Ovarian Steroid Effects on Mood and Sleep Across the Adolescent Menstrual Cycle

PROJECT SUMMARY/ABSTRACT After menarche, females are twice as likely to develop depression and sleep problems than males. Ovarian steroids have been hypothesized to play a role, but prior work has failed to clarify the effect of ovarian steroids on mood and sleep problems. Hormone sensitivity (neural vulnerability to normal fluctuations in hormones across the menstrual cycle) is a promising candidate, particularly sensitivity to estrogen withdrawal (E2), but little is known about hormone sensitivity in adolescents. This work is hindered by traditional statistical approaches (multilevel modeling (MLM) with phase contrasts), as they rely on the assumption of a regular, ovulatory cycle, which adolescents often do not have. The proposed study will characterize hormone sensitivity in adolescents by collecting daily assessments of mood ratings, sleep (via self-report and actigraphy), and ovarian steroid hormones (via dried urine strips) from 50 female adolescents, aged 11-14, at least one-year post-menarche, with regular cycles (21-45 days) and elevated depressive symptoms. For adolescents with ovulatory cycles, multilevel models (MLM) with phase contrasts will be used to evaluate menstrual cycle effects on symptoms and sleep, and the Carolina Premenstrual Assessment Scoring System (C-PASS) will be used to identify clinically significant premenstrual exacerbation of symptoms (Aim 1). I hypothesize that depressive symptoms and sleep problems will be higher in the perimenstrual phase of the cycle compared to all other phases. Across the full sample, longitudinal network models will be used to address limitations of multilevel modeling; networks of associations between E2, mood symptoms, and sleep problems across the cycle will be estimated (Aim 2), with the hypothesis that decreases in E2 will be associated with subsequent increases in sleep problems followed by increases in mood symptoms. Exploratory analyses estimate the indirect effect of E2 on mood symptoms via sleep problems (Aim 3). This knowledge could facilitate earlier identification and prevention efforts and lay the groundwork for future research on the developmental contribution of hormone sensitivity to sex differences in depression and sleep problems. The training plan closely matches the proposed research and long-term goals with an emphasis on activities that will facilitate the candidate’s development as an independent investigator. Specifically, the training goals are to (1) gain immersive training in research on the menstrual cycle and hormone sensitivity with adolescents, (2) develop competence in the assessment of sleep via actigraphy and self-report in adolescents, and (3) gain proficiency in idiographic longitudinal methods for use with menstrual cycle data. A mentorship team with expertise across these areas has been assembled, and Brown University is a world-renowned clinical research institution with an extensive history of NIH funding and supporting career development awards. Overall, the broad aim of these research and training goals is to support the candidate’s development of an independent research program examining the biological mechanisms of the sex differences in depression and sleep problems that emerge after puberty.