Idiographic ovarian hormone effects on suicidality in adolescent female psychiatric patients

About This Grant

PROJECT SUMMARY/ABSTRACT The proposed project will investigate the menstrual cycle as a predictable and recurrent risk factor for mood episodes and suicidality during adolescence. Female individuals exhibit a threefold increase in suicide risk during the peripubertal period compared to males, and emerging evidence in adults suggests that cyclical fluctuations in ovarian hormones may be a biological trigger for suicidality in those with a brain sensitivity to hormonal changes. Cross-sectional studies indicate that the two weeks surrounding menses onset represent a window of elevated suicide risk, including increased attempts and hospitalizations, and longitudinal work from the primary mentor’s lab has demonstrated corresponding spikes in suicidal ideation during this timeframe. Critically, adults with hormone sensitivity frequently report that their symptoms began during adolescence, highlighting the potential of early identification to substantially reduce life-long patient burden. Despite this, it remains unknown whether this phenomenon begins during adolescence—an urgent knowledge gap this study will be the first to address. This work also directly aligns with the NIMH Priority Research Areas by addressing the urgent public health crisis of rising suicide rates. Building on the primary mentor’s recently completed R01 (MH-122446), which followed 125 adolescent females at high suicide risk across the menstrual cycle, the proposed study adds 40 days of high-density hormone data to the 70 days of daily mood and suicidality assessments. This innovative project seeks to determine who is at risk for cyclical suicidality, when risk escalates, and how hormonal mechanisms contribute to that risk. Specifically, the study aims to: (1) estimate the prevalence of premenstrual symptoms in adolescence, (2) identify differences in symptom timing and trajectories across the menstrual cycle, and (3) examine dynamic networks between hormones and psychiatric symptoms to uncover how ovarian hormones influence adolescent suicidality. To achieve these aims, the candidate will use gold-standard diagnostic methods, novel computational modeling approaches (such as flexible nonlinear models and idiographic symptom networks), and exploratory machine learning techniques. This research will not only generate novel insights into hormone-linked suicidality but will also serve as a robust training platform for the candidate—a physician-scientist in training with research and clinical interests in reproductive mood disorders across the lifespan. Through expert mentorship in menstrual cycle research, adolescent psychopathology, and advanced quantitative methods, the candidate will gain critical skills in conducting observational and experimental research and clinical care related to reproductive mental health, suicide prevention, and adolescent medicine. This project thus aims to advance both scientific discovery and promote the career development of a future physician-scientist in foundational research on adolescent reproductive psychiatry.