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

描述（由申请人提供）：这个指导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。候选人凯瑟琳M. Sharkey，MD，PhD，是一名医生，科学家，具有睡眠和昼夜节律研究的多学科背景，并在精神病学，内科学和睡眠医学方面进行临床培训。该奖项为Sharkey博士提供遗传学，高级统计学，精神病学研究方法和妇女心理健康方面的强化培训。培训包括正式的教学法，监督动手教程，并指导研究。主要导师，玛丽A。Carskadon博士是EP布拉德利医院睡眠和时间生物学实验室的主任，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）。共同导师，Teri Pearlstein，医学博士，妇女和婴儿医院（WIH）行为健康主任，Caron Zlotnick，博士，WIH妇女行为健康研究主任，提供围产期情绪障碍的临床和研究培训。共同导师瓦莱丽Knopik，博士，主任，行为遗传学在罗得岛医院，和约翰McGeary，博士，主任，普罗维登斯VA医疗中心分子遗传学实验室，监督候选人的统计和定量，分子和精神病学遗传学的培训。Sharkey博士建议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。睡眠和情绪进行了评估，在125名妇女在怀孕第三个三个月，产后2，6和16周。参与者接受理论上选择的5-羟色胺和生物钟基因多态性的基因分型。数据分析使用潜在增长模型、结构方程模型和考克斯回归来检查睡眠、情绪和假定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一种情绪障碍中间表型：与围产期睡眠变化相关的产后情绪发作的妇女。建议的培训准备博士Sharkey未来的工作研究生物调节过程和遗传因素介导的情绪调节的相互作用。这种前瞻性的方法检查围产期睡眠作为神经行为触发情绪发作的遗传脆弱的妇女产后和其他情绪障碍的未来研究提供了一个框架。这项建议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，那么可以为那些风险最高的女性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妇女。有证据表明，产后期间的睡眠障碍会影响产妇的心理健康，这也为改善产假和重返工作岗位政策的举措提供了支持。

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.