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

测试青少年自杀的素质-压力模型：多巴胺能、社会和抑制机制

• 批准号: 10550215
• 负责人: David Pagliaccio
• 金额: $ 74.09万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10550215
• 关键词: 17 year old; Accident and Emergency department; Acute; Adolescence; Adolescent; Adult; Age; Autopsy; Behavior; Biological; Cause of Death; Characteristics; Clinical assessments; Corpus striatum structure; Data; Depressed mood; Disease susceptibility; Distal; Dopamine; Dopamine Receptor; Ecological momentary assessment; Emergency department visit; Emotional; Emotions; Enrollment; Equation; Exhibits; Feeling suicidal; Functional Magnetic Resonance Imaging; Hospitalization; Impulsivity; Individual; Insula of Reil; Interruption; Interview; Length of Stay; Life; Link; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Metabolism; Midbrain structure; Modeling; National Institute of Mental Health; Neurotransmitters; Pathway interactions; Proxy; Psychiatric therapeutic procedure; Public Health; Recording of previous events; Research; Research Priority; Rewards; Risk; Risk Behaviors; Risk Marker; Sampling; Severities; Signal Transduction; Specificity; Stress; Substantia nigra structure; Suicide; Suicide attempt; System; Testing; Theoretical model; Ventral Tegmental Area; Work; Youth; acute stress; adolescent suicide; aged; base; child depression; design; experience; follow-up; high risk; high-risk adolescents; ideation; improved; in vivo; innovation; multimodal neuroimaging; multimodality; negative mood; neural; neural circuit; neuroimaging; neuromechanism; neuromelanin; novel; pediatric emergency; peer; prospective; receptor density; recruit; response; social; social stress; stressor; suicidal adolescent; suicidal behavior; suicidal risk; suicide attempter; suicide model

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.

项目概要 自杀是一个重大的公共卫生危机，目前是 10-24 岁人群的第二大死因。 自杀念头和行为（STB）在青春期急剧增加，尤其严重。 然而，确定哪些抑郁青少年的明确标志。 自杀行为风险最高的人群尚未开展创新的多模式研究探索。 生物和社会情感机制可能阐明改善青少年自杀预测的潜在目标 并减少不必要的生命损失。 目前 STB 的素质-压力模型在易患远端素质之间呈正相互作用 个人对 STB 和近端压力源的影响，特别是社会排斥和人际损失。 强调了 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。 当前的项目针对三种远端神经机制——多巴胺能、社交和抑制缺陷—— 14-17岁青少年样本：有自杀意念（n=55）或最近自杀的抑郁青少年 尝试（n = 55）和人口统计匹配的健康对照（n = 35）首先，尸检工作涉及。 成人自杀中的多巴胺能缺陷，但检查体内多巴胺功能对于了解这一点至关重要 因此，我们将利用一种新型的磁共振成像 (MRI)。 获取对神经黑色素敏感的神经黑色素作为关键中脑投射区域多巴胺的非侵入性替代物。 考虑到多巴胺对抑郁症的奖赏和快感缺失的贡献，我们努力 多巴胺能减少在青少年 STB 中尤为突出，尤其是在自杀未遂者中。 尝试者比创意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给患者带来自杀行为的风险。 在生态上有效的聊天室 MRI 任务中，尝试者将表现出迟钝的纹状体反应 与创意者相比，岛叶对同龄同龄人的拒绝反应增加。第三，消极。 紧迫感，即在负面情绪后冲动行事的倾向，与青少年自杀有关 我们承认尝试者在尝试过程中会表现出额叶、纹状体和岛叶抑制缺陷。 情绪Go/No-Go MRI范式，遵循社会评价压力源诱发消极情绪状态。 将从儿科急诊科招募青少年的想法者和尝试者并进行跟踪 对于 3 个月的高风险期，因为 10% 的青少年会在出院后 90 天内尝试自杀。 人际压力将通过前瞻性生态瞬时评估和后续跟踪来表征 总的来说，这些新颖的多模态 MRI 和压力测量方法具有重要意义。 承诺阐明青少年自杀行为的途径，这是 NIMH 研究的重点。