Overlapping Genetic Expression in Five Psychiatric Disorders

Recently, a study published in the journal Science  (Feb 2018) by a team of U.S. and Danish scientists, plus a plethora of contributing experts, sought to identify genetic overlap between several confounding psychiatric disorders, specifically: autism; schizophrenia; bipolar disease; depression; and alcoholism. This complicated endeavor required researchers to analyze an array of gene expression profiles and patterns from brain tissue samples of 700 deceased individuals with one or more of the aforementioned conditions—plus matched controls. This comprehensive systems-level investigation and analysis has shed new light on the neurobiological architecture among persons with debilitating neuropathologies, revealing multiple pathways of molecular convergence and specificity.

The researchers were then able to narrow the pool of genetic expression that distinguished the conditions from one another, while concurrently identifying overlapping transcriptional dysregulation of single nucleotide polymorphisms (SNPs) across the selected neurobiological disorders.

Psychiatric Disorders and Genetics

The outcome data revealed that shifts in genetic brain expression were most robust in among the autism spectrum disorder cases, while bipolar disorder and schizophrenia samples fell near the middle of the spectrum. And finally, depression showed only modest expression changes, and alcohol abuse disorder did not share clear expression features with any of the other conditions.

These data suggest that shared genetic factors underlie a substantial proportion of cross-disorder expression overlap. The authors conclude…“Most of the genetic effects are likely acting indirectly, through a cascade of developmental and cell to cell signaling events rooted in genetic risk.”

Why Does This Matter?

The concordance rate for substance use disorders and depression and anxiety disorders is estimated between 45-65%, even higher in the treatment population. In addition, recent data has revealed a potentially causal relationship between the use of highly potent marijuana and psychosis or schizophrenia. Clearly, more research is needed, but treatment providers must acknowledge, and more aggressively address, the risk of co-occurring morbidity when treating patients with Substance Use Disorder.

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Gandal MJ, Haney JR, Parikshak NN, Leppa V, Ramaswami G, Hartl C, Schork AJ, Appadurai V, Buil A, Werge TM, Liu C, White KP; CommonMind Consortium; PsychENCODE Consortium; iPSYCH-BROAD Working Group, Horvath S, Geschwind DH. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science. 2018 Feb 9;359(6376):693-697. doi: 10.1126/science.aad6469.