The Cause of Depression Is Probably Not What You Think | 抑郁症的原因，可能并非你所想象

Depression has often been blamed on low levels of serotonin in the brain. That answer is insufficient, but alternatives are coming into view and changing our understanding of the disease.
人们常常将抑郁症归咎于大脑中血清素水平的低下。这个答案并不充分,但是新的理论正在浮出水面,改变我们对这种疾病的理解。

People often think they know what causes chronic depression. Surveys indicate that more than 80% of the public blames a “chemical imbalance” in the brain. That idea is widespread in pop psychology and cited in research papers and medical textbooks. Listening to Prozac, a book that describes the life-changing value of treating depression with medications that aim to correct this imbalance, spent months on the New York Times bestseller list.
人们常常认为他们知道是什么导致了慢性抑郁症。调查显示,超过80%的公众将其归咎于大脑中的“化学失衡”。这个观点在流行心理学中广为流传,并在研究论文和医学教科书中被引用。《倾听普罗萨克》这本书描述了用药物治疗抑郁症以纠正这种失衡的生活改变价值,曾在《纽约时报》畅销书榜上停留了数月。

The unbalanced brain chemical in question is serotonin, an important neurotransmitter with fabled “feel-good” effects. Serotonin helps regulate systems in the brain that control everything from body temperature and sleep to sex drive and hunger. For decades, it has also been touted as the pharmaceutical MVP for fighting depression. Widely prescribed medications like Prozac (fluoxetine) are designed to treat chronic depression by raising serotonin levels.
被提及的失衡的大脑化学物质是血清素,这是一种重要的神经递质,具有传说中的“快乐”效果。血清素帮助调节大脑中控制从体温和睡眠到性欲和饥饿的所有系统。几十年来,它也一直被吹捧为抗抑郁的药物MVP。像普洛赛克(氟西汀)这样的广泛开具的药物旨在通过提高血清素水平来治疗慢性抑郁症。

Yet the causes of depression go far beyond serotonin deficiency. Clinical studies have repeatedly concluded that the role of serotonin in depression has been overstated. Indeed, the entire premise of the chemical-imbalance theory may be wrong, despite the relief that Prozac seems to bring to many patients.
然而,抑郁症的原因远远超出了血清素缺乏的范围。临床研究反复得出结论,血清素在抑郁症中的作用被过度夸大了。实际上,尽管普洛赛克似乎为许多患者带来了缓解,但整个化学失衡理论的前提可能是错误的。

A literature review that appeared in Molecular Psychiatry in July was the latest and perhaps loudest death knell for the serotonin hypothesis, at least in its simplest form. An international team of scientists led by Joanna Moncrieff of University College London screened 361 papers from six areas of research and carefully evaluated 17 of them. They found no convincing evidence that lower levels of serotonin caused or were even associated with depression. People with depression didn’t reliably seem to have less serotonin activity than people without the disorder. Experiments in which researchers artificially lowered the serotonin levels of volunteers didn’t consistently cause depression. Genetic studies also seemed to rule out any connection between genes affecting serotonin levels and depression, even when the researchers tried to consider stress as a possible cofactor.
一篇文献综述于7月份发表在《分子精神病学》上,可能是对最简单形式的血清素假说的最新也是最响亮的丧钟。由伦敦大学学院的Joanna Moncrieff领导的一个国际科学家团队筛选了来自六个研究领域的361篇论文,并仔细评估了其中的17篇。他们没有找到令人信服的证据表明血清素水平较低会导致或者甚至与抑郁症有关。抑郁症患者的血清素活动并不可靠地比没有这种疾病的人少。在研究人员人为降低志愿者的血清素水平的实验中,也并未一致地导致抑郁症。即使研究人员试图将压力作为可能的共因素来考虑,遗传研究似乎也排除了影响血清素水平的基因与抑郁症之间的任何联系。

“If you were still of the opinion that it was simply a chemical imbalance of serotonin, then yeah, it’s pretty damning,” said Taylor Braund, a clinical neuroscientist and postdoctoral research fellow at the Black Dog Institute in Australia who was not involved in the new study. (“The black dog” was Winston Churchill’s term for his own dark moods, which some historians speculate were depression.)
“如果你仍然认为这只是血清素化学失衡的问题,那么,确实,这是相当令人震惊的,”澳大利亚黑狗研究所的临床神经科学家和博士后研究员泰勒·布朗德说,他并未参与这项新的研究。(“黑狗”是温斯顿·丘吉尔对他自己的黑暗情绪的称呼,一些历史学家推测这可能是抑郁症。)

The realization that serotonin deficits by themselves probably don’t cause depression has left scientists wondering what does. The evidence suggests that there may not be a simple answer. In fact, it’s leading neuropsychiatric researchers to rethink what depression might be.
认识到单纯的血清素缺乏可能并不会导致抑郁症,这让科学家们开始思考真正的原因是什么。证据表明,可能没有一个简单的答案。实际上,这正在引导神经精神病学研究者重新思考抑郁症可能是什么。

Treating the Wrong Disease
治疗错误的疾病

The focus on serotonin in depression began with a tuberculosis drug. In the 1950s, doctors started prescribing iproniazid, a compound developed to target lung-dwelling Mycobacterium tuberculosis bacteria. The drug wasn’t particularly good for treating tuberculosis infections — but it did bless some patients with an unexpected and pleasant side effect. “Their lung function and everything wasn’t getting much better, but their mood tended to improve,” said Gerard Sanacora, a clinical psychiatrist and the director of the depression research program at Yale University.
抑郁症中对血清素的关注始于一种结核病药物。在1950年代,医生开始开处方使用异烟肼,这是一种针对肺部定居的结核分枝杆菌的化合物。这种药物对治疗结核病感染并不特别有效——但它确实给一些患者带来了意想不到的愉快副作用。“他们的肺功能等并没有得到多大改善,但他们的情绪倾向于好转,”耶鲁大学抑郁症研究项目的临床精神病医生和主任杰拉德·萨纳科拉说。

Perplexed by this outcome, researchers began studying how iproniazid and related drugs worked in the brains of rats and rabbits. They discovered that the drugs blocked the animals’ body from absorbing compounds called amines — which include serotonin, a chemical that carries messages between nerve cells in the brain.
对这个结果感到困惑的研究人员开始研究异丙肼及相关药物在大鼠和兔子的大脑中是如何工作的。他们发现这些药物阻止了动物体内吸收被称为胺的化合物——其中包括5-羟色胺,这是一种在大脑中传递神经细胞间信息的化学物质。

Several prominent psychologists, among them the late clinicians Alec Coppen and Joseph Schildkraut, seized on the idea that depression could be caused by a chronic deficiency of serotonin in the brain. The serotonin hypothesis of depression went on to inform decades of drug development and neuroscientific research. During the late 1980s, it led to the introduction of selective serotonin reuptake inhibitor (SSRI) drugs, like Prozac. (The drugs raise levels of serotonin activity by slowing down the neurotransmitter’s absorption by neurons.) Today, the serotonin hypothesis is still the explanation most often given to patients with depression when they’re prescribed SSRIs.
几位杰出的心理学家,其中包括已故的临床医生亚历克·科本和约瑟夫·希尔德克劳特,抓住了这个想法,即抑郁症可能是由于大脑中5-羟色胺的长期缺乏引起的。5-羟色胺假说的抑郁症继续影响了几十年的药物开发和神经科学研究。在1980年代晚期,它导致了选择性5-羟色胺再摄取抑制剂(SSRI)药物,如普洛兹的引入。(这些药物通过减慢神经递质被神经元吸收的速度来提高5-羟色胺的活动水平。)今天,5-羟色胺假说仍然是最常给予被处方SSRI的抑郁症患者的解释。

But doubts about the serotonin model were circulating by the mid-1990s. Some researchers noticed that SSRIs often fell short of expectations and didn’t improve significantly on the performance of older drugs like lithium. “The studies didn’t really stack up,” Moncrieff said.
但到了20世纪90年代中期,关于血清素模型的疑虑开始流传。一些研究人员注意到,选择性血清素再摄取抑制剂(SSRIs)的效果往往不如预期,且在改善病情方面并未显著超过像锂这样的旧药物。Moncrieff说:“这些研究并未真正站得住脚。”

By the early 2000s, few experts believed that depression is caused solely by lack of serotonin, but no one ever attempted a comprehensive evaluation of the evidence. That eventually prompted Moncrieff to organize such a study, “so that we could get a view as to whether this theory was supported or not,” she said.
到了21世纪初,很少有专家相信抑郁症仅由血清素缺乏引起,但从未有人尝试对证据进行全面评估。这最终促使蒙克里夫组织了这样一项研究,“以便我们能了解这个理论是否得到支持,”她说。

She and her colleagues found that it wasn’t, but the serotonin hypothesis still has adherents. Last October — just a few months after their review appeared — a paper published online in Biological Psychiatry claimed to offer a concrete validation of the serotonin theory. Other researchers remain skeptical, however, because the study looked at only 17 volunteers. Moncrieff dismissed the results as statistically insignificant.
她和她的同事发现并非如此,但是5-羟色胺假说仍然有支持者。去年十月——就在他们的评论出现几个月后——《生物精神病学》在线发表的一篇论文声称提供了5-羟色胺理论的具体验证。然而,其他研究人员仍然持怀疑态度,因为这项研究只看了17名志愿者。Moncrieff将结果视为统计上无关紧要。

A Different Chemical Imbalance
不同的化学失衡

Although serotonin levels don’t seem to be the primary driver of depression, SSRIs show a modest improvement over placebos in clinical trials. But the mechanism behind that improvement remains elusive. “Just because aspirin relieves a headache, [it] doesn’t mean that aspirin deficits in the body are causing headaches,” said John Krystal, a neuropharmacologist and chair of the psychiatry department at Yale University. “Fully understanding how SSRIs produce clinical change is still a work in progress.”
虽然血清素水平似乎并非抑郁症的主要驱动因素,但在临床试验中,选择性5-羟色胺再摄取抑制剂(SSRIs)相较于安慰剂显示出适度的改善效果。但这种改善背后的机制仍然难以捉摸。耶鲁大学精神病学系主任、神经药理学家约翰·克里斯塔尔说:“就因为阿司匹林可以缓解头痛,并不意味着身体中阿司匹林的缺乏就是引起头痛的原因。”他还表示,“完全理解SSRIs如何产生临床变化仍在进行中。”

Speculation about the source of that benefit has spawned alternative theories about the origins of depression.
关于这种好处来源的猜测已经催生了关于抑郁症起源的替代理论。

Despite the “selective” in their name, some SSRIs change the relative concentrations of chemicals other than serotonin. Some clinical psychiatrists believe that one of the other compounds may be the true force inducing or relieving depression. For example, SSRIs increase the circulating levels of the amino acid tryptophan, a serotonin precursor which helps regulate sleep cycles. Over the last 15 years or so, this chemical has emerged as a strong candidate in its own right for staving off depression. “There’s quite good evidence from tryptophan depletion studies,” said Michael Browning, a clinical psychiatrist at the University of Oxford.
尽管它们的名字中有“选择性”,但一些SSRIs会改变除血清素以外的其他化学物质的相对浓度。一些临床精神病医生认为,其中的一种其他化合物可能是真正引发或缓解抑郁症的力量。例如,SSRIs会增加氨基酸色氨酸的循环水平,这是一种帮助调节睡眠周期的血清素前体。在过去的15年左右的时间里,这种化学物质已经成为了预防抑郁症的有力候选者。“从色氨酸耗竭研究中有相当好的证据,”牛津大学的临床精神病医生迈克尔·布朗宁说。

A number of tryptophan depletion studies found that about two-thirds of people who have recently recovered from a depressive episode will relapse when given diets artificially low in tryptophan. People with a family history of depression also appear vulnerable to tryptophan depletion. And tryptophan has a secondary effect of raising serotonin levels in the brain.
一些色氨酸耗竭研究发现,约三分之二的近期从抑郁症中恢复过来的人在摄入人为降低色氨酸的饮食后会复发。有抑郁症家族史的人似乎也容易受到色氨酸耗竭的影响。而色氨酸还有一个次要效应,那就是提高大脑中的血清素水平。

Recent evidence also suggests that both tryptophan and serotonin may contribute to the regulation of bacteria and other microbes growing in the gut, and chemical signals from these microbiota could affect mood. While the exact mechanisms linking the brain and gut are still poorly understood, the connection seems to influence how the brain develops. However, because most tryptophan depletion studies so far have been small, the matter is far from settled.
近期的证据也表明,色氨酸和血清素可能都有助于调节肠道中细菌和其他微生物的生长,而这些微生物的化学信号可能会影响情绪。虽然连接大脑和肠道的确切机制仍然不太清楚,但这种联系似乎会影响大脑的发育。然而,由于到目前为止大部分的色氨酸耗竭研究都较小,这个问题还远未解决。

Other neurotransmitters like glutamate, which plays an essential role in memory formation, and GABA, which inhibits cells from sending messages to one another, may be involved in depression as well, according to Browning. It’s possible that SSRIs work by tweaking the amounts of these compounds in the brain.
根据布朗宁的说法,像谷氨酸这样的其他神经递质,它在记忆形成中起着至关重要的作用,以及GABA,它抑制细胞之间的信息传递,也可能涉及到抑郁症。可能SSRIs的作用是通过调整大脑中这些化合物的数量。

Moncrieff sees the hunt for other chemical imbalances at the root of depression as akin to rebranding rather than a truly novel line of research. “I would suggest that they are still subscribing to something like the serotonin hypothesis,” she said — the idea that antidepressants work by reversing some chemical abnormality in the brain. She thinks instead that serotonin has such widespread effects in the brain that we may have trouble disentangling their direct antidepressant effect from other changes in our emotions or sensations that temporarily override feelings of anxiety and despair.
蒙克里夫认为,寻找其他可能导致抑郁症的化学失衡更像是品牌重塑,而非真正新颖的研究线路。“我会建议他们仍在坚持类似于血清素假说的东西,”她说——这个观点认为抗抑郁药物的作用是通过逆转大脑中的某种化学异常。她反而认为,血清素在大脑中的影响如此广泛,我们可能会难以区分其直接的抗抑郁效果和我们的情绪或感觉的其他变化,这些变化可能暂时性地覆盖了焦虑和绝望的感觉。

Genetic Answers遗传学的答案

Not all theories of depression hinge on neurotransmitter deficiencies. Some look for culprits at the genetic level.
并非所有的抑郁症理论都依赖于神经递质的缺乏。有些人在基因层面寻找罪魁祸首。

When the first roughly complete draft sequence of the human genome was announced in 2003, it was widely hailed as the foundation of a new era in medicine. In the two decades since then, researchers have identified genes that underlie a huge spectrum of disorders, including about 200 genes that have been linked to a risk of depression. (Several hundred more genes have been identified as possibly raising the risk.)
2003年,当人类基因组的第一个大致完整的草案被宣布时,它被广泛誉为医学新时代的基础。在此后的二十年里,研究人员已经确定了导致大量疾病的基因,包括大约200个与抑郁症风险相关的基因。(还有几百个基因被认为可能增加风险。)

“It’s really important that people understand that there is a genetics of depression,” Krystal said. “Until very recently, only psychological and environmental factors were considered.”
“人们理解抑郁症有遗传因素这一点非常重要,”Krystal说。“直到最近,人们只考虑了心理和环境因素。”

Our knowledge of the genetics, however, is incomplete. Krystal noted that studies of twins suggest that genetics may account for 40% of the risk of depression. Yet the currently identified genes seem to explain only about 5%.
然而,我们对遗传学的了解还不完全。Krystal指出,双胞胎研究表明,遗传可能占抑郁症风险的40%。然而,目前已经确定的基因似乎只能解释其中的5%。

Moreover, simply having the genes for depression doesn’t necessarily guarantee that someone will become depressed. The genes also need to be activated in some way, by either internal or external conditions.
此外,仅仅拥有抑郁症的基因并不一定保证某人会患上抑郁症。这些基因还需要通过某种方式被激活,无论是由内部还是外部条件引发。

“There’s a false distinction that is sometimes drawn between environmental factors and genetic factors,” said Srijan Sen, a neuroscientist at the University of Michigan. “For most common traits of interest, both genetic and environmental factors play a critical role.”
“有时人们会错误地将环境因素和遗传因素进行区分,”密歇根大学的神经科学家Srijan Sen说。“对于大多数我们关注的常见特征,遗传和环境因素都起着关键的作用。”

Sen’s lab studies the genetic basis of depression by mapping subjects’ genomes and carefully observing how individuals with different genetic profiles respond to changes in their environment. (Recently, they have looked at stress brought on by the Covid-19 pandemic.) Different genetic variations can affect whether individuals respond to certain types of stress, such as sleep deprivation, physical or emotional abuse, and lack of social contact, by becoming depressed.
Sen的实验室通过绘制受试者的基因组并仔细观察具有不同基因特征的个体如何应对环境变化,来研究抑郁症的遗传基础。(最近,他们已经开始研究由Covid-19大流行引发的压力。)不同的基因变异可能会影响个体是否会因为某些类型的压力,如睡眠剥夺、身体或情感虐待以及社交接触的缺乏,而陷入抑郁。

Environmental influences like stress can also sometimes give rise to “epigenetic” changes to a genome that affect subsequent gene expression. For example, Sen’s laboratory studies epigenetic changes in the caps on the ends of chromosomes, known as telomeres, which affect cell division. Other labs look at changes in chemical tags called methylation groups that can turn genes on or off. Epigenetic changes can sometimes even be passed down through generations. “The effects of the environment are just as biological as the effects of genes,” Sen said. “Just the source is different.”
环境影响,如压力,有时也会导致对基因组的“表观遗传”变化,从而影响后续的基因表达。例如,Sen的实验室研究了染色体末端,也就是端粒的表观遗传变化,这些变化会影响细胞分裂。其他实验室则研究了可以开启或关闭基因的化学标签,即甲基化团体的变化。表观遗传变化有时甚至可以通过世代传递。“环境的影响与基因的影响一样具有生物性,”Sen说,“只是来源不同。”

Studies of these genes may someday help identify the form of treatment a patient would respond to best. Some genes may predispose an individual to better results from cognitive behavioral therapy, while other patients might fare better with an SSRI or therapeutic ketamine. However, it’s far too early to say which genes respond to which treatment, Sen said.
对这些基因的研究或许有朝一日能帮助确定病人最能响应的治疗方式。有些基因可能使个体对认知行为疗法有更好的反应,而其他病人可能对SSRI或治疗性麻醉剂反应更佳。然而,现在要说哪些基因对哪种治疗有反应还为时过早,Sen说。

A Product of Neural Wiring
神经连线的产物

Differences in a person’s genes may predispose them to depression; so, too, may differences in the neural wiring and structure of their brain. Numerous studies have shown that individuals differ in how the neurons in their brains interconnect to form functional pathways, and that those pathways influence mental health.
一个人的基因差异可能使他们易于患上抑郁症;同样,他们大脑的神经连接和结构的差异也可能如此。大量研究已经表明,个体在大脑神经元如何相互连接以形成功能路径方面存在差异,而这些路径会影响心理健康。

In a recent conference presentation, a team led by Jonathan Repple, a psychiatry researcher at Goethe University in Frankfurt, Germany, described how they scanned the brains of acutely depressed volunteers and found that they differed structurally from those of a non-depressed control group. For example, people experiencing depression showed fewer connections within the “white matter” of the nerve fibers in their brains. (However, there is no white-matter threshold for poor mental health: Repple notes that you can’t diagnose depression by scanning someone’s brain.)
在最近的一次会议演讲中,由德国法兰克福歌德大学的精神病学研究员乔纳森·雷普尔领导的团队描述了他们如何扫描急性抑郁志愿者的大脑,并发现他们的大脑结构与非抑郁对照组有所不同。例如,经历抑郁的人在他们大脑的“白质”神经纤维中显示出较少的连接。(然而,没有白质阈值对于精神健康不良:雷普尔指出,你不能通过扫描某人的大脑来诊断抑郁症。)

After the depressed group underwent six weeks of treatment, Repple’s team ran another round of brain scans. This time, they found that the general level of neural connectivity in the depressed patients’ brains had increased as their symptoms lessened. To get the increase, it didn’t seem to matter what kind of treatment the patients received, so long as their mood improved.
在抑郁症患者经历了六周的治疗后,Repple的团队进行了另一轮的脑部扫描。这一次,他们发现随着症状的减轻,抑郁症患者的大脑神经连接水平普遍提高。无论患者接受何种治疗,只要他们的情绪有所改善,神经连接水平就会增加。

A possible explanation for this change is the phenomenon of neuroplasticity. “Neuroplasticity means that the brain actually is able to create new connections, to change its wiring,” Repple said. If depression occurs when a brain has too few interconnections or loses some, then harnessing neuroplastic effects to increase interconnectedness might help lift a person’s mood.
这种变化的可能解释是神经可塑性现象。“神经可塑性意味着大脑实际上能够创建新的连接,改变其连线方式,”Repple说。如果抑郁症是由于大脑的互连性过少或丧失了一些,那么利用神经可塑性效应增加互连性可能有助于提升一个人的情绪。

Chronic Inflammation慢性炎症

Repple warns, however, that another explanation for the effects his team observed is also possible: Perhaps the depressed patients’ brain connections were impaired by inflammation. Chronic inflammation impedes the body’s ability to heal, and in neural tissue it can gradually degrade synaptic connections. The loss of such connections is thought to contribute to mood disorders.
然而,Repple警告说,他的团队观察到的效应还有另一种可能的解释:也许是抑郁症患者的大脑连接受到了炎症的损害。慢性炎症阻碍了身体的自愈能力,在神经组织中,它可能会逐渐降解突触连接。这种连接的丧失被认为可能导致情绪障碍。

Good evidence supports this theory. When psychiatrists have evaluated populations of patients who have chronic inflammatory diseases like lupus and rheumatoid arthritis, they’ve found that “all of them have higher-than-average rates of depression,” said Charles Nemeroff, a neuropsychiatrist at the University of Texas, Austin. Of course, knowing that they have an incurable, degenerative condition may contribute to a patient’s depressed feelings, but the researchers suspect that the inflammation itself is also a factor.
有很好的证据支持这个理论。当精神病医生评估患有慢性炎症性疾病如狼疮和类风湿性关节炎的患者群体时,他们发现“所有这些人的抑郁症发病率都高于平均水平”,德克萨斯大学奥斯汀分校的神经精神病学家查尔斯·内梅罗夫说。当然,知道自己患有无法治愈的退行性疾病可能会加重患者的抑郁情绪,但研究人员怀疑炎症本身也是一个因素。

Medical researchers have found that inducing inflammation in certain patients can trigger depression. Interferon alpha, which is sometimes used to treat chronic hepatitis C and other conditions, causes a major inflammatory response throughout the body by flooding the immune system with proteins known as cytokines — molecules that facilitate reactions ranging from mild swelling to septic shock. The sudden influx of inflammatory cytokines leads to appetite loss, fatigue and a slowdown in mental and physical activity — all symptoms of major depression. Patients taking interferon often report feeling suddenly, sometimes severely, depressed.
医学研究人员发现,对某些患者引发炎症可以触发抑郁症。干扰素α,有时用于治疗慢性丙型肝炎和其他疾病,通过向免疫系统大量注入被称为细胞因子的蛋白质,引发全身性的大规模炎症反应——这些分子可以促进从轻度肿胀到败血症休克的各种反应。炎症性细胞因子的突然涌入导致食欲减退、疲劳以及精神和身体活动的减缓——这些都是重度抑郁症的症状。服用干扰素的患者常常报告说他们突然,有时严重地感到抑郁。

If overlooked chronic inflammation is causing many people’s depression, researchers still need to determine the source of that inflammation. Autoimmune disorders, bacterial infections, high stress and certain viruses, including the virus that causes Covid-19, can all induce persistent inflammatory responses. Viral inflammation can extend directly to tissues in the brain. Devising an effective anti-inflammatory treatment for depression may depend on knowing which of these causes is at work.
如果被忽视的慢性炎症是导致许多人抑郁的原因,研究人员仍需要确定炎症的来源。自身免疫性疾病、细菌感染、高压力和某些病毒,包括引起Covid-19的病毒,都可以引发持久的炎症反应。病毒性炎症可以直接扩展到大脑组织。为抑郁症设计有效的抗炎治疗可能取决于知道这些原因中的哪一个在起作用。

It’s also unclear whether simply treating inflammation could be enough to alleviate depression. Clinicians are still trying to parse whether depression causes inflammation or inflammation leads to depression. “It’s a sort of chicken-and-egg phenomenon,” Nemeroff said.
目前还不清楚仅仅治疗炎症是否足以缓解抑郁症。临床医生仍在尝试解析是抑郁症导致炎症,还是炎症引发抑郁症。“这就像是先有鸡还是先有蛋的问题,” Nemeroff说。

The Umbrella Theory伞形理论

Increasingly, some scientists are pushing to reframe “depression” as an umbrella term for a suite of related conditions, much as oncologists now think of “cancer” as referring to a legion of distinct but similar malignancies. And just as each cancer needs to be prevented or treated in ways relevant to its origin, treatments for depression may need to be tailored to the individual.
越来越多的科学家开始倡导将“抑郁症”重新定义为一系列相关病症的总称,就像肿瘤学家现在将“癌症”视为一大群相似但又不同的恶性肿瘤一样。正如每种癌症都需要根据其起源进行相应的预防或治疗,抑郁症的治疗也可能需要根据个体进行定制。

If there are different types of depression, they may present similar symptoms — such as fatigue, apathy, appetite changes, suicidal thoughts, and insomnia or oversleeping — but they might emerge from completely different mixes of environmental and biological factors. Chemical imbalances, genes, brain structure and inflammation could all play a role to varying degrees. “In five or 10 years, we won’t be talking about depression as a unitary thing,” Sen said.
如果存在不同类型的抑郁症,它们可能会表现出类似的症状——如疲劳、冷漠、食欲变化、自杀念头以及失眠或过度睡眠——但它们可能源于完全不同的环境和生物因素的混合。化学失衡、基因、大脑结构和炎症都可能在不同程度上起作用。Sen说:“在五到十年内,我们不会再把抑郁症当作一个单一的事物来讨论。”

To treat depression effectively, medical researchers may therefore need to develop a nuanced understanding of the ways it can arise. Nemeroff expects that someday the gold standard for care won’t be just one treatment — it will be a set of diagnostic tools that can determine the best therapeutic approach to an individual patient’s depression, be it cognitive behavioral therapy, lifestyle changes, neuromodulation, avoiding genetic triggers, talk therapy, medication or some combination thereof.
因此,为了有效治疗抑郁症,医学研究人员可能需要对抑郁症可能产生的方式有一个细致的理解。Nemeroff预计,有朝一日,护理的黄金标准不仅仅是一种治疗方法——它将是一套可以确定对个体患者的抑郁症最佳治疗方法的诊断工具,无论是认知行为疗法、生活方式改变、神经调节、避免基因触发、谈话疗法、药物治疗,还是其中的某种组合。

That prediction may frustrate some physicians and drug developers, since it’s much easier to prescribe a one-size-fits-all solution. But “appreciating the true, real complexity of depression takes us down a path that is ultimately going to be most impactful,” Krystal said. In the past, he said, clinical psychiatrists were like explorers who landed on a tiny unknown island, set up camp, and got comfortable. “And then we discovered that there’s this whole, enormous continent.”
这种预测可能会让一些医生和药物开发者感到沮丧,因为提供一种适合所有人的解决方案要容易得多。但是“真正理解抑郁症的复杂性会引导我们走向最终可能产生最大影响的道路,”Krystal说。他说,过去,临床精神病医生就像是登陆在一个小小的未知岛屿上的探险者,建立营地,然后安逸下来。“然后我们发现,原来还有一个庞大的大陆。”