Severe psychiatric and neurodevelopmental disorders, such as bipolar disorder, schizophrenia, and autism spectrum disorders, show remarkably high heritability. In the past decade, psychiatric genetics has made substantial progress in identifying the genetic architecture of these polygenic disorders. However, the exact mechanisms that lead from a genetic burden to the actual manifestation of psychiatric disease and how genetic factors influence the clinical outcome remain to be understood. The prevailing hypothesis in the field suggests an interplay between rare and common variants that determines not only whether a patient gets ill, but also the specific disorder, as most variants are associated with multiple disorders. A better understanding of how polygenic effects converge on different – e.g., molecular, cellular and neural – levels and how they influence the clinical phenotype, however, would be key to develop new strategies to treat or even prevent psychiatric disorders.
Our panel will focus on translational approaches that unravel these complex polygenic interactions and relate them to vulnerability, resilience and the course of the disease. A special emphasis will be on a translational perspective and potential clinical applications. Thomas Nickl-Jockschat will present, how transcriptomic analyses can help to delineate polygenic interactions. A special focus will rest upon rare variants, namely copy number variations (CNV), large deletions or duplications that can span over 40 genes, and carry significantly high risk. Schulte/Falkai will focus on translational approaches and potential clinical applications. In a third presentation, Thomas Schulze will focus on how the genetic burden influences the longitudinal phenotypes of psychiatric disorders. Finally, Stephen Glatt will shift the focus from disease to resilience: how the genotype can help to increase resilience against psychiatric disorders.