Do Certain Mental Illnesses Have a Common Cause?

Mental illness has long mystified physicians with its convoluted etiology. In a seemingly boundless constellation of likely causal agents behind the maladies of the mind, few have been definitively elucidated, and still fewer have been effectively accounted for. In too many instances, one of the only consoling insights available to those suffering has been a head nod to a vague equation involving nature, nurture, and, of course, a little bit of luck.

Thanks to the rise of genome-wide association studies, however, we are honing in more closely on at least the "nature" component of this unsatisfying trinity.

A new study by the Cross Disorders Group of the Psychiatric Genomics Consortium, which is funded by the National Institute of Mental Health, quantifies overlap in the contributions of various common genetic variations to the risk for five common mental illnesses. Individually, these common genetic variations are estimated to contribute anywhere from 17 to 28 percent of the risk for developing the illnesses in question.

Though previous studies by the PGC have established overlaps between the contributions of certain common genetic variations to illnesses like depression, bipolar disorder, schizophrenia, ADHD, and autism, the new research, published this week in the journal Nature Genetics, is the only to quantify such overlaps.

At 15 percent, overlap between heritability attributable to common genetic variation was highest between schizophrenia and bipolar disorder. Bipolar disorder and depression had the second highest overlap, measuring in at 10 percent. At 9 percent, schizophrenia and depression had a slightly lower overlap. Schizophrenia and autism had the lowest, at 3 percent.

As anybody who has looked at the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders knows, classification of mental illnesses has traditionally been symptom-based. To make treatment more effective, there has been in recent years an effort to rely on more objective biomarkers for classifying and diagnosing these illnesses. By clarifying the existence and import of these common genetic variations, this study is a step in that direction.

As Bruce Cuthbert, director of the NIMH Division of Adult Translational Research and Treatment Development, said of the study, “Such evidence quantifying shared genetic risk factors among traditional psychiatric diagnoses will help us move toward classification that will be more faithful to nature.”

The authors of the study note that by only acknowledging the contribution of common genetic variants they ignore more elusive variations dispersed throughout the genome, as well as other unknown causes. To illustrate the disparity between heritability due to common genetic variations and other causes, including environmental ones, they note that while 23 percent of schizophrenia risk can be thought of as arising from common genetic variations, evidence from past family and twin studies place its overall heritability much higher, at 81 percent. The emergence of schizophrenia is not easily tractable, and neither is that of its cohorts.

“Since our study only looked at common gene variants, the total genetic overlap between the disorders is likely higher,” explained study co-leader Naomi Wray, a researcher at the University of Queensland in Brisbane, Australia.

Future studies are bound to paint an even clearer picture of why some of us are cursed with these unfortunate chronic cognitive states, and how we may eventually right these most distressing inner wrongs. If we come to understand these illnesses, each with their own “personalities,” as having shared causes, and we deal with those causes, mental illness as a whole will be much more manageable.