Schizophrenia: No Smoking Gun
精神分裂症：缺乏“冒烟”的确凿证据
[Note: despite how some people are spinning this, tobacco is still really really bad and you should not smoke it]
【请注意：尽管许多人言之凿凿，但烟草真的真的还是很不好，不应该抽烟。】
I.
Schizophrenics smoke. A lot. Depending on the study, about 60-80% of schizophrenics smoke, compared to only about 20% of the general population. And they spend on average about 27% (!) of their income on cigarettes. Even allowing that schizophrenics don’t make much income, that’s a lot of money. Sure, schizophrenics are often poor and undereducated and have other risk factors for smoking – but even after you control for this, the effect is still pretty strong.
精神分裂症患者抽烟，而且很多。根据某项研究，大约60%至80%的精神分裂症患者会抽烟，与之相比，总人口中只有约20%。而且，他们在烟草上的花费大约占到其收入的27%（！）。即便考虑到精神分裂症患者收入不高，这也是一大笔钱。无疑，精神分裂症患者通常都很穷、受教育程度不高，并且还有其他导致其吸烟的风险因素，但即便把所有这些都加以控制，精神分裂症与抽烟之间的统计关系还是很强。
Various people have come up with various explanations. Cognitively-minded people say that schizophrenics smoke as a maladaptive coping strategy for the anxiety caused by their condition. Pharmacologically-minded people say that schizophrenics smoke because smoking accelerates the metabolism of antipsychotic drugs and so makes their side effects go away faster. Pragmatically-minded people say that schizophrenics smoke because they’re stuck in institutions with nothing to do all day. No points for guessing what the Freudians say.
许多人已经为此提出过许多各种解释。关注认知的人说，精神分裂症患者抽烟，是对该疾病所致焦虑的不良应对策略。关注药理的人会说，他们抽烟是因为抽烟会加快抗精神病药物的代谢，从而能够促使其副作用更快消失。更为务实的人会说，他们抽烟是因为他们被困在了整日无所事事的社会福利机构里面。猜测弗洛伊德主义者的说法就没必要了。
But all these theories have problems. Sure, schizophrenics are often institutionalized, but even the ones at home smoke a lot. Sure, some schizophrenics are often on antipsychotics, but even the ones who aren’t on meds smoke a lot. Sure, schizophrenics are anxious, but we don’t see people with Generalized Anxiety Disorder having 80% smoking rates.
但所有这些理论都存在问题。毫无疑问，精神分裂症患者通常都被社会福利机构收容，但即便是那些散居在家的也抽很多烟。毫无疑问，有些精神分裂症患者经常服用抗精神病药，但即便是那些不服药的也抽很多烟。毫无疑问，精神分裂症患者很焦虑，但我们并没有在患有广泛性焦虑障碍的人群中看到80%的吸烟率。
As usual, I’m more biologically-minded, so I find it interesting that some of the genes that most commonly turn up as linked to schizophrenia – especially CHRNA3, CHRNA5, and CHRNA7 – are in nicotine receptors. Indeed, some of them are also the genes identified as risk factors for smoking.
我素来更倾向从生物学方面考虑，所以我发现了一个有趣之处，那就是部分最经常被与精神分裂症联系在一起的基因，特别是CHRNA3、CHRNA5和CHRNA7，都能在尼古丁受体上找到。
Further, there’s a lot of evidence that schizophrenic people actually feel better and have fewer symptoms when they’re smoking. Further, schizophrenics tend to gravitate toward cigarettes with higher nicotine content, and smoke them in ways that maximize nicotine absorption.
实际上，部分此类基因同时也被确认为影响吸烟的风险因素。此外，大量证据表明，精神分裂症患者在吸烟时确实会更加舒坦、更少症状。此外，精神分裂症患者一般会较喜欢尼古丁含量更高的烟草，而且吸烟时会设法尽量吸收更多的尼古丁。
It seems like part of the problem with schizophrenia is that the brain’s nicotine system isn’t working well. Smoking supplements nicotine and makes the system run smoother, so schizophrenics feel better when they smoke and continue to do so. This is the widely accepted self-medication hypothesis.
精神分裂症的问题似乎部分在于患者大脑的尼古丁系统运转不良。吸烟能够补充尼古丁，从而让这一系统运转更加顺畅，所以精神分裂症患者在吸烟时会感觉更加良好，并且乐此不疲。这就是受到广泛认同的“自发用药假说”。
I like this because it’s a really elegant example of…I don’t know what you’d call it…memetic evolution? Nobody knew that nicotine helped schizophrenia, nobody told the schizophrenics that, but they sort of naturally gravitated to an effective treatment for their condition by going in the direction of things that make them feel better, even going so far as to unknowingly gravitate toward cigarette brands with more nicotine.
我喜欢这一假说，因为它真是模因进化（我不知道你们如何称呼它）的一个极好例证。原先并没人知道尼古丁有助于缓解精神分裂症，没人这么告诉患者，但他们通过追随让他们感觉良好的事物，可以说是自然地找到了有效的治疗方法，甚至不自觉地偏爱尼古丁含量更高的烟草品牌。
They did all of this before psychiatry had any idea why they were doing it, and in the face of constant protests that it was stupid and useless. This should be a warning to anyone who’s too quick to tell patients that their coping strategies are maladaptive.
早在精神病学对其做法之缘由有任何了解之前，他们就已经在这么做了，尽管当时人们一直批评这种做法既愚蠢又无用。有些人会过于仓促地认为患者的应对策略调整不佳，上述事实应当能让这些人引以为戒。
But there’s a much more important question here: does smoking cause schizophrenia? How about prevent it?
但此处还有一个更为重要的问题：吸烟会导致精神分裂症吗？又会不会防止精神分裂症呢？
II.
First, the causation argument. Gurillo et al do a meta-analysis and conclude that “daily tobacco use is associated with increased risk of psychosis and an earlier age of onset of psychotic illness. The possibility of a causal link between tobacco use and psychosis merits further examination”. That is, schizophrenics are already smoking much more at the moment their schizophrenia starts. This suggests that maybe smoking is helping to cause the schizophrenia?
首先来看因果论证。Gurillo等人做了一个荟萃分析，得出结论认为：“每日使用烟草与精神病风险的增加和精神疾病发病年龄的提早均有关。烟草使用和精神病之间存在因果关系的可能性还需要进一步研究。”也就是说，精神分裂症患者在初次发病时就已经在大量抽烟了。这是否意味着吸烟有可能增加患精神分裂症的风险？
All nice and well, except for a few things. First, this study ignores the possibility that the genes that cause schizophrenia might also cause increased smoking, even though we have some evidence that this is true (actually, it doesn’t ignore this, it mentions it, but uses it as a reason why a schizophrenia-smoking link is more plausible).
听上去很好，就是有一点点问题。首先，该研究忽略了一种可能性，即导致精神分裂症的基因可能也会导致烟瘾增加，而我们在这方面有一些证据。（实际上该研究并没有忽略这种可能性，而是有所提及，但只是把它作为精神分裂症与吸烟有关联这一说法更可信的理由）。
Second, we know that people who will later develop schizophrenia are seen as kind of odd even before they come down with the disease, and it’s possible that they’re already in some unusual brain state that smoking helps relieve. Third, this study is not controlled – meaning that we’re totally helpless before factors like “people destined to later develop schizophrenia are often poor, and poor people smoke more”.
第二，我们知道，有些后来得了精神分裂症的人早在得病之前就看起来似乎有点奇怪，可能那时候他们的大脑就已经处于某种不正常状态，而吸烟能帮助缓解这种状况。第三，该项研究没有进行对照控制，也就是说如果把某些因素考虑进去，比如“后来注定会得精神分裂症的人通常很穷，而穷人通常抽烟更多”等，我们就无力回答。
And fourth, another study shows exactly the opposite.
还有，第四，另一项研究有完全相反的发现。
Zammit et al (thanks to @allfeelsallthetime for the tip) looks at 50,000 teenage Swedish conscripts, then follows them throughout their lives to see which ones do or don’t get schizophrenia. They find that without adjusting for confounders, smokers are more likely to get schizophrenia.
Zammit等人（感谢网友@allfeesallthetime提示）选取了50000个应征入伍的瑞典青少年，然后终身追踪他们，观察哪些会得精神分裂症，哪些不会。他们发现，如果不就混杂因子【编注：混杂因子是指同时导致A与B两个因子，从而使得A与B表现出相关性的因子。】作出调整，吸烟者便看起来更可能得精神分裂症。
But when you do adjust for confounders, smokers are less likely to get schizophrenia, (hazard ratio 0.8, p = 0.003) and heavy smokers are much less likely to get schizophrenia (hazard ratio 0.5)! A dose-dependent relationship was found between smoking and protection from schizophrenia. This is really interesting.
但如果你就混杂因子作了调整，吸烟者得精神分裂症的可能性相对就会较低（风险比为0.8，p=0.003），而重度嗜烟者患精神分裂症的可能性相对而言非常低（风险比为0.5）！在吸烟与避免精神分裂症之间居然找出了这种与剂量相关的关系，真是非常有意思。
Why do we find such different results from these two studies? The only explanation I can think of is that the second study controls for various factors including cannabis use, personality variables, IQ, past psychiatric diagnoses, and place of upbringing (thanks @su3su2u1 for the tip) and the first study controls for zilch.
为什么两项研究会得出如此不同的结论？我能想到的唯一解释就是，第二项研究对照控制了许多不同因素，包括吸食大麻、个性差异、智商、既往精神病诊断史、成长地点等（感谢网友@su3su2u1提示），而第一项研究没做任何控制。
In fact, we find that the second study’s uncontrolled numbers are not that different from the first study’s uncontrolled numbers, and that the only difference is that the second study then went on to control for confounders and get the opposite result. Controlling for more things is not always better, but controlling for a few things that previous studies and common sense suggest are very relevant is pretty superior to just leaving the data entirely unprocessed. Advantage very much second study.
实际上，我们发现第二项研究中未进行控制的因子数目跟第一项研究中未进行控制的因子数目没有多大出入，两者唯一的差别就是第二项研究进一步控制了混杂因子，然后就得出了相反的结论。控制的因子并不总是越多越好，但对此前研究和基本常识都认为，对非常相关的一些事项进行控制，比对数据完全不加任何处理的做法要好得多。第二项研究因而拥有压倒优势。
III.
Unlike certain people on Facebook, I fucking hate science. Let me explain why.
跟Facebook上的某些人不同，我真他妈讨厌科学。让我来解释解释。
The first study here, Gurillo et al, was published ten years after the second study. Since it is a meta-analysis, it included the second study in it. The authors of the first study definitely read the second study. They just didn’t care.
此处提到的Gurillo等人所做的第一项研究，发表于第二项研究完成后的10年之后。由于它是一个荟萃分析，所以它的对象包括了第二项研究。该研究的作者们必定读过第二项研究。他们只是毫不在乎。
Nowhere in the first study does it say “By the way, we read this other study that got the opposite results from us, let’s try to figure out why, oh, it was because they controlled for things and we didn’t, maybe that should call our findings into question.”
第一项研究从未在任何地方说过：“此外，我们读到了另外一项研究，其结论与我们的正相对立；我们来看看原因是什么，哦，原来是因为他们对一些事项进行了控制而我们没有，这也许会对我们的发现构成质疑。”
You know what they did do? They listed the second study as finding that smoking increased schizophrenia risk, because the rules of their meta-analysis said they would only take uncontrolled data, and so they did. You can read this entire study, which cites the second study no fewer than six times, without hearing at all about the fact that the second study got the opposite result using likely better methodology.
你知道他们实际干了什么吗？他们将第二项研究列为吸烟增加精神分裂症患病风险的发现之一，因为他们做荟萃分析的一项原则是只采用未控制的数据，他们也真是这么做的。你们可以读读其全文，它引用第二项研究不下六次，但在任何地方你都看不到它提及第二项研究利用可能更好的方法得出了完全相反的结论这一事实。
Then they go on to conclude that:
然后，他们在结论中说：
Cigarette smoking might be a hitherto neglected modifiable risk factor for psychosis, but confounding and reverse causality are possible. Notwithstanding, in view of the clear benefits of smoking cessation programs in this population, every effort should be made to implement change in smoking habits in this group of patients.
吸烟可能是引发精神病的可改造风险因素之一，这一点迄今为止一直为人所忽略。但是，混杂偏差和反向因果关系也有可能存在。尽管如此，考虑到在这一人群中实施戒烟计划的明显好处，我们应该全面努力，促使这一病患群体改变吸烟习惯。
Clear benefits! Every effort! Aaaaaaah!
明显好处！全面努力！啊哈哈哈哈！
I mean, I know where they (and the Lancet editors, who write a glowing comment backing them up) are coming from. Smoking is bad because lung cancer, COPD, etc. But now we have these things called e-cigarettes! They deliver nicotine without tobacco! As far as anyone knows they carry vastly less risk of cancer, COPD, etc. If nicotine actually prevents schizophrenia rather than causing it, that is the sort of thing we should really want to know. And instead we’re just getting this “We should make schizophrenia patients stop smoking, because smoking is bad”.
我说，我知道他们（以及《柳叶刀》的编辑们，他们写了篇热情洋溢的评论支持前者）的出发点在哪儿。吸烟不好，因为会导致肺癌、慢性阻塞性肺炎等等。但我们现在已经有了所谓的电子烟！它们无需烟草就能提供尼古丁。如果尼古丁确实会预防而不是导致精神分裂症，这种事应该是我们确实想要明白知晓的。但是，我们听到的却是这样一些话：“我们应该让精神分裂症患者停止抽烟，因为抽烟不好。”
Look. I am not going to come out and say that there’s great evidence that nicotine decreases schizophrenia risk. There’s one study, which other studies contradict. I happen to think that the one study looks better than its competitors, but that’s my opinion and I have nowhere near the evidence I would need to feel really strongly about this.
注意，我不是跳出来说有很强的证据表明尼古丁有助于减少精神分裂症患病风险。有一项研究这么说，还有许多研究跟它有抵触。我只是凑巧觉得，这项研究似乎比其他研究做得更好，当然这只是我的个人看法，要说我对这一想法的信念有多强烈，那根本还缺乏必要的证据支持。
But I feel like we are very far from the point where we know enough to be pushing people at risk of schizophrenia away from nicotine, and light-years away from the point where we can use phrases like “clear benefits”.
但是，我也认为，要说我们已经具备了足够的知识，以催促有精神分裂症患病风险的人远离尼古丁，那我们现在还差得远；要说使用“明显好处”一类的说法，那我们还差着很多光年。
Possibly I am an idiot and missing something very important. But if this is true, I wish the authors of the new study, and the editors of The Lancet, would have acknowledged the existence of the conflicting study and patiently explained to their readership, many of whom are idiots like myself, “Here’s a study that looks better than ours that seems to contradict our results, but here’s why our study is nevertheless far more believable.” That’s all I ask.
也许我是个笨蛋，忽略了一些非常重要的事情。但如果真是如此，我就希望上述新研究的作者们，以及《柳叶刀》的编辑们，能够承认与他们有相互冲突的研究存在，并能耐心地向读者们解释，因为许多读者跟我一样是笨蛋。“有项研究看起来比我们做得好，结论与我们的相反，但我们的研究仍然更可信，理由如下。”这才是我希望看到的。
No matter how much of an idiot I am, I can’t possibly imagine how that wouldn’t be a straight-out gain.
不管我有多么傻，我也根本无法想象，这么做怎么会不是一件彻头彻尾的好事。
PS: Cigarette smoking definitely decreases your risk of Parkinson’s Disease. Parkinson’s is similar to schizophrenia in that both involve dopamine. But schizophrenia involves too much dopamine and Parkinson’s too little, so the analogy could go either direction.
附：吸烟绝对会减少你患帕金森症的风险。帕金森症跟精神分裂症有些类似，两者都涉及到多巴胺。只是，精神分裂症是多巴胺过多，而帕金森症则是过少，所以该类比可以指向两个方向。【译注：即吸烟可能会减低，也可能会增加精神分裂症的风险。】
PPS: Tobacco smoking is definitely still bad! Nothing in here at all suggests that tobacco smoking has the slightest chance of not being a terrible decision!
又附：吸烟仍然绝对有害！本文没有任何地方说吸烟有可能不是个糟糕的决定，没门。
翻译：沈沉（@你在何地-sxy）
校对：小册子（@昵称被抢的小册子）
编辑：辉格@whigzhou