Peri-Partum Depression/Genetics Glucocorticoid Receptor

围产期抑郁症/遗传学糖皮质激素受体

• 批准号: 7148723
• 负责人: ELISABETH B. BINDER
• 金额: $ 20.66万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7148723
• 关键词: behavioral /social science research tag; behavioral genetics; blood tests; clinical research; corticosteroid receptors; estrogens; female; genetic regulatory element; genetic susceptibility; glucocorticoids; hormone regulation /control mechanism; human genetic material tag; human pregnant subject; human subject; major depression; neuroendocrine system; postpartum depression; pregnancy; progesterone; psychopathology; single nucleotide polymorphism; women' s health

DESCRIPTION (provided by applicant): Major depression during pregnancy and the postpartum period is a major women's health concern. Previous investigations have demonstrated that maternal depression during pregnancy is a risk factor for pre-term birth and low birth weight, negative effects on child development and altered neuroendocrine responses and neurotransmitter levels in children. A recently completed collaborative investigation of predictors of maternal depression during pregnancy, demonstrated a 68% relapse rate for those discontinuing antidepressants and remarkably a 28% relapse rate in women who choose to continue antidepressants. Despite the clear public- health importance of depression during pregnancy, and the likelihood that some women may be genetically vulnerable to develop depression independent of treatment choices, the research assessing genetic factors influencing vulnerability for depression during pregnancy are sparse. This proposal will begin to address this understudied area of women's health research consistent with themes in two program announcements: Women's Mental Health in Pregnancy and Postpartum (PA-03-135) and Women's Mental Health and Sex/Gender Differences in Research (PA-03-143). The current proposal will examine the genetic influences on neurohormonal alterations that are potential modulators of maternal risk for depression during pregnancy and is planned as an Exploratory/Developmental grant (R21) in response to PA-03-135. The overarching hypothesis guiding the current proposal is that glucocorticoids and progesterone alter the expression of the glucocorticoid receptor (GR)-regulating co-chaperone FKBP5 and other GR-associated regulatory molecules, during pregnancy, leading to adaptive GR resistance during this period. Dysfunction of GR regulation due to sequence variation in genes encoding such regulatory proteins may leave some women vulnerable to GR-mediated deleterious effects in key brain regions, thus predisposing them to depressive symptoms during the ante- and postpartum periods. Relevance to public health: Expanding the knowledge base on the genetic mechanisms potentially contributing to maternal depression during pregnancy will facilitate early identification of women at risk. Such 'a priori' identification of women at risk will directly contribute to treatment planning and enhancement of perinatal health, obstetrical outcome, and infant well-being.

描述（由申请人提供）：怀孕期间和产后期间的严重抑郁症是妇女的主要健康问题。以往的研究表明，母亲在怀孕期间的抑郁症是早产和低出生体重的危险因素，对儿童发育产生负面影响，并改变儿童的神经内分泌反应和神经递质水平。最近完成的一项关于怀孕期间母亲抑郁症预测因素的合作调查显示，那些停止抗抑郁药的女性复发率为68%，而选择继续抗抑郁药的女性复发率为28%。尽管怀孕期间抑郁症对公共卫生的重要性很明显，而且一些妇女可能在遗传上容易患上抑郁症，而不受治疗选择的影响，但评估影响怀孕期间抑郁症易感性的遗传因素的研究很少。该提案将开始处理妇女健康研究这一未充分研究的领域，与两项方案公告的主题一致：怀孕和产后妇女心理健康（PA-03 - 135）和研究中的妇女心理健康和性/性别差异（PA-03 - 143）。目前的提案将研究对神经激素改变的遗传影响，这些神经激素改变是怀孕期间母亲抑郁风险的潜在调节剂，并计划作为PA-03 - 135的探索/发展补助金（R21）。指导当前提案的首要假设是，糖皮质激素和黄体酮在怀孕期间改变糖皮质激素受体（GR）调节辅伴侣FKBP 5和其他GR相关调节分子的表达，导致在此期间产生适应性GR抵抗。由于编码这种调节蛋白的基因的序列变异导致的GR调节功能障碍可能使一些妇女在关键脑区容易受到GR介导的有害影响，从而使她们在产前和产后期间易患抑郁症状。与公共卫生的相关性：扩大对可能导致母亲怀孕期间抑郁症的遗传机制的知识基础，将有助于早期识别有风险的妇女。这种"先验的"确定妇女的风险将直接有助于治疗规划和提高围产期健康，产科结果，和婴儿的福祉。