Re-inventing the DSM as a transdiagnostic model: Psychiatric disorders are extensively interconnected.

I t’s time for a necessary paradigm shift in re-conceptualizing the nosology, epidemiology, etiology, and treatment of major psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder (MDD), autism spectrum disorder, attentiondeficit/hyperactivity disorder (ADHD), anxiety, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and substance use disorders. For a long time, and prior to the neuroscience revolution that enabled probing the human brain and exploring the neurobiology of psychiatric disorders, the field of psychiatry was descriptive and simplistic. It categorized psychiatric disorders essentially as silos, defined by a set of signs and symptoms. If one or more psychiatric conditions co-occurred with a “primary diagnosis,” they were labeled as “comorbidities,” with no implications of a shared etiology or biology. Amazingly, despite the rapid accrual of evidence of shared developmental or genetic etiopathogenesis, shared dysplasia of the same brain regions on neuroimaging, and improvement with the same class of medications, the DSM-5 and its outdated schema remain the diagnostic “bible of psychiatry,” and comorbidities are not being recognized as genetically overlapping disorders. This archaic model is ripe for change and a major update. Highlights of emerging advances that justify the re-conceptualizing of the nosology of major DSM diagnostic entities, and reinterpreting the comorbidities as evidence of the substantial clinical and biological overlap and interconnectivity of psychiatric brain disorders, include: Neurodevelopmental pathology. Disruption of brain development during fetal life has been well-established across the schizophrenia spectrum syndrome and practically all the so-called comorbidities. Genetic pleiotropy. Approximately 50% of the 22,000 proteincoding genes in the human chromosomes are expressed in the brain during development. Schizophrenia and most psychiatric disorders are heavily genetic. Genetic pleiotropy has been identified across several Henry A. Nasrallah, MD University of Cincinnati College of Medicine Cincinnati, Ohio, USA