Melatonin in Menopausal Depression

褪黑激素治疗更年期抑郁症

• 批准号: 8196932
• 负责人: BARBARA L PARRY
• 金额: $ 51.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-21 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196932
• 关键词: Affect; Age; Animal Model; Animals; Area Under Curve; Arousal; Attention; Body mass index; Breeding; Cardiovascular system; Chronobiology; Circadian Rhythms; DSM-IV; Darkness; Data; Depressed mood; Depressive disorder; Development; Disease; Endocrine; Estrogens; Exposure to; Feedback; Follicle Stimulating Hormone; Frequencies; Funding; Future; Gonadal Steroid Hormones; Gonadotropins; Grant; Hamsters; Hormones; Hour; Hydrocortisone; Hypogonadism; Hypothalamic structure; Individual; Interview; Investigation; Lead; Light; Lighting; Literature; Measures; Medical; Melatonin; Menopausal Status; Menopause; Mental Depression; Modeling; Moods; Morbidity - disease rate; Neuraxis; Neurosecretory Systems; Outcome Measure; Pathogenesis; Patients; Phase; Plasma; Polysomnography; Postmenopause; Postpartum Depression; Pregnancy; Prolactin; Regulation; Reproductive system; Role; Sampling; Severities; Sleep; Sleep Wake Cycle; Steroids; System; Testing; Time; United States National Institutes of Health; Woman; Work; base; day length; depressive symptoms; effective therapy; innovation; mortality; reproductive; single episode major depressive disorder; treatment strategy

DESCRIPTION (provided by applicant): Now a clearly identified phenomenon, a major depressive episode at menopause can cause extensive morbidity and mortality. Its pathogenesis and treatment, however, have not been systematically investigated. Medical studies have focused on the cardiovascular and reproductive systems, with relatively little attention being paid to the central nervous system. We have observed increased melatonin secretion and delayed morning offset in menopausal depressed patients (DP) compared with normal control (NC) women. The aim of this revised application is to test the hypothesis that compared with NC women, menopausal DP have increased melatonin amplitude and delayed morning offset, attributable primarily to alterations in a) light/dark and sleep/wake cycles and b) reproductive and other endocrine functions. According to our conceptual model, menopausal DP have a decreased hypothalamic sensitivity to gonadal steroids, which disrupts the normal regulation of circadian rhythms, and is manifested in increased melatonin secretion with delayed morning offset. Increased arousals in dim light at night, resulting in delayed wake time with decreased and delayed exposure to morning bright light, increased daytime sleep or insufficient or decreased sensitivity to light exposure, exacerbate the problem. Reminiscent of the findings in hamsters during extended dark periods at night in winter, menopausal DP have increased melatonin duration, extended sleep time, recent hypogonadism, higher Follicle Stimulating Hormone (FSH) levels and Body Mass Index (BMI) that correlate with depression ratings. Our aim in this proposal is to extend and replicate our preliminary findings of abnormal melatonin secretion in menopausal DP and investigate the likely contributing factors of light, sleep, activity and reproductive endocrine function, as a basis for developing treatments targeted to specific pathogenic factors in future studies. In 50 peri- or post-menopausal DP by DSM-IV criteria, and in 50 NC women, matched for age and menopausal status, we will measure the phase, amplitude, waveform and temporal relations among 24-hour cycles of plasma melatonin (30 minute sampling in dim light), illumination, sleep and activity (by polysomnography and Actillume), as well as reproductive endocrine function (by gonadotropin and steroid levels) and BMI, in relation to mood. As an extension of our ongoing investigation of the chronobiology of premenstrual, pregnancy and postpartum depression, this study has the potential to lead to the development of new hypotheses and treatment strategies. The findings may impact the understanding of other depressive disorders related to the reproductive cycle in women. It also will confirm and extend our understanding of chronobiological abnormalities in depressed women as the basis for developing innovative treatments.

描述（由申请人提供）：现在是一种清晰确定的现象，更年期的主要抑郁发作可能会导致广泛的发病率和死亡率。然而，尚未系统地研究其发病机理和治疗。医学研究集中在心血管和生殖系统上，对中枢神经系统的关注很少。我们观察到与正常对照（NC）女性相比，更年期抑郁症患者（DP）的褪黑激素分泌增加并延迟了早晨反应。这项修订的应用的目的是检验以下假设：与NC妇女相比，更年期DP增加了褪黑激素振幅并延迟了早晨偏移，主要归因于a）光/黑暗和睡眠/唤醒周期以及b）生殖和其他内分泌功能。根据我们的概念模型，更年期DP对性腺类固醇的下丘脑敏感性降低，这破坏了昼夜节律的正常调节，并且表现为褪黑激素分泌的增加，而早晨延迟的抵消。夜间在昏暗的光线下增加唤醒，从而导致唤醒时间延迟，并且延迟暴露于早晨光线，白天睡眠增加或不足或对光暴露的敏感性不足或降低，这加剧了问题。让人联想到冬季夜间长期黑暗时期的仓鼠发现，更年期DP增加了褪黑激素的持续时间，延长的睡眠时间，最近的性腺功能减退，较高的卵泡刺激激素（FSH）水平和体重指数（BMI），与抑郁评分相关。我们在该提案中的目的是扩展和复制我们对绝经中DP异常褪黑激素分泌的初步发现，并研究可能在未来研究中开发针对特定病原因素的治疗的光，睡眠，活性和生殖内分泌功能的可能促成因素。 In 50 peri- or post-menopausal DP by DSM-IV criteria, and in 50 NC women, matched for age and menopausal status, we will measure the phase, amplitude, waveform and temporal relations among 24-hour cycles of plasma melatonin (30 minute sampling in dim light), illumination, sleep and activity (by polysomnography and Actillume), as well as reproductive endocrine function (by促性腺激素和类固醇水平）和BMI，与情绪有关。作为我们正在进行的对经前，妊娠和产后抑郁症年代生物学的研究的扩展，这项研究有可能导致发展新的假设和治疗策略。这些发现可能会影响对与女性生殖周期有关的其他抑郁症的理解。它还将确认并扩展我们对抑郁妇女的年度生物学异常的理解，作为发展创新治疗的基础。