Genetics of Postpartum Depression in Affective Disorders

描述（由申请人提供）：该职业发展奖提案是一个五年计划，将使候选人发展成为情感障碍遗传学的独立研究者，重点是女性激素引发的症状。这位候选人是一位接受过情绪障碍培训的学术精神科医生，目前正在寻求遗传学和遗传流行病学方面的进一步培训。J. Raymond DePaulo， Jr博士，情感性障碍遗传学研究小组主任和约翰霍普金斯精神病学系主任，将指导候选人对精神病患者进行基因研究。约翰霍普金斯大学公共卫生学院教授Terri Beaty博士将指导候选人使用统计方法和遗传流行病学。北卡罗来纳大学精神病学教授兼主席David Rubinow博士和生殖内分泌学研究主任Peter Schmidt博士将指导候选人性激素的神经行为影响以及女性心理健康的临床和表型问题。培训计划将通过一项研究计划得到加强，该研究计划的假设是，患有产后抑郁症的女性在正常荷尔蒙变化时具有遗传脆弱性，这种变化包括对雌激素敏感的一个（或多个）基因的变异。该研究计划将利用先前收集的双相情感障碍和复发性重度抑郁症的家庭样本。根据初步数据显示，产后抑郁发作在重度抑郁症和双相情感障碍的家庭中是熟悉的，候选人将完成以下三个具体目标：1)完成这一特征的连锁分析；2)进行关联研究，特别是检查相关区域的基因，这些基因含有雌激素反应成分，因此可能容易受到产后期间激素波动的影响；3)开始收集有或没有产后抑郁症的重度抑郁症妇女的试验性样本。这项研究具有重要意义，因为它将使我们更好地了解患有情绪障碍的女性产后抑郁的病理生理学，并有可能有助于理解在女性群体中观察到的抑郁发作率增加的原因。

DESCRIPTION (provided by applicant): This career development award proposal is a five-year plan that will enable the candidate to develop into an independent investigator in the genetics of affective disorders with an emphasis on hormonally-triggered symptoms in women. The candidate is an academic psychiatrist with training in mood disorders who now seeks further training in genetics and genetic epidemiology. Dr. J. Raymond DePaulo, Jr, director of the Affective Disorders Genetics Research Group and Chair of the Johns Hopkins Department of Psychiatry will mentor the candidate on conducting genetic research in the psychiatric patient. Dr. Terri Beaty, Professor at the Johns Hopkins School of Public Health, will mentor the candidate on using statistical methods and genetic epidemiology. Dr. David Rubinow, Professor and Chair of Psychiatry at the University of North Carolina and Dr. Peter Schmidt, Chief of the Unit on Reproductive Endocrinology Studies, will mentor the candidate in both the neurobehavioral effects of gonaldal steroids as well as clinical and phenotypic issues in women's mental health. The training program will be enhanced by a research plan based on the hypothesis that women with postpartum depressive episodes have a genetic vulnerability to times of normal hormonal change that consists of variation in a gene (or genes) that is estrogen responsive. The research plan will take advantage of previously collected family samples of bipolar disorder and recurrent major depression. Based on preliminary data demonstrating the familiality of postpartum depressive episodes in families with major depression and bipolar disorder, the candidate will complete the following three specific aims: 1) complete a linkage analysis for this trait; 2) perform association studies, specifically examining genes in regions of interest which contain estrogen-response elements and thus may be susceptible to the hormone fluctuations that occur during the postpartum period; and 3) begin collection of a pilot sample of women with major depression with and without postpartum depression. The proposed research is significant because it will lead to a better understanding of the pathophysiology of postpartum depression in women with mood disorders as well as potentially contribute to understanding the increased rate of depressive episodes observed in women as a group.