DFG-Research Group 2107
Affective disorders, i.e. major depressive disorder (MDD) and bipolar disorder (BD), are complex and heterogeneous phenotypes. Genetic and environmental risk factors contribute to and interact with their etiology and the longitudinal course. The neurobiological correlates by which these predispositions exert their influence on brain structure and function are poorly understood. The aims of this Research Unit (FOR; DFG Forschergruppe) are to integrate clinical and neurobiological associations of genetic and environmental risk factors and their interaction involved in the etiology, onset and course of affective disorders.
The ultimate goal is to decipher neurobiological mediators and pathways leading from individual configurations of genetic and (interacting) environmental risk factors to clinical presentations of symptoms and the course of illness. These data will be assessed in a large human cohort (N=2500) of patients, subjects at genetic and/or environmental risk, and control subjects (Marburg-Münster Affective Cohort Study, MACS; WP1). All participants will undergo an extensive state-of-the-art deep-phenotyping including multimodal structural and functional neuroimaging, clinical, neuropsychological, and personality characterization, and thorough assessment of environmental risk (e.g., stressful life-events). Biomaterial such as blood will be stored in a central biobank project (CP1). Subjects will be genotyped for genetic and epigenetic markers (WP5, CP1). The MACS participants will be longitudinally re-assessed after 2 years. The human cluster further includes a methodological work package (WP6) developing statistical methods for phenotypic data reduction, genome-wide association of MRI data, and quality assurance for longitudinal MRI data reliability.
The human part will be mirrored by an animal project cluster, paralleling and experimentally manipulating known risk factors in rodents (WP2). Genetic risks will be introduced by rodent models interacting with environmental risk.
Furthermore, a set of innovative experimental projects connect and integrate data from the human and animal part, investigating the role of microRNA/ neuroplasticity markers (WP3), inflammation markers (CP1 and WP2), and cellular stress (WP4).
This DFG Research Unit will provide novel possibilities to investigate gene x environment interactions on different levels of pathology and brain function over time. It will delineate pathophysiological entities with common neurobiological underpinnings and pave the way for an etiologic understanding of affective disorders, potentially leading to their prevention and novel therapies in the future.