LAUSR

Background Genetic diseases are individually rare but collectively common. Many genetic conditions can mimic mental health disorders, with psychiatric symptoms that are difficult to treat with regular medications. Treatment of the underlying genetic disease can cure the associated psychiatric symptoms or help regular medications work better. Discovery of rare genetic diseases in psychiatric patients would reveal specific treatment options, and give information about the chances of other family members being affected. In this study, we test the hypothesis that psychiatric populations are enriched for pathogenic variants associated with selected treatable genetic disorders. Methods Using targeted exome sequencing, we screened 2,046 schizophrenia, bipolar and major depressive disorder patients for variants in genes associated with Niemann-Pick disease type C (NPC), Wilson Disease (WD), Homocystinuria (HOM), and Acute Intermittent Porphyria (AIP). Results Our study is the first to explore the prevalence of NPC, WD, HOM and AIP gene variants in well-defined psychiatric populations. We found carrier rates of 0.88%, 0.88% and 0.20% for NPC, WD and HOM, respectively. Furthermore, an AIP affected rate of 0.20% was observed across the entire psychiatric cohort, a 200X enrichment in comparison to what is expected in the general population. Discussion Discovering genetic diseases in psychiatric patients will shift how health care is delivered to these vulnerable patients by addressing underlying conditions rather than masking symptoms with medications and will especially help patients who don't respond to regular medications. This will lead to significant cost savings to the health care system.