The Impact of Folate, Obesity and Genetics on Maternal Depression

描述（由申请人提供）：此修订后的K 01指导研究职业发展奖重新提交将为Avalos博士提供必要的培训，以建立一个独立的研究计划，重点是了解孕产妇抑郁症的决定因素，为高危人群提供信息和制定有针对性的预防和治疗干预措施。基础科学和流行病学的研究表明，营养和遗传学是制定预防干预措施和可能对目前的孕产妇抑郁症药物疗法进行后续治疗的两个有前途的领域。在这个奖项，她建议扩大她在生殖和围产期流行病学的背景，她的培训和研究目标集中在营养和遗传因素与孕产妇抑郁症。她建议通过课程和营养、抑郁和遗传学方面的定制教程进行指导培训。产妇抑郁症的患病率范围为6-12%的产前抑郁症（APD）和15%-20%的产后抑郁症（PPD）。目前的治疗方案的局限性认为，研究，以了解产妇抑郁症的决定因素，以制定安全有效的干预措施。研究表明叶酸和抑郁症之间存在联系。叶酸在母亲抑郁症中的重要性突出表现在怀孕期间需求增加，研究表明，尽管加强了食物供应和补充，但孕妇的膳食叶酸摄入量不足。叶酸的推荐每日摄入量并没有为抑郁症建立，目前还不知道什么水平可能会影响抑郁症，或者是否有某些女性由于肥胖或遗传而更容易受到影响。第一个研究目标是检查怀孕早期的膳食叶酸摄入量和血清叶酸水平是否会影响母亲抑郁的风险。Avalos博士还将探讨肥胖女性是否特别容易受到叶酸对母亲抑郁症的影响。第二个目的是评估与PPD相关的叶酸代谢途径的遗传变异。肥胖的作用将再次确定。为了实现这些目标，Avalos博士将把北方加州凯泽永久机构（KPNC）基因、环境和健康研究项目的两项研究的调查数据和EMR数据联系起来。第一项研究是1555名在基线时没有抑郁症的孕妇，他们完成了食物频率问卷，其中一个子样本提供了血液样本。EMR数据将用于确定APD和PPD的筛查和诊断信息。第二项研究包括3458名妇女（655名患有PPD，2803名没有PPD），他们参加了成人健康和老龄化队列的遗传流行病学研究，该研究已经进行了基因分型。KPNC的研究部门是一个理想的环境，进行拟议的研究给予广泛的电子病历数据库，访问大量不同的成员，和国际公认的调查。拟议的培训和研究计划对于为Avalos博士提供一个成功竞争R 01资金的平台，使其成为孕产妇抑郁症的领先研究人员至关重要。

DESCRIPTION (provided by applicant): This revised K01 Mentored Research Career Development Award resubmission will provide the training necessary for Dr. Avalos to establish an independent research program focused on understanding determinants of maternal depression to inform and develop targeted prevention and treatment interventions for high-risk populations. Research from the basic sciences and epidemiology suggest two promising areas for developing prevention interventions and possibly for adjunctive treatment to current pharmacotherapy for maternal depression are nutrition and genetics. In this award she proposes to expand her background in reproductive and perinatal epidemiology by focusing her training and research aims on nutritional and genetic factors in relation to maternal depression. She proposes mentored training through coursework and tailored tutorials in nutrition, depression and genetics. The prevalence of maternal depression ranges from 6-12% for antepartum depression (APD) and 15%-20% for postpartum depression (PPD). Limitations with current treatment options argue for research to understand determinants of maternal depression for the purpose of developing safe and effective interventions. Research suggests a link between folate and depression. The significance of folate in maternal depression is underscored by increased needs during pregnancy and research indicating inadequate dietary folate intake by pregnant women, despite fortification of the food supply and supplementation. The Recommended Daily Allowance for folate was not established for depression, and it is not known what levels may impact depression or if there are certain women who may be more vulnerable due to obesity or genetics. The first research aim will examine whether dietary folate intake and serum folate levels in early pregnancy impact the risk of maternal depression. Dr. Avalos will also explore whether obese women are particularly vulnerable to the impact of folate on maternal depression. The second aim is to evaluate genetic variations of the folate metabolic pathway in relation to PPD. The role of obesity will again be determined. To address these aims, Dr. Avalos will link survey data and EMR data for two studies in Kaiser Permanente Northern California's (KPNC) Research Program on Genes, Environment and Health. The first study is a pregnancy cohort of 1555 women without depression at baseline who completed a Food Frequency Questionnaire and of whom a subsample gave a blood sample. EMR data will be used to ascertain screening and diagnostic information on APD and PPD. The second study includes 3458 women (655 with PPD and 2803 without PPD) who participated in the Genetic Epidemiology Research in Adult Health and Aging cohort which has been genotyped. KPNC's Division of Research is an ideal environment for conducting the proposed research given the extensive EMR databases, access to a large diverse membership, and internationally- recognized investigators. The proposed training and research plan are crucial for providing a platform for Dr. Avalos to compete successfully for R01 funding to become a leading researcher in maternal depression.