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

描述(由申请者提供)：这份以患者为导向的研究职业发展奖(K23)建议概述了5年的培训和研究，以装备候选人作为独立调查者检查情绪障碍的神经行为和遗传方面。候选人凯瑟琳·M·夏基，医学博士，是一名内科科学家，拥有睡眠和昼夜节律研究的多学科背景，并接受过精神病学、内科和睡眠医学的临床培训。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女性心理健康方面的强化培训。培训包括正式的教学、有指导的实践教程和有指导的研究。首席导师Mary A.Carskadon博士是EP Bradley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，妇女和婴儿医院(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。罗德岛医院行为遗传学部门主任Valerie Knopik博士和普罗维登斯VA医学中心分子遗传学实验室主任John McGeary博士共同指导候选人在统计学、定量、分子和精神病学遗传学方面的培训。夏基博士建议的核心是一项前瞻性的纵向研究，研究有严重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。125名妇女在怀孕第三个月、产后2周、6周和16周进行睡眠和情绪评估。参与者接受理论上选择的5-羟色胺和生物钟基因多态的基因分型。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、情绪和可能的风险基因多态之间的关联。该项目的一个重要成果是定义了情绪障碍的中间表型：与围产期睡眠变化有关的产后情绪发作的女性。拟议中的培训为夏基博士未来研究生物调节过程和调节情绪调节的遗传因素之间的相互作用做好了准备。这种前瞻性的方法研究了围产期睡眠作为遗传脆弱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一个框架。这项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。如果一组妇女在基因上容易受到产后睡眠障碍的影响，可以为那些风险最高的人开发创新的预防和治疗策略。在未来，这项工作可以扩展到包括没有精神病史的妇女。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倡议提供了支持。

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.