Neurobiological mechanisms of susceptibility to estradiol fluctuation in female adolescents at risk of suicide: An expiremental approach.
2025 Award: $200,000
Female adolescents are 2-3 times more likely than their male peers to experience severe mental illness, possibly due to sensitivity to changing ovarian hormones (e.g., estradiol). Yet, the biological mechanisms that contribute to this elevated risk in females remain unclear. In this study, we will examine relationships between estradiol and depressive symptoms across the adolescent menstrual cycle to identify distinct windows of vulnerability to estradiol change, and use the experimental stabilization of estradiol to isolate the role of estradiol on depressive symptoms and underlying brain circuitry in female adolescents at risk of suicide.
Need/Problem: Rates of suicidal ideation and attempts increase dramatically at the adolescent transition, particularly among females, yet remarkably little is known about why. With suicide being a leading cause of death in adolescents, identifying early risk factors is critical for informing prediction and prevention efforts and will have a major health impact.
Grant Summary: We will study depressive symptoms and underlying brain circuitry involved in emotional processing during naturally fluctuating estradiol change, and during the experimental stabilization of estradiol in female adolescents at risk of suicide.
Goals & Projected Outcomes: We will investigate depressive symptoms linked to changes in ovarian hormones (e.g., estradiol) and brain circuitry that may contribute to this hormone sensitivity. For the first time, we will also experimentally stabilize estradiol to identify the role of estradiol in depressive symptoms in female adolescents at risk of suicide. Data from this study will support a future NIH grant proposal to investigate the efficacy of estradiol stabilization in adolescent psychopathology.
Elizabeth Andersen, Ph.D.
Grant Details: Risk of severe psychopathology increase dramatically during adolescence, especially for females. This project will be the first to use an ultra-high field MRI to examine susceptibility to adolescent estradiol fluctuation and probe the susceptible brain circuitry by stabilizing estradiol to potentially modify depressive symptoms. We will use a cross-over placebo-controlled experimental design to study each participant’s depressive symptoms and associated neural circuitry during natural fluctuation of estradiol (placebo) and during experimental stabilization of estradiol (active). Findings from this study will help us identify biological mechanisms of risk that could be targeted in future research to inform alternative intervention and novel treatment targets.
