Testing a Diathesis-Stress Model of Adolescent Suicide: Dopaminergic, Social, and Inhibitory Mechanisms

项目摘要 自杀是一个重大的公共卫生危机，目前是10-24岁人群的第二大死亡原因， 岁。自杀的想法和行为（STB）在青春期急剧增加，特别是 在抑郁的青少年中很常见然而，确定哪些抑郁青少年 最有可能出现自杀行为的人。创新的多模式研究探索 生物学和社会情绪机制可能阐明改善青少年自杀预测的潜在目标 减少不必要的生命损失。 目前STB的素质-应激模型研究了易患STB的远端素质之间的相互作用， 个人STB和近端压力源，特别是社会排斥和人际关系的损失。最近评测 突出了STB的潜在神经素质，但研究结果有限，特别是对于高危青少年。 目前的项目针对三个远端神经机制-多巴胺能，社会和抑制缺陷-在一个 14-17岁青少年样本：有自杀意念（n=55）或近期自杀的抑郁青少年 尝试（n=55）和人口统计学匹配的健康对照（n=35）。首先，验尸工作表明 成年人自杀中多巴胺能的缺陷，但在体内检查多巴胺功能是理解的关键 青少年STB的潜在风险。因此，我们将利用一种新的磁共振成像（MRI） 采集敏感的神经黑色素作为一个非侵入性代理多巴胺在关键的中脑投射区。 考虑到多巴胺对抑郁症中奖赏和快感缺失的作用，我们假设， 多巴胺能减少在青少年STB中将是突出的，特别是在肥胖者中。第二，自杀 与构思者相比，构思者经历更多的人际压力，因此，拟议的项目将澄清是否 社会处理神经回路的改变会增加自杀行为的风险。我们假设 在一个生态有效的聊天室MRI任务中， 相对于创意者，同龄人的接受度和对拒绝的反应增加。第三，消极 紧迫感，即在负面情绪之后冲动行事的倾向，与青少年自杀有关。 行为。我们假设，在一个特定的时间段内，大脑皮层将表现出额叶、纹状体和岛叶抑制缺陷。 情绪Go/No-Go MRI范式，遵循社会评价应激源以诱导消极情绪状态。 将从儿科急诊科招募青少年构想者和构想者， 高风险的3个月期间，因为10%的青少年将在出院后90天内尝试自杀。 人际压力将通过前瞻性生态瞬时评估在随访期间进行表征， 深入的回顾性访谈。总的来说，这些新的多模态MRI和应力测量具有很大的优势。 承诺阐明青少年自杀行为的途径，这是NIMH研究的重点。

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.