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.