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

自杀行为的多级生物标志物：青春期女孩纵向研究中从人际压力到基因表达

• 批准号: 9265135
• 负责人: MATTHEW K NOCK
• 金额: $ 95.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-25 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9265135
• 关键词: Acute; Address; Adolescent; Age; Antiviral Agents; Area; Autonomic nervous system; Behavioral; Bioinformatics; Biological; Biological Assay; Biological Markers; Cause of Death; Cessation of life; Childhood; Clinical; Congresses; Data; Data Collection; Development; Distal; Down-Regulation; Estradiol; Event; Feeling suicidal; Female Adolescents; Fibrinogen; Gene Expression; Genes; Genetic Transcription; Genomics; Goals; Hormones; Inflammation; Laboratories; Lead; Life; Link; Longitudinal Studies; Measurement; Measures; Mental disorders; Methods; Molecular; National Institute of Mental Health; Participant; Performance; Physiological; Prevention; Procedures; Process; Puberty; Public Health; Reaction; Recruitment Activity; Regulation; Reporting; Research; Research Domain Criteria; Risk; Risk Factors; Scientist; Stimulus; Stress; Suicide; Suicide attempt; Surgeon; System; Testing; Time; Transact; Translational Research; United States Dept. of Health and Human Services; Up-Regulation; Visit; Vulnerable Populations; Work; Youth; acute stress; aged; attentional bias; base; behavioral response; biological adaptation to stress; biological systems; dehydroepiandrosterone; depressive symptoms; design; early adolescence; evidence base; executive function; experience; follow-up; genome-wide; girls; high risk population; hypothalamic-pituitary-adrenal axis; ideation; indexing; informant; innovation; pubertal timing; public health relevance; response; social; statistics; stressor; suicidal behavior; suicidal risk; theories

 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.

 描述（由适用提供）：回应美国总统，国会，外科医生，以及最近的NIMH-COSOSED自杀研究优先考虑议程，拟议的研究将研究自杀思想和尝试如何在自杀风险中最脆弱的人群之一（即青少年女孩）中发展。这项工作将 研究女孩在身体，基因组和行为单位分析的非典型急性压力反应如何减轻远端自杀危险因素（即抑郁症状/生命周期跨性别际交往广告）的实际经历与自杀危险因素的实际经验之间的关联。此外，这项研究将研究这些远端风险因素如何通过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，将抑制性控制作为自杀思想和自杀企图之间关联的主持人。这项研究将确定自杀风险的众多生物标志物，从而在识别和预防巨大的公共卫生问题方面取得了长足的进步，这些问题已被充分理解，并且不存在基于证据的方法。 Using a combination of a RDoC conceptual framework, experimental lab-based stressor paradigm, biologic assessments, 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 been relied on cross-sectional, single-informant, retrospective reports of suicide.参与者将在发展前，周期和后期的发展阶段包括200名女孩（9-14岁）。招聘将超出抑郁症状/终生际交往广告的升高女孩，以参加基于实验室的研究，涉及在实验引起的社会压力源后对身体，基因组和行为反应的评估。将在为期一年的纵向间隔内进行多波浪评估，以获取有关自杀念头和随着时间的尝试的广泛数据。将收集生物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（使用基于微阵列的基于基因组的转录分析）和青春期发育。该调查团队正在进行的研究，利用许多相同的招聘，数据收集和分析程序强烈支持拟议研究的可行性。