders, which is why the field of genetics dominates psychiatric/psychological research and continues to do so. If we view mental illness as a genetic disorder, or at least significantly influenced by genetics, then it is not much of a leap to say that these are effectively physical disorders that should be treated in much the same way as, say, diabetes or coronary artery disease. This provides a useful justification for the medicalization of psychiatry. It is a reductive and simplistic understanding of the mind, in my view, while harkening back to eugenic ideas that I had assumed were a dark point in our history, never to return.

Psychiatrists do not spend a lot of time discussing this kind of research, so it might not be obvious on the surface what a far-reaching effect it has had on our practice. If you are comfortably operating under the assumption that you are treating genetically based disorders, there is little you need to do other than prescribe the “right” medication. If the research purports to show that mental disorders, personality traits and intelligence are genetically based, then the paradigm will go unquestioned. As I progressed in my residency and the early years of my career as a psychiatrist, it was clear that this view was held by most of my colleagues, leaving me to cringe when I heard fellow psychiatrists say, both amongst themselves and to patients, things like, “Depression is from a lack of serotonin in the brain and Prozac makes up the deficit,” or, “Mental illnesses are biological disorders rooted in genetics.”

My arguments against these claims, and in support of a more dynamic view of the human mind, generally fell on deaf ears. “The studies are proving this,” they would say. Even when the studies didn’t make such bold claims, by the time they were picked up by mainstream media sources, one would see headlines like, “Genes for Schizophrenia Discovered,” and, “Depression: It’s in Your Genes.” Few people actually read the studies, so whatever the abstract and news stories claimed was accepted as the truth. For that reason, I decided to read these dry studies to see just how definitive these findings were.

For those unfamiliar with these studies, they generally involve a “scan” of thousands of human genes (these studies are now called “genome-wide association studies” [GWAS]), looking for slight variations of genes that are found to be more common for people possessing whatever trait you are looking at (schizophrenia, depression, IQ, ADHD, etc.). If these variations (single nucleotide polymorphisms [SNP]) are found significantly more frequently in the group with the trait, then it is presumed to be related to the trait, somehow. Generally, in the early days, they would find a few genetic variants that were more common for a particular trait. However, when I looked through the literature to review these results, I noticed something peculiar. One study would find a few genes related to a trait, but the follow-up study would find entirely different genes, with the genes from the previous study not reproduced. This is a problem, since you want your findings to be “replicated” in follow-up studies.

So, for example, you might have a GWAS that purported to find SNPs that were more common in people with depression, maybe even making the front page of major newspapers, then the next study would find entirely different genes associated with depression, yet none of the previous genes were found to be associated with depression in this new study. Rather than retract the previous findings, the new findings would also make a splash, creating the perpetual impression that genes for these disorders were being discovered left and right. This seemed like a shell game of sorts, so I set out to challenge the studies by writing letters to the various psychiatric journals, challenging the results and suggesting they wouldn’t replicate. The journals initially were reasonably abiding, probably because I seemed to be the only one taking on the science of these studies directly, and the only other dissent was the occasional letter from a psychoanalyst, who they would humor like some old haberdasher complaining about the declining quality of men’s clothing.

The letters were not well received in a research community that believed they were on the verge of unmasking the secrets to mental illness, intelligence, criminality, personality traits, etc. Generally, my letters were dismissed without addressing their merit and my points were not taken seriously. My supervisors even hinted that perhaps these letters were not so good for my career, a point underscored by the Journal of Clinical Psychiatry, when they declined to publish one of my letters unless I could get two other psychiatrists to vouch for my character in writing. The practicalities of life left me with little choice but to abandon my quixotic opposition to something that was, in my view, impeding and destroying the potential worth and evolution of psychiatry.

Fortunately, during my hiatus, there was a burgeoning backlash towards these genetic studies due to a “replication crisis”, and they were brought into question by some leaders in the field, even fading somewhat from the literature. My hope was that this trend would continue and that we could move on to a more dynamic view of the human mind, which turned out to be naïve. I underestimated the driving force of this materialistic view, especially when coupled with the massively expanded genetic databases available to researchers through commercial enterprises like Ancestry.com and 23andMe, as well as other genetic database programs like the UK Biobank. The rationale was that the original studies did not have enough people in them and these bigger databases would make it possible to elucidate the “right” genes. Thus, the studies caught a second wind.

Some of the current researchers are holdouts from the early 2000s, like Robert Plomin noted above, and Stephen Faraone, clinging to what one might assume are entrenched views of the human mind as genetic arbiter, despite the failure of evidence to back it up. There is always the light at the end of the tunnel and the assumption that the current research is vindicating their unbridled enthusiasm. While I might criticize the validity of these claims, their persistence in making the claim and indefatigable ability to ward off failures has admittedly paid off in allowing them to win the turf war for psychiatric/psychological research. In reality, psychological research is arduous and often ambiguous, thus in addition to the financial incentive to generate research viewing mental health as physical phenomena, genetic studies have the benefit of providing a lot of hard, numerical data, which gives it an air of authenticity, regardless of the qualitative value of the data.

In addition to the old-timers, though, there is a whole new crop of young researchers with backgrounds in economics, statistics, and genetic subspecialties, who have little patience or interest in delving into the human mind beyond which gene they might correlate for which trait. The idea of exploring any deeper psychological principles, much less philosophy or metaphysics, probably seems quaint and even absurd to many of them. There is only interest in finding statistical correlations between a genetic variant and whatever trait they are searching for, whether it’s depression, schizophrenia, IQ, church attendance, risk-taking behavior, loneliness, your preferred flavor of ice cream, or just about anything you can quantify in a brief questionnaire. They have unwavering faith in their cause and no doubt the positive feedback received from published studies only enhances their zeal.

At first, these newer, larger studies seemed to be meeting with some success. With massive amounts of data at one’s fingertips, a strong belief in one’s cause and the ability to analyze data in any number of ways, one is able to make some statistical correlations for anything you wish. Instead of just a few genes for a trait, now they were “discovering” hundreds. This has given us a boundless supply of studies claiming genetic correlations and fanciful claims of trait predictions based on the number of particular genetic variants one has (polygenic scores). However, despite the larger database sizes with which these researchers have to work, and the multitude of alleged correlations, they have had little more success than their predecessors in finding an actual cause or mechanism for much of anything. Just like in the past, the studies open with a lot of fanfare (now bolstered even more by social media), then seem to fade before anything of utility can be garnered from them, leaving the impression that something “important” was discovered, but with little meat to it.

Much as has happened in the physical sciences, there has been an abandonment of the philosophical roots of the field, as if everyone from Plato to Freud, to Jung, to Adler to Kubler Ross, had little to offer and, arrogantly, we could start with a clean slate. Thus, there is little room for philosophy, the unconscious, dreams, and certainly no room for metaphysics. We have, instead, a bizarre reductionism in which the human mind is now entirely conflated with the human brain, with researchers trying to elucidate through genetic studies, MRI’s, EEG’s, etc., what makes humans human. This is likely to be as successful as someone trying to understand the functioning of a car by looking only at the electrical wiring.

Thus, mental illness is viewed as some sort of miswiring of the brain, or a bad combination of genetic variants that in some unknown way cause the mind to work “abnormally.” Although there is little concrete evidence to back up this medical model of psychiatry, it holds the field hostage to a kind of regressive formalism. Under its [smug] aegis, psychiatry has atrophied, replaced with a facile form of psycho-pharmacology. The inherent fatalism of this view not only effects psychiatry, but has seeped both consciously and unconsciously into the public domain and these views pervade many aspects of lives, such as our educational system, our understanding of criminality and punishment, and even our understanding of life’s meaning. What we have been given is an overly individualistic view of society, where our failures are viewed in terms of genetic, biologic deficiencies, rather than turning the microscope back onto the world we have created. When we start talking about genes for ADHD, or PTSD, or anorexia nervosa, I think we are running away from a reality of our own creation.

Unfortunately, that is the direction that we continue to follow. The promise is always that we are on the verge of some big discoveries and that this paradigm will be verified and elucidated. Yet, what I’m seeing is that this whole façade appears to be crumbling.   These genome-wide associations studies or their stepchild, “polygenic scores,” are again being called into question, with the suggestion that much of it is overreach and possibly just false positive results infusing some noise into otherwise useless studies. As neuroscientist and author, Kevin Mitchell, summed it up recently:

Simply put, nothing really definitive comes out. In fact, the strongest result from these studies is a general one, and it is “negative”: there are no convergent patterns of gene expression in adult brain that characterise these various psychiatric conditions…we can now say it has strong empirical support.”

In other words, “back to the drawing board.” And while this won’t dissuade scientists from abandoning a reductionist model of the human mind, they might have to finally abandon this one. It was and is a fairly far-fetched notion if one really examines it without the cloak of scientific arrogance. The idea that some combination of hundreds or thousands of genetic variants somehow “tickle” the brain in some slightly different way, causing a person to be depressed, or schizophrenic or risk-taking or more intelligent, has always seemed, to me, a ludicrous proposition. No one can explain the mechanics of it, even hypothetically. The premise has deteriorated from one gene to a few genes to hundreds, or even thousands of genes (polygenic) causing a trait, not because of discoveries made, but because they have simply failed to find anything with teeth, so they assume that there must be more and more genes involved with each failure to pin down anything specific. Currently, they are even suggesting an “omnigenic” model in which all genes have some effect on all traits. Leaving aside the question of its merits, this is a nebulous idea that probably can’t be proven or disproven, and appears to be the last stand on this subject. So, again, what happens if and when this genetic sideshow collapses?   What are we left with as a field, and who will lead us out of the woods we have wandered into?

I doubt there will be much on offer from the current “experts” in the field, who are largely psychopharmacologists, who speak about metabolic pathways and neuroreceptors like pilots in white gloves, and took their cues from this genetic research, generally viewing any mental aberration as a brain dysfunction that must be fought off with the proper medication. From such individuals, we should expect very little once the Sword of Damocles falls. Perhaps they will find another way to reboot this tired paradigm, with some new speculative science to continue to justify this obsession with a physical/genetic view of the mind and brain. That is certainly possible, but I think it is also plausible that we might have at least a brief vacuum in which new theories and ideas could spring up outside of the medical model.

I consider this an exciting prospect, and one that could reinvigorate the field with real thought and meaningful debate extending all the way to the meaning of life. If we are going to survive as a species, we will need a holistic view of humanity, or at least a broader vision of the human mind and maybe this vacuum will lead us to a new paradigm that accomplishes that. That is, perhaps, optimistic, and what matters in the end is a view that rings true, but it’s hard to imagine anything more stifling and limiting than the paradigm with which we are saddled now. I hope I can one day dance on its grave. Perhaps I’ll even come out of retirement.