7 February 2018: From molecules to madness: identifying network-level signatures of psychiatric illness risk

Avram Holmes
Department of Psychology
Yale University

Research in my laboratory seeks to establish reliable links between genetic variation, system-level brain function, and behavior in the general population. A core motivation that drives this work is the search for specific network-level signatures or “fingerprints” that co-vary with heritable behavioral variation in the general population and mark vulnerability for psychiatric illness onset. To date, research on the biological origins of psychopathology has largely focused on discrete illness categories. Although patient groups within this diagnostic system are treated as distinct entities, there are often murky boundaries between health and disease and across the disorders themselves. To establish the etiology of these complex syndromes, we must account for diagnostic heterogeneity, both relatively selective and disorder-spanning symptoms, and the dimensional nature of genetic risk. In this talk, I will present two converging lines of research from my laboratory that aim to identify neurobiological markers of psychiatric illness. First, I will discuss a recent effort to link individual variation in the collective set of functional brain connections with the nature and severity of symptom profiles across unipolar depression, bipolar depression, and schizophrenia. Second, I will discuss an ongoing line of research that examines the molecular mechanisms that support the formation and maintenance of functional networks. The results of these analyses suggest that gene expression patterns recapitulate the topography of distributed brain networks and provide novel insights into potential molecular mechanisms contributing to psychiatric illnesses marked by abnormal cortico-striatal function.