"Mental disorders put a great burden on society and their impact on personal life can be devastating. Most mental disorders begin in childhood or adolescence and co-occur with somatic disease. In children, the most common problems are ADHD and anxious/depression and these problems often co-occur with additional behavioral and emotional problems. In adults, depression is the major mental disorder. It frequently co-occurs with anxiety disorders, substance abuse, migraine, cardiovascular disease and its associated risk factors. Indeed, depression is the largest cause of nonfatal disease burden in Western countries and increasingly in low and middle income countries worldwide as well. This application focuses on the genetics of common mental disorders, co-morbid traits and diseases across the lifespan. Its primary aim is the discovery of developmental paths into risk of depression and co-morbid disorders, using genetic epidemiological, molecular genetic and gene-environment interaction models. The introduction of multivariate and longitudinal models, in particular methods introduced by my group, into these areas will lead to substantial increases in power to unravel the contributions of genotype, environment and their interactions. The project described in this application addresses three interrelated topics: 1. Neuropsychiatric disorders and cognition 2. Depression, anxiety, substance use, abuse and dependence 3. Depression, migraine and cardiovascular risk As a connecting methodological framework it will develop models for the genetic analysis of these complex traits, especially gene-environment interaction and genome-wide association models. My ambition is to discover which genes influence the risk for mental disorder and co-morbid biomedical traits, to identify the causal variants, and to explore their interaction with environmental risk factors."