Background and aims: Epidemiological data on the prevalence of mood disorders demonstrate that major depressive disorder (MDD) is approximately twice as common in women as in men and that its first onset peaks during the reproductive years. We aimed to review key social, psychological, and biological factors that seem strongly implicated in the etiology of major depression and to focus on sex-specific aspects of depression, such as the role of a woman's reproductive life cycle in depressive symptomatology. Methods: A review of the literature, from 1965 to present, was conducted. Results: An integrated etiological model best explains gender and sex differences in depression. Social, psychological, and biological variables must be simultaneously taken into account. These vulnerabilities include (but are not limited to) gender-specific roles in society, life stress such as trauma, a tendency toward ruminative coping strategies, and the effects of sex hormones and genetic factors. Conclusions: To effectively treat MDD in women and to prevent the recurrence of illness in vulnerable women, clinicians must understand the sex-specific aspects of mood disorders over the longitudinal course of women's reproductive lives. A biopsychosocial approach should, therefore, be the main focus of future research and practice, to eventually result in an integrated etiological model of depression in women. Based on the prevalence of MDD in women, timely screening, diagnosis, and intervention should be public health priorities.
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