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、卫生局局长的公开呼吁，以及最近NIMH联合赞助的自杀研究优先议程，拟议的研究将研究自杀念头和企图如何在最脆弱的自杀风险人群(即青春期女孩)中发展。这项工作将 研究女孩在生理、基因组和行为分析单元对人际压力的非典型急性应激反应如何调节具有远端自杀风险因素(即抑郁症状增加/终生人际逆境)的女孩的实际人际压力经历和自杀意念之间的联系。此外，这项研究将研究这些远端风险因素如何与青春期过程交互作用，从而产生非典型急性应激反应的风险。最后，抑制性控制将作为自杀意念和自杀企图之间联系的调节因素而被研究。这项研究将确定许多自杀风险的生物标志物，极大地推动在识别和预防这一巨大的公共卫生问题方面取得进展，这一问题一直被不幸地研究不足，而且没有基于证据的方法。使用RDoC概念框架、基于实验室的实验应激源范式、生物分析、基于执行功能的绩效评估、纵向方法和用于测量基因表达的创新生物信息学方法的组合，这项工作在几乎完全依赖横断面、单一信息者、回顾性自杀报告的领域内取得了实质性进展。参与者将包括200名处于青春期前、青春期和青春期后发育阶段的女孩(年龄在9-14岁之间)。招募将对抑郁症状升高/终身人际关系逆境的女孩进行过抽样，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应激源后的生理、基因组和行为反应。将在一年的纵向间隔内进行多波评估，以获得关于一段时间内自杀念头和自杀企图的广泛数据。将收集生物学数据来测量自主神经系统、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图谱)和青春期发育。这一调查小组利用许多相同的招聘、数据收集和分析程序进行的持续研究有力地支持了拟议研究的可行性。

 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.