2/2 - Familial Early-Onset Suicide Attempt Biomarkers

 描述（由申请人提供）：美国的自杀率与60年前相同。更好的预防需要更多关于风险和复原力生物标志物的数据。我们试图确定重性抑郁症（MDD）中自杀企图的弹性和脆弱性潜在内在表型。这两种内表型可能有助于估计风险，并为预防干预提供新的目标。研究设计比较了健康志愿者（第1组）与父母患有MDD和自杀行为的未服药成年后代，这些后代已过风险年龄，因此可以分为弹性组（第4组），具有MDD素质的组（第2组）和具有MDD和自杀企图素质的组（第3组）。第2组和第3组的比较表明了自杀行为的素质。组1和组4的比较表明了弹性表型。第1组与第2组的比较显示了MDD的素质。本研究是基于我们几乎完整的纵向双位点随访研究的新方向（PI，J. John Mann，MD，MH 056390，哥伦比亚大学，纽约市和PI，大卫布伦特，MD，MH 056612，UPMC，匹兹堡）的701名后代的334名先证者患有情绪障碍，标题为：“早发性自杀企图的家庭途径”，试图确定自杀行为风险从父母传递给后代的机制。我们在认知、情绪调节和压力反应领域的风险特征的研究结果，以及一个新的5-HT 1A自身受体脑PET成像领域，该领域调节5-羟色胺的释放，将集中研究弹性和脆弱性表型。这项研究将涉及与2015年1月结束的当前资助申请相同的两个性能站点。这两个团队已经合作了超过15年，两个团队都对抑郁症和自杀患者进行了PET研究。我们将从旧的研究中招募合格的后代，并根据需要为四组招募新的后代。两家研究中心将使用相同的方案进行临床和认知评估、压力测试和PET/MRI扫描。纽约中心将作为数据管理中心，包括图像分析和统计以及皮质醇测定。

 DESCRIPTION (provided by applicant): The suicide rate in the USA is the same as 60 years ago. Better prevention needs more data on risk and resilience biomarkers. We seek to determine both resilience and vulnerability potential endophenotypes for suicide attempts in major depressive disorder (MDD). Both endophenotypes may aid estimation of risk and provide new targets for prevention intervention. The study design compares healthy volunteers (Group 1) with medication-free adult offspring of a parent with MDD and suicidal behavior who are through the age of risk and can thus be divided into a resilient group (Group 4), a group with a diathesis for MDD (Group 2) and one with diatheses for MDD and suicide attempts (Group 3). Comparison of Groups 2 and 3 indicates the diathesis for suicidal behavior. Comparison of Group 1 and 4 indicates the resilience phenotype. Comparison of Group 1 and Group 2 indicates the diathesis for MDD. This study is a new direction based on our almost complete longitudinal two-site follow-up study (PI, J. John Mann, MD, MH056390, Columbia University, NYC and PI, David Brent, MD, MH056612, UPMC, Pittsburgh) of 701 offspring of 334 probands with mood disorder entitled: "Familial Pathways to Early-Onset Suicide Attempts" that has sought to identify mechanisms by which suicidal behavior risk is transmitted from parent to offspring. Our findings on risk traits in the domains of cognition, mood regulation and stress responses, together with a new domain of brain PET imaging of the 5-HT1A autoreceptor that regulates serotonin release, will focus the search for resilience and vulnerability phenotypes. This study will involve the same two performance sites as the current funded application that ends January 2015. The teams have worked together for >15 years and both teams have conducted PET studies of depressed and suicidal patients. We will recruit eligible offspring from the old study and recruit new offspring as needed for the four groups. Both sites will perform clinical and cognitive assessments, stress tests and PET/MRI scans using identical protocols. The New York site will be the data management site including image analyses and statistics, and assay cortisols.