Multilevel Biomarkers for Suicidal Behavior: From Interpersonal Stress to Gene Expression in a Longitudinal Study of Adolescent Girls

 描述（由申请人提供）：为了响应美国总统，国会，外科医生的公开呼吁，以及最近NIMH共同赞助的自杀研究优先议程，拟议的研究将研究自杀意念和企图如何在最脆弱的自杀风险人群中发展（即，青春期女孩）。这项工作将 研究女孩在生理、基因组和行为分析单位对人际压力的非典型急性压力反应如何调节具有远端自杀风险因素的女孩中人际压力的实际经历与自杀意念之间的关联（即，升高的抑郁症状/终身人际逆境）。此外，本研究将探讨这些远端风险因素如何与青春期过程进行交易，以产生非典型急性应激反应的风险。最后，抑制控制将被视为自杀意念和自杀企图之间关系的调节者。这项研究将确定许多自杀风险的生物标志物，显着推进识别和预防一个巨大的公共卫生问题的进展，这个问题一直被严重研究不足，而且没有基于证据的方法存在。使用RDoC概念框架，基于实验室的应激源范式，生物测定，基于执行功能的评估，纵向方法和创新的生物信息学方法测量基因表达的组合，这项工作提供了一个领域内的实质性进展，几乎完全依赖于横截面，单线人，自杀的回顾性报告。参与者将包括200名处于青春期前、青春期后和青春期后发育阶段的女孩（9-14岁）。招募将对抑郁症状升高/终身人际关系逆境的女孩进行过度抽样，以参与一项基于实验室的研究，该研究涉及评估实验诱导的社会压力后的生理，基因组和行为反应。将在一年的纵向间隔内进行多波评估，以获得关于自杀意念和自杀企图随时间推移的广泛数据。将收集生物学数据，以测量自主神经系统、下丘脑-垂体-肾上腺轴系统、基因表达（使用基于微阵列的全基因组转录谱）和青春期发育。该调查小组正在进行的研究利用许多相同的招聘，数据收集和分析程序，强烈支持拟议的研究的可行性。

 DESCRIPTION (provided by applicant): In response to public calls from the US President, Congress, Surgeon General, and a recent NIMH-co- sponsored Suicide Research Prioritization Agenda, the proposed research will examine how suicidal ideation and attempts develop within one of the most vulnerable populations at risk for suicide (i.e., adolescent girls). This work will examine how girls' atypical acute stress responses to interpersonal stress at physiological, genomic, and behavioral units of analysis moderate the association between actual experiences of interpersonal stress and suicidal ideation among girls with distal suicide risk factors (i.e., elevated depressive symptoms/lifetime interpersonal adversity). Moreover, this research will examine how these distal risk factors transact with pubertal processes to produce risk for atypical acute stress responses. Last, inhibitory control will be examined as a moderator of the association between suicide ideation and suicide attempts. This research will identify numerous biomarkers of suicide risk, significantly advancing progress towards identification and prevention of an enormous public health issue that has been woefully understudied and for which no evidence- based approaches exist. Using a combination of a RDoC conceptual framework, experimental lab-based stressor paradigm, biological assays, performance-based assessments of executive function, longitudinal methods, and innovative bioinformatics approaches for measuring gene expression, this work offers a substantial advance within a field that almost exclusively has relied on cross-sectional, single-informant, retrospective reports of suicidality. Participants will include 200 girls (age 9-14 years) at pre-, peri-, and post-pubertal stages of development. Recruitment will oversample girls with elevated depressive symptoms/lifetime interpersonal adversity to participate in a lab-based study involving the assessment of physiological, genomic, and behavioral responses following an experimentally-induced social stressor. A multi-wave assessment occurring over a one-year longitudinal interval will be conducted to obtain extensive data on suicidal ideation and attempts over time. Biological data will be collected to measure the autonomic nervous system, hypothalamic-pituitary-adrenal axis system, gene expression (using microarray-based genome-wide transcriptional profiling), and pubertal development. Ongoing research conducted by this investigative team utilizing many of the same recruitment, data collection, and analytic procedures strongly supports the feasibility of the proposed research.