Fig. 3.

Involvement of genetic and environmental factors in the onset of depression. Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. In addition, excess stressors lead to development of adult-onset neuropsychiatric disorders. A mild isolation stress affects mesocortical projection of dopaminergic neurons in which DNA hypermethylation of the tyrosine hydroxylase gene is elicited, only when combined with a relevant genetic risk for neuropsychiatric disorders. Associated with these molecular changes, several neurochemical and behavioral deficits occur in this mouse model, all of which are blocked by a glucocorticoid receptor antagonist. These results show an underlying mechanism by linking adolescent stressors to epigenetic controls in neurons via glucocorticoids. In addition, the face and predictive validities of the mice offer a model for psychotic depression. Control: CTL, environmental factor: E, genetic factor: G, combination of G and E: GXE.