Gene-environment interaction and the genetics of depression.

Depression is a group of brain disorders with varied origins, complex genetics and obscure neurobiology. Definitions of clinical phenotypes are not rooted in their neurobiology, and animal models of behavioural despair have considerable limitations. Nevertheless, investigation of subtle alterations in gene expression, of correlations between genotype and brain activity, and of environmental variables interacting with genetic variants have advanced research into the genetics of depression. Although the postgenomic era is still in its infancy, several milestones have already been reached: variation in gene expression has been confirmed to play a predominant role in individual differences; gene-environment interactions have been established in humans and in a nonhuman primate model; gene-phenotype correlations have been substantiated by functional neuroimaging; and the notion of gene networks that control brain development is increasingly recognized. Given the etiologic and psychobiologic complexity of mood disorders, it is not surprising that the identification of specific genetic factors is extremely difficult and continues to be among the last frontiers of gene hunting.