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　　大半夜睡不着？研究人员给你一些科学的建议

　　导读：未能得到良好的睡眠驱使人们去尝试许多干预措施：一些是有科学依据的，其他的则没有

　　众多研究人员参加了在科罗拉多州丹佛市举办的2016年睡眠（SLEEP）会议。略读一些摘要，人们可以发现不同研究主题，比如“需要更好的睡眠吗？”“谈到认知混乱问题，”以及“认知正常的老年人中，嗜睡和疲劳与脑萎缩的关联性”，这些研究主题都显示出，关于睡眠的许多问题仍未得到解答。

　　很明显，睡眠——这个占我们生活三分之一时间的日常活动——应该得到学术界更多的关注。未能得到良好的睡眠驱使人们去尝试许多干预措施：一些是有科学依据的，其他的则没有。

　　让我们从一个普通的例子开始：为了更好的睡眠，请避免蓝色光线

　　减少蓝色光线

　　研究人员发现，暴露于蓝色光线下会延迟睡眠时间，降低睡眠质量，并增加半夜觉醒的次数。我们的大脑把短波蓝光当作清晨的信号，把红色光线当作日落信号。七年前，一批开发商推出f.lux，已经被下载超过1500万次的软件。在夜晚，f.lux通过去除从您计算机屏幕发出蓝色光而发挥作用，使您的生活环境更接近自然光暗周期。随着蓝光照射的较少，你的大脑不再接收人工的“早晨”信号。为了回应从苹果手机发出的、扰乱睡眠模式的、蓝色光的批评，苹果在IOS 9.3更新版本推出了夜间设置。

　　蓝色光（不是红色或绿色）不利于睡眠，因为它会与视网膜光感细胞中的黑视素进行相互作用。在1998年之前，人们认为只有两个感光细胞，视杆细胞和视锥细胞，它们在视网膜中帮助我们看到周围环境。相反，黑视素给我们提供的是“非视觉图像形成”，它对光的反应帮助调节我们的生理节奏。黑视素对蓝光最敏感，所以蓝光对黑视素受体的影响最大，在晚上过多的蓝色光会扰乱睡眠。

　　发表在PLOS生物学研究上的论文中，来自牛津大学的研究表明，蓝色光辉引起行为障碍，延迟入睡，导致野生老鼠糖皮质激素水平升高。研究人员对这些老鼠通过基因工程，让它们缺乏视黑素，同样的蓝色光却能提高睡眠水平，与之前是完全不同的反应！除了证实蓝光对睡眠影响中视黑素的示范意义，同时研究也发现，视黑素能够调节应对蓝光时糖皮质激素水平的升高。糖皮质激素连接应激和兴奋，增加糖皮质激素水平阻碍睡眠。当研究人员用糖皮质激素受体拮抗剂阻断糖皮质激素升高的影响时，蓝光对睡眠的影响被逆转了。

　　黑视素能够调节睡眠激素——褪黑素的释放，大脑分泌出松果体之后，褪黑素在人体内循环。在清晨，黑视素感受到明亮的光线，就会抑制激素的释放，从而导致褪黑素水平下降。在睡前，褪黑素水平上升，因为此时黑视素不再活跃。但这是人造光出现之前的情况，现在，在床上使用智能手机、平板电脑和电子阅读器使得我们在夜晚更多地暴露于蓝色光线下。如果蓝色光在黑视素本来不该活跃的时候，却激活了它，就会进一步阻止褪黑素水平上升，导致睡眠困难。

　　对于褪黑素补充剂，我们了解多少？

　　鉴于褪黑素在睡眠调节中的重要作用，对于难以入眠的人来说，褪黑素补充剂成为市场上一种常见的非处方药选择。此外，含有褪黑素的安神饮料在市场上的受欢迎程度也在上升。

　　这些产品真的有效吗？临床试验表明，褪黑激素对于治疗失眠效果一般，它的作用仅限于降低入睡前的等待时间，也就是降低约七分钟的程度。与之相反，褪黑激素对改善时差症状的影响更有效。

　　尽管褪黑素补充剂对人类的益处还存在争议，但是它的风险却是实实在在的。首先，它有副作用，比如第二天昏昏沉沉、恶心、烦躁。此外，褪黑素和其它神经活性物质如酒精混合，会导致危险的情况。《自然神经科学》的一篇社论曾经提示过消费者和监管机构，这些安神饮料的风险，包括这些含有褪黑素的饮料的风险，并敦促他们要铭记，这些看似安全的饮料与酒精一起饮用已经导致了几例死亡事件。最后，FDA发表了一封关于褪黑素布朗尼的警告信，表示要谨慎对待褪黑素对神经系统的潜在影响。这封信得到了23篇研究论文的证据支持。

　　如果你想服用褪黑素补充剂，那么一定要咨询医生。2015年赫芬顿邮报采访他的时候，来自哥伦比亚大学的睡眠医安德鲁 韦斯特伍德博士就提出与褪黑素补充剂有关的另一个问题：它们“能够让你产生一定的抗药性，让你对低剂量的褪黑素没有反应。然后，如果你不再服用补充剂，就会有睡眠障碍，你得需要更多的褪黑素才能入睡。” 韦斯特伍德说，在许多情况下，人们真正要做的是，改变他们的行为，比如在睡觉前几小时，避免明亮的光线，不使用电子设备。

　　现在我们能做什么？

　　在星期六晚上，我读完了我的博客文章的所有资料后，我决定进行睡眠实验。遵照科学家们的建议，我把智能手机、平板电脑和笔记本电脑放在起居室里。然后，我让卧室处于暗淡的光线下，翻开纸质书，在睡觉前读一些短篇故事。整个早上和下午大部分时间我都在睡觉。看来那些发光的电子设备让我背上了沉重的睡眠债务，数以百万计的人可能也会有类似的问题。

　　美国国家睡眠障碍研究中心发现，睡眠相关的问题大约影响了所有年龄段的7000万美国人。虽然这些人睡眠问题的原因可能是社交方面的，心理上的，甚至更复杂的问题，但是你都可以做一点小事情来改善睡眠问题，在睡前一个小时的做点简单的事情让自己放松。在这一个小时里，你可以看一本印刷书（正如我所做的），或听轻松的音乐，这些事情都能帮助你进入Delta睡眠（注：表示处于最深的睡眠状态）。

　　“英文原文”

　　Can't sleep? Here's some science-based advice

　　thousands of researchers gathered in Denver, Colorado for the SLEEP 2016 meeting. Skimming over the abstracts, one can find diverse research topics like "Need better sleep? Consider the cognitive shuffle," and "Sleepiness and fatigue associated with brain atrophy in cognitively normal elderly," showcasing the many questions that remain unanswered regarding sleep.

　　It's clear that sleep – a daily activity comprising one-third of our lives – deserves a lot of attention from the research community. And the failure to get a good sleep drives people to try numerous interventions: some based on science, others not.

　　Let's start with a common example: avoiding blue light for better sleep.

　　Subtracting blue light

　　Researchers have shown that exposure to blue light delays sleep onset, decreases sleep quality, and increases arousal. Our brains respond to short-wavelength blue light as a signal of morning, and red light as a signal of sunset. Seven years ago, a group of developers launched f.lux, software that has since been downloaded over 15 million times. f.lux works by subtracting the blue light emitted from your computer's screen at night, making your daily environment more similar to the natural light-dark cycle. With less blue light exposure, your brain no longer receives artificial "morning" signals. In response to criticisms about blue light from the iPhone disrupting sleep patterns, Apple introduced a night shift setting in the iOS 9.3 update.

　　Blue light, but not red or green light, is bad for sleep due to its interaction with the retinal photoreceptor melanopsin. Before 1998, people thought there were only two photoreceptors, rods and cones, in the retina to help us form images of our surroundings. In contrast, melanopsin gives us a "non-image forming" response to light to help regulate our circadian rhythms. Melanopsin is most sensitive to blue light, so blue light has the greatest influence on the melanopsin receptor, and too much blue light at night can disrupt the sleep schedule.

　　In a PLOS Biology study published in June, researchers from the University of Oxford showed that blue light caused behavioral arousal, delayed sleep onset, and elevated levels of glucocorticoids in wild-type mice. When they genetically engineered these animals to make them melanopsin-deficient, the same blue light actually enhanced sleep, a completely different response! Besides demonstrating melanopsin's significance for blue light's effects on sleep, the same study also found that melanopsin mediates the increase in glucocorticoid levels in response to blue light. Glucocorticoids link stress and arousal, and increasing glucocorticoid levels hinders sleep. When the researchers blocked the effects of elevated glucocorticoids using a glucocorticoid receptor antagonist, the effect of blue light on sleep was reversed.

　　In humans, melanopsin regulates the release of a sleep hormone, melatonin, which circulates in the body after secretion from the pineal gland in the brain. Melatonin levels fall in the early morning as melanopsin senses bright daylight and suppresses the hormone. Melatonin levels then rise before bedtime because melanopsin is no longer active. But that is before the era of artificial light, and the exposure to bright blue light at night is worsened by usage of cell phones, tablets, and e-readers in bed. If blue light activates melanopsin at a time when it shouldn't be active, it will further prevent the natural melatonin rise and lead to sleep difficulty.

　　What do we know about melatonin supplements?

　　Given melatonin's role in sleep regulation, melatonin supplements are a common over-the-counter option for people with difficulty falling asleep. Moreover, melatonin-containing relaxation drinks on the market have also increased in popularity.

　　Are these products truly helpful? Clinical trials have shown that the efficacy of melatonin is low for insomnia, only decreasing sleep latency for about seven minutes. On the contrary, melatonin's effect on improving jet lag symptoms is more substantial.

　　Despite questionable benefits in humans, melatonin supplements have some known risks. First of all, there are side effects like next-day grogginess, nausea and irritability. In addition, combining melatonin with other neuroactive substances like alcohol could lead to dangerous conditions. Aneditorial in Nature Neuroscience warned consumers and regulatory agencies about the risks of relaxation drinks, including those containing melatonin, and urged them to remember that combining seemingly safe energy drinks with alcohol has caused several deaths. Finally, the FDA issued a warning letter about melatonin-laced brownies, voicing caution over melatonin's potential effects on the nervous system. The letter is backed up by evidence from 23 research papers.

　　Consulting a doctor is also a good idea if you're interested in melatonin supplements. When interviewed by Huffington Post in 2015, sleep physician Dr. Andrew Westwood from Columbia University addressed another issue related to melatonin supplements: they "can de-sensitize your receptors so they're no longer responsive to lower doses of melatonin. Then, if you come off [the supplements], you might have difficulty sleeping—and require more and more melatonin to fall asleep." Westwood says that, in many cases, people actually need to modify their behavior, like avoiding bright light and blue light from electronic devices a few hours before bed.

　　What you can do today

　　After I had finished reading all the materials for my blog post on Saturday evening, I decided to conduct my own sleep experiment. Carefully following the scientists' suggestions, I placed my smart phone, tablet, and laptop in the living room. Then, I turned on a dimmer light in the bedroom, opened a paper book, and read several short stories before sleepiness (or the natural melatonin tide) knocked me out. I slept through the whole morning and most of the afternoon. It seems I had a heavy sleep debt from my glowing backlit gadgets, and millions of others may have a similar problem.

　　The National Center on Sleep Disorder Research found that sleep-related problems affect around 70 million Americans of all ages. While the reason for sleep problems among these millions could be social, psychological or even more complicated, there are always small things one can do, something as simple as freeing yourself from those gadgets for an hour before bedtime. In this hour, you could read a printed book (as I did), or listen to relaxing music, whose power seems to lie in delta waves.