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

退伍军人精神病学家职业发展奖(CDA-1)(RFP#CX-20-020)将提供以下两方面的培训 退伍军人自杀行为高危人群的临床护理及神经影像研究这项提案将收集 同时进行的行为学和fMRI数据研究中脑多巴胺能回路的功能障碍 在退伍军人的异常奖励处理过程中，检查了不同水平的自杀未遂(SA)历史和 意图的杀伤力。 在过去的二十年里，退伍军人的自杀率与普通人群的自杀率不成比例地上升， 将自杀预防作为退伍军人健康管理局的首要研究重点。我们有能力 开发有效的、基于神经生物学的自杀行为干预措施因缺乏明确的 明确了完全自杀的临床路径。虽然大多数自杀案例都与可诊断的 在精神疾病方面，没有一种精神障碍是唯一与高风险相关的。针对一个 跨诊断背景，识别与奖赏加工结构相关的独特心理病理 有SA病史的退伍军人将允许开发针对自杀行为的治疗，而不是 共病障碍 这项建议将在男性和女性OEF/OIF/OND退伍军人(n=60)中调查奖励关系 对与自杀行为有关的中脑核团神经活动的处理。为此，我们的研究人群 将包括有和没有自杀未遂史的退伍军人，包括各种其他合并症。 从这个现实的、跨诊断的退伍军人样本中，我们将检查神经异常是如何 奖赏加工的底物与SA的历史有关。 冲动地倾向于立即获得回报与自杀企图的发生率更高有关。然而， 高致命性意图通常涉及重要的计划，这暗示了一种与奖励相关的替代病理 高危亚组。尽管之前自杀意图的严重程度往往严重脱节 和医学上的致命性，个人完全自杀的慢性风险大大增加 有高致命性意图的历史。描绘了与意向水平相关的独特的精神病理学 将有助于在高危亚群中制定有针对性的干预措施。这项提案将研究神经 多巴胺能中脑奖赏环路的活动与特质病理性奖赏加工有关 退伍军人自杀未遂水平、自杀历史和自杀意向致死率。 确定独特的神经生物学基础--例如异常的奖赏处理和 中脑/多巴胺能功能障碍--使退伍军人倾向于自杀，这将使我们能够开发出新的 干预措施。这一系列研究的目标是确定临床上有用的自杀神经影像生物标记物。 将在今后的研究中使用的脆弱性，以期制定有针对性和更有效的 药物治疗干预。

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.