The Causes of Schizophrenia: It’s Probably Not Genetics
For more than a century, researchers have had a deeply-held belief that schizophrenia is one form of mental illness that has its basis in genetics. In the intervening years, hundreds of millions of person-hours and billions of dollars have been funneled pursuing the genetic theory of schizophrenia.
Despite all of this enormous effort, researchers are starting to understand that perhaps the genetic component of schizophrenia has been overemphasized. And, in fact, the heritability estimates are not the 80-85 percent that some researchers claimed, but instead are far less.
A new review article published in Psychiatry Research (Torrey & Yolken, 2019) reminds us how high initial hopes were for genetics to help explain the cause of schizophrenia:
[…By] the end of the 20th century genetic theories had become predominant. It was said that schizophrenia “is an undoubtedly genetic disorder” with “heritability estimates of approximately 80%–85%” (Pearlson and Folley, 2008, Cardno and Gottesman, 2000).
Some geneticists even suggested “a strong possibility that most or all of the remaining small proportion of variance can be explained by non-transmissible changes in gene structure or expression” (McGuffin et al., 1994). In other words, schizophrenia might be 100% genetic with environmental factors playing little or no role.
Since that time, researchers have found nothing like what they expected:
According to one recent analysis, “the current trend in psychiatric genetics is to use enormous samples to find genes of minuscule effects” (Leo, 2016).
A schizophrenia geneticist, noting the “relatively sparse findings of [genetic]-based associations,” noted that “among scientists in the field, there is a sense of disappointment in the air” (Gershon et al., 2011).
In short, genetics may play a role in the cause of schizophrenia. But it is much, much smaller than anyone had anticipated — with a heritability estimate closer to 30 percent than 80. The data suggest that genetics appear to play approximately the same-sized role as they do in other mental disorders and physical diseases.
Other Possible Causes of Schizophrenia
There are many other promising avenues of research to pursue. However, the National Institute of Mental Health is still so focused on genetics — despite its clear failure to deliver — that it provides limited funding to pursue these other possible causes.
Toxoplasma gondii is one such possible cause discovered by researchers. It is a parasite carried by cats that causes toxoplasmosis when humans become infected by it. As the researchers note, “An association between schizophrenia and Toxoplasma exposure is supported by several meta-analyses indicating odds ratios ranging from 1.8- 2.7 (Sutterland et al., 2015, Torrey et al., 2012), levels which are substantially higher than that of any common variant from [genetic] studies.” The symptoms associated with toxoplasmosis and how it is transmitted could mimic a genetic disease, the researchers suggest.
The microbiome — your gut bacteria — has recently become the focus of many researchers searching for the causes of various mental disorders. “The microbiome is largely inherited from the mother during and after the birth process although fathers and other members of the family also contribute to its overall composition (Korpela et al., 2018) during the first years of life. Diet and other family based environmental exposures also contribute to the composition of the microbiome during childhood and later life.”
Research has demonstrated a connection between our gut bacteria and its impact on human behavior and thinking. “In the case of schizophrenia, studies have found substantial alterations in the composition of the gastrointestinal (Nguyen et al., 2018) and oropharyngeal (Yolken et al., 2015) microbiomes in individuals with schizophrenia as compared to controls.”
Today, just as it was one hundred years ago, we still don’t know what causes schizophrenia. But researchers are still hard at work trying to figure out the cause, with the belief that by doing so, it would be possible to create better, more effective treatments. To that end, it may be ultimately a good thing that schizophrenia is not primarily a genetic disease, because most genetic diseases have turned out to be difficult to treat (e.g., Huntington’s, sickle cell, etc.).
Sutterland, G. Fond, A. Kuin, et al. (2015). Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis Acta Psychiatr. Scand, 132, 161-179.
Torrey, E.F. & Yolken, R.H. (2019). Schizophrenia as a pseudogenetic disease: A call for more gene-environmental studies. Psychiatry Research, 278, 146-150.
Yolken, E.G. Severance, S. Sabunciyan, et al. (2015). Metagenomic sequencing indicates that the oropharyngeal phageome of individuals with schizophrenia differs from that of controls. Schizophr. Bull., 41, 1153-1161
My thanks to Elsevier’s ScienceDirect for access to the primary research that provided invaluable to this article.
Grohol, J. (2019). The Causes of Schizophrenia: It’s Probably Not Genetics. Psych Central. Retrieved on April 5, 2020, from https://psychcentral.com/blog/the-causes-of-schizophrenia-its-probably-not-genetics/