Postpartum Depression: Role of Sleep & Genetic Risk in Postpartum Mood Disorders

产后抑郁症：睡眠的作用

基本信息

批准号：
8044602
负责人：
Katherine M Sharkey
金额：
$ 17.97万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-12 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8044602
关键词：
Acute Affect Antidepressive Agents Award Behavioral Genetics Biological Models Bipolar Disorder Child Childbirth Chronic Chronobiology Circadian Rhythms Clinical Clinical Research Complication Cox Models DNA Data Analyses Depressed mood Development Diagnostic Doctor of Philosophy Economics Enrollment Equation Evaluation Future Genes Genetic Genetic Polymorphism Genetic Processes Genetic Risk Genotype Goals Growth Hamilton Rating Scale for Depression Hospitals Individual Infant Internal Medicine Interview Investigation Laboratories Link Longitudinal Studies Major Depressive Disorder Manic Maternity leave Measures Mediating Medical center Medicine Mental Health Mentored Patient-Oriented Research Career Development Award Mentors Modeling Molecular Genetics Mood Disorders Moods Morbidity - disease rate Mothers Outcome Participant Patients Pattern Perinatal Phenotype Physicians Play Policies Postpartum Depression Postpartum Period Postpartum Women Pregnancy Pregnancy Trimesters Prevention strategy Psychiatry Public Policy Quantitative Genetics Recording of previous events Relapse Research Research Methodology Research Personnel Research Project Grants Research Training Rhode Island Risk Risk Factors Role Scientist Serotonin Sleep Sleep Deprivation Sleep disturbances Structural Models Subgroup Suicide Symptoms System Testing Time Training Woman Work actigraphy base behavioral health biobehavior biological systems circadian pacemaker depressive symptoms economic cost experience follow-up high risk hypomania improved innovation modifiable risk mood regulation mortality multidisciplinary neurobehavioral policy implication prospective psychogenetics single episode major depressive disorder statistics treatment strategy

项目摘要

DESCRIPTION (provided by applicant): This Mentored Patient-Oriented Research Career Development Award (K23) proposal outlines 5 years of training and research to equip the candidate to examine neurobehavioral and genetic aspects of mood disorders as an independent investigator. The candidate, Katherine M. Sharkey, MD, PhD, is a physician-scientist with a multidisciplinary background of sleep and circadian rhythms research and clinical training in psychiatry, internal medicine, and sleep medicine. This award provides Dr. Sharkey intensive training in genetics, advanced statistics, psychiatric research methods, and women's mental health. Training includes formal didactics, supervised hands-on tutorials, and mentored research. Principal mentor, Mary A. Carskadon, PhD, Director of the EP Bradley Hospital Sleep and Chronobiology Laboratory, oversees the training plan and mentors the candidate on biobehavioral measures (e.g., sleep). Co-mentors, Teri Pearlstein, MD, Director of Women and Infants' Hospital (WIH) Behavioral Health, and Caron Zlotnick, PhD, Director of Research for Women's Behavioral Health at WIH, provide clinical and research training in perinatal mood disorders. Co-mentors Valerie Knopik, PhD, Director, Division of Behavioral Genetics at Rhode Island Hospital, and John McGeary, PhD, Director, Providence VA Medical Center Molecular Genetics Laboratory, supervise the candidate's training in statistics and quantitative, molecular, and psychiatric genetics. The centerpiece of Dr. Sharkey's proposal is a prospective longitudinal study of mood, sleep, and genetic risk in perinatal women with a history of major depressive disorder or bipolar disorder. Sleep and mood are assessed in 125 women at 3rd trimester of pregnancy, and 2, 6, and 16 weeks postpartum. Participants undergo genotyping for theoretically selected serotonin and circadian clock gene polymorphisms. Data analyses use latent growth modeling, structural equation modeling, and Cox regression to examine associations between sleep, mood, and putative risk genetic polymorphisms. An important outcome of the project is to define a mood disorder intermediate phenotype: women who develop a postpartum mood episode related to their perinatal sleep changes. The proposed training prepares Dr. Sharkey for future work examining interactions of bioregulatory processes and genetic factors mediating mood regulation. This prospective approach examining perinatal sleep as a neurobehavioral trigger for mood episodes in genetically vulnerable women provides a framework for future studies of postpartum and other mood disorders. The line of inquiry in this proposal has clinical and public policy implications. Sleep disturbance may be a modifiable risk factor for development of a postpartum mood episode. If a subset of women is genetically vulnerable to postpartum sleep disturbance, innovative prevention and treatment strategies can be developed for those at highest risk. In the future, this work can be extended to include women without a psychiatric history. Evidence that sleep disturbance during the postpartum period impacts maternal mental health also provides support for initiatives to improve maternity leave and return-to-work policies. PUBLIC HEALTH RELEVANCE: Postpartum depression is the most common complication of childbirth; it has been linked to morbidity and mortality (including suicide) in new mothers, poor child outcomes, and high economic costs. This study examines whether postpartum depression is related to sleep changes after childbirth in a subgroup of women, and whether genetics play a role in who is at risk. If we find that changes in sleep around the time of childbirth increase the risk of postpartum depression in certain women, prevention and treatment strategies aimed at stabilizing sleep during pregnancy and the postpartum period can be developed.

描述（由申请人提供）：这项以患者为导向的研究职业发展奖 (K23) 提案概述了 5 年的培训和研究，以使候选人能够作为独立研究者检查情绪障碍的神经行为和遗传方面。该候选人凯瑟琳·M·夏基 (Katherine M. Sharkey) 医学博士、哲学博士是一位医师兼科学家，拥有睡眠和昼夜节律研究以及精神病学、内科和睡眠医学方面的临床培训的多学科背景。该奖项为夏基博士提供遗传学、高级统计学、精神病学研究方法和女性心理健康方面的强化培训。培训包括正式教学、有监督的实践教程和指导研究。首席导师、EP Bradley 医院睡眠和时间生物学实验室主任 Mary A. Carskadon 博士负责监督培训计划并指导候选人进行生物行为测量（例如睡眠）。联合导师是妇婴医院 (WIH) 行为健康主任 Teri Pearlstein 医学博士和 WIH 妇女行为健康研究主任 Caron Zlotnick 博士，提供围产期情绪障碍的临床和研究培训。共同导师 Valerie Knopik 博士（罗德岛医院行为遗传学部主任）和 John McGeary 博士（普罗维登斯退伍军人医疗中心分子遗传学实验室主任）负责监督候选人在统计和定量、分子和精神遗传学方面的培训。夏基博士提案的核心是对有重度抑郁症或双相情感障碍病史的围产期妇女的情绪、睡眠和遗传风险进行前瞻性纵向研究。对 125 名女性在妊娠第三个月以及产后 2、6 和 16 周的睡眠和情绪进行了评估。参与者对理论上选择的血清素和生物钟基因多态性进行基因分型。数据分析使用潜在生长模型、结构方程模型和 Cox 回归来检查睡眠、情绪和假定的风险遗传多态性之间的关联。该项目的一个重要成果是定义情绪障碍中间表型：出现与围产期睡眠变化相关的产后情绪发作的女性。拟议的培训为夏基博士未来研究生物调节过程和介导情绪调节的遗传因素之间的相互作用做好准备。这种前瞻性方法将围产期睡眠视为遗传易受影响女性情绪发作的神经行为触发因素，为未来产后和其他情绪障碍的研究提供了框架。该提案中的调查路线具有临床和公共政策影响。睡眠障碍可能是产后情绪发作的一个可改变的危险因素。如果一部分女性在遗传上容易受到产后睡眠障碍的影响，那么可以为高危人群制定创新的预防和治疗策略。将来，这项工作可以扩展到没有精神病史的女性。产后睡眠障碍影响产妇心理健康的证据也为改善产假和重返工作岗位政策的举措提供了支持。公众健康相关性：产后抑郁症是最常见的分娩并发症；它与新妈妈的发病率和死亡率（包括自杀）、不良的儿童结局以及高昂的经济成本有关。这项研究探讨了产后抑郁症是否与女性亚群分娩后的睡眠变化有关，以及遗传是否在高危人群中发挥作用。如果我们发现分娩前后的睡眠变化会增加某些女性患产后抑郁症的风险，那么就可以制定旨在稳定怀孕期间和产后期睡眠的预防和治疗策略。