GENDER DIFFERENCES IN EFFECTS OF SEASON ON PATTERNS OF NOCTURNAL MELATONIN

季节对夜间褪黑激素模式影响的性别差异

• 批准号: 6162949
• 负责人: T A WEHR
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162949
• 关键词: circadian rhythms; clinical research; gender difference; human subject; human therapy evaluation; melatonin; phototherapy; pineal body; seasonal affective disorder; seasons; secretion

In animals, the hormone, melatonin, plays an important role as a chemical mediator of the effects of season on behavior. In many instances, changes in the length of the night serve as the environmental signal that triggers seasonal changes in behavior. Melatonin is secreted exclusively at night, and the duration of its secretion varies with seasonal variations in the length of the night. Because of these properties, many organisms use changes in the duration of nocturnal melatonin secretion as a chemical cue to trigger changes in functions, such as breeding, that vary on a seasonal basis. Our recent research (Z01 MH 02424-01 CP) showed that humans, in the course of their evolution, have conserved brain mechanisms similar to those that exist in animals that enable them to detect seasonal changes in night-length and modify the duration of nocturnal melatonin secretion. Human responses to change in photoperiod were detected in experimental conditions in which individuals were exposed to long and short artificial "days". In a subsequent experiment (Z01 MH 02424-01 CP) we investigated whether healthy individuals living in a modern, urban environment (metro Washington, DC area), in which they are routinely exposed to artificial light, are still able to detect seasonal changes in the duration of the night and to respond to these changes by modifying the duration of the nocturnal period of melatonin secretion. We found that patterns of nocturnal melatonin secretion in women responded to seasonal changes in the duration of the night, while those in men did not. This finding suggests that there may be gender differences in responsiveness to artificial light of mechanisms that track seasonal changes in the length of the night. Because of the importance of the duration of nocturnal melatonin secretion as a transducer of the effects of seasonal changes in the length of the night on animal behavior, it would be important to investigate whether melatonin plays a role in the pathogenesis of seasonal affective disorder (SAD) with recurrent winter depression. Accordingly, in this project, we are assessing whether or not the duration of nocturnal melatonin secretion varies on a seasonal basis in women with SAD, as it does in healthy women. In 28 patients and 30 matched controls, melatonin was abnormally unresponsive to change of season in women with SAD, raising the possibility that SAD results when the pineal gland fails to exhibit a seasonal response that normally occurs in healthy women. In contrast, 9 patients and 15 matched controls, we found that melatonin is responsive to change of season in men with SAD but not in healthy men, a result that is consistent with the classic hypothesis that changes in duration of melatonin secretion trigger winter depression in SAD. The number of male subjects will be increased during the next two years to rule out Type II error. An important post hoc finding in these studies was that seasonal changes in the intrinsic duration of nocturnal melatonin secretion are almost entirely a function of seasonal changes in the timing of morning offset of secretion. This finding indicates that the degree to which individuals' melatonin secretion responds to seasonal changes in night length as a function of their exposure to, or processing of, morning light. This finding provides an important clue in our quest to understand why some individuals respond to change of season while others do not.

在动物体内，褪黑激素作为一种化学物质， 季节对行为影响的中介。 在许多情况下， 作为环境信号， 行为的季节性变化。 褪黑激素只在晚上分泌， 其分泌的持续时间随季节变化而变化， 夜晚的长度。 由于这些特性，许多生物体 夜间褪黑激素分泌持续时间的变化作为化学线索 以触发功能的变化，如繁殖，在季节性变化， 基础 我们最近的研究（Z 01 MH 02424-01 CP）表明， 在进化的过程中，它们保留了类似于 这些存在于动物体内的蛋白质，使它们能够检测到季节性变化， 夜间长度和修改夜间褪黑激素分泌的持续时间。 在实验中检测了人类对光周期变化的反应。 个人暴露在长时间和短时间的人工 “天”。 在随后的实验（Z 01 MH 02424-01 CP）中，我们研究了 无论是生活在现代城市环境中的健康人（地铁）， 华盛顿，DC地区），在那里他们经常暴露在人工 光，仍然能够检测季节变化的持续时间， 夜间，并通过修改持续时间来应对这些变化， 褪黑激素的夜间分泌。 我们发现， 女性夜间褪黑激素分泌对季节变化的反应 夜，而人，则不为所动。 这一发现 这表明，在对以下问题的反应方面可能存在性别差异： 人工照明的机制，跟踪季节性变化的长度 夜晚。 由于夜间褪黑激素分泌持续时间的重要性 作为一个传感器的影响，季节变化的长度， 在动物行为的夜晚，重要的是要调查是否 褪黑激素在季节性情感障碍的发病机制中起作用 (SAD)冬季抑郁症复发 因此，在本项目中，我们 正在评估夜间褪黑激素分泌的持续时间 与健康女性一样，SAD女性的季节性变化也不同。 在28名患者和30名匹配的对照者中， 对SAD女性的季节变化反应迟钝， SAD的可能性，当松果体未能表现出 季节性反应，通常发生在健康女性身上。 相比之下，9 患者和15名匹配的对照组中，我们发现褪黑激素对 季节的变化在SAD患者中，但在健康男性中则不然，这是一个结果， 与经典假设一致， 褪黑激素分泌触发SAD患者冬季抑郁。 的男 未来两年将增加受试者，以排除II型 错误. 这些研究中一个重要的事后发现是， 在夜间褪黑激素分泌的内在持续时间几乎 完全是季节性变化的函数， 分泌物 这一发现表明，在多大程度上， 褪黑激素的分泌响应于夜间长度的季节性变化， 它们暴露于或处理晨光的功能。 这 这一发现为我们提供了一条重要线索， 个体对季节变化有反应，而其他个体则没有。