Project Summary Suicide is a major public health crisis and, currently, is the second leading cause of death among 10-24- year-olds. Suicidal thoughts and behaviors (STB) increase drastically during adolescence and are particularly common among depressed adolescents. However, definitive markers to identify which depressed adolescents are most at-risk for suicidal behaviors have not been developed. Innovative, multimodal studies probing biological and socioemotional mechanisms may elucidate potential targets to improve prediction of youth suicide and reduce the needless loss of life. Current diathesis-stress models of STB posit interactions between distal diatheses that predispose individuals to STB and proximal stressors, particularly social rejection and interpersonal loss. Recent reviews highlight potential neural diatheses for STB, yet findings are limited, particularly for high-risk adolescents. The current project targets three distal neural mechanisms–dopaminergic, social, and inhibitory deficits–in a sample of 14-17-year-old adolescents: depressed adolescents either suicidal ideation (n=55) or a recent suicide attempt (n=55) and demographically matched healthy controls (n=35). First, post-mortem work has implicated dopaminergic deficits in adult suicide, but examining dopamine function in vivo is critical to understand prospective risk for adolescent STB. Thus, we will leverage a novel Magnetic Resonance Imaging (MRI) acquisition sensitive to neuromelanin as a non-invasive proxy for dopamine in key midbrain projection regions. Given the contribution of dopamine to reward and anhedonic deficits in depression, we hypothesize that dopaminergic reductions will be prominent in adolescent STB, particularly among attempters. Second, suicide attempters experience more interpersonal stress than ideators, and thus, the proposed project will clarify whether alterations in social processing neural circuitry confer heightened risk for suicidal behaviors. We hypothesize that, during an ecologically valid Chatroom MRI task, attempters will exhibit blunted striatal response to acceptance and increased insula response to rejection by same-age peers relative to ideators. Third, negative urgency, the tendency to act impulsively following negative emotions, is implicated in adolescent suicidal behaviors. We hypothesize that attempters will exhibit frontal, striatal, and insular inhibition deficits during an emotional Go/No-Go MRI paradigm, following a social-evaluative stressor to induce a negative mood state. Adolescent ideators and attempters will be recruited from a pediatric emergency department and followed for a high-risk 3-month period, as 10% of adolescents will attempt suicide within 90 days of hospital discharge. Interpersonal stress will be characterized over follow-up via prospective ecological momentary assessment and in-depth retrospective interviews. Collectively, these novel multimodal MRI and stress measures hold great promise to elucidate the pathway to adolescent suicidal behaviors, a key NIMH research priority.

Project Narrative Adolescent suicidal thoughts and behaviors are a public health crisis and definitive neural markers of risk have not been identified. Building on current diathesis-stress theoretical models of suicide, we will test how alterations in three neural systems–midbrain dopamine, social processing, and inhibitory control–contribute to suicide risk in the face of acute social stress. In-depth neuroimaging and clinical assessments will be combined with prospective and retrospective measures of stress to predict longitudinal risk for suicidal behaviors among high- risk adolescents.