Do Genes Cause Mental Illness?



By Eric M. Plakun, M.D., DLFAPA, FACPsych

Dr. Eric Plakun M.D., DLFAPA, FACPsychAs I noted in my last entry, although I am a member of the APA Assembly and have dedicated my career to the practice of psychiatry, I fear that contemporary psychiatry is blindly missing some of the messages emerging from research. In its biological reductionism, contemporary psychiatry appears to be comfortably accepting 4 false assumptions. Here they are:


  1. Genes are the source of vulnerability to mental illness
  2. Patients usually present with single disorders
  3. That single disorder is well treated with a single evidence based treatment
  4. The best treatments come in the form of pills

When the field corrects these 4 false assumptions, I suspect we will see a dramatic shift in how mental disorders are understood and treated, I suspect psychodynamic psychiatry will be in ascendancy, and I suspect patients will receive better care. Let’s look at the first false assumption here.

False assumption 1: Genes are the source of vulnerability to mental illness

About fifteen years ago the human genome was decoded and the search for genetic causes of all kinds of diseases followed—with considerable success. Using an approach known as the Genome Wide Association Study [GWAS], molecular geneticists began to look for bits of DNA [single nucleotide polymorphisms or SNPs (pronounced “snips”)] across tens of thousands of people that seemed to account for vulnerability to a particular disease state. SNPs that conferred a risk of type 2 diabetes, Crohn’s disease and some cancers were found, demonstrating that a significant part of the risk of developing these disorders was heritable. What happened when GWAS was used to search for SNPs associated with a common mental disorder like major depressive disorder? Looking at the DNA of 16,000 patients with major depressive disorder and 60,000 controls without depression, no SNPs associated with depression were found (1). Nada. None at all. This is as large a GWAS as was needed to find SNPs for the above medical disorders, but no SNPs were associated with depression. The authors conclude there are 2 possibilities. Either we need a still bigger study to find SNPs associated with depression, bigger than for medical disorders because the inherited vulnerability is that slight, or the answer to understanding depression is not so much in the genes as in the impact of environmental factors on the genes—the area known as epigenetics. Over recent decades psychiatry has tended to ignore environmental factors [“nurture”], while favoring the importance of genetic factors [“nature”]. The GWAS depression data means psychiatry has to consider the power and importance of environmental factors again. 

Another study published in The Lancet, a British journal, looked at the genomes of tens of thousands of people. Some SNPs were found that were associated with 5 separate and distinct psychiatric disorders: depression, ADD, autism, schizophrenia and bipolar disorder (2). This association suggests some heritability of these disorders, but something else beyond simply genes may well account for why one person develops ADD and another depression and a third schizophrenia, and a fourth several of these together. Again, a reasonable clinician would want to consider the impact of environmental factors on genes to understand how disorders unfold in individuals.

There is still more emerging genetic evidence suggesting the importance of environment factors. In the next posting I’ll take a look at research into the serotonin transporter pump—the one SSRI drugs like Prozac purportedly affect--and how its genetics suggest a model for how genes and the environment work together. 


Poet Robert Browning and the DSM-5 Controversy

Genes and Mental Illness - Four False Assumptions of Contemporary Psychiatry Part Three

1.  MDD Work Group of Psychiatric GWAS Consortium, Sullivan, 2012

2. Cross-Disorder Group of the Psychiatric Genomics Consortium, Smoller, JW et al., 2013


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