Influences on the familiality of Major Depression among African-Americans

描述（由申请人提供）：这是一个新的申请职业过渡补助金在健康差距（K22），其中包括一个为期2年的研究培训在健康差距在美国国立卫生研究院的校内阶段，其次是一个为期3年的额外的指导和培训和执行本提案中所述的研究计划的校外阶段。该奖项的目标是发展候选人在精神疾病基因环境研究方法方面的专业知识，并促进候选人过渡到健康差异的独立研究生涯。世界卫生组织预测，到2020年，严重抑郁症将成为残疾和发病的第二大原因。虽然流行病学研究表明，非裔美国人的MDD发病率低于白人，但患有这种疾病的黑人比白人表现出更大的损害和慢性化。虽然一些研究表明，黑人中5-羟色胺转运蛋白5-HTTLPR基因变异频率较高可能对MDD具有保护作用，但由于缺乏数据证明与该人群中MDD和相关表型相关，因此尚未得到经验支持。目前，对黑人MDD的遗传和环境风险因素了解甚少，也没有正式的以家庭为基础的非裔美国人MDD研究。家庭研究特别有价值，因为它们可以提供有关特定疾病或病症的环境和可能的遗传因素的重要线索。在该奖项的校外阶段，候选人将执行一项研究计划，其具体目标是（1）成功地从纽约市地区招募120名患有重度抑郁症（MDD）的黑人先证者和120名年龄和性别匹配的非MDD“对照”样本，每个先证者最多有2名一级亲属，（2）确定先证者状态与一级亲属中MDD发生率之间的关联强度;（3）通过从唾液样本中提取DNA来收集DNA。先证者和亲属的精神病史将通过结构化诊断访谈和家族史访谈获得，并伴有关于早期环境生活事件、创伤性生活事件和人格特质的问卷调查。特定目标（2）的发现有望成为R 01资助的基础，用于分析为非裔美国人MDD基因-环境关联研究收集的DNA。候选人将把拟议的研究活动与全面的指导和培训计划相结合，该计划涵盖了以家庭为基础的遗传研究设计和方法（与导师Ruth Wellman博士，和顾问Myrna Weissman博士），家庭和遗传统计（与顾问Priya Wickramaratne博士，和Sue Hodge博士）以及文化和心理社会对非裔美国人中重度抑郁症流行病学的影响（与顾问詹姆斯杰克逊博士合作）。

DESCRIPTION (provided by applicant): This is a new application for a Career Transition Grant in Health Disparities (K22), which includes a 2-year intramural phase of research training in health disparities at the National Institutes of Health followed, by a 3-year extramural phase of additional mentoring and training and execution of the research plan described in this proposal. The goal of this award is to develop the candidate's expertise in gene-environment research methodology for psychiatric disorders, and to facilitate transition of the candidate into an independent research career in health disparities. The World Health Organization has projected that Major Depression will be the 2nd largest cause of disability and morbidity by the year 2020. Although epidemiological studies have documented lower rates of MDD among African-Americans than whites, blacks who suffer from the disorder evidence greater impairment and chronicity than Whites. While some research has suggested a possible protective effect against MDD caused by a higher frequency of the serotonin transporter 5-HTTLPR gene variant among Blacks, this has not been empirically supported due lack of data demonstrating an association to the MDD and related phenotypes in this population. Currently, the genetic and environmental risk factors for MDD in Blacks are poorly understood, and there have been no formal family-based studies of MDD in African-Americans. Family studies are particularly valuable because they can provide important clues about both environmental and possible genetic contributing factors to a particular illness or condition. During the extramural phase of this award, the candidate will execute a research plan, the specific aims of which are to (1) successfully recruit from the New York City area, a sample of 120 black probands with Major Depressive Disorder (MDD) and 120 non-MDD "controls" matched by age and sex, with up to 2 first degree relatives per proband, (2) determine the strength of the association between proband status and rates of MDD among first-degree relatives, and (3) collect DNA through extraction from saliva samples, which will be . Psychiatric history from probands and relatives will be obtained from structured diagnostic interviews and family history interviews, accompanied by questionnaires on early environmental life events, traumatic life events, and personality traits. The findings from specific aim (2) are expected to form the basis of an R01 grant to analyze the DNA collected for a gene- environment association study of MDD in African-Americans. The candidate will integrate the proposed research activities with a comprehensive mentoring and training plan, which covers family-based genetic research design and methodology (with mentor Ruth Ottman, Ph.D., and Consultant Myrna Weissman, Ph.D.), family and genetic statistics (with consultants Priya Wickramaratne, Ph.D., and Sue Hodge, Ph.D.,) and cultural and psycho-social influences on the epidemiology of Major Depressive Disorder in African-Americans (with consultant James Jackson, Ph.D).