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Published Online:https://doi.org/10.1176/ajp.156.6.816

OBJECTIVE: Depression is twice as common in women as in men, but the reason for this sexual dimorphism is unknown. This article reviews recent studies of the role of childhood sexual abuse in the subsequent development of major depressive disorder, and the biological and psychosocial mechanisms by which early stressors may contribute to adult-onset depression in women. Particular attention is paid to investigations of the long-term effects of early stress on hypothalamic-pituitary-adrenal (HPA) axis function. METHOD: Studies were identified by means of computerized and manual searches; further references were obtained from the bibliographies of reviewed articles. RESULTS: Childhood sexual abuse is associated with adult-onset depression in both men and women, and occurrence of such abuse is more common in girls than in boys. There is evidence from both animal and human studies that early stressors produce long-term dysregulation of the HPA axis similar to that seen in depressed patients and that such dysregulation results in a differential response to stressors in adulthood. In addition, it appears that the HPA axis in females may be more susceptible to stress-induced dysregulation, which might contribute to an increased vulnerability to depression in adulthood. CONCLUSIONS: Childhood sexual abuse is an important early stressor that may predispose individuals to adult-onset depression by means of dysregulation of the HPA axis. Investigation of the mechanisms mediating the relationship between childhood sexual abuse and adult-onset depression, and the study of gender differences in exposure to this and other stressors, may improve our understanding of the etiology of depressive illness in general.