In recent months, two teams of researchers in the U.K and the U.S. published complementary findings about the epigenetic origins of schizophrenia that have scientific communities who indulge in ‘genetic conspiracy theories’ abuzz. Both groups claim to have garnered evidence that epigenetic alterations during fetal development are more likely to occur in regions of the genome with sequence variations that have been loosely associated with the probability of being diagnosed with schizophrenia. In the words of Hannon and Spiers, the lead researchers in the UK group:
“[G]enetic variants exhibiting genome-wide significant association with schizophrenia showed a fourfold enrichment amongst fetal brain mQTLs, directly implicating altered gene regulation during fetal brain development in the etiology of the disorder. … [W]e report, to the best of our knowledge, the first systematic analysis of genetically mediated DNA methylation in the developing human brain.” (Italics added).
While these results are intriguing, and no doubt involve pathbreaking research methodologies, this line of thought represents a decontextualized understanding both of the symptoms that are typically associated with schizophrenia, and their cause. I’ll begin with some well-rehearsed issues: 1) the implausibility that schizophrenia, as it is currently diagnosed, is a unitary condition, 2) the lengthy, failed search for the ‘candidate’ gene for schizophrenia, and 3) the vagaries of the Genome Wide Association (GWA) research on which their findings are premised. Genetic theories of schizophrenia disregard large bodies of data from other disciplines such as the impact of prenatal exposures to neurotoxins and stress hormones. As a result, they fail to train a wide angle, multidisciplinary lens on psychological disturbance.
Schizophrenia Is Not a Unitary Condition
The construct of schizophrenia as a discrete illness originated with Kraeplin’s 1899 Classification of Mental Disorders, the conceptual precursor to the DSM, in which he differentiated schizophrenia (then called dementia praecox) from other mental illnesses such as manic depressive insanity (now termed bipolar disorder). The relatively lengthy history of schizophrenia, harkening back to Kraeplin’s nosology, is often cited as evidence that it is, in fact, a bonafide disease. It is ironic that by 1920 Kraepelin himself expressed serious reservations about whether schizophrenia and bipolar disorder were separate entities. In his own words; “It is becoming increasingly clear that we cannot distinguish satisfactorily between these two illnesses, and this brings home the suspicion that our formulation of the problem may be incorrect.” But Kraeplin’s reservations are all but forgotten.
With its broad symptom picture which can range from vivid hallucinations, to paranoia, or social withdrawal, and in light of the repeated failure of scores of researchers to find a cohesive cause, it is long past time to suggest, as Kraepelin himself did a century ago, that we may need to abandon the idea that schizophrenia is a discreet illness. This does not negate the fact that most people who are diagnosed with schizophrenia are experiencing considerable psychic distress, and that in some cases, there is a biological dimension to their suffering. But grouping these varied, multi-determined symptoms together and labeling them as an illness with a shared etiology, obstructs our ability to understand and alleviate their suffering.
Thomas Insel, former director of the NIMH, arrived at a similar conclusion in his now infamous ‘director’s blog’ posted on the NIMH website on April 29, 2013. In it, he questioned the validity of DSM diagnoses:
“… Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.”
The Relentless Search For the Genetic Origins of Schizophrenia
In his February 15, 2013 Mad In America blog post, psychologist Jay Joseph persuasively summed up the misbegotten search for the genetic origins of schizophrenia: “Despite the sequencing of the human genome and the publication of more than 1,700 schizophrenia molecular genetic studies, we have witnessed over 40 years of gene finding claims, and over 40 years of subsequently non-replicated findings.” Insel fanned the dying embers of this misbegotten theory in his July 22, 2014, NIMH ‘director’s blog’ in which he waxed enthusiastic about “[a] report in Nature this week from the Psychiatric Genomics Consortium, a team of investigators in more than 80 institutions across 25 countries … [whose] genome-wide association study revealed 108 different loci where variations were associated with schizophrenia[.]” Insel goes on to explain that “these are not 108 genes for schizophrenia. These are areas of the genome where variations in sequence are associated with schizophrenia. Most of these are not in or even near genes. And any one of these 108 regions contributes only a tiny fraction of risk in the population.” And yet, he does not allow the poor predictive value of these findings about an ill-defined condition to curb his enthusiasm. He concludes that “Nevertheless, this is a major step forward in describing the genetic risk for schizophrenia.” (Italics added) It is on the shoulders of these tepid findings that the latest epigenetic research was built.
How do we make sense of the relentless search for the genetic origins of schizophrenia? Neuropsychologist Richard Francis offers a valuable insight in his 2012 book Epigenetics, How Environment Shapes Our Genes. He traces the history of ‘preformationism’ – an enduring line of thought, spanning millennia, in which our future self already exists in its entirety at conception. As Francis points out, in its latest incarnation “[g]enetic preformationism was successfully packaged through a series of intuitively appealing metaphors[.]” The ‘genetic blueprint’ became the ‘genetic recipe’ which begat the ‘genetic program’, and the ‘executive gene’ became the ‘executive genome’. Francis contrasts this belief system with the ‘epigenetics perspective’ in which:
“… [Y]ou do not exist prior to development, either manifestly or latently. Rather, development is the process whereby you come to exist. Development is not just a matter of unfolding; it is a creative process. This is not to deny that the genes and other biochemicals in the zygote are essential for your development – they most certainly are. But they don’t contribute to your development by being a preformed you. … You couldn’t cook up a single cell, much less a human being, given the instructions in the genetic recipe. Much of what you need to know lies elsewhere.”
And yet, as Francis observes;
“[T]he intuitive appeal of preformationism gives it a whack-a-mole capacity for resurrection. Every time the latest version gets crushed, a new version pops up to replace it. I will call the latest version of preformationism the ‘genetic-epigenetic program.’ The genetic-epigenetic program metaphor acknowledges the central role of epigenetic events in development but views them through a preformationist lens. In essence, the idea is that the epigenetic events described earlier are programmed by the executive genome.” (Italics added)
And this, of course, is precisely what this recent spate of research is claiming: that particular variants in the genome are predisposed to epigenetic alterations which in turn increase the risk for schizophrenia. This perspective once again puts the cart (gene) before the horse (environment). It blatantly ignores existing research on environmental toxins that cause epigenetic changes during fetal and infant brain development. (After all, why hold corporations accountable for getting their poisons out of our biosphere, when they can earn additional billions pursuing high-tech genetic interventions of dubious worth, while polishing their credentials as good corporate citizens?) I will return to this later.
Left Versus Right Brain Models of Mental Health and Illness
It seems so often that we are preaching to the choir. Those of us who read/contribute to Mad In America share a worldview that focuses on the person rather than the disease, that privileges human connection in relieving human suffering, that considers the complexities and vagaries of the human condition. This perspective stands in stark contrast to the language that describes the ‘science of mental illness’ with its narrow focus on disease processes, and its mechanistic computer metaphors with which to describe the workings of the genome, brain and body. In The Master and His Emissary: The Divided Brain and the Making of the Western World, Iian McGilchrist offers an insight into this language barrier. The left and right hemispheres of the brain are connected by a band of nerve fibers called the corpus callosum. Recent research has revealed that many of these nerve fibers are inhibitory, serving to separate further rather than connect the two hemispheres, and the more we move up the evolutionary ladder, the more they are divided. And so it appears that having two distinct modes of being, carries an evolutionary advantage. Also, both anatomically and functionally, it is the right hemisphere that is designed to play a leading role, as opposed to the more talkative left hemisphere (which houses two language centers).
McGilchrist’s thesis is that the left hemisphere is designed to help us with basic tasks of survival, and as such it focuses narrowly on detail, breaking the world down into component parts and abstracting a mechanistic, disembodied understanding of the world. It offers great clarity and power to manipulate that which is already known, decontextualized, explicit, disembodied, but ultimately lifeless. The left brain is relentlessly optimistic because it refuses to consider that which does not fit with its pre-existing models. It is easy to see the compatibility of left brain modes of thinking with the genetic model of schizophrenia, research be damned. In contrast, the right brain attends to the sweeping panorama of sensory experience, attunes us empathically to others, and is comfortable with novelty, and uncertainty. This describes the mode of attention utilized by therapists who are deeply attuned to their clients, in all of their complexity and uniqueness.
McGilchrist is fond of saying that while ‘the right brain knows that it needs the left brain, the left brain doesn’t know what it doesn’t know.’ By the same token, those of us who practice humanistically oriented ‘right brain’ modes of healing, mustn’t be dismissive of ‘left brain’ science. The brain is an unfathomably complex and delicate, piece of living tissue that can come to harm. Biological understandings of the brain and body are not the enemy of compassion and healing.
While the right hemisphere enables us to love and to experience awe and wonder, it also attunes us to anguish, mourning, and suffering. It is much easier, for example, to be a climate change denier if you choose to ignore right brain consciousness. It can be tempting to forgo joy in order to escape anguish, by escaping into the left brain, with its highly effective defense mechanisms, and our postmodern society makes it increasingly easier to do so. Beginning in infancy, millions of children are already immersed in screen technologies, circumventing the messiness and unpredictability of the living world. There was a time when there were natural brakes on our capacity to escape from living in the moment, but technologies increasingly make it feasible to dwell in virtual worlds that place no limits on our flight from reality.
Right Brain Deficiencies, Epigenetics, and Human Suffering
While DSM driven diagnostic categories are reductionistic and mechanistic, we cannot deny the explosion in the number of children and adults suffering from symptoms associated with schizophrenia, as well as autism, learning disorders, bipolar disorder, depression, anxiety, etc. And just as it is simplistic and dangerous to dwell exclusively in left hemisphere models of mental illness, it is also misguided to deny research that treats the brain as a living organ that can come to physical harm, and that demonstrates that the genome, the microbiome, and the brain, are vulnerable to environmental influence.
McGilchrist believes that the growing epidemic of psychiatric conditions can be tied to right brain deficiencies. For example, symptoms of depersonalization and derealization that lead to a diagnosis of schizophrenia, are also typical of people who have suffered massive strokes or damage to the right hemisphere. Decades ago, Erich Fromm coined the phrase ‘escape from freedom’; the idea that the freedom that human consciousness confers can at times be terrifying. McGilchrist suggests that we are now fleeing from right hemisphere consciousness, into the soothing straightjacket of left hemisphere certainty. Additionally, the right hemisphere ‘comes online’ well before the left hemisphere, during prenatal and infant development, when brain development is at its most rapid and vulnerable to injury. And right hemisphere development has been rendered all the more precarious because of the tens of thousands of industrial toxins we have introduced into the biosphere, 1,000 of which have been identified as neurotoxins by leading environmental health researchers Philip Landrigan and Phillipe Grandjean. Several of these neurotoxins impact prenatal brain development epigenetically.
And so this takes us full circle to the latest epigenetic research on schizophrenia, but with emphasis on environmental causes that are well understood, and for which we have the means (but apparently not the will) to address, as opposed to genomic variants that have little if any specificity to symptoms somewhat arbitrarily bundled into the label of schizophrenia.
 Hannon, E., Spiers, H., Viana, J., Pidsley, R., Burrage, J., Murphy, T. M., … & Bray, N. J. (2016). Methylation QTLs in the developing brain and their enrichment in schizophrenia risk loci. Nature neuroscience, 19(1), 48-54.
 Jaffe, A. E., Gao, Y., Deep-Soboslay, A., Tao, R., Hyde, T. M., Weinberger, D. R., & Kleinman, J. E. (2015). Mapping DNA methylation across development, genotype and schizophrenia in the human frontal cortex. Nature neuroscience. (Full text online)
 After some resistance, even the most conservative of thinkers have adopted an epigenetic as opposed to a genetic lens through which to understand genetic influence. Epigenetics refers to alterations in regions of the genome – often through methylation – which upregulate or downregulate genetic activity.
mQTLs or methylation quantitative trait loci – refer to epigenetic alterations of a specific region of the genome.