抑鬱症從何而來（中英對照）

來自專欄 世界之大

The discovery of genes that are linked to the crippling condition throws up exciting new possibilities for its successful treatment

前言：科學家發現抑鬱症致病基因，或為這種危害極大的疾病帶來新療法的曙光。

Depression runs in families, we know. But it is only very recently, and after considerable controversy and frustration, that we are beginning to know how and why. The major scientific discoveries reported last week by the Psychiatric Genomics Consortium in Nature Genetics are a hard-won breakthrough in our understanding of this very common and potentially disabling disorder.

正文：我們已經知道，抑鬱症常以家庭為單位發病，但對其成因卻所知甚少。學界圍繞這個問題一直爭論不休，科學家艱難的求索也從未停止，直到最近，人類才首次了解到抑鬱症背後的秘密。上周，精神病與基因組研究團隊在《自然雜誌?遺傳學》上發表論文，標誌著人類對抑鬱症——這一常見卻又危害巨大的疾病——的了解終於迎來了突破。

If your parents have been depressed, the chances that you have been or will be depressed are significantly increased. The background risk of depression in the general population is about one in four – each of us has a 25% chance of becoming depressed at some point in our lives. And if your parents have been depressed, your risk jumps by a factor of three.

如果你的父母患有抑鬱症，那麼你患病的幾率將會大大增加。普通人患病的幾率約為4分之1，即每個人都有25%的幾率，會在一生中的某個階段患上抑鬱症。可如果你的父母也有抑鬱症的話，你得病的可能性將上漲3倍。

However, controversy has long swirled around the question of nature or nurture. Is the depressed son of a depressed mother the victim of her inadequate parenting and the emotionally chilly, unloving environment she provided during the early years of his life? Or is he depressed because he inherited her depressive genes that biologically determined his emotional fate, regardless of her parenting skills? Is it nature or nurture, genetics or environment, which explain why depression runs in families?

一直以來，圍繞抑鬱症都存在先天還是後天的爭論。假設一位母親和孩子都患有抑鬱症。孩子會得病，是因為母親沒有盡到為人母的責任嗎？母親性情冷淡，孩子在年幼的時候沒有得到足夠的關愛（所以才患病）？還是因為孩子遺傳了母親的致病基因，無論母親如何養育他，最後都難逃疾病的命運？究竟是先天還是後天、是遺傳還是環境，導致了抑鬱症與家庭的關聯？

In the 20th century, psychiatrists ingeniously teased out some answers to these questions. For example, it was found that pairs of identical twins, with 100% identical DNA, were more likely to have similar experiences of depression than were pairs of non-identical twins, with 50% identical DNA. This indicated clearly that depression is genetically heritable. But well into the 21st century, the precise identity of the 「genes for depression」 remained obscure. Since 2000, there has been a sustained international research effort to discover these genes, but the field has been bedevilled by false dawns and inconsistent results.

早在上個世紀，科學家就抽絲剝繭，巧妙地找到了部分答案。科學家發現，同卵雙胞胎（兩個孩子的DNA①完全相同）有相似抑鬱經歷的可能性，比異卵雙胞胎（兩個孩子僅有50%的DNA相同）更高，表明抑鬱症確實和遺傳有關。但直到21世紀，科學家都無法準確識別導致抑鬱症的基因。2000年後，儘管國際上相關研究不斷，但收效甚微，無法自圓其說的結論比比皆是，希望如曇花一現。

注①：DNA：又名脫氧核糖核酸，是一種攜帶生物遺傳信息的分子，可以決定生物的性狀。

That is why the study published last week is such a significant milestone. For the first time, scientists around the world, with leading contributions from the UK』s world-class centres of psychiatric genetics research largely funded by the Medical Research Council at the University of Cardiff University, University of Edinburgh University and King』s College London, have been able to combine DNA data on a large enough sample to pinpoint which locations on the genome are associated with an increased risk of depression. So we now know, with a high degree of confidence, something important about depression that we didn』t know this time last year. We know that there are at least 44 genes, out of the 20,000 genes comprising the human genome, which contribute to the transmission of risk for depression from one generation to the next.

所以，上周發布的論文是抑鬱症研究的里程碑。這是科學家首次在人類的基因組上，精確定位會導致患抑鬱症風險上升的基因，這次實驗的數據足夠大，研究人員是來自英國精神病遺傳學領域的世界級權威，由卡迪夫大學（譯者註：一所位於英國威爾斯的頂尖大學）、愛丁堡大學（譯者註：世界著名大學）和倫敦國王學院（譯者註：英國頂尖名校之一）旗下的英國醫學研究理事會出資贊助。現在，我們可以自信的說，人類基因組中的兩萬個基因，至少有44個導致了抑鬱症在親子之間的遺傳，這是之前科學家不知道的。

However, this raises at least as many issues as it resolves. Let』s first dwell on the fact that there are many risk genes, each of which contributes a small quantum of risk. In other words, there is not a single smoking gun, a solitary rogue gene that works like a binary switch, inevitably causing depression in those unfortunate enough to inherit it. More realistically, all of us will have inherited some of the genes for depression and our chances of becoming depressed will depend in part on how many and their cumulative impact. As research continues and even larger samples of DNA become available for analysis, it is likely that the number of genes associated with depression will increase further still.

但是這一發現帶來的問題和它解決的一樣多。首先，致病基因不是一個而是許多，每個基因都會小幅度地增加罹患抑鬱症的風險。換句話說，並沒有一個所謂特定的流氓基因，好像開關一樣讓人得上抑鬱症。更準確的說法是，我們每一個人都遺傳了部分致病基因，至於是否會變得抑鬱，則取決於這些基因的數量以及它們之間的相互作用。現在，相關研究還在繼續，DNA樣本越來越多，相信未來會發現更多和抑鬱症有關的基因。

This is telling us that we shouldn』t be thinking about a black-and-white distinction between us and them, between depressed patients and healthy people: it is much more likely that our complex genetic inheritance puts all of us on a continuous spectrum of risk.

這也意味著正常人和抑鬱症患者之間並沒有顯著差別，不應該帶著有色眼鏡看他們。人類複雜的遺傳機制使每一個人都有得抑鬱症的風險。

What are these genes and what do they tell us about the root causes of depression? It turns out that many of them are known to play important roles in the biology of the nervous system. This fits with the basic idea that disturbances of the mind must reflect some underlying disturbance of the brain.

這些基因是如何運作的，它們又是怎麼導致抑鬱症的？研究發現，大部分致病基因和人類神經系統的生理機能息息相關，這和一般人認為的，思想的混亂實際上是大腦的混亂相吻合。

More surprisingly, many of the risk genes for depression also play a part in the workings of the immune system. There is growing evidence that inflammation, the defensive response of the immune system to threats such as infection, can cause depression. We are also becoming more aware that social stress can cause increased inflammation of the body. For decades we』ve known that social stress is a major risk factor for depression. Now it seems that inflammation could be one of the missing links: stress provokes an inflammatory response by the body, which causes changes in how the brain works, which in turn cause the mental symptoms of depression.

更讓人驚訝的是，大部分致病基因還和免疫系統有關。越來越多的證據表明，人體對抗健康威脅（如感染）的防禦手段之一：發炎，也會導致抑鬱症。現在，人們對社會壓力會加劇人體炎症的認識不斷加深。過去數十年來，我們知道社會壓力是導致抑鬱症的主要原因。現在看來，炎症才是被忽視的一環：壓力激起人體的炎症反應，炎症反應又會改變大腦機能，而大腦機能的改變則會導致抑鬱症癥狀的出現。

Knowing the risk genes for depression also has important implications for practical treatment. There have been no major advances in treatment for depression since about 1990, despite it being the major single cause of medical disability in the world. We need to find new ways forward therapeutically and new genetics is a great place to start the search for treatments that can cut through more precisely to the cause or mechanism of depression. It is easy to imagine how new antidepressant drugs could in future be designed to target inflammatory proteins coded by depression risk genes. It is exciting to think that the new genetics of depression could unlock therapeutic progress in psychiatry as well.

找到抑鬱症致病基因對治療幫助很大。1990年以後，針對抑鬱症的治療手段就止步不前，而抑鬱症是全世界病理性殘疾的主要原因。我們急需新的方法推進治療手段進步。基因研究是個不錯的切入點，因為基因研究直指抑鬱症的病根和運作機理。相信在不久的將來，就會生產出新的抗抑鬱藥物，專門用來消滅由致病基因編碼的炎症蛋白。更讓人振奮的是，抑鬱症的基因研究將會推動整個精神病治療領域前進。

Finally, although I think these genetic discoveries are fundamental, I don』t see them as ideologically divisive. They don』t prove that depression is 「all in the brain」 or that psychological treatment is pointless. The genetics will be biologically pre-eminent but, as we understand more about what all these 「genes for depression」 do, we may discover that many of them control the response of the brain or the body to environmental stress. In which case, the treatment that works best for an individual patient could be a drug targeting a gene or intervention targeting an environmental factor such as stress.

最後，雖然對抑鬱症展開基因研究至關重要，但我並不認為基因研究和其他研究勢同水火——抑鬱症和基因有關，並不意味著抑鬱症全是「腦袋裡的事」，也不意味著心理療法毫無意義。從生物學的角度來講，基因研究是大勢所趨，但隨著對致病基因了解的加深，或許還會發現這些基因主宰著大腦和機體對環境壓力的反應。這樣一來，針對抑鬱症的最好療法，就是生產針對基因的靶向藥物，以及實施對可能導致抑鬱症環境的干預。

In short, I believe that a deeper understanding of the genetics of depression will lead us beyond the question we started from: is it nature or nurture, gene or environment? The answer will turn out to be both.

簡而言之，我相信隨著對抑鬱症基因領域了解得越來越多，問題最終會脫離本源：即抑鬱症究竟是外部因素還是內部因素、是基因還是環境導致的。我想答案會是，二者兼而有之。

原文作者：Edward Bullmore

原文網址：This revolution in our understanding of depression will be life-transforming | Edward Bullmore