Reframing Psychiatry for Precision Medicine

The art of observing and describing behaviors has driven diagnosis and informed basic science in psychiatry. In recent times, studies of mental illness are focused on understanding the brain's neurobiology but there is a paucity of information on the potential contributions from peripheral activity to mental health. In precision medicine, this common practice leaves a gap between bodily behaviors and genomics that we here propose to address with a new layer of inquiry that includes gene expression on tissues inclusive of brain, heart, muscle-skeletal and organs for vital bodily functions. We interrogate gene expression on human tissue as a function of disease-associated genes. By removing genes linked to disease from the typical human set, and recomputing gene expression on the tissues, we can compare the outcomes across mental illnesses, well-known neurological conditions, and non-neurological conditions. We find that major neuropsychiatric conditions that are behaviorally defined today (e.g., autism, schizophrenia, and depression) through DSM-observation criteria have strong convergence with well-known neurological conditions (e.g., ataxias and Parkinson's disease), but less overlap with non-neurological conditions. Surprisingly, tissues majorly involved in the central control, coordination, adaptation and learning of movements, emotion and memory are maximally affected in psychiatric diagnoses along with peripheral heart and muscle-skeletal tissues. Our results underscore the importance of considering both the brain-body connection and the contributions of the peripheral nervous systems to mental health.