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.
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.
让我们先来谈谈白血病, 急性淋巴细胞白血病,缩写ALL, 是一种在儿童中最常见的癌症类型。 当我是学生时, 它的死亡率是 95%左右。 30年后的今天,我们所谈论的(ALL) 的死亡率 已经降低了 85%。 每年有6000名 原本会死于白血病的患儿,现今得以治愈 如果你想要更有说服力的数字, 让我们来看看心脏病的数据 心脏病曾经是最大的杀手, 尤其是对于40 多岁的男子。 如今,我们可以看到 心脏病的死亡率减少了 63 %, 成就是如此显著,每年减少110万起心脏病死亡数 更难以置信的是,艾滋病, 在上个月里刚被定义为一种慢性疾病, 也就是说一个20岁感染艾滋病毒的人, 要是在十年前,人们会觉得他活不过几周 几个月,至多几年, 但现在被认为会再活数十年, 也许会在他六七十岁时死于其他并发症。 对于这些"致命杀手"而言, 这些都是非常显著的变化。 特别值得一提的是 你大概不大清楚 ---中风, 一般伴随心脏病, 是本国最大健康杀手之一, 也是现在我们所知道的一种疾病 如果病人能在发病3小时之内 得到紧急医治, 大约 30%的病人能在出院时, 不留任何残疾或后遗症。
不幸的是,并非全都是好消息。 我们来谈谈另外一个故事, 与自杀有关。 当然,就自杀本身而言,它不是一种疾病, 是一种状况或是一种现象, 最终导致死亡。 你可能没有意识到这种现象是多么的普遍, 在美国,每年有38000起自杀事件发生, 这意味着每15分钟就有一起。 在导致青少年死亡的常见原因中 排名第三位。 这是多么的令人震惊 自杀是谋杀数量的两倍 是更为普遍的死亡来源 比本国交通事故的死亡数还要高。 现在,当我们讨论自杀, 不能忽视医学可能带来的改善, 因为 90%的自杀事件 与精神疾病有关: 如抑郁症、 躁郁症、 精神分裂症、 厌食症,边缘人格等等 (请回忆“早发现”和“早治疗”) 许多精神失常的症状往往出现在幼年期。
当我们谈论大脑时, 绝非一维和简化。 当然,这取决于以什么尺度 或什么范畴来谈此事, 它是一个极其复杂的器官, 我们对它的了解才刚刚起步 还谈不上研究它,无论是对 大脑皮层上1000 亿的神经元, 还是连结各个“ 交通枢纽”的 100 兆的神经突触, 我们刚刚开始,试图找出答案: 我们如何运用大脑这个能够 处埋惊人信息的非凡机器, 同时使用我们自己的头脑来解释 这个非凡的大脑是如何支配我们的行为。 听上去十分跷舌,又很滑稽的理论, 好象我们的大脑发育 不够健全,连自己都不了解自己~ 从某种意义上讲,大脑有时让你感觉到, 在研究已知的行为或认知 尤其是对你可以观察到的东西时, 它是简单直观的, 而不是让人费解 ,神秘的器官, 使我们刚刚萌生兴趣。
现在,对于“大脑失常” 正如我前面所说的 抑郁症,强迫症, 创伤后应激障碍, 虽然我们还不甚了解大脑是 如何失灵, 或病发后做何处理, 但我们已经能够辨别出脑部神经 在连接上的差异 或者脑部神经路线异样 这些神志错乱病人的通常症状。 我们把这称之为脑部神经连接组, 你可以把它想象成 大脑的线路连接图, 下面会多次提到的。 重要一点是,当提及这些病人, 每五个健康人中就有一个, 不同程度的患有精神疾病, 你可以发现大脑出现变异情况 是多么的纷繁复杂 但我们还是了解到一些可预测的模式, 可以预测到发病倾向。 我所说的大脑失常与平时常见的稍有不同, 像亨廷顿氏症或帕金森症或老年痴呆症等, 是部分大脑皮层缺损。 而这里我们谈论是交通堵塞,或是绕道而行, 或只是连接方式出了问题, 或大脑功能性障碍。 你可以这样,如果一定要比较的话, 那就想象心肌梗塞、突发性心脏病, 是由于心脏中坏死组织所致, 还有心律失常、心脏运行不正常, 是由于其内部的输导功能出了问题。 任何一种病症都会导致死亡, 但只有一项是主要病变。
除了想象,最好还是举个实例, 个例分析, 是精神分裂症。 我觉得这是个非常好的例子, 揭示进行大脑失常研究的深远意义。 国家精神健康研究所茱蒂和她的同事们 提供了这些研究扫描图, 他们研究了存在精神分裂症迹象的儿童, 你已经能看到在顶部, 那些红色、橙色、黄色的区域, 取代了应有的灰质, 随后追踪了五年多, 再进行年龄匹配对照, 你可以看到,特别是在 延髓背外侧前额叶皮层 或上级颞回,(这些孩子的)大脑灰质严重缺损。 这些非常重要,如果通过建模进行量化, 你可以理解在正常发育中 大脑皮层质量是会减少,或是灰质轻微损失, 但精神分裂症患者的这些损失量超标, 在某些时候, 正是超过这个标准值, 我们说这个人患有精神分裂症, 此时他的行为异常,多数呈现出 幻觉和妄想, 这些我们肉眼所能观察到的异常行为, 但仔细看看这个图,你会发现其实他们跨过了不同的标准值, 而且出现得很早, 并不是在(行为失常的)22岁或20岁, 其实在15岁或16岁已经出现明显迹象, 发展轨迹大不相同, 这是从大脑发育来说的,而不是指(后期的)行为方式,
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