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The Harvard Study of Moods and Cycles

Lee S. Cohen, MD; Claudio N. Soares, MD, PhD; Allison F. Vitonis, BA; Michael W. Otto, PhD; Bernard L. Harlow, PhD

Arch Gen Psychiatry. 2006;63:385-390.

Context  Transition to menopause has long been considered a period of increased risk for depressive symptoms. However, it is unclear whether this period is one of increased risk for major depressive disorder, particularly for women who have not had a previous episode of depression.

Objective  To examine the association between the menopausal transition and onset of first lifetime episode of depression among women with no history of mood disturbance.

Design  Longitudinal, prospective cohort study.

Setting  A population-based cross-sectional sample.

Participants  Premenopausal women, 36 to 45 years of age, with no lifetime diagnosis of major depression (N = 460), residing in 7 Boston, Mass, metropolitan area communities.

Main Outcome Measure  Incidence of new onset of depression based on structured clinical interviews, Center for Epidemiologic Studies Depression Scale scores, and an operational construct for depression.

Results  Premenopausal women with no lifetime history of major depression who entered the perimenopause were twice as likely to develop significant depressive symptoms as women who remained premenopausal, after adjustment for age at study enrollment and history of negative life events. The increased risk for depression was somewhat greater in women with self-reported vasomotor symptoms.

Conclusions  The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness.

Author Affiliations: Perinatal and Reproductive Psychiatry Clinical Research Program (Drs Cohen and Soares) and Department of Psychiatry, Harvard Medical School (Drs Cohen, Soares, and Otto), Massachusetts General Hospital, and Obstetrics and Gynecology Epidemiology Center at Brigham and Women's Hospital and Harvard Medical School (Ms Vitonis and Dr Harlow), Boston.

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