Figure 1.

A. From genes to behavior. Genes encode for molecules, not specific symptoms. The abnormal behaviors observed in psychiatric disorders (such as delusions, hallucinations and cognitive deficits in schizophrenia) are the product of intermediate steps that occur between genes and behavior, such as cell activity and neural circuits. An intermediate phenotype is a heritable trait that is located on the pathogenesis path from genetic predisposition to psychopathology and is likely associated with a more basic and proximal etiological process and therefore more amenable to genetic investigation. B. Genetic risk on vulnerable brain circuits. B1. Identification of neuroimaging intermediate phenotypes – which are alterations in neural circuit functions in patients with psychiatric disorders as well as in high genetic risk subjects (i.e. unaffected relatives). B2. Imaging genetics defines neural systems that are modulated by genetic variations, including genetic variations that have been associated with increased risk for psychiatric disorders. B3. To increase the probability that the observed biological modulation by the risk genetic variation is the mechanism through which that gene increases the risk for a psychiatric disorder, it is important to demonstrate that the gene modulates a neuroimaging intermediate phenotype.