The Impact of Folate, Obesity and Genetics on Maternal Depression

描述（由申请人提供）：本次修订的K01指导研究职业发展奖将为Avalos博士提供必要的培训，以建立一个独立的研究项目，专注于了解母亲抑郁症的决定因素，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。来自基础科学和流行病学的研究表明，营养和遗传学是两个有希望发展预防干预措施的领域，也可能是目前药物治疗对产妇抑郁症的辅助治疗。在这个奖项中，她建议通过将她的培训和研究目标集中在与母亲抑郁症相关的营养和遗传因素上，扩大她在生殖和围产期流行病学方面的背景。她建议通过课程和营养、抑郁症和遗传学方面的量身定制教程进行指导培训。产前抑郁（APD）的发生率为6-12%，产后抑郁（PPD）的发生率为15%-20%。当前治疗方案的局限性要求研究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。怀孕期间叶酸需求的增加和研究表明，尽管加强了食物供应和补充，但孕妇饮食中叶酸摄入量不足，这突显了叶酸在母亲抑郁症中的重要性。叶酸的每日推荐摄取量并不是针对抑郁症制定的，也不知道什么水平的叶酸会影响抑郁症，也不知道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妊娠早期膳食叶酸摄入量和血清叶酸水平是否会影响产妇患抑郁症的风险。阿瓦洛斯博士还将探讨肥胖女性是否特别容易受到叶酸对产妇抑郁症的影响。第二个目的是评估与PPD相关的叶酸代谢途径的遗传变异。肥胖的作用将再次被确定。为了实现这些目标，阿瓦洛斯博士将把凯泽医疗北加州（KPNC）基因、环境和健康研究项目的两项研究的调查数据和电子病历数据联系起来。第一项研究是对1555名没有抑郁症的孕妇进行队列研究，她们完成了一份食物频率调查问卷，其中一个子样本提供了血液样本。电子病历数据将用于确定APD和PPD的筛查和诊断信息。第二项研究纳入了3458名参加成人健康与老龄化遗传流行病学研究的女性（其中有PPD的655名，无PPD的2803名），并进行了基因分型。KPNC的研究部是开展拟议研究的理想环境，因为它拥有广泛的EMR数据库，可以访问大量不同的成员，以及国际公认的研究人员。拟议的培训和研究计划至关重要，它为阿瓦洛斯博士提供了一个平台，使他能够成功地竞争R01基金，成为母亲抑郁症领域的领先研究人员。

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.