2/2 - Familial Early-Onset Suicide Attempt Biomarkers

 描述(申请人提供)：美国的自杀率与60年前持平。更好的预防需要更多关于风险和弹性生物标记物的数据。我们试图确定严重抑郁障碍(MDD)患者自杀企图的复原力和易损性的潜在内在表型。这两种内表型可能有助于风险的估计，并为预防干预提供新的靶点。这项研究设计将健康志愿者(第1组)与患有MDD和自杀行为的父母的未服用药物的成年子女进行比较，这些子女处于危险年龄，因此可以分为弹性组(第4组)、有MDD素质的组(第2组)和有MDD和自杀企图的疾病组(第3组)。第二组和第三组的比较表明自杀行为的素质。组1和组4的比较表明为弹性表型。组1和组2的比较表明MDD的素质。这项研究是一个新的方向，基于我们几乎完整的纵向两点跟踪研究(Pi，J.John Mann，MD，MH056390，哥伦比亚大学，NYC和Pi，David Brent，MD，MH056612，UPMC，匹兹堡)，对334名患有情绪障碍的先证者的701名子女进行了题为《早发性自杀企图的家庭路径》的跟踪研究，试图确定自杀行为风险从父母传递给子女的机制。我们在认知、情绪调节和应激反应领域的风险特征方面的发现，以及调节5-HT1A自身受体释放的5-HT1A自身受体的脑部PET成像的新领域，将集中在寻找韧性和脆弱性表型。这项研究将涉及与目前资助的应用程序相同的两个业绩站点，截止日期为2015年1月。这两个团队已经合作了15年，两个团队都对抑郁症和自杀患者进行了PET研究。我们将从旧研究中招募符合条件的后代，并根据需要为四个组招募新的后代。这两个网站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。纽约站点将是数据管理站点，包括图像分析和统计以及皮质醇分析。

 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.