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Thomas Insel 談邁向瞭解精神疾病之新途徑

Thomas Insel: Toward a new understanding of mental illness

 

Photo of three lions hunting on the Serengeti.

講者:Thomas Insel

2013年1月演講,2013年4月在TEDxCaltech上線

 

翻譯:洪曉慧

編輯:朱學恆

簡繁轉換:洪曉慧

後製:洪曉慧

字幕影片後制:謝旻均

 

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MAC及手持裝置版本請按此下載

閱讀中文字幕純文字版本

 

關於這場演講

目前,拜早期發現之賜,心臟病死亡人數比幾十年前降低63%。美國國家心理衛生研究所(NIMH)主任Thomas Insel思索:我們是否能對憂鬱症及精神分裂症如法炮製?他說新研究途徑的第一步是一項重要的觀念改變:別再將精神疾病視為「精神障礙」,應將其視為「腦部障礙」。(攝於TEDxCaltech)

 

關於Thomas Insel

美國國家心理衛生研究所主任Thomas Insel所做的研究,將有助於我們瞭解、治療,甚至預防精神障礙。

 

為什麼要聽他演講

自從2002年成為美國國家心理衛生研究所(NIMH)主任後,Thomas Insel已在瞭解精神障礙方面取得諸多進展。擔任此職位期間,他在臨床試驗、自閉症研究及遺傳在精神疾病中扮演的角色等方面取得重大突破。

 

任職於NIMH之前,Insel是Emory大學精神病學教授,研究複雜社會行為之神經生物學。當時他是美國國家科學基金會行為神經科學中心之創始主任,及美國國家衛生研究所(NIH)資助之自閉症研究中心主任。他曾經發表超過250篇科學論文,出版過四本書,服務於眾多學術、科學和專業委員會及董事會。他是美國國家醫學研究院及美國神經心理藥物學院成員,曾經榮獲美國公共衛生服務部頒發之傑出服務獎,及2010年La Fondation IPSEN神經可塑性獎。

 

Thomas Insel的英語網上資料

Bio: NIMH

Blog: NIMH Director's Blog

 

[TED科技‧娛樂‧設計]

已有中譯字幕的TED影片目錄(繁體)(簡體)。請注意繁簡目錄是不一樣的。

 

Thomas Insel 談邁向瞭解精神疾病之新途徑

 

讓我們用一些好消息作開場白。這些好消息和基於生物醫學研究所得的資訊有關,它確實改變許多嚴重疾病的結果。

 

我們從白血病談起。急性淋巴性白血病,ALL,兒童最常見的癌症。在我學生時期,這種疾病的死亡率約為 95%;25、30年後的今天,其死亡率已下降 85%,每年有6000名過去將死於這種疾病的兒童獲得治癒。如果你想瞭解更顯著的進展,請看心臟病統計數據。心臟病曾經是健康的頭號殺手,尤其對40多歲的男性而言。今天我們發現,心臟病的死亡率下降 63%。值得注意的是,每年死亡人數減少110萬。令人驚訝的是,愛滋病剛於上個月被歸類為慢性疾病,意味著遭受愛滋病毒感染的20歲年輕人,將不會像我們十年前所預期的,僅存活幾星期、幾個月或幾年,而有機會存活數十年,或許在60或70歲死於其他原因。這是相當驚人的變化,對某些致命疾病的前景而言,尤其是其中一種,你或許不知道-中風。它通常伴隨心臟病發生,是我國死亡率最高的疾病之一。現在我們知道,以這種疾病來說,如果能在發病三小時內將病患送入急診室,大約 30% 病患能平安出院,沒有任何後遺症。

 

令人驚嘆的故事,人類的福音。這一切的結果是,瞭解某些關於疾病的資訊,使我們能早期發現、早期治療。早期發現、早期治療,這是人類對抗疾病的勝利史。

 

不幸的是,並非全都是好消息。我們談談另一個故事,和自殺有關。現在,當然,它本身並非疾病,而是導致死亡的條件或情況。你或許不知道這種情形多麼普遍。美國每年有38,000人自殺,意味著大約每15分鐘一位,它是15至25歲年齡層中第三大死亡原因。這是一個令人震驚的故事,當你知道因此死亡的人數為謀殺的兩倍時。事實上,以我國來說,這是比交通事故更常見的死因。現在,當我們談到自殺,醫學上對這方面的研究亦有貢獻,因為 90% 的自殺與精神疾病有關-憂鬱症、躁鬱症、精神分裂症、厭食症、邊緣型人格-許多精神疾病與此有關。如我之前提過的,這些疾病往往發生於人生早期。

 

但自殺不僅與這些疾病的死亡率有關,也與其罹患率有關。如果觀察致殘程度,根據世界衛生組織以所謂的「傷殘調整生命年」所做的衡量-沒人想到它會成為一種度量單位,除了經濟學家。它是藉由醫學因素導致的失能,估算健康壽命損失的方法。如各位所見,在所有醫學因素導致的失能中,約 30%歸因於精神障礙、精神症狀。

 

你或許認為這並不合理。我的意思是,癌症似乎更加嚴重,心臟病似乎更加嚴重。但各位可以看見,事實上它們位於這張列表的下方,因為我們所討論的是失能。導致這些疾病產生失能情況的原因為何?例如精神分裂症、躁鬱症和憂鬱症?為何它們在這張列表中獨占鰲頭?

 

好,有三個可能原因。第一,這些疾病非常普遍,大約五分之一的人在人生過程中將罹患其中一種。第二,當然,對某些人來說,這會造成真正的失能,比例約為 4%~5%,大約20人中即有1人。但真正造成這些數據、這種高罹患率,以某種程度來說,亦是高死亡率的原因,在於這些疾病發生於人生早期。50% 病患將於14歲前發病,75% 病患將於24歲前發病。這是截然不同的情形-相較於癌症,或心臟病、糖尿病、高血壓等大多數主要疾病,即我們一般認為的罹病和死亡原因。這確實是屬於年輕人的慢性病。

 

現在,我以一些好消息作開場白,顯然這並非其中之一。這或許是其中最難以啟齒的部分,以某種意義來說,這算是我的告解。我的工作是確保在這所有的疾病上取得進展。我為聯邦政府工作,其實算是為你們工作,你們付我薪水。或許以這點來說,當你們知道我所做的事,或我無法做到的事之後,或許會認為我應該被解僱。我當然明白這一點,但我想提出的建議和我來在這裡的原因是告訴你們,我認為我們應該以截然不同的觀點看待這些疾病。

 

到目前為止,我一直使用精神障礙這個詞彙,即精神方面的疾病。事實上,現今這已成為一個相當不受歡迎詞彙。人們認為-無論出於何種原因-原則上最好使用行為障礙這個詞彙,稱這些疾病為行為障礙。確實,它們屬於行為障礙,亦屬於精神障礙。但我想提出的建議是,這兩個已使用超過一世紀的詞彙,事實上阻礙了進展。我們必須在觀念上取得的進展是,將這些疾病歸類為腦部障礙。

 

現在,有些人會說,「天哪,又來了!我們將聽到關於生化失衡,或關於藥物的知識,或聽到一些過度簡化的觀念,將我們的主觀經驗轉變成分子層面的理解;或某種單純而簡要的概念,說明它與憂鬱症或精神分裂症的關係。」

 

當我們談到大腦時,絕非單調、簡要或可簡化的概念。這取決於,當然,你希望以什麼層面或範圍思考。但它是一個相當複雜的器官,我們才剛開始瞭解如何研究它。無論你考量的是皮層中上百億個神經元,或上千億個連接神經元的突觸,我們才剛開始試著瞭解如何研究這個複雜至極的機器。它能進行驚人的訊息處理程序,用我們自己的大腦理解這個掌控我們心智、複雜至極的大腦,可說是演化的殘酷把戲。我們並未擁有聰明到足以理解它本身的大腦。以某種程度來說,它確實使你感受到,當你處於學習行為或認知的安全區域時,你可觀察到某些東西,以較為單純和直接的方式感受,而非試著參與這個複雜而神秘至極的器官運作-我們正開始試著瞭解它。

 

現在,以我所談論腦部障礙為例:憂鬱症、強迫症、創傷後壓力症候群,我們尚無法深入瞭解其運作的異常之處,或大腦和這些疾病的關係。對罹患這些疾病的人來說,我們已能確定一些連接上的差異,或某些通訊線路上的差異,我們稱之為人類連接組。你可以將連接組想成大腦接線圖,你將在幾分鐘內聽見更多相關敘述。其中一個重要關鍵是,當你開始觀察罹患這些疾病的人-我們當中的五分之一,以某種程度來說正與其抗爭。你將發現大腦接線方式發生許多變化,但其中存在一些可預測的模式,這些模式對這些疾病的發展來說是危險因素。這與我們對腦部障礙的認知稍有不同,例如亨丁頓舞蹈症、帕金森氏症或阿爾海默症,其原因在於大腦皮層某部分受到損害。我們所談論的是線路阻塞,有時是繞道而行,有時問題僅在於線路連接方式及大腦運作方式。如果有興趣,你可以將它與心肌梗塞、心臟病發作比較,其原因在於心臟組織壞死,導致心律不整、器官無法正常運作,因為其中存在通訊問題。兩者都足以致命,但你僅能於其中一種當中發現主要病變。

 

當我們思考這一點時,或許最好稍微深入探討某種特定疾病,即精神分裂症。因為我認為這是很好的例子,有助於理解為何可將其視為一種腦部障礙。這是Judy Rapoport和她同事所做的的掃描圖,來自美國國家心理衛生研究院。他們研究罹患早發性精神分裂症的兒童。你可以看見,上方圖片中已出現紅色、橙色或黃色區域,這是灰質較少的地方。他們追蹤這些兒童五年,相較於同齡的控制組,你可以看見,尤其是前額葉皮質或顳葉顳上回,存在嚴重的灰質喪失情況。這十分重要。如果你試著將其模式化,你可將正常發展視為皮質喪失、灰質喪失的過程,精神分裂症的情況則是超越這個標度。在某個時刻,當超越這個標度時,相當於跨越一道門檻,這個門檻即我們對精神分裂症患者的定義。因為他們開始出現行為症狀,例如幻覺和妄想,這是我們可觀察到的部分。但仔細觀察這張圖,你可以看見,事實上他們跨越了另一道門檻。他們在相當早期即跨越大腦的門檻,也許不是在22或20歲,而是在15或16歲。你可以開始看見其發展軌跡截然不同-以大腦層面而言,而非行為層面。

 

為何這十分重要?好,首先,對腦部障礙來說,行為是最後發生改變的部分。我們知道,阿茲海默症、帕金森氏症、亨丁頓舞蹈症皆是如此。大腦發生變化十年或更長時間後,才能看見行為改變的最初跡象。我們目前擁有的工具,可使我們早期檢測到腦部的變化,遠早於症狀的出現。但最重要的是,回到演講開頭部分,醫學上的福音是早期發現、早期治療;如果等到心臟病發作,我國每年將因心臟病而喪失110萬人的生命。這正是我們目前的處境。當我們確定,每位擁有其中一種腦部障礙-大腦線路發生障礙的病患,都將發生行為障礙時,卻等到行為出現變化才開始治療,這並非早期發現、早期治療。

 

坦白說,我們尚未準備好進行這件事,我們還不明白所有事實。事實上,我們甚至不知道可使用什麼工具,或如何精確檢測所有病例,在行為發生改變前進行治療。但這讓我們明白思索這一點的必要性,及需要努力的方向。

 

我們是否很快就能達成目標?我認為未來幾年內將會有所進展。但我想引用一句話作結尾,試著預測未來發展的情形。這句話來自某位對觀念和科技變化擁有精闢見解的人。

 

「我們總是高估未來兩年將發生的變化,低估未來十年將發生的變化。」-比爾‧蓋茲

 

十分感謝。

 

(掌聲)

 

以下為系統擷取之英文原文

About the Talk

Today, thanks to better early detection, there are 63% fewer deaths from heart disease than there were just a few decades ago. Thomas Insel, Director of the National Institute of Mental Health, wonders: Could we do the same for depression and schizophrenia? The first step in this new avenue of research, he says, is a crucial reframing: for us to stop thinking about “mental disorders” and start understanding them as “brain disorders.” (Filmed at TEDxCaltech.)
 
About the Speaker
The Director of the National Institute of Mental Health, Thomas Insel supports research that will help us understand, treat and even prevent mental disorders.
 
About the Transcript
So let's start with some good news, and the good news has to do with what do we know based on biomedical research that actually has changed the outcomes for many very serious diseases?
 
Let's start with leukemia, acute lymphoblastic leukemia, ALL, the most common cancer of children. When I was a student, the mortality rate was about 95 percent. Today, some 25, 30 years later, we're talking about a mortality rate that's reduced by 85 percent. Six thousand children each year who would have previously died of this disease are cured. If you want the really big numbers, look at these numbers for heart disease. Heart disease used to be the biggest killer, particularly for men in their 40s. Today, we've seen a 63-percent reduction in mortality from heart disease -- remarkably, 1.1 million deaths averted every year. AIDS, incredibly, has just been named, in the past month, a chronic disease, meaning that a 20-year-old who becomes infected with HIV is expected not to live weeks, months, or a couple of years, as we said only a decade ago, but is thought to live decades, probably to die in his '60s or '70s from other causes altogether. These are just remarkable, remarkable changes in the outlook for some of the biggest killers. And one in particular that you probably wouldn't know about, stroke, which has been, along with heart disease, one of the biggest killers in this country, is a disease in which now we know that if you can get people into the emergency room within three hours of the onset, some 30 percent of them will be able to leave the hospital without any disability whatsoever.
 
Remarkable stories, good-news stories, all of which boil down to understanding something about the diseases that has allowed us to detect early and intervene early. Early detection, early intervention, that's the story for these successes.
 
Unfortunately, the news is not all good. Let's talk about one other story which has to do with suicide. Now this is, of course, not a disease, per se. It's a condition, or it's a situation that leads to mortality. What you may not realize is just how prevalent it is. There are 38,000 suicides each year in the United States. That means one about every 15 minutes. Third most common cause of death amongst people between the ages of 15 and 25. It's kind of an extraordinary story when you realize that this is twice as common as homicide and actually more common as a source of death than traffic fatalities in this country. Now, when we talk about suicide, there is also a medical contribution here, because 90 percent of suicides are related to a mental illness: depression, bipolar disorder, schizophrenia, anorexia, borderline personality. There's a long list of disorders that contribute, and as I mentioned before, often early in life.
 
But it's not just the mortality from these disorders. It's also morbidity. If you look at disability, as measured by the World Health Organization with something they call the Disability Adjusted Life Years, it's kind of a metric that nobody would think of except an economist, except it's one way of trying to capture what is lost in terms of disability from medical causes, and as you can see, virtually 30 percent of all disability from all medical causes can be attributed to mental disorders, neuropsychiatric syndromes.
 
You're probably thinking that doesn't make any sense. I mean, cancer seems far more serious. Heart disease seems far more serious. But you can see actually they are further down this list, and that's because we're talking here about disability. What drives the disability for these disorders like schizophrenia and bipolar and depression? Why are they number one here?
 
Well, there are probably three reasons. One is that they're highly prevalent. About one in five people will suffer from one of these disorders in the course of their lifetime. A second, of course, is that, for some people, these become truly disabling, and it's about four to five percent, perhaps one in 20. But what really drives these numbers, this high morbidity, and to some extent the high mortality, is the fact that these start very early in life. Fifty percent will have onset by age 14, 75 percent by age 24, a picture that is very different than what one would see if you're talking about cancer or heart disease, diabetes, hypertension -- most of the major illnesses that we think about as being sources of morbidity and mortality. These are, indeed, the chronic disorders of young people.
 
Now, I started by telling you that there were some good-news stories. This is obviously not one of them. This is the part of it that is perhaps most difficult, and in a sense this is a kind of confession for me. My job is to actually make sure that we make progress on all of these disorders. I work for the federal government. Actually, I work for you. You pay my salary. And maybe at this point, when you know what I do, or maybe what I've failed to do, you'll think that I probably ought to be fired, and I could certainly understand that. But what I want to suggest, and the reason I'm here is to tell you that I think we're about to be in a very different world as we think about these illnesses.
 
What I've been talking to you about so far is mental disorders, diseases of the mind. That's actually becoming a rather unpopular term these days, and people feel that, for whatever reason, it's politically better to use the term behavioral disorders and to talk about these as disorders of behavior. Fair enough. They are disorders of behavior, and they are disorders of the mind. But what I want to suggest to you is that both of those terms, which have been in play for a century or more, are actually now impediments to progress, that what we need conceptually to make progress here is to rethink these disorders as brain disorders.
 
Now, for some of you, you're going to say, "Oh my goodness, here we go again. We're going to hear about a biochemical imbalance or we're going to hear about drugs or we're going to hear about some very simplistic notion that will take our subjective experience and turn it into molecules, or maybe into some sort of very flat, unidimensional understanding of what it is to have depression or schizophrenia.
 
When we talk about the brain, it is anything but unidimensional or simplistic or reductionistic. It depends, of course, on what scale or what scope you want to think about, but this is an organ of surreal complexity, and we are just beginning to understand how to even study it, whether you're thinking about the 100 billion neurons that are in the cortex or the 100 trillion synapses that make up all the connections. We have just begun to try to figure out how do we take this very complex machine that does extraordinary kinds of information processing and use our own minds to understand this very complex brain that supports our own minds. It's actually a kind of cruel trick of evolution that we simply don't have a brain that seems to be wired well enough to understand itself. In a sense, it actually makes you feel that when you're in the safe zone of studying behavior or cognition, something you can observe, that in a way feels more simplistic and reductionistic than trying to engage this very complex, mysterious organ that we're beginning to try to understand.
 
Now, already in the case of the brain disorders that I've been talking to you about, depression, obsessive compulsive disorder, post-traumatic stress disorder, while we don't have an in-depth understanding of how they are abnormally processed or what the brain is doing in these illnesses, we have been able to already identify some of the connectional differences, or some of the ways in which the circuitry is different for people who have these disorders. We call this the human connectome, and you can think about the connectome sort of as the wiring diagram of the brain. You'll hear more about this in a few minutes. The important piece here is that as you begin to look at people who have these disorders, the one in five of us who struggle in some way, you find that there's a lot of variation in the way that the brain is wired, but there are some predictable patterns, and those patterns are risk factors for developing one of these disorders. It's a little different than the way we think about brain disorders like Huntington's or Parkinson's or Alzheimer's disease where you have a bombed-out part of your cortex. Here we're talking about traffic jams, or sometimes detours, or sometimes problems with just the way that things are connected and the way that the brain functions. You could, if you want, compare this to, on the one hand, a myocardial infarction, a heart attack, where you have dead tissue in the heart, versus an arrhythmia, where the organ simply isn't functioning because of the communication problems within it. Either one would kill you; in only one of them will you find a major lesion.
 
As we think about this, probably it's better to actually go a little deeper into one particular disorder, and that would be schizophrenia, because I think that's a good case for helping to understand why thinking of this as a brain disorder matters. These are scans from Judy Rapoport and her colleagues at the National Institute of Mental Health in which they studied children with very early onset schizophrenia, and you can see already in the top there's areas that are red or orange, yellow, are places where there's less gray matter, and as they followed them over five years, comparing them to age match controls, you can see that, particularly in areas like the dorsolateral prefrontal cortex or the superior temporal gyrus, there's a profound loss of gray matter. And it's important, if you try to model this, you can think about normal development as a loss of cortical mass, loss of cortical gray matter, and what's happening in schizophrenia is that you overshoot that mark, and at some point, when you overshoot, you cross a threshold, and it's that threshold where we say, this is a person who has this disease, because they have the behavioral symptoms of hallucinations and delusions. That's something we can observe. But look at this closely and you can see that actually they've crossed a different threshold. They've crossed a brain threshold much earlier, that perhaps not at age 22 or 20, but even by age 15 or 16 you can begin to see the trajectory for development is quite different at the level of the brain, not at the level of behavior.
 
Why does this matter? Well first because, for brain disorders, behavior is the last thing to change. We know that for Alzheimer's, for Parkinson's, for Huntington's. There are changes in the brain a decade or more before you see the first signs of a behavioral change. The tools that we have now allow us to detect these brain changes much earlier, long before the symptoms emerge. But most important, go back to where we started. The good-news stories in medicine are early detection, early intervention. If we waited until the heart attack, we would be sacrificing 1.1 million lives every year in this country to heart disease. That is precisely what we do today when we decide that everybody with one of these brain disorders, brain circuit disorders, has a behavioral disorder. We wait until the behavior becomes manifest. That's not early detection. That's not early intervention.
 
Now to be clear, we're not quite ready to do this. We don't have all the facts. We don't actually even know what the tools will be, nor what to precisely look for in every case to be able to get there before the behavior emerges as different. But this tells us how we need to think about it, and where we need to go.
 
Are we going to be there soon? I think that this is something that will happen over the course of the next few years, but I'd like to finish with a quote about trying to predict how this will happen by somebody who's thought a lot about changes in concepts and changes in technology.
 
"We always overestimate the change that will occur in the next two years and underestimate the change that will occur in the next 10." -- Bill Gates.
 
Thanks very much. (Applause)

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