Examining Suicide Risk from a Biopsychosocial Framework: A Large-Scale Cross-Sectional Study

项目总结/摘要 自杀仍然是国家和全球的重大公共卫生危机。与自杀有关的想法和行为 是与异质性生物心理社会风险指标相关的跨诊断现象。结果 表明自杀风险与不同静息态功能连接、结构脑 差异和多基因风险评分（PRS）概况。在我们的理解中存在着明显的差距， 自杀的生物心理社会脆弱性第一个研究差距涉及缺乏对以下方面的深入了解： 用于区分只考虑自我导向暴力的个体与 最终企图自杀的人第二个研究差距涉及缺乏对如何 生物风险指标与心理社会风险指标相结合，会增加自杀风险。理解 最有可能最终死于自杀的个体的生物心理社会风险状况仍然至关重要， 加强自杀风险检测策略，并制定有针对性的干预措施。为了弥补这些差距， 拟议项目的总体目标是研究大脑结构和 连接性，遗传和行为风险指标自杀。生物心理社会学数据， 将对从英国生物样本库中抽取的4566名参与者进行分析，以区分那些有自杀行为风险的人。 自我导向的暴力思想这项提议为汤普森先生制定一项 一项研究计划，调查自杀风险的生物心理社会标志物。拟议项目的目标1是 比较两组之间的大脑结构和连接，遗传和心理社会风险指标：成年人 终生自杀企图和终生自我导向暴力思想的成年人。目标二是 通过比较分类来确定生物学和社会心理学候选标记物的相对重要性 利用生物学的算法（即，大脑结构和连接性，遗传变异）， 仅心理社会风险指标就可以区分这两个群体。这些发现将推动我们 了解与自杀相关的生物心理社会风险指标，以突出机制，提高 风险检测，并最终为有针对性的干预战略提供信息。总体而言，拟议项目的目标 将在一个旨在发展以下专业知识的研究培训计划的背景下完成：（1） 自杀的生物心理社会基础，（2）先进的统计学和机器学习，（3）多模式 神经影像学，（4）PRS的生成，和（5）学术传播技能。培训计划包括 参加选定的讲习班、科学写作和学术会议报告，以及个人 由具有互补专业知识的赞助商和合作者团队进行监督和指导。

PROJECT SUMMARY/ABSTRACT Suicide remains a significant public health crisis nationally and globally. Suicide-related thoughts and behaviors are transdiagnostic phenomena associated with heterogeneous biopsychosocial risk indicators. Findings suggest that suicide risk is associated with distinct resting-state functional connectivity, structural brain differences, and polygenetic risk score (PRS) profiles. There are notable gaps in our understanding of biopsychosocial vulnerabilities for suicide. The first research gap involves a lack of in-depth understanding of candidate markers for differentiating between individuals who only think about self-directed violence versus those who ultimately attempt suicide. The second research gap involves a lack of an in-depth understanding of how biological risk indicators in combination with psychosocial risk indicators contribute to suicide risk. Understanding the biopsychosocial risk profile for individuals most at risk for eventual death by suicide remains critical for enhancing suicide risk detection strategies and developing targeted interventions. To address these gaps, the overall objective of the proposed project is to investigate the combined associations of brain structure and connectivity, genetic, and behavioral risk indicators for suicide. Biopsychosocial data from an estimated 4566 participants drawn from the UK Biobank will be analyzed to differentiate those at risk for suicidal behavior from self-directed violence thoughts alone. This proposal sets the stage for Mr. Thompson’s goal to develop a program of research investigating biopsychosocial markers of suicide risk. Aim 1 of the proposed project is to compare brain structure and connectivity, genetic, and psychosocial risk indicators between two groups: adults with lifetime suicide attempt(s) and adults with lifetime self-directed violence thoughts alone. Aim 2 is to determine the relative importance of biological and psychosocial candidate markers by comparing classification algorithms utilizing biological (i.e., brain structure and connectivity, genetic variance), above and beyond psychosocial risk indicators alone, in differentiating between these two groups. Findings will advance our understanding of the biopsychosocial risk indicators associated with suicide to highlight mechanisms, improve risk detection, and ultimately inform targeted intervention strategies. Overall, the goals of the proposed project will be accomplished within the context of a research training program aimed at developing expertise in (1) biopsychosocial underpinnings of suicidality, (2) advanced statistics and machine learning, (3) multimodal neuroimaging, (4) generation of PRS, and (5) scholarly dissemination skills. The training plan includes attendance at selected workshops, scientific writing and academic conference presentations, and individual supervision and mentorship by a team of sponsors and collaborators with complementary areas of expertise.