GENDER DIFFERENCES IN EFFECTS OF SEASON ON PATTERNS OF NOCTURNAL MELATONIN

在动物体内，褪黑激素作为一种化学物质起着重要的作用。 季节对行为影响的中介者。在许多情况下，变化 在长夜中充当环境信号，触发 行为的季节性变化。褪黑激素只在夜间分泌， 它的分泌持续时间随着季节的变化而变化 漫漫长夜。由于这些特性，许多生物体使用 作为化学信号的夜间褪黑素分泌持续时间的变化 触发功能的变化，如繁殖，这种变化会随着季节的变化而变化 基础。我们最近的研究(Z01 MH 02424-01 CP)表明，人类在 在它们进化的过程中，有类似于 那些存在于动物体内的物质，使它们能够检测到 延长夜间并改变夜间褪黑激素分泌的持续时间。 在实验中检测到了人类对光周期变化的反应 个人暴露在长短人工环境中的情况 “天”。在随后的实验(Z01 MH 02424-01 CP)中，我们研究了 生活在现代城市环境(地铁)中的健康人 华盛顿特区)，在那里他们经常暴露在人工 光，仍然能够检测到季节变化的持续时间 夜间，并通过修改 夜间褪黑激素分泌期。我们发现它们的模式 女性夜间褪黑激素分泌对季节变化的反应 夜间的持续时间，而男性则不是。这一发现 这表明在反应方面可能存在性别差异 跟踪长度季节性变化的机制的人造光 夜幕降临。 因为夜间褪黑激素分泌的持续时间很重要 作为季节变化的影响的换能器 动物行为之夜，重要的是要调查 褪黑素在季节性情感障碍发病机制中的作用 (悲伤)患有反复发作的冬季抑郁症。因此，在这个项目中，我们 正在评估夜间褪黑激素分泌的持续时间 在患有SAD的女性中，它在季节性的基础上变化，在健康女性中也是如此。 在28名患者和30名匹配的对照组中，褪黑激素异常 患有SAD的女性对季节变化无反应，提高了 当松果体不能表现出 健康女性通常会出现的季节性反应。相比之下，9 患者和15名匹配的对照组，我们发现褪黑素对 患有SAD的男性的季节变化，但健康男性不是，结果是 与经典的假设一致，即持续时间的变化 褪黑激素的分泌会引发SAD患者的冬季抑郁。男性的数量 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季节性变化 在夜间分泌褪黑素的内在持续时间几乎是 完全是早晨抵消的时间的季节性变化的函数 分泌物。这一发现表明，个体的 褪黑激素的分泌对夜间长度的季节性变化做出反应 他们暴露在晨光下或对晨光进行处理的功能。这 发现提供了一条重要的线索，帮助我们了解为什么有些人 个体会对季节的变化做出反应，而其他人则不会。

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.