Feasibility Study of Childhood Gender Nonconformity and Early Risk for Suicidal Behavior

/ Abstract Suicide is a leading cause of death among adolescents, and early identification of risk for suicidal behavior among youth remains a challenge. Novel approaches to identify earlier developmental indicators of risk for later psychiatric problems, including risk for suicidal behavior, are needed. Children who exhibit gender nonconformity (GNC) have higher risk for experiencing childhood abuse and rejection from parents and peers. Early psychosocial stressors related to GNC could dysregulate stress responses, leading to biological dysregulation in the hypothalamic-pituitary-adrenal axis and inflammatory pathways. Biological dysregulation in these pathways is associated with psychiatric symptoms and risk for suicidal behavior. Furthermore, psychosocial stressors and biological dysregulation have the potential to augment neurocognitive correlates of suicidal behavior among youth exhibiting GNC, including increased impulsivity and reactive aggression. Thus, psychosocial stress and biological dysregulation during childhood could contribute to psychiatric symptoms prior to adolescence among youth exhibiting GNC. While GNC could have utility in identifying children who will have future elevated risk for engaging in suicidal behavior, the existing literature examining associations between GNC and risk for suicidal behavior among children is critically limited. The proposed longitudinal feasibility study is designed to examine how GNC is associated with early indicators of risk for suicidal behavior among children ages 7–10, including psychosocial stressors, biological dysregulation, psychiatric diagnoses and symptoms, neurocognitive correlates of risk for suicidal behavior, and suicidal ideation. The aims of the proposed study are to accrue feasibility data by enrolling a sample of children enriched for GNC, collecting data on all variables of interest (clinical interview and self-report data from children and parents as well as biological and neurocognitive behavioral task data from children), and retaining participants in the longitudinal study at follow-ups over 9 months. We will develop a testable conceptual model for a future R01 study by examining associations between GNC, psychosocial stressors, biological dysregulation, psychiatric symptoms, suicidal ideation, and neurocognitive correlates of suicidal behavior. Results from the proposed study will facilitate the design of a future R01 proposal to conduct a long-term prospective study to enroll a large sample of children enriched for GNC and follow them into adolescence to assess developmental trajectories of GNC, psychosocial stress, and risk for suicidal behavior. This line of work has the potential to provide critical information to facilitate early identification of youth at risk for suicidal behavior, providing the information and time necessary to intervene prior to the development of risk for suicidal behavior among adolescents. Project Number: 1R21MH137564-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Brian Thoma | Institution: UNIVERSITY OF PITTSBURGH AT PITTSBURGH, PITTSBURGH, PA | Award Amount: $437,250 | Activity Code: R21 | Study Section: Psychosocial Development, Risk and Prevention Study Section[PDRP] View on NIH RePORTER: https://reporter.nih.gov/project-details/11137496