Geramiah Drew, “Exploring the Role of Steroid Hormones in Adolescent Depression”
Mentor: Polymnia Georgiou, Psychology
Poster #53

Major depressive disorder affects approximately 13% of adolescents in the U.S. While classical antidepressant treatments effectively reduce depressive symptoms in adolescents, low remission rates and potential adverse effects, such as suicide-related thoughts, highlight the need for the development of novel pharmacotherapies for the treatment of adolescent depression. During adolescence, there is a surge in steroid gonadal hormones, impacting behavior and brain functions in both humans and mice. Stress in the form of victimization and bullying is prevalent among adolescents and when combined with increased gonadal hormones, is associated with adolescent depression and suicidality. We hypothesize that the increased risk of depression in adolescents is due to the combined effects of increased stress and heightened production of gonadal hormones in both sexes. Therefore, we propose that targeting gonadal steroid hormone systems could serve as an intervention for adolescent depression and suicidality. To test this hypothesis, we subjected adolescent male and female mice to acute foot-shock stress and assessed the development of anhedonia, social preference deficits, and anxiety-like behavior using the sucrose preference test, social interaction test, and light/dark box test, respectively. We found that stressed adolescent mice displayed social interaction deficits, but no changes were observed in anxiety behavior or anhedonia. To investigate the role of gonadal hormone systems in these effects, we conducted RNAseq analysis on the prefrontal cortex of depressed patients, comparing adults and adolescents. The gene ontology analysis for biological processes revealed significant downregulation in cholesterol metabolic and biosynthetic processes in adolescent patients compared to adult patients. Cholesterol serves as the precursor for most steroid gonadal hormones. Additionally, pathway enrichment analysis indicated downregulation in steroid biosynthesis. These findings suggest that dysregulation in steroid gonadal hormone synthesis during adolescence may elevate the risk of developing depression. Consequently, targeting these systems could represent a novel strategy for treating adolescent depression.