Stress axis as the locus of gene-environment interactions in major depressive disorder

Evidence from family, twin, and adoption studies indicates that there is a significant genetic contribution to major depressive disorder. However, the majority of individuals with a positive family history of depression do not develop depression. Thus, current hypotheses about the role of genes for the development of depression collectively favor the stress-diathesis theory. The latter postulates that repeated or chronic exposure of a vulnerable genotype to stressful life events may trigger the development of depression. The hypothalamic-pituitary-adrenal (HPA) axis is discussed as a missing link between genes, stress, and depression. The genetic variation of coping behavior in response to stress and the depression-related dysregulation of HPA axis confirm a strong impact of both genetic and environmental factors on the manifestation of depressive disorders. Such interactions would facilitate the manifestation of environmental effects in a depressive phenotype preferentially in the presence of a permissive genetic background.