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

这个职业发展奖（CDA-1）的VA精神科医生（RFP #CX-20-020）将提供培训， 临床护理和神经影像学研究的退伍军人在高风险的自杀行为。该提案将汇集 研究中脑多巴胺能回路功能障碍的同时行为和功能磁共振成像数据显示， 在退伍军人的异常奖励处理过程中，检查了自杀企图（SA）历史的各个级别， 意图的致命性。 在过去的二十年里，退伍军人的自杀率与普通人群不成比例， 将自杀预防作为退伍军人健康管理局的首要研究任务。的能力 发展有效的，基于神经生物学的自杀行为干预措施受到缺乏明确的 定义了自杀完成的临床路径。虽然大多数自杀病例与可诊断的 精神疾病，没有一种精神疾病是与风险升高唯一相关的。针对 transdiagnosis背景，识别与奖励处理结构相关的独特精神病理学， 有SA病史的退伍军人将允许开发针对自杀行为的治疗方法，而不是 共病性疾病 本提案将在男性和女性OEF/OIF/OND退伍军人（n=60）中调查奖励与 处理中脑核团的神经活动，因为它与自杀行为有关。为此，我们的研究人群 将包括有和没有自杀企图史的退伍军人，包括各种其他合并症。 从这个现实的，transdiagnosis样本的退伍军人，我们将研究如何异常的神经系统， 奖赏加工的底物与SA的历史有关。 对即时奖励的冲动偏好与自杀企图的发生率较高有关。然而，在这方面， 高杀伤力的意图往往涉及重要的计划，这表明在这种情况下， 高危亚组。虽然之前自杀意图的严重程度 以及自杀未遂的医学致命性，个体自杀未遂的慢性风险大大增加 有高度致命意图的人描述了与意图水平相关的独特精神病理学 将有助于在高风险亚组中制定有针对性的干预措施。该提案将研究神经 多巴胺能中脑奖励回路的活动与特质病理性奖励处理相关 退伍军人自杀企图史和自杀意图的致命性水平。 识别独特的神经生物学基础-如异常奖励处理和 中脑/多巴胺能功能障碍-使退伍军人易于自杀企图将使我们能够开发新的 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学生物标志物 今后的研究将利用脆弱性， 药物干预。

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.