The Impact of Folate, Obesity and Genetics on Maternal Depression

描述(由申请人提供)：这份修订后的K01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，专注于了解产妇抑郁的决定因素，以告知和开发针对高危人群的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，营养和遗传学是开发预防干预措施的两个有希望的领域，可能还可以作为目前治疗产妇抑郁症药物治疗的辅助治疗。在这一奖项中，她建议通过将她的培训和研究目标集中在与产妇抑郁有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。她建议通过课程作业和营养、抑郁症和遗传学方面的量身定做的教程进行辅导培训。产妇抑郁的患病率从产前抑郁的6-12%和产后抑郁的15%-20%不等。目前治疗方案的局限性要求进行研究，以了解母亲抑郁的决定因素，以开发安全有效的干预措施。研究表明，叶酸与抑郁症之间存在联系。尽管加强了食物供应和补充，但孕期需求增加和研究表明，孕妇饮食中叶酸摄入量不足，这突显了叶酸在孕产妇抑郁中的重要性。推荐的叶酸每日摄入量并不是为抑郁症制定的，也不知道什么水平可能会影响抑郁症，也不知道是否有某些女性可能由于肥胖或遗传而更容易受到影响。第一个研究目标将检验怀孕早期饮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。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的影响。第二个目的是评估叶酸代谢途径的遗传变异与产后抑郁的关系。肥胖症的作用将再次被确定。为了实现这些目标，阿瓦洛斯博士将在北加州凯撒永久研究计划(KPNC)关于基因、环境和健康的两项研究中，将调查数据和EMR数据联系起来。第一项研究是1555名在基线水平没有抑郁的妇女的怀孕队列，她们完成了食物频率问卷，其中一个子样本提供了血液样本。电子病历数据将被用来确定apd和ppd的筛查和诊断信息。第二项研究包括3458名妇女(655名PPD患者和2803名非PPD患者)，她们参加了已进行基因分型的成人健康和老龄化队列遗传流行病学研究。KPNC的研究部是进行拟议研究的理想环境，因为它有广泛的电子病历数据库，可以接触到大量不同的成员，并且有国际公认的调查人员。拟议的培训和研究计划至关重要，可以为阿瓦洛斯博士提供一个平台，让他成功竞争R01的资金，成为产妇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.