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

产后抑郁症：睡眠的作用

• 批准号: 8580939
• 负责人: Katherine M Sharkey
• 金额: $ 16.88万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 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/8580939
• 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; public health relevance; single episode major depressive disorder; statistics; treatment strategy

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.

描述（由申请人提供）：这项指导的面向患者的研究职业发展奖（K23）提案概述了5年的培训和研究，以使候选人作为独立研究员的神经行为和遗传障碍的神经行为和遗传方面。候选人凯瑟琳·M·沙基（Katherine M.该奖项为Sharkey博士提供了遗传学，高级统计，精神病研究方法和妇女心理健康的培训。培训包括正式的教学，有监督的动手教程和指导研究。 EP Bradley Hospital Sleep and Chronobiology实验室主任Mary A. Carskadon的首席导师，负责监督培训计划，并指导候选人生物行为措施（例如睡眠）。妇女和婴儿医院（WIH）行为健康总监Teri Pearlstein的联合官员和WIH妇女行为健康研究研究主任Caron Zlotnick博士提供围产期情绪障碍的临床和研究培训。联合给出者Valerie Knopik博士，罗德岛医院行为遗传学部主任和普罗维登斯·麦吉里（John McGeary）博士，普罗维登斯·弗吉尼亚州医学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对候选人的培训。 Sharkey博士提议的核心是对患有重度抑郁症或躁郁症病史的围产期女性的情绪，睡眠和遗传风险的前瞻性纵向研究。在怀孕的第三个三个月以及产后2、6和16周的125名妇女中评估睡眠和情绪。参与者接受理论选择的5-羟色胺和昼夜节律基因多态性的基因分型。数据分析使用潜在的增长模型，结构方程模型和COX回归来检查睡眠，情绪和推定风险遗传多态性之间的关联。该项目的一个重要结果是定义情绪障碍中间表型：发展与围产期睡眠变化有关的产后情绪发作的女性。拟议的培训为Sharkey博士准备了未来的工作，以研究生物调节过程的相互作用和介导情绪调节的遗传因素的相互作用。这种前瞻性方法将围产期睡眠视为遗传脆弱女性情绪发作的神经行为触发因素，为未来对产后和其他情绪障碍的研究提供了框架。该提案中的调查线具有临床和公共政策的影响。睡眠障碍可能是发展产后情绪发作的可修改风险因素。如果一部分妇女在遗传上容易受到产后睡眠障碍的攻击，则可以为处于最高风险的人开发创新的预防和治疗策略。将来，这项工作可以扩展到包括没有精神病史的女性。产后期间睡眠障碍影响孕产妇心理健康的证据也为改善产假和重返工作政策的举措提供了支持。