Investigation of Social and Circadian Rhythm Dysregulation in the Development of Depression Symptoms During the Menopause Transition

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Project Summary The menopausal transition is a high-risk period for the development of clinically significant depression symptoms in women. The likelihood of depression during the transition to menopause (i.e., perimenopause) is approximately 3 times greater relative to the pre-menopause period. There is a critical need to understand the mechanisms of these increased depression rates to optimally inform prevention and risk-management strategies. Circadian rhythms are altered in menopause and have been linked to depression broadly and in menopausal women specifically. Recent research has also shown that sensitivity to fluctuations in estrogen may be linked to depression symptoms during this reproductive transition. What has yet to be thoroughly elucidated is 1) the degree to which altered circadian rhythms are linked to the development of depression symptoms during the perimenopausal period and 2) whether circadian alterations are influenced purely by hormonal changes or also by environmental dysregulation of social rhythms. The goal of this R21 proposal is to explore simultaneously the relationship of both hormonal and social rhythm influences on circadian rhythms in women transitioning into menopause both with (n=20) and without (n=20) clinically significant symptoms of major depressive disorder (MDD). Baseline assessments will include clinical interview and self-report measures of depression, a detailed interview of current stressors and their impact on daily routines, and questionnaires about sleep, chronotype, and social rhythm regularity. Participants will also complete a blood draw for reproductive hormones estradiol and follicle stimulating hormone. Over the course of 4 weeks, participants will provide morning salivary samples of estradiol and progesterone every 4 days for a total of 7 samples. Participants will also wear a wrist actigraph during the study period to examine rest/activity rhythms and participate in once daily ecological momentary assessments of mood, stress, and routines allowing for deeper analysis of contextual factors that may affect circadian rhythms and mood. At the end of week 4, participants will undergo a repeat blood draw and complete follow-up assessments of stress and mood. These methods will set the stage for an R01 that will investigate the mediational role of circadian and social rhythm disruption in the development of depression symptoms in a large and diverse sample of perimenopausal women.