The Impact of Folate, Obesity and Genetics on Maternal Depression

叶酸、肥胖和遗传对孕产妇抑郁症的影响

• 批准号: 9104220
• 负责人: Lyndsay Ammon Avalos
• 金额: $ 20.53万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-25 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9104220
• 关键词: Accounting; Address; Adult; Aging; Anabolism; Area; Award; Basic Science; Blood specimen; Breast Feeding; California; Cohort Studies; Complex; DHFR gene; Data; Databases; Development; Diet; Diet Modification; Dopamine; Drug Kinetics; Effectiveness; Enrollment; Environment; Epidemiologic Studies; Epidemiology; FOLH1 gene; Family; Female of child bearing age; Fetus; Folic Acid; Food; Food Supplementation; Food Supply; Frequencies; Funding; Future; Genes; Genetic; Genetic Variation; Genotype; Health; High Risk Woman; Infant; Intake; Intervention; K-Series Research Career Programs; Link; MTHFR gene; Mental Depression; Mentored Research Scientist Development Award; Mentors; Metabolic Pathway; Metabolism; Mothers; Neurotransmitters; Norepinephrine; Nutrient; Obesity; Participant; Perinatal Epidemiology; Pharmacotherapy; Play; Population; Population Heterogeneity; Postpartum Depression; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnant Women; Prevalence; Prevention; Preventive Intervention; Public Health; Questionnaires; Recommended Daily Allowances; Recruitment Activity; Research; Research Personnel; Research Priority; Research Training; Resources; Risk; Role; SLC19A1 gene; Safety; Serotonin; Serum; Serum Folate Level; Single Nucleotide Polymorphism; Surveys; TYMS gene; Training; United States National Institutes of Health; Variant; Woman; alternative treatment; antepartum depression; base; cohort; critical period; depression prevention; diagnostic screening; dietary supplements; effective intervention; ethnic diversity; experience; folic acid metabolism; fortification; gene environment interaction; genetic epidemiology; genetic profiling; genetic variant; high risk; maternal depression; neurotransmitter metabolism; nutrition; nutrition related genetics; prevent; programs; reproductive epidemiology; response

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.

描述（由申请人提供）：这项修订后的K01研究职业发展奖重新提交将为Avalos博士提供必要的培训，以建立一项独立的研究计划，旨在了解孕产妇抑郁症的决定因素，以告知和开发针对高风险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，开发预防干预措施的两个有希望的领域，可能是针对当前药物治疗的孕产妇抑郁症的辅助治疗方法是营养和遗传学。在这个奖项中，她建议通过将培训和研究重点放在与孕产妇抑郁症有关的营养和遗传因素上，以扩大生殖和围产期流行病学的背景。她建议通过课程和量身定制的营养，抑郁和遗传学教程进行培训。孕产妇抑郁症的患病率范围为6-12％的抑郁症（APD）和产后抑郁症（PPD）的15％-20％。目前的治疗方案的局限性主张研究以理解孕产妇抑郁症的决定因素，以制定安全有效的干预措施。研究表明叶酸与抑郁症之间有联系。叶酸在孕产妇抑郁症中的重要性是由怀孕期间增加的需求和研究表明孕妇的饮食叶酸摄入量不足，尽管食物供应和补充剂进行了强化。建议的叶酸的每日津贴不是为抑郁症建立的，尚不知道什么水平会影响抑郁症，或者是否有某些妇女由于肥胖或遗传学​​而可能更脆弱。第一个研究目的将检查饮食叶酸摄入量和早期妊娠早期血清叶酸水平是否会影响孕产妇抑郁症的风险。阿瓦洛斯博士还将探索肥胖妇女是否特别容易受到叶酸对孕产妇抑郁症的影响。第二个目的是评估叶酸代谢途径相对于PPD的遗传变异。肥胖的作用将再次确定。为了解决这些目标，Avalos博士将在Kaiser Permanente Northerente（KPNC）基因，环境和健康研究计划中将调查数据和EMR数据联系起来。第一项研究是一项妊娠队列，由1555名基线时没有抑郁症的妇女填写了食物频率问卷，其中一个子样本给出了血液样本。 EMR数据将用于确定有关APD和PPD的筛选和诊断信息。第二项研究包括3458名妇女（655名PPD和2803名没有PPD的女性），他们参加了基因分型的成人健康和衰老队列的遗传流行病学研究。鉴于广泛的EMR数据库，获得大量不同的会员资格以及国际认可的研究人员，KPNC的研究部是进行拟议研究的理想环境。拟议的培训和研究计划对于为Avalos博士提供了一个成功竞争R01资金的平台至关重要，以成为孕产妇抑郁症的主要研究人员。

项目成果

The Kaiser Permanente Northern California research program on genes, environment, and health (RPGEH) pregnancy cohort: study design, methodology and baseline characteristics.

• DOI: 10.1186/s12884-016-1150-2
• 发表时间: 2016-11-29
• 期刊: BMC pregnancy and childbirth
• 影响因子: 3.1
• 作者: Hedderson MM;Ferrara A;Avalos LA;Van den Eeden SK;Gunderson EP;Li DK;Altschuler A;Woo S;Rowell S;Choudhary V;Xu F;Flanagan T;Schaefer C;Croen LA
• 通讯作者: Croen LA