Toward a new understanding of mental illness Thomas Insel

[Music]

[Music]

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 start with

leukemia acute lymphoblastic leukemia a

ll most common cancer of children when I

was a student the mortality rate was

about 95 percent today some 2530 years

later we’re talking about a mortality

rate that’s reduced by 85 percent 6000

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 big has just

been named in the past month a chronic

disease meaning that a 20 year old it

becomes infected with HIV as expected

not to live weeks months are a couple of

years as we said only a decade ago that

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% of

them will be able to leave the hospital

without any disability whatsoever

remarkable stories good news stories all

of which boiled 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

thirty eight thousand 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 ninety 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 in economists

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% 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’re 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 the second of course is that

for some people these become truly

disabling and it’s about four to five

percent perhaps one in twenty

but what really drives the

numbers this high morbidity and to some

extent the high mortality is the fact

that these start very early in life

50% will have onset by age 14 75% 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 and maybe at

this point when you know what I do or

maybe what I 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 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

gonna say oh my goodness here we go

again we’re gonna hear about a

biochemical imbalance so 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 MA

molecules or maybe into some sort of

very flat unit dimensional understanding

of what it is to have depression or

schizophrenia when we talk about the

brain it is anything but uni-dimensional

or simplistic or reductionistic it

depends of course of 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 hundred billion neurons that

are in the cortex or the hundred

trillion synapses they 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 and

use our own minds to understand this

very complex brain that supports it

supports our own minds it’s a 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

well we don’t have a 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 very

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 if you were 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 neighbor

is Mia where that organ simply isn’t

functioning because of the communication

problems within it either one would kill

you and only one of them will you find a

major lesion as we think about this

maybe it’s better to actually go a

little deeper into one particular

disorder and that would be schizophrenia

yes 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 dorsal

lateral prefrontal cortex or the

superior temporal gyrus there’s a

profound loss of gray matter 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 talk 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 that 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 that 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]

[音乐]

[音乐]

所以让我们从一些好消息开始,

这个好消息与我们所

知道的生物医学研究有关,它

实际上已经改变了

许多非常严重的疾病的结果,从白血病开始

当我还是学生的时候,儿童癌症

的死亡率在

今天大约 95% 大约 2530 年

后,我们谈论的是

死亡率降低了 85% 如果你

愿意,每年有 6000 名

以前死于这种疾病的儿童被

治愈 真正的大数据

着眼于心脏病的这些数字

心脏病曾经是最大的

杀手,尤其是对于 40 多岁的男性来说,

今天我们已经看到心脏病死亡率降低了 63%

每年显着避免 110 万人死亡 艾滋病令人难以置信的大已经

在过去的一个月里刚刚被命名为一种慢性病,

这意味着一个 20 岁的人

感染了 HIV,因为预计

不会活几周是一对夫妇

十年前我们说过,

被认为活了几十年的人可能

会在 60 多岁或 70 多岁时死于其他原因,

这些只是一些最大杀手

的前景的显着显着变化

尤其是你可能 不

知道中风

与心脏病有关

这个国家最大的杀手之一是一种疾病

将能够在

没有任何残疾的情况下离开医院 任何

非凡的故事 好消息

所有这些都归结为

了解一些疾病

使我们能够及早发现和干预

早期发现 早期干预

这就是这些成功的故事

不幸的是新闻 不是很好

让我们谈谈另一个与自杀有关的故事

现在这

当然不是一种疾病本身它是一种

条件 或者这是一种导致死亡的情况

你可能没有意识到

美国每年有 38000 起自杀事件有多普遍,这意味着

大约每 15 分钟就有 1 起是不同年龄段人群中第三大最常见

的死因

在 15 和 25 之间,这是一个

非同寻常的故事,当你

意识到在这个国家,这是凶杀的两倍

,实际上比交通事故更常见的死亡来源

现在当我们谈论自杀时,

这里也有医疗贡献

,因为 90% 的

自杀与精神疾病有关

抑郁症 双相情感障碍

精神分裂症 厌食症 边缘型

人格 有很长的

疾病清单,正如我

之前经常提到的,在生命早期,

但不仅仅是这些疾病的死亡率,

如果你

看一下,它也是发病率 世界卫生组织衡量的残疾,

他们称之为残疾调整生活

这是一种除了经济学家之外没有人会想到的指标,

除了它是一种试图

捕捉因医疗原因造成的残疾损失的方法

,正如你所见,

几乎 30% 的所有

医疗原因造成的残疾都可以归因于 到

精神疾病神经精神

综合征,你可能认为这

没有任何意义我的意思是癌症

似乎更严重心脏病

似乎更严重但你可以看到

它们实际上在这个列表的后面

,那是因为我们在这里谈论

关于残疾 是什么导致

精神分裂症、双相情感障碍和抑郁症等这些疾病的残疾

为什么它们在这里排名第一

可能有三个原因 一个是

它们非常普遍 大约五分之一的

人将

在课程中患上这些疾病中的一种 他们

一生中的第二个当然是,

对于某些人来说,这些变得真正

残疾,大约是百分之四到五,

也许是二分之一

但真正推动这些

数字如此高的发病率和在

某种程度上高死亡率的事实

是,这些数字在生命的早期

就开始了 50% 将在 14 岁时发病 75% 到 24 岁

一幅与

人们想象的非常不同的情况 看看你是在

谈论癌症还是心脏病 糖尿病

高血压 大多数

我们认为是

发病率和死亡率的主要疾病 这些确实

是年轻人的慢性疾病

现在我首先告诉你

有一些好消息 故事 这

显然不是其中

之一 这可能是其中最

困难的部分,从某种意义上说,这

对我来说是一种忏悔 我的工作是

真正确保我们

在我工作的所有这些疾病上取得进展

联邦政府实际上我为

你工作你支付我的薪水,也许

此时你知道我做了什么或者

我没有做什么,你会

认为我可能应该被解雇,我

可以肯定 你明白这一点,但

我想提出的建议以及我

来这里的原因是要告诉你,当我们考虑这些疾病时,我认为

我们将进入一个非常不同的世界

到目前为止,精神障碍

疾病实际上已经成为一个相当

不受欢迎的术语,人们

认为无论出于何种原因

,使用行为障碍这个术语在政治上更好,

并将

这些作为行为障碍进行讨论,

足够公平,它们是行为障碍

它们是精神障碍,但

我想向您建议的是,

这两个已经

使用了一个世纪或更长时间的术语实际上

现在都阻碍了进步,我们

需要在概念上取得进步

是重新思考这些

现在对你们中的一些人来说,像脑部疾病一样的疾病你们

会说哦,天哪,我们

又来了,我们会听到

生化失衡,所以我们会

听到关于药物的事,或者我们会

听听一些非常简单的概念,

它将我们的主观经验

转化为 MA

分子,或者可能转化为某种

非常扁平的单位维度

理解,当我们谈论

大脑时,它绝不是单一的 维度

或简单化或简化,这

当然取决于

您想要考虑的规模或范围,但这

是一个超现实复杂性的器官,我们

才刚刚开始了解

如何研究它,无论您是否正在考虑数

千亿个神经元

它们在皮层或数百

万亿个突触中,它们构成了所有的

连接,我们刚刚开始试图

弄清楚我们如何使用这个非常

复杂的机器,它可以进行

非凡的信息处理,并

用我们自己的头脑来理解这一点

支持它的复杂大脑

支持我们自己的思想 它

实际上是一种残酷的

进化伎俩,我们根本没有

雨似乎连接得很好,

可以在某种意义上理解自己,它

实际上让你觉得当你

在研究行为或认知的安全区域时,

你可以观察到某些东西,

在某种程度上

比试图参与更简单和简化

这个非常复杂的神秘器官,

我们现在已经开始尝试理解

,在

我一直在和你

谈论抑郁症强迫

症创伤后应激

障碍的脑部疾病的情况下,我们没有 - 深入

了解它们是如何被异常

处理的,或者大脑在

这些疾病中做了

什么 人类连接组,你

可以把连接组想象

成大脑的接线图,

你会在几分钟内听到更多关于这个

的重要信息 也就是说,

当你开始观察患有

这些疾病的人时,我们中有五分之一的

人以某种方式挣扎,你会

发现大脑的连接方式有很多,但

有一些可预测的模式和

那些 模式是

发展其中一种疾病的风险因素 它

与我们

对亨廷顿氏

症、帕金森氏症或阿尔茨海默氏

症等脑部疾病的看法略有不同 或者有时

只是

事物连接方式和大脑运作方式的问题,

如果你想将

其与一方面

心肌梗塞相比,心脏病发作,你的心脏中有

死亡组织,而邻居

是 Mia,那里 器官根本无法

运作,因为

它内部的沟通问题要么会杀死

你,而且只有其中一个会发现

我们认为的重大病变 关于这一点,

也许最好

更深入地研究一种特定的

疾病,那就是

精神分裂症 国家

心理健康研究所,他们研究了

患有早期

精神分裂症的儿童,你已经可以看到

在顶部有红色或橙黄色的区域是

灰质较少的地方,他们

跟踪他们超过五年

年龄匹配控制 您可以看到,

特别是在背

外侧前额叶皮层或

颞上回等区域

,灰质严重丢失

如果您尝试对此进行建模,这很重要,您

可以将正常发育视为

皮质质量损失的损失 皮质

灰质和

精神分裂症中发生的事情是你超越了那个

标记,并且在某个时候当你

你越过了一个门槛,这就是

我们所说的那个门槛,我们说这

是一个患有这种疾病的人,因为

他们有幻觉和妄想的行为症状,

是我们可以观察到的,但仔细观察

,你会发现

实际上他们' 已经跨越了一个不同的

阈值,它更早地越过了大脑阈值

,可能不是在 22

或 20 岁,但即使在 15 或 16 岁时,你也可以

开始看到在大脑水平上的

发展轨迹完全不同,而

不是在大脑水平上。

行为 为什么这很重要

因为对于大脑疾病 行为

是最后

改变的事情 我们知道对于

阿尔茨海默氏症 对于帕金森氏症 对于

亨廷顿氏症

在您看到

行为改变的最初迹象之前十年或更长时间,大脑就会发生变化 我们

现在让我们能够在症状出现之前很久就检测到这些大脑

变化,

但最重要的是

回到我们开始好的地方 WS

医学故事是早期发现

早期干预如果我们

等到心脏病发作,我们将

在这个国家每年为心脏病牺牲 110 万人的生命,这

正是我们今天所做的,当我们

决定每个患有这些脑部疾病之一的人的

大脑 电路障碍

有一种行为障碍 我们

等到行为变得明显

这不是早期发现 那不是

早期干预 现在要清楚 我们还

没有完全准备好这样做 我们没有

所有的事实 我们甚至不

知道什么 工具将不是

在每种情况下都需要精确寻找的

东西才能在行为出现不同之前到达那里,

但这告诉我们

我们需要如何思考它以及

我们需要去哪里我们很快就会到达那里

吗? 认为这

将在未来

几年内发生,但我想以一句话作为

结尾,关于试图预测这

将如何发生在一个深思熟虑

的人 关于观念的

变化和技术

的变化我们总是高估

未来两年

会发生的变化,低估未来10年会发生的变化

比尔·盖茨非常感谢

[鼓掌]