Intermediate phenotypes and genetic mechanisms of psychiatric disorders

Using schizophrenia as an example, Meyer-Lindenberg and Weinberger review the effectiveness of the intermediate phenotype concept for characterizing the neural systems affected by risk gene variants, with a view to elucidating mechanistic aspects of brain function implicated in psychiatric disease. Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion.