纽约时报杂志的长文，追述人类和抑郁症斗争的历史。人类对抑郁症的认识，从无知到了解，从回避到积极应对，这是一个旷日持久的过程，并且还在进行着。好消息是我们已经越来越了解抑郁的机理，并且有越来越有效的治疗方法。用知识武装自己，战胜抑郁。
翻译者们和他们想说的一句话：
@峰哥何峰 希望通过我的翻译，把国外最准确，最实时的信息带给中文读者！
@简里里 大家一起Have Fun 哈！
@双末芥arolf
@Freddie Lyon (´･ω･｀)
@你才是懒猫 哈 有点心慌。。。
@瑜儿小 第一次翻译心理类的文章，一起学习~
@小弱_人参淫家 最近对心理学的东西愈发感兴趣了~
@卡帕的小红狐
@sar
@惊蛰 水平不高求轻拍!~
@dseye 大家速度好快
@清净 功夫不负有心人 下载浏览器/重启电脑/耐心等待若干回合后 终于传上来啦~~~~
（特别感谢@清净！一晚上把未翻译的部分都补上了）
@MichaBerri 速度真快 翻完了？嗯 校正
@Caren Nice to have fun.
@Anonymous 大家效率好高，时差党跟不上啊啊～！
@木绕子日屯 希望以后多参与，嘿嘿
@抠鼻屎的人 太有效率了，而且质量高
=========
原文来自纽约时报网站，链接
http://www.nytimes.com/2012/04/22/magazine/the-science-and-history-of-treating-depression.html April 19, 2012
Post-Prozac Nation
By SIDDHARTHA MUKHERJEE
2012年4月19日
后百忧解之国
作者 Siddhartha Mukherjee
Few medicines, in the history of pharmaceuticals, have been greeted with as much exultation as a green-and-white pill containing 20 milligrams of fluoxetine hydrochloride — the chemical we know as Prozac. In her 1994 book “Prozac Nation,” Elizabeth Wurtzel wrote of a nearly transcendental experience on the drug. Before she began treatment with antidepressants, she was living in “a computer program of total negativity . . . an absence of affect, absence of feeling, absence of response, absence of interest.” She floated from one “suicidal reverie” to the next. Yet, just a few weeks after starting Prozac, her life was transformed. “One morning I woke up and really did want to live. . . . It was as if the miasma of depression had lifted off me, in the same way that the fog in San Francisco rises as the day wears on. Was it the Prozac? No doubt.”
在药物史中，几乎没有什么药品会像一颗白绿相间的小药丸那样，受到市场的狂热追捧。这种含20毫克盐酸氟西汀的药丸，就是我们熟知的百忧解。1994年，Elizabeth Wurtzel在她的自传体小说《百忧解之国》（译注：后改编为电影）中描述了服用百忧解后近乎超现实的体验。 在服用抗抑郁药剂之前，她的生活俨然是“一个崩溃的电脑程序：毫无情绪，没有感觉，失去回应，缺乏兴致”，在各种自杀幻想中沉浮。然而在她服用了百忧解的几周之后，人生发生了变化。“有天早上，我醒来发现自己真的想要活下去……抑郁的瘴气驱散了，就好像旧金山的雾气消逝在晨光中一样。是百忧解的缘故吗？毫无疑问。”
Like Wurtzel, millions of Americans embraced antidepressants. In 1988, a year after the Food and Drug Administration approved Prozac, 2,469,000 prescriptions for it were dispensed in America. By 2002, that number had risen to 33,320,000. By 2008, antidepressants were the third-most-common prescription drug taken in America.
就像 Wurtzel, 数以百万的美国人欣然接受抗抑郁药物。1988年，食品和药物管理局批准百忧解后的一年间，美国人消化了2,469,000份百忧解处方。到2002年，这个数字增长到了33,320,000。到2008年，抗抑郁药物成为美国第三大最常见的处方药。
Fast forward to 2012 and the same antidepressants that inspired such enthusiasm have become the new villains of modern psychopharmacology — overhyped, overprescribed chemicals, symptomatic of a pill-happy culture searching for quick fixes for complex mental problems. In “The Emperor’s New Drugs,” the psychologist Irving Kirsch asserted that antidepressants work no better than sugar pills and that the clinical effectiveness of the drugs is, largely, a myth. If the lodestone book of the 1990s was Peter Kramer’s near-ecstatic testimonial, “Listening to Prozac,” then the book of the 2000s is David Healy’s “Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.”
时间快进到2012年，这些曾激发起人们极大热情的抗抑郁药物却成了现代精神病药物学的反面教材。人们认为这些化学药品被过度炒作，在处方中也被滥用，反映了我们正处于一种“嗜药文化”中，即总想着为解决复杂的心理问题找到捷径。心理学家Irving Kirsch在其文章《皇帝的新药》中坚称，抗抑郁药物并不比糖片（译注：安慰剂）更有用，在很大程度上，它的临床疗效也存疑。在20世纪90年代，如果说最引人注目的书是Peter Kramer的《聆听百忧解》，在这本书中他近乎狂喜地褒扬了百忧解；那么21世纪伊始，最引人注目的书当属David Healy的《让他们去服用百忧解吧——制药工业和抑郁症之间的危险关系》。
In fact, the very theory for how these drugs work has been called into question. Nerve cells — neurons — talk to one another through chemical signals called neurotransmitters, which come in a variety of forms, like serotonin, dopamine and norepinephrine. For decades, a central theory in psychiatry has been that antidepressants worked by raising serotonin levels in the brain. In depressed brains, the serotonin signal had somehow been “weakened” because of a chemical imbalance in neurotransmitters. Prozac and Paxil were thought to increase serotonin levels, thereby strengthening the signals between nerve cells — as if a megaphone had been inserted in the middle.
事实上，这些药物的工作机理饱受质疑。神经细胞-神经元-它们之间通过神经递质来传递化学信号。这些神经递质有很多种形式，比如血清素、多巴胺和去肾上腺素。数十年来，在精神病学领域，一个关键的理论是：抗抑郁的药物是为了提高人大脑中血清的水平。在抑郁症患者的大脑中，血清素的信号水平由于神经递质的水平不均而“被削弱”的。百忧解和Paxil是被认为提高血清素水平的，以此来强化神经细胞之间的信号水平——就像在两者之间加了一个扩音器。
But this theory has been widely criticized. In The New York Review of Books, Marcia Angell, a former editor of The New England Journal of Medicine, wrote: “After decades of trying to prove [the chemical-imbalance theory], researchers have still come up empty-handed.” Jonathan Rottenberg, writing in Psychology Today, skewered the idea thus: “As a scientific venture, the theory that low serotonin causes depression appears to be on the verge of collapse. This is as it should be; the nature of science is ultimately to be self-correcting. Ideas must yield before evidence.”
但是这个理论饱受争议。在纽约书评（美国一个颇有影响力的书评期刊），《新英格兰医学杂志》的前任编辑Marcia Angell写道：“即使经过了数十年对于'化学平衡理论'的验证，研究者仍然毫无斩获。” Jonathan Rottenberg,在《今日心理学》中针对这个观点如是说：“作为科学冒险，低血清致抑郁的理论正在崩溃的边缘。事情也应当如此；科学的本质归根到底就是自我修正。想法必须让位于证据。”
Is the “serotonin hypothesis” of depression really dead? Have we spent nearly 40 years heading down one path only to find ourselves no closer to answering the question how and why we become depressed? Must we now start from scratch and find a new theory for depression?
难道抑郁症研究中的“血清素理论”真的行不通了吗？难道我们朝着这个方向花了将近40年的时间，结果发现我们对于如何、为何会得患抑郁这个问题的答案，几乎毫无进展？我们此时是否要重头开始，选择和寻找一个关于抑郁症的新的理论？
Science may be self-correcting, but occasionally it overcorrects — discarding theories that instead need to be rejuvenated. The latest research suggests that serotonin is, in fact, central to the functioning of mood, although its mechanism of action is vastly more subtle and more magnificent than we ever imagined. Prozac, Paxil and Zoloft may never turn out to be the “wonder drugs” that were once advertised. But they have drastically improved our understanding of what depression is and how to treat it.
科学会进行自我修正，但在有些情况下，会矫枉过正，抛弃了那些原本可以重获新生的理论。最新的研究显示，血清素确实对于调节心情起着关键作用，虽然血清素的工作机能比我们之前想象得远为微妙和神奇。百忧解、帕罗西汀、左洛复（抗抑郁药物）也许永远不可能成为像之前广告宣称的“神器”，但它们在很大程度上增加了人们对于什么是抑郁症以及如何来治疗抑郁症的认识。
Our modern conception of the link between depression and chemicals in the brain was sparked quite by accident in the middle of the last century. In the autumn of 1951, doctors treating tubercular patients at Sea View Hospital on Staten Island with a new drug — iproniazid — observed sudden transformations in their patients’ moods and behaviors. The wards — typically glum and silent, with moribund, lethargic patients — were “bright last week with the happy faces of men and women,” a journalist wrote. Patients laughed and joked in the dining hall, as if a dark veil of grief had lifted. Energy flooded back and appetites returned. Many, ill for months, demanded five eggs for breakfast and then consumed them with gusto. When Life magazine sent a photographer to the hospital to investigate, the patients could no longer be found lying numbly in their beds: they were playing cards or dancing in the corridors.
上世纪中叶，关于抑郁症和大脑中化学物质之间的联系的先进认知，在偶然机会中被或多或少地激发了。1951年秋，当位于斯坦顿岛的Sea View医院的医生用一种新药－－异烟酰异丙肼来治疗结核病病人时，医生观察到了这些病人的情绪和行为的突然变化。一名记者写道，往常病房里住着垂死的病人，忧郁沉默，但上周病房里很明亮，病人露出开心的面庞。病人们在餐厅里欢笑，似乎悲伤都已经消散。大家都有了精神，有了食欲。许多病了几个月的病人早餐要了五个鸡蛋，吃得狼吞虎咽。当《生活》杂志派一名摄像师来医院进行调查时，他发现病人不再木讷地躺在他们的病床上，相反，他们有的正在打牌，有的在走廊里跳舞。
If the men and women at Sea View were experiencing an awakening, then a few hundred miles south, others at Duke’s hospital encountered its reverse. In 1954, a 28-year-old woman was prescribed Raudixin to control her blood pressure. A few months later, she returned to the hospital, complaining of crying spells, dullness and lethargy. She felt futile, guilty and hopeless, she told her doctors. A few months later, when she returned, the sense of futility had turned into hostility. A 42-year-old woman prescribed Raudixin told her doctor that “God would cause her to become insane” before she could repent. The “feeling blue,” as another patient described it, persisted until the drug was discontinued. At another hospital, one patient treated with Raudixin attempted suicide. Several people had to be admitted to psychiatric wards and administered electroconvulsive therapy before the symptoms were alleviated.
如果在Sea View医院的病人们感受到了一丝复苏生机，那么在距离Sea View以南几百英里的杜克医院的病人们的经历恰恰相反。1958年，医生给一位28岁的女性开了萝芙碱来控制她的血压。几个月之后，她回到医院，诉说自己变得爱哭，反应迟钝，无精打采。她告诉医生，她感到疲倦、内疚、绝望。再过了几个月，她再次到医院来的时候，无力感已经转变成了敌意。另一位服用萝芙碱的42岁女性告诉医生，上帝会在她忏悔之前，把她变疯的。另一位病人说，“抑郁感”在停用这种药后才消失了。在另一家医院，一位服用萝芙碱的病人试图自杀。有些人甚至需要进入精神病病房，进行电痉挛疗法才能缓解症状。
Psychiatrists and pharmacologists were quick to note these bizarre case reports. How, they wondered, could simple, seemingly unrelated chemicals like Raudixin or iproniazid produce such profound and opposite effects on mood? It was around this same time that scientists were learning that the brain itself was immersed in a soup of chemicals. In the early part of the century, scientists wondered how nerve cells talked to one another. By the late 1960s, evidence suggested that signals between neurons were carried by several chemicals, including the neurotransmitter serotonin. Might iproniazid and Raudixin have altered the levels of some neurotransmitters in the brain, thereby changing brain signaling and affecting mood? Strikingly so, scientists found. Raudixin — the “feeling blue” drug — drastically lowered the concentration of serotonin and closely related neurotransmitters in the brain. Conversely, drugs known to increase euphoria, like iproniazid, increased those levels.
精神病学家和药理学家很快就注意到了这些奇怪的案例报告。他们感到困惑，那些简单且看来毫无联系的化学物质，比如萝芙碱或异烟酰异丙肼，为何能对情绪产生如此强烈而又相反的影响？ 正在此时，科学家们弄明白了大脑是被浸没在一碗充满化学物质的汤里的。20世纪初期，科学家们还在疑惑神经细胞是如何互相交流的。 到了60年代末，有证据显示，神经元之间的信号是由一些化学物质传递的，其中包括复合胺。难道是异烟酰异丙肼和萝芙碱改变了大脑中某些神经传递介质的水平，从而改变了大脑的信号传递并影响了情绪吗？令人惊奇的是，科学家们发现事实的确如此。萝芙碱，那种让人有“抑郁感”的药，大幅降低了大脑中血清素和与其关联的神经递质的浓度。相反地，那些让人精神愉悦的药物，例如异烟酰异丙肼，却增加了那些化学物质的浓度。
These early findings led psychiatrists to propose a radical new hypothesis about the cause and treatment of depression. Depression, they argued, was a result of a “chemical imbalance” of neurotransmitters in the brain. In the normal brain, serotonin shuttled between mood-maintaining neurons, signaling their appropriate function. In the depressed brain, this signal had somehow gone wrong. The writer Andrew Solomon once evocatively described depression as a “flaw in love” — and certainly, the doctors using Raudixin at Duke had seen that flaw emerge grimly in real time: flaws in self-love (guilt, shame, suicidal thoughts), love for others (blame, aggression, accusation), even the extinction of a desire for love (lethargy, withdrawal, dullness). But these were merely the outer symptoms of a deeper failure of neurotransmitters. The “flaw in love” was a flaw in chemicals.
这些早期的发现引导精神病学家对抑郁症的成因和治疗提出了一种激进的新假设。他们认为，抑郁症是大脑中的神经递质“化学失衡”的结果。正常情况下，大脑中控制情绪的神经元借助血清素往返穿梭，从而传导恰当的信号。而大脑处于抑郁时，这种传导机制不知为何失灵了。作家Andrew Solomon曾把抑郁症生动地称作“爱的瑕疵”———当然，杜克医院那些用萝芙碱的医生们已经见识过这些瞬时发作的可怕缺陷了：缺乏自爱（产生内疚、羞耻、自杀的想法），不懂关爱他人（归咎、攻击、谴责他人），甚至不存在爱的欲望（死气沉沉、不断逃避、精神迟钝）。但是，这些只是外在症状，根源在于神经递质深层次的传导失败。“爱的瑕疵”其实是化学上的缺陷。
Powerful vindication for this theory came from the discovery of new medicines that specifically elevated serotonin concentrations. The first such drug, Zimelidine, was created by a Swedish researcher, Arvid Carlsson. Following Carlsson’s lead, pharmaceutical chemists threw their efforts and finances into finding serotonin-enhancing drugs, and the new giants of the antidepressant world were born in rapid succession. Prozac was created in 1974. Paxil appeared in 1975, Zoloft in 1977 (the trade names were introduced years later).
专门提高血清素浓度的新药物的发现是对这个理论的有力证明。第一种这类药物Zimelidine是由瑞典研究员Arvid Carlsson发明的。在Carlsson之后，药剂师们将精力和财力投入到提高血清素类药物的研究上，使得抗抑郁剂世界的新贵一个接着一个地出现：1974年的百忧解，1975年的帕罗西汀，还有1977年的左洛复（这些商业名称是几年以后引进的）。
In 2003, in Boston, I began treating a 53-year-old woman with advanced pancreatic cancer. Dorothy had no medical problems until she developed an ominous sign known to every cancer specialist: painless jaundice, the sudden yellowing of skin without any associated pinch of discomfort. Painless jaundice can have many causes, but the one that oncologists know best, and fear most, is pancreatic cancer.
2003年在波士顿，我开始治疗一个53岁的患有晚期胰腺癌的女人（译注：乔布斯得的就是胰腺癌）。Dorothy的身体一直很健康，直到她发现自己身上出现了无痛性黄疸（皮肤突然变黄而没有疼痛感），这是每个癌症专家都知道的患癌前的不祥预兆。出现无痛性黄疸的原因有很多种，但是对于肿瘤学家来说，他们最熟悉也最担心的，就是胰腺癌了。
In Dorothy’s case, the mass in the pancreas turned out to be large and fist-shaped, with malignant extensions that reached backward to grip blood vessels, and a solitary metastasis in the liver. Surgical removal was impossible, chemotherapy the only option.
在Dorothy的案例中，胰腺里的肿块较大，拳头状，恶性的增生向后延伸到血管，并且癌细胞孤立转移到了肝脏。手术摘除是不可行的，只有化疗了。
The suddenness of the diagnosis struck her like an intravenous anaesthetic, instantly numbing everything. As we started chemotherapy in the hospital, she spent her mornings in bed sleeping or staring out of the window at the river below. Most disturbing, I watched as she lapsed into self-neglect. Her previously well-kept hair grew into a matted coil. The clothes that she had worn to the hospital remained unchanged. There were even more troubling signs: tiny abrasions in the skin that were continuously picked at, food left untouched by the bedside table and a gradual withdrawal of eye contact. One morning, I walked into what seemed like a daily emotional flare-up: someone had moved a pillow on the bed, Dorothy had been unable to sleep and it was somehow her son’s fault.
这个突如其来的诊断让她觉得自己像是被打了静脉麻醉注射剂,所有一切立刻变得麻木.当我们在医院里进行化疗时,她整个早上都躺在床上睡觉或者呆望着窗外的河边.最让人烦扰的,是我眼睁睁的看着她陷入自我忽视之中.她之前那头精心保养的秀发变得乱糟糟的一团.衣服也仍然是之前进医院时穿的那套.甚至还有更糟糕的迹象:皮肤上的细小伤疤天天被扒开,食物放在床边的桌子上一动未动,并且她渐渐回避起眼神交流.一天早上,我碰到一场看起来像是每日必有的情绪爆发:有人把床上的枕头移动过了,Dorothy完全难以入睡,而匪夷所思地怪她儿子.
This grief, of course, was fully provoked by the somberness of her diagnosis — to not grieve would have been bizarre in these circumstances — but she recognized something troubling in her own reaction and begged for help. I contacted a psychiatrist. With her consent, we prescribed Prozac.
让人绝望的诊断结果给她带来了巨大的痛苦——在这种情况下不痛苦那才是奇葩——但她意识到了自己所感受到的混乱并且寻求了帮助。我联系了一个精神病专家。在她的同意下，我们给她开了百忧解。
In the first weeks, we waited watchfully, and nothing happened. But when I saw her again in the clinic after a month and a half, there were noticeable changes. Her hair was clean and styled. Her cuts had disappeared, and her skin looked good. Yet she still felt sad beyond measure, she said. She spent her days mostly in bed. The drug certainly affected many of the symptoms of depression, yet had not altered the subjective “feeling” of it. It healed the flaws in her skin but not all the flaws in love.
开始地几周，我们耐心观察，但什么也没有发生。但当我一个半月之后再在诊所看到她时，她有了显著的变化。她的头发干净有型，皮肤上的伤痕已经消失不见了，皮肤看起来也很好。但她说仍旧感到十分悲伤。她大部分时间都是在床上度过的。显然药物影响了抑郁症的许多症状，但是没有改变患者的主观感受。她皮肤上的伤痕得到了治愈，但是爱的缺陷并没有获得痊愈。
Any sane reader of this case would argue that a serotonin imbalance was not the initiating cause of Dorothy’s depression; it was, quite evidently, the diagnosis of a fatal disease. Should we be searching for a chemical cause and cure when the provocation of grief is so apparent?
任何正常的读者在此时都会说，很显然致命疾病的诊断是Dorothy抑郁的起因，而不是血清素的失衡。当悲痛的缘由是如此明显时，我们应该从化学角度去寻找病因和治愈方法吗？
Pause for a moment, though, to consider the physiology of a heart attack. A heart attack can be set off by a variety of causes — chronic high blood pressure or pathologically high levels of “bad” cholesterol or smoking. Yet aspirin is an effective treatment of a heart attack regardless of its antecedent cause. Why? Because a heart attack, however it might have been provoked, progresses through a common, final pathway: there must be a clot in a coronary artery that is blocking the flow of blood to the heart. Aspirin helps to inhibit the formation and growth of the clot in the coronary artery. The medicine is clinically effective regardless of what events led to the clot. “Aspirin,” as a professor of mine liked to put it, “does not particularly care about your medical history.”
我们先偏题一下，来看看心脏病的发病机理。一系列原因都可以引起心脏病——慢性高血压或者胆固醇的生理水平过高或者吸烟都有可能。但是无论起因是什么，阿司匹林对治疗心脏病来说都是有效的。为什么？因为不管是如何引起的，心脏病最终都会形成这么一种状况：冠状动脉中必有一个凝块阻挡血液流向心脏。阿司匹林能帮助抑制冠状动脉中的这种凝块的形成和生长。不论造成凝块的起因是什么，这种药物在临床上都是有效的。就像我的一位教授说的，“阿司匹林并不管你的病史。”
Might major depression be like a heart attack, with a central common pathway and with serotonin as its master regulator? There was certainly precedent in the biology of the nervous system for such unifying pathways — for complex mental states triggered by simple chemicals. Fear, for instance, was found to involve a common hormonal cascade, with adrenaline as the main player, even though its initiators (bears, spiders or in-laws) might have little resemblance to one another.
抑郁症是否可能像心脏病一样，有一个主要的共同发病途径并且用血清素作为它的主要调节物？在神经系统生物学中有这种统一途径的先例——复杂的精神状态是由简单的化学物质引起的。例如，研究发现尽管引起恐惧的种种原因（熊，蜘蛛或者遗传原因）之间可能几乎没有什么相似的地方，但都包含了一个主要由肾上腺素起作用的共同的荷尔蒙级联。
But such a line of inquiry can’t tell us whether the absence of serotonin causes depression. For that, we need to know if depressed men and women have measurably lower levels of serotonin or serotonin-metabolites (byproducts of serotonin breakdown), in their brains. In 1975, pathologists performed autopsies on depressed patients to measure serotonin levels. The initial findings were suggestive: depressed patients typically tended to have lower levels of brain serotonin compared with controls. But in 1987, when researchers in Scandinavia performed a similar experiment with newer tools to measure serotonin more accurately, serotonin levels were found to be higher in depressed patients. Further experiments only deepened these contradictions. In some trials, depressed patients were found to have decreased serotonin levels; in others, serotonin was increased; in yet others, there was no difference at all.
然而，这一连串的探究都无法告诉我们抑郁是否由缺乏血清素引起的。为此，我们需要知道抑郁的人们大脑中是否是有相对较低的血清素或血清代谢物水平（血清代谢物指血清分解的副产物）。1975年，病理学家对抑郁病人验尸来测量他们的血清水平。最初的发现是有建设性的：与控制组相比，抑郁症的病人的大脑血清水平通常较低。 但在1987年，当斯堪的纳维亚的研究人员使用更新的工具进行了相似的试验，试图更准确地测量血清水平时，却发现抑郁的病人具有更高的血清水平。之后的试验更是深化了这些矛盾。在一些试验中，会发现抑郁的病人有较低的血清素水平；在另一些试验中，血清素含量则会升高；此外还有一些试验，两者的血清水平会相较无差。
What about the converse experiment? In 1994, male subjects at McGill University in Montreal were given a chemical mixture that lowered serotonin. Doctors then measured the fluctuations in the mood of the men as serotonin levels dipped in the blood. Though serotonin was depleted, most of them experienced no significant alterations in their mood.
相反的实验是怎样的呢？1994年，蒙特利尔的麦吉尔大学给男性测试者一种能够降低血清素水平的化学混合试剂。然后医生来测量，随着血液中血清素的降低，这些测试者的情绪变化。尽管血清素都耗尽了，但是绝大多数测试者的情绪并没有显著的变化。
At first glance, these studies seem to suggest that there is no link between serotonin and depression. But an important fact stands out in the McGill experiment: lowering serotonin does not have any effect on healthy volunteers with no history of depression, but serotonin-lowering has a surprisingly brisk effect on people with a family history of depression. In these subjects, mood dipped sharply when serotonin levels dropped. An earlier version of this experiment, performed at Yale in 1990, generated even more provocative findings. When depressed patients who were already responding to serotonin-enhancing drugs, like Prozac, were fed the serotonin-lowering mixture, they became acutely, often profoundly, depressed. Why would serotonin depletion make such a difference in a patient’s mood unless mood in these patients was, indeed, being controlled by serotonin?
初看上去，这些研究似乎表明， 血清素和抑郁症之间并没有任何关联。但是，在麦吉尔的实验中却突显了一个重要的事实：降低血清素不会对那些从未有过抑郁症病史的健康志愿者产生影响，但血清素的降低对有家族抑郁症病史的人产生了极快的效用。在这些人中，当血清素水平下降时，他们的情绪也急剧下降。而在1990年，由耶鲁大学进行的早期实验中，产生了更令人振奋的结果。当那些已经对能促使血清素升高的药物（例如百忧解）产生反应的患者服用降低血清素的药物时，他们快速并强烈地陷入抑郁中。为什么血清素的降低能让病人的情绪一落千丈？除非，这些患者的情绪，确实受到了血清素的操控。
Other experiments showed that though depressed patients generally didn’t have consistently lower levels of serotonin, suicidal patients often did. Might contemplating suicide be the most extreme form of depression? Or is it a specific subtype of mood disorder that is distinct from all the other forms? And if so, might depression have multiple subtypes — some inherently responsive to treatment with serotonin-enhancing drugs and some inherently resistant?
其他实验表明，抑郁症患者并不是持续的处于血清素浓度极低的状态，但有自杀倾向的病人却是这样。也许是因为自杀是抑郁症最为极端的形式？或者自杀是一个不同于其他所有形式的特定类型的情绪障碍症？如果是这样，抑郁症可能会有多个分支——一些形态的抑郁症能够对增强血清素的药物做出反应，而另一些这类药物对其毫无效用。
We may not understand how serotonin-enhancing antidepressants work, but do we know whether they work at all?
我们可能还不了解血清素具体是如何发挥效用的，但退一步说，血清素本身究竟是否有效？
In the late 1980s, studies examined the effect of Prozac on depressed subjects. Several of these trials showed Prozac reduced the symptoms of depression when compared with a placebo. Depression is usually assessed using a standardized rating scale of different symptoms. In general, some patients reported clinically meaningful improvements, although the effects were often small and varied from trial to trial. In real-world terms, such a change could be profound: a transformation in anxiety, the lifting of the ache of guilt, an end to the desire to commit suicide. But for other patients, the changes were marginal. Perhaps the most important number that emerged from these trials was the most subjective: 74 percent of the patients reported feeling “much” or “very much” better on antidepressants.
19世纪80年代末期有一些研究针对百忧解对抑郁症的效果。其中一些实验显示，和安慰剂相比，百忧解减少了抑郁症或者的症状。抑郁症通常由不同的症状的标准化评分来衡量。大部分情况下，很多患者在临床表现上都有改进，尽管效果甚微且因案例而异。在现实世界中，这点改变是有深远意义的，焦虑症的转变，悔恨感减轻，或者不再有自杀的意图。而对其他的一些患者，改变却是微小的。或许这些实验产生的最重要的数据也是最主观的：74%的患者反应对抗抑郁药物感觉”很好“或者”非常好“。
In 1997, a psychologist, Irving Kirsch, currently at the Harvard Medical School, set out to look at the placebo effect in relation to depression. In part, the placebo effect works because the psyche acutely modifies the perception of illness or wellness. Kirsch wondered how powerful this effect might be for drugs that treat depression — where the medical condition itself happens to involve an alteration of the psyche.
在1997年，一位名叫Irving Kirsch的心理学家（现在哈佛医学院）开始观察有关抑郁症的安慰剂效应。安慰剂效应有作用，一部分是因为它使心智改变了对疾病和健康的认知。Kirsch想知道这种效应对于用来治疗抑郁症有多有效，因为忧郁症恰好涉及到心智的改变问题。
To measure this effect, Kirsch combined 38 trials that included patients who had been given antidepressants, placebos or no treatment and then applied mathematical reasoning to estimate how much the placebos contributed to the improvements in mood. The analysis revealed two surprises. First, when Kirsch computed the strength of the placebo effect by combining the trials, he found that 75 percent of an antidepressant’s effect could have been obtained merely by taking the placebo. When Kirsch and his collaborators combined the published and unpublished studies of antidepressants (they obtained the unpublished data from the F.D.A. via the Freedom of Information Act), the effects of the antidepressants were even more diluted — in some cases, vanishingly so. Now, the placebo effect swelled to 82 percent (i.e., four-fifths of the benefit might have been obtained by swallowing an inert pill alone). Kirsch came to believe that pharmaceutical companies were exaggerating the benefits of antidepressants by selectively publishing positive studies while suppressing negative ones.
为了测量这种效应，Kirsch结合了38个试验，其中包括使用抗抑郁药物、安慰剂或者没有治疗的病人，然后用数学推理来估算安慰剂对情绪的促进作用。分析结果中有两点让人惊讶。首先，当Kirsch通过综合试验来计算安慰剂的效用时，他发现，仅仅服用安慰剂能发挥抗抑郁药物作用的75%。当Kirsch和他的合作者将那些对抗抑郁药物发表或者未发表的研究结合起来（他们从食品和药品管理局，通过“信息自由法”，获得未发表的数据），抗抑郁药物的作用更小，甚至在一些个案中，几乎没有。目前，安慰剂效应已经膨胀到了百分之82（也就是说，通过服食一枚毫无药性的药丸，即可实现4/5的作用）。 Kirsch开始相信，制药公司是通过有选择地发表正面研究，并且抑制负面研究，从而夸大了抗抑郁药物的益处。
But there are problems in analyzing published and unpublished trials in a “meta-trial.” A trial may have been unpublished not just to hide lesser effects but because its quality was poor — because patients were enrolled incorrectly, groups were assigned improperly or the cohort sizes were too small. Patients who are mildly depressed, for example, might have been lumped in with severely depressed patients or with obsessive-compulsives and schizophrenics.
但是解释'试验元'中发表的和发表的试验却有点麻烦.一个没被发表的试验不仅仅是因为其影响较小,还有可能是其质量较差--因为选择了错误的病人,分组不当或分组样本量太小。举个例子,那些患有轻度抑郁的病人也许会和重度抑郁患者/强迫症患者/精神分裂症患者集中到一组。
In 2010, researchers revisited Kirsch’s analysis using six of the most rigorously conducted studies on antidepressants. The study vindicated Kirsch’s conclusions but only to a point. In patients with moderate or mild depression, the benefit of an antidepressant was indeed small, even negligible. But for patients with the most severe forms of depression, the benefit of medications over placebo was substantial. Such patients might have found, as Andrew Solomon did, that they no longer felt “the self slipping out” of their hands. The most severe dips in mood were gradually blunted. Like Dorothy, these patients most likely still experienced sorrow, but they experienced it in ways that were less self-destructive or paralyzing. As Solomon wrote: “The opposite of depression is not happiness, but vitality, and my life, as I write this, is vital.”
2010年,研究者用最严谨的对抗抑郁剂的研究中的六个研究重新审视了Kirsch的解释.这为Kirsch的结论提供了辩护,不过仅仅是其中的一个方面。对于患有中度或者轻度抑郁症的患者,抗抑郁剂的效果微乎其微。但对那些有着最严重形式的抑郁症患者来说药物治疗而不是安慰剂会带来更大的益处。这些病人也许会发现,就像Andrew Solomon一样,他们仍会持续性的感到悲伤,但是是以一个不那么自我毁灭或者让人陷入瘫痪的方式来经受痛苦。正如Solomon写的:'抑郁的反面并不是快乐,是生机,而我的一生,就像我写的一样,是生机勃勃的。'
These slippery, seemingly contradictory studies converge on a surprisingly consistent picture. First, patients with severe depression tend to respond most meaningfully to antidepressants, while patients with moderate or mild depression do not. Second, in a majority of those who do respond, serotonin very likely plays an important role, because depleting serotonin in depressed patients often causes relapses. And third, the brain-as-soup theory — with the depressed brain simply lacking serotonin — was far too naïve.
这些不靠谱、似乎矛盾的研究汇聚起来却成为一副极为统一的图画。首先，抗抑郁药物对重度抑郁的患者往往最见效，对中度或者轻微程度的抑郁患者则并非如此。其次，对抗抑郁药物有反应的患者中的大多数，血清素很有可能起到了至关重要的作用，因为当抑郁症患者血清素减少时通常会旧病复发。再次，大脑即汤羹的理论，即抑郁症仅仅是因为患者大脑缺乏血清素—这个理论太轻率。
As is often the case in science, a new theory emerged from a radically different line of inquiry. In the late 1980s, a neuroscientist named Fred Gage became interested in a question that seemed, at first, peripheral to depression: does the adult human brain produce new nerve cells?
就像科学中经常发生的那样，新的理论往往是从一系列完全不同的质问中引发出来。19世界80年代末期，一位名叫Fred Gage的神经学家对一个起初似乎和抑郁症没有关系的问题产生了兴趣：成人的大脑会生成新的神经细胞么？
The dogma in neurobiology at the time was that the adult brain was developmentally frozen — no new nerve cells were born. Once the neural circuits of the brain were formed in childhood, they were fixed and immutable. After all, if new neurons were constantly replacing old ones, wouldn’t memories decay in that tide of growth? But Gage and other scientists revisited old findings and discovered that adult mice, rats and humans did, in fact, experience the birth of new neurons — but only in two very specific parts of the brain: in the olfactory bulb, where smells are registered, and in the hippocampus, a curl of tissue that controls memories and is functionally linked to parts of the brain that regulate emotion.
当时的神经生物学的教条这样解释，成人的大脑已完全发育成型——不会再有新的神经细胞生成。一旦儿童时期神经结构形成就固定不变。毕竟，如果新的神经细胞不断替代了原本的，是否记忆也会随这种替换而减退呢？但Gage和其他科学家重新审视了以往的研究结果并发现，成年小鼠、大鼠和人类事实上会生成新的神经元-－不过只在两个非常特定的大脑部位：嗅觉泡，即感受嗅觉的部位，还有海马体，即控制记忆并在功能上连接着大脑中调节情绪的部位的卷状组织。
Could there be a connection between emotion and neuronal birth in the hippocampus? To find out, Gage and his collaborators began to study stressed mice. When mice are chronically stressed — by sudden changes in their living environments or by the removal of their bedding — they demonstrate behavioral symptoms like anxiety and lethargy and lose their sense of adventurousness, features that mimic aspects of human depression. Researchers found that in these mice, the burst of nerve cells in the hippocampus also diminished.
情绪和海马体产生的神经元之间会有联系吗？为了找到答案，Gage和他的同伴开始研究应激的小白鼠。当小鼠处于慢性应激状态时 ——通过突然改变它们的生存环境或者移除它们的垫子—— 小白鼠在行为上的症状表现为焦虑或者昏睡并且不再冒险尝试，与人类的抑郁症特点相似。研究人员发现，这些小白鼠海马体中神经细胞的激活率也发生了减少。
The converse turned out to be true as well. When mice are housed in an “enriched” environment — typically containing mazes, nesting materials and toys — they become more active and adventurous. They explore more; they learn faster; they seek pleasure. Enrichment, in short, acts behaviorally like an antidepressant. When Gage examined the brains of these enriched mice, he found that more neurons were being born in the hippocampus.
反之亦然.当小白鼠在一个丰富的环境中安家--一般有迷宫,筑巢材料和玩具--它们变得更加活跃也更具冒险性.它们探索得更多，学习得更快，还自己找乐子。简而言之,丰富性,在行为上会起到抗抑郁剂的效果.当Gage检测了这些在丰富环境中的小白鼠,他发现它们的海马体中有更多神经元的产生.
At Columbia University, another neuroscientist, René Hen, was intrigued by Gage’s studies. Hen, working with other researchers, began to investigate the link between Prozac and nerve growth. The birth of neurons in the mice takes about two or three weeks — about the same time it takes for antidepressants to take effect. Might the psychiatric effects of Prozac and Paxil be related to the slow birth of neurons and not serotonin per se?
在哥伦比亚大学，另一位神经科学家René Hen被Gage的实验激发了。Hen和其他研究人员开始研究Prozac和神经生长的关系。新生的小白鼠神经元大约需要两到三周——正是抗抑郁药生效所需的时间。那么，氟西汀和帕罗西汀的精神影响是否与神经元的缓慢新生而非血清素有关？
Hen began to feed his mice Prozac. Over the next few days, their behaviors changed: anxiety they had exhibited decreased, and the mice became more adventurous. They looked for food in novel environments and were quick to adopt newly learned behaviors. And newborn neurons appeared in the hippocampus in precisely the location that Gage found with the environmentally enriched mice. But when Hen selectively blocked the birth of neurons in the hippocampus, the adventurousness and the food-exploration instincts of the Prozac-fed mice vanished. Prozac’s positive effects, in other words, depended on the birth of nerve cells in the hippocampi of these mice.
Hen 开始向这些小白鼠喂食百忧解。在接下来的几天，小白鼠的行为发生了变换，焦虑减少了，并且小白鼠变的更加活跃。小白鼠在全新的环境中找寻食物，接受新的行为也很迅速。新的神经元在这些小白鼠的海马体中出现，位置正是Gage实验中那些在丰富环境中小白鼠生成新神经元的位置。然而当Hen选择性的阻断了海马体中神经元的生长后，使用了百忧解的小白鼠的活跃特征和找寻食物的本能消失了。也就是说，百忧解的正面效果依赖于这些小白鼠海马体中神经元细胞的生成。
In 2011, Hen and his colleagues repeated these studies with depressed primates. In monkeys, chronic stress produces a syndrome with symptoms remarkably similar to some forms of human depression. Even more strikingly than mice, stressed monkeys lose interest in pleasure and become lethargic. When Hen measured neuron birth in the hippocampi in depressed monkeys, it was low. When he gave the monkeys antidepressants, the depressed symptoms abated and neuron birth resumed. Blocking the growth of nerve cells made Prozac ineffective.
2011年，Hen和他的同事通过抑郁的灵长类动物重复了上述实验。用猴子作实验时，慢性长期压力产生的症状和人类抑郁的症状大部分相似。比小白鼠更为明显的是，受压的猴子不愿找寻乐趣而且无精打采。Hen测量了受压猴子海马体中的神经元生长后发现，生长的不多。给猴子服用抗抑郁药物后，抑郁症状减少且神经元开始生长。阻止神经细胞的生长使得百忧解无效。
Hen’s experiments have profound implications for psychiatry and psychology. Antidepressants like Prozac and Zoloft, Hen suggested, may transiently increase serotonin in the brain, but their effect is seen only when new neurons are born. Might depression be precipitated by the death of neurons in certain parts of the brain? In Alzheimer’s disease, areas of the brain involved in cognition degenerate, resulting in the characteristic dementia. In Parkinson’s disease, nerve cells involved in coordinating movement degenerate, resulting in the characteristic trembling. Might depression also be a degenerative disease — an Alzheimer’s of emotion, a dementia of mood? (Even our language begins to fail in this description. Dementia describes a breakdown of “mentation” — thinking — but we lack a similar word for a degeneration of mood: is it disaffection?)
Hen的实验对精神病学和心理学有深远的影响，Hen 认为Prozac和Zoloft之类的抗抑郁药物只是暂时的提高大脑中血清素的含量，但是只在新的神经元生成时这些药物才有效。难道抑郁症是因为大脑中某些部位神经元的死亡而引发？阿尔茨海默症中，神经细胞和行动衰退有关联，导致典型的发抖。难道抑郁症也是一种功能退化疾病——之中情感的阿尔茨海默症，一种情绪的痴呆？（我们的语言也无法描述。痴呆描述了精神状态的衰竭，但是我们缺少一个描述情绪衰退的类似的词语：可以用“情绪功能退化”吗？）
And how, exactly, might the death of neurons in the tiny caul of the hippocampus (a part of the brain typically associated with the storage of memory) cause this disorder of mood? Traditionally, we think that nerve cells in the brain can form minuscule biological “circuits” that regulate behaviors. One set of nerve cells, for instance, might receive signals to move the hand and then relay these signals to the muscles that cause hand movement. It is easy to imagine that dysfunction of this circuit might result in a disorder of movement. But how does a circuit of nerves regulate mood? Might such a circuit store, for instance, some rules about adapting to stress: what to say or do or think when you are sick and nauseated and facing death and your son has moved a pillow? Did such a degeneration provoke a panic signal in the brain that goaded Wurtzel’s deadly reverie: cellular death leading to thoughts of suicide.
海马体（大脑中典型的和存储记忆有关的部位）细小胎膜中这个神经元的死亡是如何引起情绪的紊乱的？传统上我们认为大脑中的神经细胞会形成细小的管理行为的生物结构。例如，一组神经细胞接收移动手的信号然后将这些信号转播给已发手部活动的肌肉。这一生物机构的机能失调会引发行为紊乱，这一点很好理解。可是神经结构如何管理情绪？难道这个神经结构存储着一些例如规则之类，有关适应压力的：生病时、恶心时、面对死亡时、儿子移动枕头时这些情况下你要说什么你要怎么思考？是不是这种大脑神经结构衰退引发恐慌的讯息从而激发了Wurtzel寻死的念头——细胞死亡引发自杀的意图？
And how, then, does the birth of cells heal this feeling? Are new circuits formed that restore vitality, regenerating behaviors that are adaptive and not destructive? Is this why Prozac or Zoloft takes two or three weeks to start working: to become “undepressed,” do we have to wait for the slow rebirth of new parts of the brain?
那么，细胞的生成如何治愈这些感受？是否新的结构生成重新恢复活力，重生有适应能力且不具破坏性的行为？这就是为何Prozac或者Zoloft要花上两到三周才开始起效的原因吗？为了“摆脱抑郁”，我们必须要等待大脑中新的部分的缓慢重生吗？
If an answer to these questions exists, it may emerge from the work of Helen Mayberg, a neuroscientist at Emory University. Mayberg has been mapping anatomical areas of the brain that are either hyperactive or inactive in depressed men and women. Tracing such sites led her to the subcallosal cingulate, a minuscule bundle of nerve cells that sit near the hippocampus and function as a conduit between the parts of the brain that control conscious thinking and the parts that control emotion. Think of the subcallosal cingulate as a potential traffic intersection on the road between our cognitive and emotional selves.
如果这些问题存在答案的话，那可能是来自埃默里大学Helen Mayberg的工作，Mayberg了解了抑郁症患者大脑中活跃和非活跃结构区域。追踪这些部位后她找到了胼胝体下区色带，即海马体胖的一个细小神经细胞束，其功能是连接大脑中控制意识和控制情绪的部位，可以将胼胝体下区色带比作人类认知和情绪之路的潜在交叉点。
When Mayberg stimulated this area of the brain with tiny bursts of electricity using probes in patients resistant to antidepressant therapy, she found remarkable response rates: about 75 percent of them experienced powerful changes in their moods during testing. Seconds after stimulation began, many patients, some of them virtually catatonic with depression, reported a “sudden calmness” or a “disappearance of the void.” The stimulator can be implanted in patients and works like a depression pacemaker: it continues to relieve their symptoms for years. When the battery runs low, patients slowly relapse into depression.
Mayberg用探测器轻微电击对抗抑郁药物治疗有抵抗力的患者的大脑这一部位时，
她发现了显著的反应比率：75%的患者的情绪在测试时经历了强烈的变化。刺激开始后几秒钟，很多患者几乎没有了抑郁的状态，据说是“忽然的冷静”或者“空虚的消失”。刺激器可以植入患者，作为抑郁起搏器来使用：持续缓解患者的症状。电池电量低时，患者的抑郁又旧病复发。
At first glance, Mayberg’s studies would appear to bypass the serotonin hypothesis. After all, it was electrical, not chemical, stimulation that altered mood. But the response to Mayberg’s electrical stimulation also seemed to be linked to serotonin. The subcallosal cingulate is particularly rich in nerve cells that are sensitive to serotonin. Researchers found that if they blocked the serotonin signal in the brains of depressed rats, the pacemaker no longer worked.
乍一看，Mayberg的研究避开了血清素一说。毕竟，她的研究是基于电击而不是化学药品刺激而引起的情绪变动。但是Mayberg的电击的反应和血清素一说还是有关联的。在胼胝体下区色带这个部位，对血清素敏感的神经细胞异常丰富，研究人员发现，如果他们阻止了抑郁小白鼠大脑中的血清素信号，起搏器就不再有效。
A remarkable and novel theory for depression emerges from these studies. Perhaps some forms of depression occur when a stimulus — genetics, environment or stress — causes the death of nerve cells in the hippocampus. In the nondepressed brain, circuits of nerve cells in the hippocampus may send signals to the subcallosal cingulate to regulate mood. The cingulate then integrates these signals and relays them to the more conscious parts of the brain, thereby allowing us to register our own moods or act on them. In the depressed brain, nerve death in the hippocampus disrupts these signals — with some turned off and others turned on — and they are ultimately registered consciously as grief and anxiety. “Depression is emotional pain without context,” Mayberg said. In a nondepressed brain, she said, “you need the hippocampus to help put a situation with an emotional component into context” — to tell our conscious brain, for instance, that the loss of love should be experienced as sorrow or the loss of a job as anxiety. But when the hippocampus malfunctions, perhaps emotional pain can be generated and amplified out of context — like Wurtzel’s computer program of negativity that keeps running without provocation. The “flaw in love” then becomes autonomous and self-fulfilling.
这些研究引发了对抑郁症显著且新颖的理论。或许，有些形式的抑郁症源于刺激、遗传、环境或者压力导致海马体中神经细胞的死亡。在未患抑郁症的人的大脑中，海马体的神经细胞结构会向胼胝体下区色带发送信号，从而管理情绪。色带继而整合这些信号并转播至大脑中更有意识的部位，因为我们就可以将情绪或者行为登记在其中。而在抑郁病患者的大脑中，海马体中神经细胞的死亡使这些信号发生紊乱——部分信号为打开状态而部分信号为关闭状态——因而就将意识登记为了悲伤和焦虑。“抑郁是毫无征兆的情绪痛楚”，Mayberg说。她还说到，“在未患抑郁症的人的大脑中，海马体帮助人们将情绪要素放置进一个背景中“——告知我们的大脑，譬如，爱的失去表现为悲伤，或者事业的表现为焦虑。但是当海马体的功能受损时，可能情绪的痛楚会在没有缘由的情况下产生并扩大——就如Wurtzel那永远运行的消极电脑程序。”爱的瑕疵“就会自动生成并且自我实现。
We “grow sorrowful,” but we rarely describe ourselves as “growing joyful.” Imprinted in our language is an instinct that suggests that happiness is a state, while grief is a process. In a scientific sense too, the chemical hypothesis of depression has moved from static to dynamic — from “state” to “process.” An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire. Rather, it appears to change the wiring itself. Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits. The painter Cézanne, confronting one of Monet’s landscapes, supposedly exclaimed: “Monet is just an eye, but, God, what an eye.” The brain, by the same logic, is still a chemical soup — but, God, what a soup.
我们会'变得沮丧,'但是我们很少形容自己'变得快乐'.深植于我们语言中的是一种本能,暗示着快乐是一种状态,而悲伤则是一个过程.在科学意义上也是如此,化学上对抑郁的假说从静态到动态--由'状态'到'过程'.这些新的研究表明,像帕罗西汀或者百忧解这样的抗抑郁剂,也许并不是被动的增强信号.它并不像之前假设的那样,单纯增加血清素或向大脑的情绪保持线路传送更多的电流.取而代之的是,它更倾向于改变线路本身.像血清素一类的神经化学物质仍在这个新的抑郁症理论中占据核心地位,但是其起得作用不同了:作为使神经生长的动力,甚至也许形成新的回路.画家Cezanne在莫奈的一幅风景画前感慨:'莫奈只是一个视角,但是,天呐,多牛X的视角.'依这个逻辑来说,大脑就只是富含化学元素的一碗羹而已--但是,天呐,这是多牛x的一碗羹啊!
There are, undeniably, important gaps in this theory — and by no means can it claim to be universal. Depression is a complex, diverse illness, with different antecedent causes and manifestations. As the clinical trials show unequivocally, only a fraction of the most severely depressed patients respond to serotonin-enhancing antidepressants. Do these patients respond to Prozac because their depression involves cellular death in the hippocampus? And does the drug fail to work in mild to moderate depression because the cause of that illness is different?
不可否认的是，这理论中有重要的漏洞 -- 并且无论如何都不能说这理论是普遍适用的。抑郁是一个复杂，多样的疾病，有不同的前因和体现。临床实验已经一致证明，serotonin-enhancing antidepressants ［血清素含量提高型抗抑郁药物］只对抑郁最严重的患者中的一部分人起作用。Prozac对这些病人起作用是因为他们的抑郁跟海马体中的细胞死亡有关么？这药物对轻度、中度病人无效，是否因为病因不同？
The differences in responses to these drugs could also be due to variations in biological pathways. In some people, neurotransmitters other than serotonin may be involved; in yet others, there may be alterations in the brain caused by biological factors that are not neurotransmitters; in yet others, there may be no identifiable chemical or biological factors at all. The depression associated with Parkinson’s disease, for instance, seems to have little to do with serotonin. Postpartum depression is such a distinct syndrome that it is hard to imagine that neurotransmitters or hippocampal neurogenesis play a primary role in it.
对这些药物不同的反应也可能是因为生物路径的不同。一些人可能涉及到神经递质而非血清素；而对另外一些人，大脑中存在一些不是神经传导素的生物因素引起的变化；还有一些人，根本就没有刻意确认的化学物质或者生物因素。比如说，和帕金森症相关的抑郁症就和血清素关系不大。产后抑郁症又是一个比较特殊的症状，很难想象神经传导素或者海马趾神经形成对其有关键作用。
Nor does the theory explain why “talk therapies” work in some patients and not in others, and why the combination of talk and antidepressants seems to work consistently better than either alone. It is very unlikely that we can “talk” our brains into growing cells. But perhaps talking alters the way that nerve death is registered by the conscious parts of the brain. Or talking could release other chemicals, opening up parallel pathways of nerve-cell growth.
理论既没有解释为何“谈话治疗法”对一些病人有效果而对别的病人没效果，也没有解释谈话和抗抑郁药物的综合使用比两者单独使用效果更好。我们不可能通过“谈话”使大脑生成细胞。但是也许大脑某个控制意识的部分记录了聊天会改变神经死亡的方式.抑或是因为谈话可以释放其他化学物质，打开了神经细胞生长的平行路径。
But the most profound implications have to do with how to understand the link between the growth of neurons, the changes in mood and the alteration of behavior. Perhaps antidepressants like Prozac and Paxil primarily alter behavioral circuits in the brain — particularly the circuits deep in the hippocampus where memories and learned behaviors are stored and organized — and consequently change mood. If Prozac helped Dorothy sleep better and stopped her from assaulting her own skin, might her mood eventually have healed as a response to her own alterations of behavior? Might Dorothy, in short, have created her own placebo effect? How much of mood is behavior anyway? Maybe your brain makes you “act” depressed, and then you “feel” depressed. Or you feel depressed in part because your brain is making you act depressed. Thoughts like these quickly transcend psychiatry and move into more unexpected and unsettling realms. They might begin with mood disorders, but they quickly turn to questions about the organizational order of the brain.
但是，最为重要的结果和如何理解神经生长、情绪变化和行为改变中间的关联是有关系的。或许Prozac和Paxil这些抗抑郁药物主要改变大脑中的行为结构——尤其是海马体内部负责存储和组织记忆以及既定行为继而改变情绪的结构。如果Prozac帮助Dorothy有了更好的睡眠并抑制她不再毁坏自己的皮肤，她的情绪最终因为她自身的行为改变得以治愈了吗？简而言之，Dorothy生成了她自己的安慰效果吗？哪些情绪是行为？可能你的大脑使你“行为”抑郁，继而你“感受”抑郁。或许你感到抑郁一部分是因为你的大脑使你行为抑郁。类似的考虑很快就超越了精神病学的领域并进入了一个更不可预知更混乱的领域。因为情绪紊乱而起，但是迅速的转向有关大脑组织秩序的问题了。
John Gribbin, a historian of science, once wrote that seminal scientific discoveries are inevitably preceded by technological inventions. The telescope, which situated the earth and the planets firmly in orbit around the sun, instigated a new direction in thinking for astronomy and physics. The microscope, taking optics in a different direction, ultimately resulted in the discovery of the cell.
科学史家John Gribbin曾经写到过，开创性的科学发现总是不可避免的被技术发明超越。望远镜的出现使人们认识到地球和行星是紧紧围绕太阳运转的，也使得人们对于天文学和物理学有了新的认识。望远镜使得光学朝着不同的方向发展，正是这样，才有了后来细胞的发现。
We possess far fewer devices to look into the unknown cosmos of mood and emotion. We can only mix chemicals and spark electrical circuits and hope, indirectly, to understand the brain’s structure and function through their effects. In time, the insights generated by these new theories of depression will most likely lead to new antidepressants: chemicals that directly initiate nerve growth in the hippocampus or stimulate the subcallosal cingulate. These drugs may make Prozac and Paxil obsolete — but any new treatment will owe a deep intellectual debt to our thinking about serotonin in the brain. Our current antidepressants are thus best conceived not as medical breakthroughs but as technological breakthroughs. They are chemical tools that have allowed us early glimpses into our brains and into the biology of one of the most mysterious diseases known to humans.
我们能够用来探寻有关情绪情感这个未知宇宙的设备仍然很少。目前，我们只能综合化学治疗、电疗和希望（心理疗法？），通过这三钟疗法所产生的效果，间接地了解大脑的构造及其所属功能。但是随着时间的推移，这些有关抑郁的新理论所形成的深刻见解将会最终极大的推动新的抗抑郁药剂的产生：新的药物将直接刺激生长在海马或下扣带回深部的神经生长。这些新药物的投入使用可能会使百忧解和帕罗西汀退出市场，不过任何一种新的治疗都会影响我们大脑中5-羟色胺的含量从而影响大脑的思维能力。我们目前的抗抑郁药剂研究有着最为先进的理念，但技术上的突破却远不及医学上的。是化学科学上的成功，让我们能够初窥人类的大脑，以及初始这生物学领域内为人所知的最神秘的疾病之一。
Siddhartha Mukherjee is an assistant professor of medicine in the division of medical oncology at Columbia University. He is the author of ''Emperor of All Maladies: A Biography of Cancer.’’
Siddhartha Mukherjee 是哥伦比亚大学肿瘤科的医学系助理教授。他的著作有《病中之王：癌症传记》。
Editor: Ilena Silverman
This article has been revised to reflect the following correction:
Correction: May 6, 2012
An article on April 22 about depression and the drugs used to treat it misidentified a drug that affects serotonin levels in the brain. It is iproniazid, not isoniazid.
编辑：Ilena Silverman
本文已经根据以下做出纠正：
纠正：2012年5月6日
四月22日的有关抑郁症及其药物治疗的文章搞错了一款影响大脑中 serotonin 水平的药物名称。该药物是 iproniazid, 而不是 isoniazid.
