Identifying neurobiological vulnerabilities in reward processing associated withsuicidal behavior in Veterans.

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This Career Development Award (CDA-1) for VA psychiatrists (RFP #CX-20-020) will provide training in both the clinical care and neuroimaging research of Veterans at high-risk for suicidal behavior. This proposal will gather concurrent behavioral and fMRI data investigating dysfunction of midbrain dopaminergic circuitry manifested during abnormal reward processing in Veterans, examined across levels of suicide attempt (SA) history and lethality of intent. Over the past two decades, the rate of suicide in Veterans has risen out of proportion with the general population, mandating suicide prevention as a top research priority for the Veterans’ Health Administration. Our ability to develop effective, neurobiological-based interventions for suicidal behavior is hindered by the lack of a clearly defined clinical pathway to completed suicide. While most cases of suicide are comorbid with a diagnosable mental illness, there is no one psychiatric disorder that is uniquely associated with elevated risk. Against a transdiagnostic background, identifying unique psychopathologies related to constructs of reward processing in Veteran’s with a history of SA will allow for the development of treatments targeting suicidal behavior rather than comorbid disorders This proposal will investigate in male and female OEF/OIF/OND Veterans (n=60) the relationship of reward processing to neural activity in midbrain nuclei as it relates to suicidal behaviors. To this end, our study population will include Veterans with and without history of suicide attempt, inclusive of a variety of other comorbidities. From this realistic, transdiagnostic sample of Veterans, we will examine how abnormalities in the neural substrates of reward processing relate to history of SA. Impulsive preference for an immediate reward is associated with a higher incidence of suicide attempt. However, high lethality intent often involves significant planning suggesting an alternative reward-related pathology in this high-risk subgroup. While there is often an acute disconnect between the severity of the preceding suicidal intent and the medical lethality of the attempt, the chronic risk of completed suicide is greatly increased in individuals with a history of high lethality intent. Delineating the unique psychopathology associated with the level of intent will be helpful in developing targeted interventions in high-risk subgroups. This proposal will investigate neural activity in dopaminergic midbrain reward circuits associated with trait pathological reward processing across levels of suicide attempt history and lethality of suicidal intent in Veterans. Identifying unique neurobiological underpinnings–such as abnormal reward processing and midbrain/dopaminergic dysfunction–that predispose a Veteran to a suicide attempt will allow us to develop novel interventions. The goal of this line of research is to define clinically useful neuroimaging biomarkers of suicide vulnerability to be used in future studies towards the development of targeted and more effective pharmacotherapeutic interventions.