Dr. Karen Parker: The Causes & Treatments for Autism
Andrew Huberman:
安德鲁·休伯曼：
Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
欢迎来到休伯曼实验室播客，我们在这里讨论科学和基于科学的日常生活工具。
I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
我是安德鲁·胡伯曼，斯坦福大学医学院神经生物学和眼科教授。
My guest today is Dr. Karen Parker.
今天我的客人是凯伦·帕克博士。
Dr. Karen Parker directs the Social Neurosciences Research Program at the Stanford University School of Medicine.
凯伦·帕克博士负责斯坦福大学医学院的社会神经科学研究项目。
The goal of her laboratory's research is to understand the biological basis of social functioning at every stage of the lifespan.
她实验室的研究目标是了解生命周期各个阶段社会功能的生物学基础。
So this includes the bonds that form between infant and parent or parents, as well as the bonds that occur between children as they grow up, which of course form the template for social functioning when we become adults.
因此，这包括婴儿与父母之间形成的纽带，以及孩子成长过程中形成的纽带，这当然构成了我们成年后社会功能的模板。
Dr. Parker's research is heavily focused on autism, and indeed, on all forms of autism spectrum disorders.
帕克博士的研究主要集中在自闭症，实际上是所有形式的自闭症谱系障碍。
Today, we discuss autism, we talk about the prominent theories and current understanding of the biological basis for autism, as well as what still remains mysterious and unresolved about the causes of autism.
今天，我们讨论自闭症，我们谈论自闭症生物学基础的著名理论和当前的理解，以及关于自闭症原因仍然神秘和未解决的问题。
You may have heard that the incidence, or perhaps just the diagnosis of autism, has dramatically increased in the last 10 to 15 years, and today we discuss why it is, in fact, that the incidence, not just the diagnosis, but the incidence of autism has so dramatically increased.
您可能听说过，在过去 10 到 15 年中，自闭症的发病率（或者只是诊断率）急剧增加，今天我们讨论为什么事实上，自闭症的发病率（不仅仅是诊断率，而且是自闭症的发病率）急剧增加。
And perhaps most excitingly, Dr. Parker shares with us brand-new research findings from her laboratory that point to a new understanding of what causes autism, as well as a novel treatment for autism.
也许最令人兴奋的是，帕克博士与我们分享了她实验室的全新研究结果，这些结果表明对自闭症病因的新认识，以及自闭症的新颖治疗方法。
Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
在开始之前，我想强调一下，这个播客与我在斯坦福大学的教学和研究角色是分开的。
It is, however, part of my desire and effort to bring zero-cost to consumer information about science and science-related tools to the general public.
然而，我的愿望和努力的一部分是向公众提供有关科学和科学相关工具的零成本消费者信息。
In keeping with that theme, I'd like to thank the sponsors of today's podcast.
为了与这个主题保持一致，我要感谢今天播客的赞助商。
Speaker 3:
演讲者3：
Propel Fitness Water.
推动健身水。
With Gatorade electrolytes, zero sugar, and vitamins, Propel hydrates better than water to help you get the most out of your workout and get back to your best self.
Propel 含有佳得乐电解质、零糖和维生素，比水更好地补充水分，帮助您充分利用锻炼并恢复最佳状态。
What propels you?
是什么推动着你？
Propel with Gatorade electrolytes.
用佳得乐电解质推动。
Speaker 4:
演讲者4：
Sierra has all the best active and outdoor brands for the super athletic stuff, like running gear for cruising up the trail.
Sierra 拥有所有最好的运动和户外品牌的超级运动用品，例如用于巡航的跑步装备。
Woo!
哇！
And the super athlete-ish stuff, like fishing gear for chilling by the creek.
还有超级运动员风格的东西，比如在小溪边消暑的渔具。
Nice cast.
演员阵容不错。
Fitness apparel to push for higher reps.
健身服装可推动更高次数。
You got this.
你得到了这个。
And golf balls priced so you can afford to lose one.
高尔夫球的价格也让您可以承受失去一颗高尔夫球的损失。
Or a few.
或者几个。
Head to Sierra or sierra.com for the brands you want at the prices that let you do it all.
前往 Sierra 或 sierra.com 以实惠的价格购买您想要的品牌。
From athletic to athlete-ish, Sierra's got it.
从运动型到运动员型，塞拉都做到了。
Andrew Huberman:
安德鲁·休伯曼：
And now for my discussion with Dr. Karen Parker.
现在我与凯伦·帕克博士进行讨论。
Dr. Karen Parker, welcome.
凯伦·帕克博士，欢迎光临。
Dr. Karen Parker:
凯伦·帕克博士：
Thank you.
谢谢你。
It's great to be here.
很高兴来到这里。
Andrew Huberman:
安德鲁·休伯曼：
This is going to be perhaps one of the longer conversations that we've been able to have over the years, in part because whenever I see you on campus, we're headed in our respective directions.
这可能是我们多年来能够进行的较长对话之一，部分原因是每当我在校园里见到你时，我们都会朝着各自的方向前进。
But I'm very excited because the topic of autism is one that is on a lot of people's minds, and I think the first question that always comes up, it seems, is whether or not the frequency of autism is indeed increasing or whether or not the field of medicine is getting better at detecting what was always there over time.
但我很兴奋，因为自闭症这个话题是很多人关注的话题，我认为总是出现的第一个问题似乎是自闭症的发病率是否确实在增加，或者医学领域是否越来越善于检测随着时间的推移一直存在的东西。
Do we have any clear answers to that?
对此我们有明确的答案吗？
Dr. Karen Parker:
凯伦·帕克博士：
Well, I think it's a multifactorial answer.
嗯，我认为这是一个多因素的答案。
So we're getting better at detecting autism, right?
所以我们在检测自闭症方面做得越来越好，对吗？
So in the past, we were diagnosing kids at nine or 10 years of age, right?
所以过去我们是在九岁或十岁的时候诊断孩子，对吗？
And now clinicians are able to reliably diagnose kids at two to three years of age, right?
现在临床医生能够可靠地诊断两到三岁的孩子，对吧？
So there's more people.
所以人就多了。
Pediatricians have autism screeners now, so when you bring in your baby, and over the first couple years of life, you're filling out screeners that are looking for autism symptoms, right?
儿科医生现在有自闭症筛查表，所以当你带宝宝进来时，在生命的最初几年里，你正在填写寻找自闭症症状的筛查表，对吗？
So there's just a lot more awareness around autism.
因此，人们对自闭症的认识有了更多的提高。
But the rates have increased to now 1 in 36 US children have a diagnosis of autism.
但这一比率已上升至目前每 36 名美国儿童中就有 1 人被诊断为自闭症。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Karen Parker:
凯伦·帕克博士：
Which is over two years ago, it was 1 in 44, so.
两年多前，这个比例是四十四分之一，所以。
Andrew Huberman:
安德鲁·休伯曼：
1 in 36.
36 分之一。
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Wow, I feel like it was just yesterday when it was 1 in 80.
哇，我觉得就在昨天，当时是 80 分之一。
But is 1 in 36 the average across boys and girls?
但男孩和女孩的平均比例是三十六分之一吗？
Does it skew differently if you look at just male births versus female births?
如果只考虑男性出生率和女性出生率，其偏差是否会有所不同？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah, that's a great question.
是的，这是一个很好的问题。
So autism is male-biased in prevalence, so you have-- and again, the studies vary.
因此，自闭症的患病率以男性为主，因此，研究结果也各不相同。
It's worth noting that autism is a highly clinically heterogeneous disorder, which means that if you've met one kid with autism, you've met one kid with autism, right?
值得注意的是，自闭症是一种临床上高度异质性的疾病，这意味着如果你遇到过一个患有自闭症的孩子，那么你也遇到过一个患有自闭症的孩子，对吗？
So we have to bear that in mind as we have this conversation.
因此，在我们进行这次谈话时，我们必须牢记这一点。
But different studies show that about for every one girl, there's three to four boys that are impacted by autism.
但不同的研究表明，大约每有一个女孩，就有三到四个男孩受到自闭症的影响。
So there's differences in the prevalence rate, and also there's different monitoring sites.
所以患病率存在差异，监测地点也不同。
So the way in the US that these data are generated is the CDC has 11 monitoring sites across the country.
所以在美国，这些数据的生成方式是CDC在全国有11个监测点。
And so they follow children, and then that's where the prevalence rates come from, and they release new prevalence rates every few years.
所以他们跟踪儿童，这就是患病率的来源，他们每隔几年就会发布新的患病率。
Andrew Huberman:
安德鲁·休伯曼：
So if physicians are able to detect autism early, say in a two-year-old or a three-year-old-
因此，如果医生能够及早发现自闭症，比如两岁或三岁的孩子——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
I have to imagine that they're working off of tests that don't rely heavily on language, because even though you can get some verbose two and three-year-olds, most two and three-year-olds don't have a very extensive vocabulary.
我必须想象他们正在进行的测试并不严重依赖语言，因为即使你可以让一些两岁和三岁的孩子进行冗长的测试，但大多数两岁和三岁的孩子都没有非常广泛的词汇量。
And I'm guessing that they're also relying on things like visual gaze, among other things.
我猜测他们还依赖于诸如视觉凝视之类的东西。
We've already made clear that this is not a discussion to allow people to diagnose themselves or others.
我们已经明确表示，这不是一个让人们诊断自己或他人的讨论。
But with that said, what are some of the diagnostic tools that people use?
但话虽如此，人们使用的诊断工具有哪些？
Is it language?
是语言吗？
Is it vision?
是愿景吗？
Or does it present as, you know abnormal auditory processing.
或者它是否表现为，你知道异常的听觉处理。
Maybe you could give us a sampling.
也许你可以给我们一个样品。
Dr. Karen Parker:
凯伦·帕克博士：
So autism is a behavioral diagnosis, right?
所以自闭症是一种行为诊断，对吗？
So unlike other areas of medicine where you might be able to take a blood test or there's other sort of tools, it's all a behavioral diagnosis by an expert, so usually a psychiatrist or a psychologist, and they look for two core features.
因此，与其他可以进行血液测试或其他类型工具的医学领域不同，这都是专家（通常是精神病学家或心理学家）的行为诊断，他们寻找两个核心特征。
So this is based on the DSM-5, and the two core features are pervasive social interaction challenges and the presence of restricted, repetitive behavior.
所以这是基于 DSM-5 的，两个核心特征是普遍存在的社交互动挑战和受限、重复行为的存在。
But there are a lot of people with autism who have anxiety.
但有很多自闭症患者患有焦虑症。
There are a lot of people with sensory challenges.
有很多人都面临感官挑战。
There are a lot of people with seizure disorders, sleep disorders.
有很多人患有癫痫症、睡眠障碍。
So again, it's each person with autism has this sort of unique collection of traits and that's how they get diagnosed.
再说一次，每个自闭症患者都有这种独特的特征，这就是他们被诊断的方式。
Andrew Huberman:
安德鲁·休伯曼：
We're going to talk a lot today about interventions, but how early are some of the behavioral interventions, and I should just say any interventions introduced nowadays?
今天我们要讨论很多关于干预措施的内容，但是一些行为干预措施有多早，我应该说现在引入的干预措施有哪些？
So if someone brings their child to the pediatrician, and they take one of these tests, and that child is deemed as having autism, will the one-year-old or the two-year-old immediately go into behavioral interventions?
因此，如果有人带孩子去看儿科医生，他们做了其中一项测试，并且该孩子被视为患有自闭症，那么一岁或两岁的孩子会立即进行行为干预吗？
Dr. Karen Parker:
凯伦·帕克博士：
Well, so usually you need to have the diagnosis of autism, and then there are behavioral interventions or a variety of different ones that are used.
嗯，通常你需要诊断出自闭症，然后采取行为干预措施或各种不同的干预措施。
There are some studies where, because autism's highly heritable, you can have one child with autism, and then if you have subsequent children, you're at an increased risk of having subsequent children with autism, and these are called baby sibling studies.
有一些研究表明，由于自闭症具有高度遗传性，因此您可以生一个患有自闭症的孩子，然后如果您有后续的孩子，那么您再生下患有自闭症的孩子的风险就会增加，这些被称为婴儿兄弟姐妹研究。
So what you're doing is enriching the population of infants that you follow prospectively, who are more likely to receive an autism diagnosis.
因此，您所做的就是丰富您前瞻性跟踪的婴儿群体，这些婴儿更有可能被诊断为自闭症。
And there are studies where some of those children are enrolled in behavioral studies, even when they're, quote-unquote, at risk.
有研究表明，其中一些孩子参加了行为研究，即使他们确实处于危险之中。
Andrew Huberman:
安德鲁·休伯曼：
I've heard before that parents in which one or typically both parents are, say, of the engineering, mathy, physics, quote-unquote, hard science type, are more likely to have autistic children.
我以前听说过，父母之一或通常父母双方都是工程、数学、物理、自然科学、硬科学类型的父母，更有可能生出自闭症孩子。
Is that true?
这是真的吗？
Does that bear out in the data?
数据证实了这一点吗？
If you look at profession or undergraduate major, does any of that correlate with the probability of having an autistic child?
如果你看看职业或本科专业，这些与生出自闭症孩子的可能性有关系吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Well, what I can say is that there's been some studies.
嗯，我能说的是已经有一些研究了。
So what we know is that autistic traits are continuously distributed across the general population.
所以我们知道，自闭症特征在普通人群中持续分布。
And there was a study, and there's a couple different instruments that are used to be able to measure these autistic traits.
有一项研究，有几种不同的仪器可以用来测量这些自闭症特征。
So there's something called the Social Responsiveness Scale, and then that's a US-based instrument, and there's an autism quotient that's a similar measure that was designed in England.
所以有一个叫做社会反应量表的东西，这是一个基于美国的工具，还有一个自闭症商数，它是在英国设计的类似衡量标准。
And what we know from work with the AQ is that individuals that are in intense STEM fields like engineering, physics, and math have a greater burden of autistic traits, even if they don't have an autism diagnosis.
我们从 AQ 的研究中了解到，从事工程、物理和数学等密集的 STEM 领域的人具有更大的自闭症特征，即使他们没有被诊断为自闭症。
Andrew Huberman:
安德鲁·休伯曼：
Okay, so that leads me to wonder whether or not this whole business of a spectrum-
好吧，这让我想知道整个频谱业务是否-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is actually multiple spectra.
实际上是多个光谱。
Spectrums.
光谱。
Is it spectrums or spectra?
是光谱还是光谱？
Someone will put it in the comments on YouTube.
有人会把它放在 YouTube 的评论中。
We know that for sure.
我们肯定知道这一点。
Please let me know.
请告诉我。
I would like to know.
我想知道。
What is the plural of spectrum?
频谱的复数是什么？
Spectrums?
光谱？
Because when we hear the word spectrum, we think, okay, there's a spectrum of severity, right?
因为当我们听到“谱系”这个词时，我们会想，好吧，有一个严重程度的谱系，对吧？
And in fact, I have some experience with severe autism, not in my family, but where I went to undergraduate university, UC Santa Barbara.
事实上，我有一些严重自闭症的经历，不是在我的家庭，而是我就读的大学，加州大学圣巴巴拉分校。
Down the way from that school was the Devereux School, which was a school which has been there for a long time that parents would send their kids if they were, quote-unquote, "severely autistic." It was actually where Dustin Hoffman went to study for his role in "Rain Man."
从那所学校往下走就是德弗罗学校，这所学校已经存在很长时间了，如果孩子是“严重自闭症”，家长们就会把他们送去。实际上，达斯汀·霍夫曼曾在这里学习《雨人》中的角色。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And the kids, who were really delightful, they used to come into town every once in a while to the coffee shop where I'd study, and they would also continue on from there to Kmart, which is why the Dustin Hoffman character would say, "Got to go to Kmart.
孩子们真的很令人愉快，他们过去偶尔会进城去我学习的咖啡店，他们也会从那里继续去凯马特，这就是为什么达斯汀霍夫曼的角色会说，“必须去凯马特。
Got to go to..." He would do that repetition.
得去……”他会重复这个动作。
Dr. Karen Parker:
凯伦·帕克博士：
That's fascinating.
这很有趣。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
That Kmart was down the road from-
凯马特就在这条路上——
Dr. Karen Parker:
凯伦·帕克博士：
Huh
呵呵
Andrew Huberman:
安德鲁·休伯曼：
...
...
our college housing and the Devereux School.
我们的大学宿舍和德弗罗学校。
Those kids were literally in a away from home facility full time.
这些孩子实际上是全职在远离家乡的设施中。
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
And I spoke to some of the parents at one point, and they were at that facility, meaning the parents had sent their children away to live there-
我曾经和一些家长交谈过，他们就在那个设施里，这意味着父母已经把他们的孩子送到那里去住了——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
full time.
全职。
Of course, they'd get visits, and they'd get visits home, because they were, I suppose we could say, at the far end of some spectrum that made it, at least to the parents' idea, impossible for them to be at home.
当然，他们会被探望，他们会被探望回家，因为我想我们可以说，他们处于某种范围的远端，这使得他们不可能在家，至少在父母看来是这样。
Okay, now, at the other end of the spectrum, if one is just simply thinking in terms of severity, I know people who have self-identified as autistic.
好吧，现在，在光谱的另一端，如果一个人只是简单地考虑严重性，我知道有些人自认为是自闭症患者。
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
That's how they've referred to it, so I feel comfortable saying that they've said, "I am autistic."
他们就是这么说的，所以我可以放心地说，他们说过，“我是自闭症患者。”
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And they seem pretty high-functioning, meaning they have driver's licenses, drive cars, are in healthy relationships, and manage life apparently well.
他们看起来功能很高，这意味着他们有驾照，会开车，有健康的人际关系，而且生活管理得很好。
They have some traits that, yes, I would agree are a little bit different, right?
他们有一些特征，是的，我同意有点不同，对吧？
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
So this is where we get into neurodivergence.
这就是我们陷入神经分歧的地方。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But I guess the point is should we think about autism as on a spectrum, or given the fact that there are these kind of collections of different traits, could there be a spectrum of severity, also a spectrum of more stereotype behaviors, another spectrum that intersects with that that has to do with obsession with a particular topic?
但我想重点是我们是否应该将自闭症视为一个谱系，或者考虑到存在这些不同特征的集合这一事实，是否可能存在一个严重程度的谱系，以及一系列更多的刻板印象行为，另一个与对特定主题的痴迷有关的谱系相交叉的谱系？
You could imagine that there are 50 or 60 different spectra or spectrums-
你可以想象有 50 或 60 个不同的光谱或光谱 -
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
I still don't know which one to say.
我还是不知道该说哪一个。
And that when we talk about the spectrum, we're really talking about something that's in multiple dimensions and not just one line that goes from severe to mild.
当我们谈论频谱时，我们实际上谈论的是多个维度的东西，而不仅仅是从严重到轻微的一条线。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Does that make sense?
这有道理吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
I think this is where understanding the biological basis of behavior would then allow us to be able to say You're like, "Here's these different dimensions," right?
我认为这就是理解行为的生物学基础将使我们能够说，“这是这些不同的维度，”对吗？
But not understanding the biology, you're left with, okay, are we lumpers or splitters?
但如果不了解生物学，你就会想，好吧，我们是混蛋还是分裂者？
How do we think about this?
我们如何看待这个问题？
Because autism is highly heritable, so there's about 40% to 80% of autism is genetic, right?
因为自闭症具有高度遗传性，所以大约有40%到80%的自闭症是遗传性的，对吗？
So these vary wildly, right?
所以这些差异很大，对吗？
But the common thinking is that the majority, about 50% of autism is associated with common genetic variants.
但普遍的看法是，大多数（约 50%）自闭症与常见的基因变异有关。
And so the way that we've always thought about this is that autism is largely an inherited polygenic condition.
因此，我们一直认为自闭症很大程度上是一种遗传性多基因疾病。
But what I mean by that is that you have a lot of common variants that are additive.
但我的意思是，有很多常见的附加变体。
And so if you think about this collection of common genetic variants that underlie this spectrum, right?
因此，如果您考虑一下构成该谱系的常见遗传变异的集合，对吗？
So if you have less of a dosing of some of these common variants, you might see somebody who's higher functioning, like you said.
因此，如果您减少某些常见变体的剂量，您可能会看到功能更高的人，就像您所说的那样。
And if you end up with one of these single gene, highly penetrant disorders, you might see severe intellectual disability and sort of lower functioning on the other end of the spectrum.
如果您最终患有这些单基因、高度渗透性疾病中的一种，您可能会看到严重的智力障碍和另一端的功能较低。
But I think that there is a lot that we don't know.
但我认为还有很多我们不知道的事情。
And what you're bringing up, I think, underlines sort of an issue with autism, which is common for many brain disorders, which is if you don't understand the underlying biological basis, it also gets very difficult to diagnose and treat, right?
我认为你提出的问题强调了自闭症的一个问题，这是许多大脑疾病的常见问题，如果你不了解潜在的生物学基础，它也会变得非常难以诊断和治疗，对吗？
And that's where we are with a lot of different psychiatric and neurodevelopmental disorders.
这就是我们面临的许多不同的精神和神经发育障碍的情况。
Andrew Huberman:
安德鲁·休伯曼：
To date, has there been any specific neural network that we can point to and say, "Ah, that's the neural network that seems to be different in people who are on the autism spectrum"?
迄今为止，是否有任何特定的神经网络可供我们指出并说：“啊，这就是自闭症谱系人群中似乎有所不同的神经网络”？
I saw a study published recently that seemed to point to the idea that the genes that are altered in autism at least include a large number of genes that are altered, or the proteins that are the consequence of those genes are altered and exist at the synapse, at the connections between neurons.
我看到最近发表的一项研究似乎指出了这样一种观点，即自闭症中被改变的基因至少包括大量被改变的基因，或者是这些基因改变的结果的蛋白质被改变并存在于突触、神经元之间的连接处。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I'm asking it that way because some years ago, I was at a talk on autism at Stanford, and someone raised their hand and says, "Do we even know that autism is a brain issue?" Right?
我这样问是因为几年前，我在斯坦福大学参加一个关于自闭症的演讲，有人举手说：“我们知道自闭症是一个大脑问题吗？”正确的？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
"Couldn't it be an issue of the immune system or the cardiovascular system?" Which, at the time, seemed like, okay, gosh, of course it's the brain.
“难道不是免疫系统或心血管系统的问题吗？”当时看来，好吧，天哪，当然是大脑了。
But wait, then you stop and you think, that's a really good question.
但是等等，然后你停下来想，这是一个非常好的问题。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
How do we know it's a challenge of the brain?
我们怎么知道这是对大脑的挑战？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
I think that's a great question, right?
我认为这是一个很好的问题，对吧？
And there may be people talk about autisms, right?
可能有人谈论自闭症，对吗？
And so when you think about where the major player is, we're at the infancy of thinking about this, right?
因此，当你想到主要参与者在哪里时，我们还处于思考这个问题的初级阶段，对吧？
And so maybe for some people, it's more of a brain-based disorder.
所以也许对于某些人来说，这更多的是一种基于大脑的疾病。
Maybe for some people, it's the connection with the gut and the brain, right?
也许对某些人来说，这是与肠道和大脑的联系，对吧？
I think what's also really tricky, right, so one thing that you have to ask is, what are the barriers to progress in understanding autism, right?
我认为这也很棘手，对吧，所以你必须问的一件事是，在理解自闭症方面取得进展的障碍是什么，对吧？
And so the way I think about this is that, let's just take for a moment that this is a brain disorder.
所以我的想法是，让我们暂时认为这是一种大脑疾病。
How do you study it in people, right?
你如何在人身上研究它，对吗？
So it's very difficult to get access to either cerebral spinal fluid, which is a fluid that bathes the brain, brain tissue biopsies.
因此，获取脑脊液（一种沐浴大脑的液体）和脑组织活检都非常困难。
It's very hard to get people, especially children, that are really impacted into a brain scanner, right?
让那些真正受到影响的人，尤其是儿童，接受脑部扫描仪是非常困难的，对吧？
Because they can't sit still.
因为他们坐不住了。
They may have sensory issues.
他们可能有感官问题。
They don't want to go into a scanner, right?
他们不想进入扫描仪，对吧？
So a lot of the tools that neuroscientists or psychiatrists have to think about looking at the brain are limited, right?
因此，神经科学家或精神病学家必须考虑使用的许多观察大脑的工具都是有限的，对吗？
And then the other part is, how do you model?
然后另一部分是，你如何建模？
So the other way we might think about getting access or thinking about model systems, what we need to do is think about the control animals, and we need to make sure that the species that we're modeling them in has features of control humans, if you will.
因此，我们可能会考虑访问或考虑模型系统的另一种方式，我们需要做的是考虑对照动物，并且如果您愿意的话，我们需要确保我们正在建模的物种具有控制人类的特征。
So we need to have complex cognitive abilities.
所以我们需要有复杂的认知能力。
We need to have complex social skills.
我们需要具备复杂的社交技能。
We need to have an organism that has vision as its primary sensory modality, right?
我们需要一个以视觉作为主要感觉方式的有机体，对吗？
Potentially sleep consolidating.
可能会巩固睡眠。
So we need to think about all of those.
所以我们需要考虑所有这些。
And the tricky part, I think, until fairly recently, was that we were doing all of this work in mouse models.
我认为，直到最近，棘手的部分是我们在小鼠模型中完成所有这些工作。
And the control mice just fundamentally lack many of the characteristics that are needed to model autism with fidelity, right?
对照小鼠从根本上缺乏保真自闭症模型所需的许多特征，对吗？
And I think when we look at drug development pipelines, about 50% of preclinical failures, so that would be something that's tested in an animal that works and then fails in a human clinical drug trial, 50% of those failures can be attributed to poorly selected animal models.
我认为，当我们审视药物开发渠道时，大约 50% 的临床前失败，因此在动物身上进行测试，效果良好，然后在人体临床药物试验中失败，其中 50% 的失败可归因于动物模型选择不当。
And so I think part of where we will be getting traction is developing sophisticated models as a sort of point of entry into being able to understand some of these things that are really difficult to study in people.
因此，我认为我们将获得关注的部分原因是开发复杂的模型，作为理解某些很难在人类身上研究的事物的切入点。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, it's such a key point.
是的，这就是一个关键点。
And for those that have not heard of preclinical models, preclinical models are non-human models.
对于那些没有听说过临床前模型的人来说，临床前模型是非人类模型。
So it could be mouse, could be non-human primate, could be flies or worms for that matter.
所以它可能是老鼠，可能是非人类灵长类动物，可能是苍蝇或蠕虫。
But we're going to talk a lot about non-human primate preclinical models and the work that you've been doing, and of course, also the work that you've been doing in humans, the other animal.
但我们将谈论很多关于非人类灵长类动物临床前模型和您一直在做的工作，当然，还有您在人类（另一种动物）身上所做的工作。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
The other primate.
另一种灵长类动物。
Andrew Huberman:
安德鲁·休伯曼：
The other primate.
另一种灵长类动物。
Right, exactly.
对，完全正确。
I love to remind people that we're primates, old world primates, so thank you for doing that.
我喜欢提醒人们我们是灵长类动物，旧世界的灵长类动物，所以谢谢你这样做。
So you've been talking about the genetic influences on autism, and of course, genes and the environment interact.
所以你一直在谈论遗传对自闭症的影响，当然，基因和环境是相互作用的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
It's never nature or nurture.
这从来都不是先天或后天培养的。
It's always an interaction, and that isn't just about the epigenome.
这始终是一种相互作用，而这不仅仅是表观基因组的问题。
It's also just about the fact that nature impacts the genome, and our genome impacts the way that we interact with the environment, et cetera.
这也与自然影响基因组这一事实有关，而我们的基因组影响我们与环境互动的方式等等。
So what is the role of the environment in autism, both the frequency and the presentation of autism?
那么环境在自闭症中扮演什么角色，无论是自闭症的发生频率还是表现形式呢？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So there are, again, lots of different epidemiological studies.
因此，同样存在许多不同的流行病学研究。
So advanced parental age, prematurity, severe prematurity is a risk factor for autism, maternal illness during pregnancy.
所以父母高龄、早产、重度早产是孕期产妇自闭症的危险因素。
So there's a bunch of different things that have been associated with an increased risk for autism.
因此，有很多不同的因素与自闭症风险增加有关。
Andrew Huberman:
安德鲁·休伯曼：
In terms of environmental influences and how they can intersect with biology, one of the things that I was really struck by in the early 2000s, that at least by my read of the literature hasn't really gone anywhere, was this idea that was proposed by Pasco Rakic-
就环境影响以及它们如何与生物学相交叉而言，我在 2000 年代初期真正震惊的事情之一是 Pasco Rakic 提出的这个想法，至少从我阅读的文献来看并没有真正取得任何进展。
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
who used to run the neurobiology department-
谁曾经负责神经生物学系-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at Yale, expert in brain neuroanatomy in non-human primates and in humans, embryology, really a luminary of our field.
耶鲁大学非人类灵长类动物脑神经解剖学和人类胚胎学专家，确实是我们领域的杰出人物。
And he had a series of papers exploring how the migration of neurons during early development, as you and I both know, but most people out there probably don't know because we haven't covered this in the podcast, it's not typical dinner table conversation.
他发表了一系列论文，探讨神经元在早期发育过程中如何迁移，正如你我都知道的那样，但大多数人可能不知道，因为我们没有在播客中介绍这一点，这不是典型的餐桌谈话。
When a human embryo is developing, the neurons are born at one location, and they migrate out some distance to their final resting place, where then they grow out their connections and connect with one another.
当人类胚胎发育时，神经元在一个位置诞生，然后它们迁移一段距离到最终的安息地，然后在那里它们生长出连接并相互连接。
And that process of neuronal migration is oh so critical for the eventual wiring of the brain.
神经元迁移的过程对于大脑的最终连接至关重要。
And Rakic had this idea that perhaps, and I really want to emphasize perhaps, that the more frequent incidents of autism might be correlated with the increase in early prenatal ultrasound.
拉基奇有这样的想法，也许，也许我真的想强调，自闭症事件的频繁发生可能与早期产前超声检查的增加有关。
And he had these papers published in a number of really high-profile journals, including Proceedings of the National Academy and Science and elsewhere, showing that in a mouse model, if you do ultrasound, with each successive ultrasound, you got more migration errors.
他在许多备受瞩目的期刊上发表了这些论文，包括《美国国家科学院院刊》和《科学》等期刊，表明在小鼠模型中，如果进行超声检查，则每次连续超声检查都会出现更多的迁移错误。
Right?
正确的？
So, to me, it was an interesting example of the environment, frequency of ultrasound, and cell migration having some sort of interaction.
所以，对我来说，这是一个有趣的例子，说明环境、超声波频率和细胞迁移之间存在某种相互作用。
But it seemed like it never went anywhere.
但它似乎从来没有去任何地方。
It never got tacked to, okay, you should keep in mind the number of ultrasounds that you're getting for your child.
它从来没有被固定，好吧，你应该记住你为你的孩子做的超声波检查的次数。
And, of course, ultrasounds are critical for pregnant women to get because they can stave off a number of developmental issues, and they're super important.
当然，超声波检查对于孕妇来说至关重要，因为它们可以避免许多发育问题，而且非常重要。
But we've heard about ultrasound within the scientific literature, and then occasionally we'll hear other theories about, okay, it's having two parents who are both engineers, and then we'll hear, oh, it's toxicity in the food environment.
但我们在科学文献中听说过超声波，然后偶尔我们会听到其他理论，好吧，它有两个都是工程师的父母，然后我们会听到，哦，它在食品环境中具有毒性。
We've heard hypotheses about vaccines or the adjuvants that the vaccines are contained in.
我们听说过有关疫苗或疫苗所含佐剂的假设。
In that large cloud of theories, has anything really emerged from them as, okay, there really seems to be at least one major risk factor, environmental risk factor.
在这一大堆理论中，有什么真正从中出现的吗？好吧，似乎确实至少存在一个主要风险因素，即环境风险因素。
Because I feel like all those theories come up, get some popular press, bunch of papers are published.
因为我觉得所有这些理论都出现了，得到了一些受欢迎的媒体，发表了一堆论文。
Sometimes those papers are retracted, like in the case of the vaccines.
有时这些论文会被撤回，就像疫苗的情况一样。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And then the theory kind of dies.
然后这个理论就消失了。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So is there any specific environmental influence on autism that we can say, yes, there really seems to be something there?
那么，环境对自闭症是否有任何特定的影响，我们可以说，是的，似乎确实有什么影响？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
It's a really spectacularly good question.
这真是一个非常好的问题。
I think the tricky part about it is that every single person that comes into a trial has a different genetic background, right?
我认为棘手的部分是每个参与试验的人都有不同的遗传背景，对吗？
And so until we can have these a priori stratified trials where you could then, as a good scientist, you would only manipulate maybe one, two variables at a time, right?
因此，在我们能够进行这些先验分层试验之前，作为一名优秀的科学家，您一次只能操纵一个、两个变量，对吗？
But when you're doing these large epidemiological studies, because it's very difficult to do experimental studies, right, especially with developing children, I think that's an incredibly difficult study to do, right?
但是当你进行这些大型流行病学研究时，因为做实验研究非常困难，对吧，特别是对于发育中的儿童，我认为这是一项非常困难的研究，对吧？
So there's been an interest in this field of, there's these neurogenetic syndromes that have high penetrance for autism, which basically means that you could have a disorder or another genetic condition, let's say.
因此，人们对这个领域很感兴趣，这些神经遗传综合症对自闭症的外显率很高，这基本上意味着你可能患有某种疾病或另一种遗传疾病。
It doesn't have to be a single gene.
它不一定是单个基因。
But that a lot of those kids tend to also get an autism diagnosis.
但其中很多孩子往往也被诊断出自闭症。
And so there's been work in, so for instance, fragile X is a good example, where because autism is so diverse in terms of clinical presentation, that let's say you have a medication that could work for a handful of kids in the trial, you may not be statistically powered to see it, right?
例如，脆弱的 X 就是一个很好的例子，因为自闭症在临床表现方面是如此多样化，假设你有一种药物可以对试验中的少数孩子有效，你可能没有统计能力看到它，对吗？
So, the way I think about the autism world is there's so little we don't know.
所以，我对自闭症世界的看法是，我们不知道的事情太少了。
So think about being in a dark room, and you have a flashlight, and you only see where you shine the light, right?
所以想象一下，在一个黑暗的房间里，你有一个手电筒，你只能看到你照射的地方，对吗？
And so if you think about a very genetically heterogeneous study, it's going to be very difficult to tease out these pieces because an environmental risk factor might be a driver for one kid but not another, right?
因此，如果你考虑一项遗传异质性很强的研究，那么就很难梳理出这些片段，因为环境风险因素可能是一个孩子的驱动因素，但不是另一个孩子的驱动因素，对吗？
And so I think what we need to do is to have these genetically defined subgroups of individuals and then be able to test the gene by environment interactions, or in this genetically defined group of individuals, can we test this certain medication to see if it's beneficial for this subgroup of children.
所以我认为我们需要做的是拥有这些基因定义的个体亚群，然后能够通过环境相互作用来测试基因，或者在这个基因定义的个体群体中，我们可以测试这种特定的药物，看看它是否对这个亚群的儿童有益。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
So you mentioned fragile X-
所以你提到了脆弱的X-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which we know presents with autism-like symptoms in some cases.
我们知道在某些情况下会出现类似自闭症的症状。
And then I think of another disease like Timothy syndrome.
然后我想到了另一种疾病，比如蒂莫西综合症。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
A mutation in an L-type calcium channel, which for those of you that don't know what these L-type calcium channels are, they're not just important for the function of neurons in the brain, they're really important for the function of neurons in other tissues, including heart tissue, right?
L 型钙通道的突变，对于那些不知道这些 L 型钙通道是什么的人来说，它们不仅对大脑中神经元的功能很重要，而且对其他组织（包括心脏组织）中神经元的功能也非常重要，对吗？
So kids with Timothy syndrome have cardiac issues.
因此，患有蒂莫西综合症的孩子有心脏问题。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And they have autism.
他们患有自闭症。
So, I think it's important for us to kind of explore this a bit because in most people's minds, kids with autism have autism, and occasionally they'll have other issues, gut issues or heart issues or musculoskeletal issues, but we often think that that's the consequence of the autism, but oftentimes they have multiple things going on.
所以，我认为我们对此进行一些探索很重要，因为在大多数人看来，患有自闭症的孩子患有自闭症，偶尔他们还会有其他问题，肠道问题或心脏问题或肌肉骨骼问题，但我们经常认为这是自闭症的后果，但通常他们有多种情况发生。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And the autism actually could be secondary or independent of the other thing that's going on.
自闭症实际上可能是次要的或独立于正在发生的其他事情。
So this is what leads me back to this idea of a spectrum.
这就是让我回到频谱这个概念的原因。
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Is it possible that what we call autism is actually 50 different disorders or 50 different conditions, depending on what one wants to call them?
我们所说的自闭症是否有可能实际上是 50 种不同的疾病或 50 种不同的状况，这取决于人们想要如何称呼它们？
What is autism really?
自闭症到底是什么？
What does it really center around?
它真正以什么为中心？
And I think here maybe it's useful to go, do we go to the diagnostic criteria?
我认为这里也许有用的是，我们是否要了解诊断标准？
How do we decide if a child has autism if they also have a bunch of other things-
如果孩子还有很多其他症状，我们如何判断他们是否患有自闭症？
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
that are challenging them?
那些正在挑战他们？
Dr. Karen Parker:
凯伦·帕克博士：
I think that that's the $64,000 question, right?
我想这就是 64,000 美元的问题，对吧？
And again, in other areas of medicine, so if you think about, let's think about cancer biology, right?
再说一次，在医学的其他领域，所以如果你想一想，让我们考虑一下癌症生物学，对吧？
Decades ago, somebody would come in with cancer, and you would hit them with radiation chemotherapy, and that was the best that we could do, right?
几十年前，有人患有癌症，你会用放射化疗来治疗他们，这是我们能做的最好的事情，对吧？
But with the invention of a lot of molecular tools, you can remove a tumor, and you can do molecular profiling and even have personalized medications made, right, to attack that tumor.
但随着许多分子工具的发明，你可以切除肿瘤，你可以进行分子分析，甚至可以制作个性化药物来攻击该肿瘤。
And so, what's really tricky when you have a behavioral diagnosis that's not biologically defined, you see a lot of heterogeneity.
因此，当你的行为诊断不是生物学定义的时，真正棘手的是，你会看到很多异质性。
So it's incredibly difficult, I think, to answer this question because we don't know how many kinds of autisms there are, right?
所以我认为回答这个问题非常困难，因为我们不知道有多少种自闭症，对吗？
There will be people who say if you have a disorder like fragile X or Prader-Willi syndrome or Timothy syndrome or a variety of these other conditions, I've heard clinicians say, "Well, that's not really autism, right?
有人会说，如果你患有脆性X染色体疾病、普瑞德-威利综合征、蒂莫西综合征或其他各种疾病，我听临床医生说，“嗯，这不是真正的自闭症，对吧？
That's a piece of fragile X, right?" But if it's a behavioral diagnosis and they meet behavioral criteria, it becomes this weird circular argument, right?
那是一块脆弱的X，对吧？”但如果这是一个行为诊断并且他们符合行为标准，那就变成了这种奇怪的循环论证，对吗？
So until we really understand what autism is, I think that it's going to be very tricky to start sub-defining different aspects of the condition.
因此，在我们真正了解自闭症是什么之前，我认为开始对这种疾病的不同方面进行细分定义将是非常棘手的。
Speaker 3:
演讲者3：
Propel Fitness Water.
推动健身水。
With Gatorade electrolytes, zero sugar, and vitamins, Propel hydrates better than water to help you get the most out of your workout and get back to your best self.
Propel 含有佳得乐电解质、零糖和维生素，比水更好地补充水分，帮助您充分利用锻炼并恢复最佳状态。
What propels you?
是什么推动着你？
Propel with Gatorade electrolytes.
用佳得乐电解质推动。
Andrew Huberman:
安德鲁·休伯曼：
Well, this is probably a good time for us to think about the work that you've done in terms of trying to tack the biology of social communication and behavior-
好吧，这可能是我们思考你在试图解决社会沟通和行为生物学方面所做的工作的好时机——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
how those things interact, not just language, but also behavior, to autism in humans using non-human primate models.
使用非人类灵长类动物模型，这些事物如何与人类自闭症相互作用，不仅是语言，还包括行为。
And then, of course, to also discuss some of the work that you've been doing in humans.
当然，接下来还要讨论您在人类身上所做的一些工作。
And we can't have that discussion without first having a discussion about two neuropeptides that I think most people have heard of at least one of them, and I think there's a lot of misunderstanding about, but you're going to clarify that for us, which are oxytocin and vasopressin.
如果不首先讨论两种神经肽，我们就不能进行这样的讨论，我认为大多数人至少听说过其中一种，而且我认为这方面存在很多误解，但你要为我们澄清这一点，即催产素和加压素。
So before we dive into the important work that you've been doing on vasopressin in particular, but also oxytocin and autism, what are oxytocin and vasopressin really?
因此，在我们深入探讨您特别是关于加压素以及催产素和自闭症方面所做的重要工作之前，催产素和加压素到底是什么？
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
So they're these small little peptide, they're nine amino acids long, so very tiny.
所以它们就是这些小肽，它们有九个氨基酸长，所以非常小。
They only differ by two amino acids.
它们仅存在两个氨基酸不同。
And they're these ancient peptides that are hundreds of millions of years old.
它们是具有数亿年历史的古老肽。
And in almost any species studied, whether it's the current version, you might have vasotocin or other mesotocin, which are sort of precursor forms in other species, but they're highly evolutionarily conserved.
在几乎所有研究的物种中，无论是当前的版本，都可能含有催产素或其他中产素，它们是其他物种中的前体形式，但它们在进化上高度保守。
And they're involved in social behavior, in pretty much any, it could be egg-laying, it could be the reproduction and social behavior across the phylogenetic taxes, actually.
它们参与了几乎所有的社会行为，实际上可能是产卵，也可能是系统发育税中的繁殖和社会行为。
Andrew Huberman:
安德鲁·休伯曼：
So house cats make vasopressin and oxytocin.
所以家猫会产生加压素和催产素。
Humans obviously make vasopressin-
人类显然会产生加压素-
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
and oxytocin, and pretty much every other species that has to interact with and connect with other members of its species.
和催产素，以及几乎所有其他必须与其物种的其他成员相互作用和联系的物种。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Especially mammals, right?
尤其是哺乳动物，对吧？
So oxytocin and vasopressin are pervasive in mammalian species.
因此，催产素和加压素在哺乳动物中普遍存在。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Do the different species tend to make oxytocin and vasopressin in similar brain areas and tissues?
不同物种是否倾向于在相似的大脑区域和组织中产生催产素和加压素？
Dr. Karen Parker:
凯伦·帕克博士：
Yes, but not completely overlapping.
是的，但不完全重叠。
But I think the thing that the beautiful mystery about these and the infuriating piece of them is that because they're so structurally similar, they can have similar effects.
但我认为这些美丽的神秘之处和令人恼火的部分是，因为它们在结构上非常相似，所以它们可以产生相似的效果。
And there's four receptors that they bind to.
它们结合了四种受体。
So if you think about a hormone or a neurotransmitter, so oxytocin, vasopressin, if you think about them like a key and a receptor like a lock, and you have to put them together to open a door or open behavior, they can bind to these four receptors.
所以，如果你想到一种激素或神经递质，比如催产素、加压素，如果你把它们想象成一把钥匙，把一个受体想象成一把锁，你必须把它们放在一起才能打开一扇门或打开行为，它们可以与这四种受体结合。
So it can be very difficult to disentangle which one is acting and at which receptor and where in the brain.
因此，很难弄清楚哪一个在起作用，作用于哪个受体以及大脑中的哪个位置。
Andrew Huberman:
安德鲁·休伯曼：
Oh, so oxytocin and vasopressin are chemically similar?
哦，那么催产素和加压素在化学上是相似的吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Interesting.
有趣。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And where would you say lies their greatest output divergence, which is just nerd speak for, is there an example of something that oxytocin does that vasopressin doesn't and vice versa?
你会说它们最大的输出差异在哪里，这只是书呆子所说的，有没有一个例子可以说明催产素可以做而加压素却不能做的事情，反之亦然？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Okay.
好的。
So what's really fascinating is these two neurotransmitters or hormones were discovered for their peripheral effects, which basically means not in their brain, but somewhere in their body.
真正令人着迷的是，这两种神经递质或激素被发现具有外周效应，这基本上意味着不是在他们的大脑中，而是在他们身体的某个地方。
And so oxytocin's involved in uterine contractions and milk letdown, and so was during lactation.
因此，催产素与子宫收缩和泌乳有关，在哺乳期间也是如此。
So people sort of always thought of it as the female hormone.
所以人们总是认为它是女性荷尔蒙。
And then vasopressin has, at least in the peripheral system, has been involved in urinary output regulation, blood pressure.
然后，加压素至少在外周系统中参与了尿量调节和血压。
And so we only knew about their physiological roles as sort of classic hormones for decades.
因此，我们几十年来才了解它们作为经典激素的生理作用。
And what was interesting is these Like naming conventions are fascinating in medicine, right?
有趣的是，这些命名约定在医学上很有趣，对吧？
So you could name a virus after where it was first found, right?
所以你可以根据病毒首次发现的地点来命名它，对吗？
Or it could be named after somebody who discovered the disease, like Alzheimer's, for instance, is a good example.
或者它可以以发现这种疾病的人的名字命名，例如阿尔茨海默氏症就是一个很好的例子。
And what was interesting, oxytocin was only named once.
有趣的是，催产素只被命名过一次。
Vasopressin was named twice.
加压素被命名两次。
So it's either called arginine vasopressin or antidiuretic hormone.
所以它要么被称为精氨酸加压素，要么被称为抗利尿激素。
And so it had two different names.
所以它有两个不同的名字。
And so as you can imagine, sometimes genes are named twice.
正如你可以想象的那样，有时基因会被命名两次。
And so somebody in cancer is studying one gene, and somebody in autism is studying another, and they're not even communicating because they don't even realize that they've, at least historically, now we have all kinds of gene annotation sites, so it's less likely to happen now.
因此，患有癌症的人正在研究一种基因，而患有自闭症的人正在研究另一种基因，他们甚至没有进行交流，因为他们甚至没有意识到，至少在历史上，我们现在拥有各种基因注释位点，所以现在发生这种情况的可能性较小。
But what was fascinating is these hormones were named, oxytocin is Greek for quick birth.
但令人着迷的是这些激素的名字是“催产素”，在希腊语中是“快速分娩”的意思。
So for decades, people only appreciated their physiological roles.
所以几十年来，人们只重视它们的生理作用。
But there were neuroanatomists saying, "Hey," so these are both made-- They're made in a lot of different places, but the action sort of happens in the hypothalamus where they're made.
但有神经解剖学家说，“嘿，”所以这些都是制造的——它们是在很多不同的地方制造的，但这种作用发生在制造它们的下丘脑中。
And there were anatomists that said, "Wait, these sort of project back into the brain.
有解剖学家说，“等等，这些东西会投射回大脑。
What are these doing in the brain?" And one of my favorite historical stories was, I had a mentor, a colleague, who I didn't train with, but he was a real source of wisdom to me for many years, and his name's Court Peterson.
这些东西在大脑里做什么？”我最喜欢的历史故事之一是，我有一位导师，一位同事，我没有和他一起训练，但多年来他是我真正的智慧源泉，他的名字叫考特·彼得森。
And he told me this wonderful story about this Duke zoologist named Peter Klopfer.
他给我讲了一个关于杜克大学动物学家彼得·克洛普弗的精彩故事。
And Peter was studying ungulates, so sheep and goats.
彼得正在研究有蹄类动物，也就是绵羊和山羊。
And he wrote a story, a paper in 1971 called "Mother Love: What Turns It On." And one thing about science is I love going back and seeing where do the pearls of wisdom come from.
他在 1971 年写了一个故事，一篇论文，名为《母爱：是什么开启了它》。关于科学的一件事是我喜欢回顾并看看智慧的珍珠从何而来。
And so he wrote this and said, "Oxytocin is orchestrating all these events of motherhood." And there are sheep and goats in particular that have offspring that are precocious, meaning they're basically born ready, within an hour, they can run with the herd, unlike our species, which is altricial, meaning we have very helpless infants.
所以他写了这篇文章并说：“催产素正在精心策划所有这些母性事件。”尤其是绵羊和山羊，它们的后代早熟，这意味着它们基本上已经出生了，一小时内，它们就可以与牛群一起奔跑，这与我们的物种不同，我们的物种是晚熟的，这意味着我们有非常无助的婴儿。
And mom needs to bond really quickly with that baby if it's going to be running around, and from an evolutionary perspective, you want to be investing in the baby that's yours, not somebody else's, right?
如果宝宝要到处乱跑，妈妈就需要很快地与宝宝建立联系，从进化的角度来看，你想投资于你的宝宝，而不是别人的，对吗？
And he hypothesized that it was oxytocin that was being co-released into the brain and during milk letdown, that was what turned mother love on.
他推测，正是催产素被共同释放到大脑中，在泌乳过程中，这就是激发母爱的原因。
And that was really the beginning of this whole field of thinking, and so that opened up thinking about oxytocin in rodent maternal care and a variety of other instances.
这确实是整个思考领域的开始，因此开启了对啮齿动物产妇护理和各种其他情况下催产素的思考。
Andrew Huberman:
安德鲁·休伯曼：
Can I just briefly interrupt you?
我可以简单地打断一下你吗？
Because I find this so interesting, and I know it's interesting to everyone listening as well because, yes, and thank you for making it clear that oxytocin has many different roles.
因为我觉得这很有趣，而且我知道每个听的人也很有趣，因为，是的，感谢您明确指出催产素有许多不同的作用。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But this role of mother love and-
但这个母爱的角色和——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
bonding to infant has me needing to ask whether or not the idea was that oxytocin is released in the mother when she interacts with her own baby.
与婴儿的联系让我需要问，当母亲与自己的婴儿互动时，是否会释放催产素。
And that leads me to the question, is oxytocin also released in the baby in reaction to the mother?
这引出了我的问题，催产素是否也会随着母亲的反应而在婴儿体内释放？
And how long is that effect lasting?
这种效果能持续多久？
Because in order to have a pervasive bond with that baby and not just some other baby, and of course, we still have visual cues and-
因为为了与那个婴儿而不只是其他婴儿建立普遍的联系，当然，我们仍然有视觉提示，并且——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
we know our baby versus another baby in most instances.
在大多数情况下，我们知道自己的孩子与另一个孩子的情况。
There are rare exceptions, or perhaps not so rare exceptions, but leaving those aside, the mechanism that would allow for mother-infant bonding and infant-mother bonding by way of oxytocin presumably is something that is literally changing their brains.
有罕见的例外，或者也许不是那么罕见的例外，但抛开这些不谈，通过催产素实现母婴联系和婴儿母亲联系的机制可能正在真正改变他们的大脑。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Saying, "You are the center of my life."
说：“你是我生命的中心。”
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
And the baby, of course, is saying, "Well, you are my life-
当然，婴儿是在说：“好吧，你就是我的生命——
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
because you are the source of life," right?
因为你是生命的源泉，”对吧？
Certainly for the early part of life, and nowadays it seems that can extend well into the teens and 20s for some people.
当然，对于生命的早期阶段来说，现在对于某些人来说，这种情况似乎可以延续到十几岁和二十几岁。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But how is oxytocin working?
但催产素是如何发挥作用的呢？
Is it working over the course of minutes, hours?
它的工作时间是几分钟、几小时吗？
Is there some specificity of this baby and this mom-
这个宝宝和这个妈妈有什么特别之处吗——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that links them in some more pervasive way?
以某种更普遍的方式将它们联系起来？
How is oxytocin doing this-
催产素是如何做到这一点的？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
magic of bonding?
粘合的魔力？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
It's very species specific, right?
这是非常具体的物种，对吧？
And you need to think about the evolutionary history of the species, right?
你需要考虑物种的进化历史，对吧？
So if you think about sheep or goats, the early studies that were done are the passage through the vaginal canal was what, so you would've activated oxytocin receptors that way.
因此，如果你想到绵羊或山羊，早期进行的研究就是通过阴道管的通道是什么，所以你会通过这种方式激活催产素受体。
But if you gave an oxytocin antagonist, meaning you would give into the brain something that blocked the oxytocin receptor, so if the oxytocin is being released into the brain, but you have a pharmacological agent blocking its ability to bind to its receptors, these sheep and goats wouldn't bond to their baby, for instance.
但是，如果你给予催产素拮抗剂，这意味着你会向大脑注入一些阻断催产素受体的物质，因此，如果催产素被释放到大脑中，但你有一种药物阻止其与其受体结合的能力，那么这些绵羊和山羊就不会与它们的婴儿建立联系。
Andrew Huberman:
安德鲁·休伯曼：
So literally the passage of the baby out of the vaginal canal triggers the oxytocin pathway, the release of oxytocin.
因此，从字面上看，婴儿离开阴道管会触发催产素途径，即催产素的释放。
Dr. Karen Parker:
凯伦·帕克博士：
Right, as in-
对了，如——
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Karen Parker:
凯伦·帕克博士：
...
...
lactation does too.
哺乳期也是如此。
Andrew Huberman:
安德鲁·休伯曼：
Nature is so beautiful-
大自然是如此美丽——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
because if you had to pick one event-
因为如果你必须选择一项活动——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to trigger the release of oxytocin, if oxytocin's role is to create bonding-
触发催产素的释放，如果催产素的作用是建立联系-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
with offspring, that would be the event, because that's a tough one to mistake.
对于后代来说，这就是大事，因为这是很难犯错误的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Dr. Karen Parker:
凯伦·帕克博士：
But what I will say, because I think to avoid you getting attacked on Twitter or wherever you might get attacked.
但我要说的是，因为我想避免你在 Twitter 上或任何可能受到攻击的地方受到攻击。
Andrew Huberman:
安德鲁·休伯曼：
I'm going to get attacked anyway.
无论如何我都会受到攻击。
If not for this discussion, then another one.
如果不是为了这个讨论，那么另一个。
But I'm tougher than I look.
但我比看上去更坚强。
Dr. Karen Parker:
凯伦·帕克博士：
But it's really species specific, right?
但这确实是物种特异性的，对吧？
So if you think about our species and a lot of primate species, we live in these extended family groups, and that's how we evolved.
因此，如果你考虑一下我们的物种和许多灵长类物种，我们生活在这些大家庭中，这就是我们进化的方式。
And so unlike a goat or a sheep that might live in a herd where there's a lot of non-relatives, we lived in a community of relatives, right?
因此，与可能生活在有很多非亲属的群体中的山羊或绵羊不同，我们生活在一个由亲属组成的社区中，对吗？
And we do all kinds of care of extended relatives.
我们还为远亲做各种照顾。
And so you wouldn't necessarily expect in a primate species where you have this long rearing history, where help from the family, and biparental care, where it takes a village to raise the baby.
因此，你不一定会期望灵长类动物有如此悠久的抚养历史，需要家庭的帮助，需要双亲的照顾，需要整个村庄来抚养婴儿。
We readily adopt in primate societies, right?
我们很容易在灵长类动物社会中收养，对吗？
I mean, I'll tell you something personal.
我的意思是，我会告诉你一些私人的事情。
I had a C-section, and I had a lot of postpartum complications, and so lactation didn't work out that well for me.
我进行了剖腹产，并且有很多产后并发症，因此哺乳对我来说效果不太好。
One of my friends would say-- I had massive DVTs and pulmonary emboli, and so I almost died after my son was born the first time.
我的一个朋友会说——我患有严重的深静脉血栓和肺栓塞，所以在我儿子第一次出生后我差点就死了。
And so I didn't have a vaginal delivery.
所以我没有阴道分娩。
I couldn't-
我不能-
Andrew Huberman:
安德鲁·休伯曼：
A DVT is deep vein thrombosis.
DVT 是深静脉血栓形成。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And it was sort of like welcome to motherhood, and I was in the ICU and had to get a filter put in, an inferior vena cava filter, to stop me from dying because I had scattershot clots all over my lungs.
这有点像欢迎成为母亲，我在重症监护室，必须安装一个过滤器，一个下腔静脉过滤器，以阻止我死亡，因为我的肺部到处都是散乱的血栓。
And so I didn't do a vaginal delivery.
所以我没有进行阴道分娩。
I had a C-section, and I wasn't really able to lactate.
我进行了剖腹产，但实际上无法哺乳。
And man, I love that baby.
伙计，我爱那个孩子。
Right?
正确的？
So, what I will say is it's really different in primates, and we don't really understand how bonding occurs.
所以，我要说的是，灵长类动物的情况确实不同，我们并不真正了解结合是如何发生的。
But what I will say is that bonding between a mother, you really need to think about the evolutionary selective pressures.
但我要说的是，母亲之间的联系，你真的需要考虑进化的选择压力。
So I was an evolutionary biologist before I found neuroscience, right?
所以在我发现神经科学之前我是一名进化生物学家，对吗？
And so everything I do, I think about from an evolutionary perspective.
所以我所做的每一件事，我都会从进化的角度来思考。
Many people go into the oxytocin vasopressin field because they have a lot of questions about social interactions, right?
很多人进入催产素加压素领域是因为他们对社交互动有很多疑问，对吗？
I think if you think about us as being social is actually one of the core characteristics of our species, right?
我想如果你认为我们的社会性实际上是我们物种的核心特征之一，对吗？
So social interactions are rewarding from infancy.
因此，社交互动从婴儿期起就是有益的。
They keep us alive, as you mentioned, right?
正如你提到的，他们让我们活下去，对吗？
And so I think it's not an accident that the way we think about disorder in our species is many disorders are disorders because of lack of social connectedness, right?
因此，我认为我们对人类紊乱的看法是许多紊乱是由于缺乏社会联系而导致的紊乱，这并非偶然，对吗？
So it could be something like autism, where there's these pervasive social interaction impairments.
因此，这可能类似于自闭症，存在普遍的社交互动障碍。
It could be something like drug abuse, where a risk factor for drug abuse is feeling socially disconnected and alone.
这可能类似于药物滥用，药物滥用的一个危险因素是感觉与社会脱节和孤独。
Right?
正确的？
Social isolation or loss of a loved one is a very strong predictor of the onset of a stress-related depressive anxiety disorder.
社会孤立或失去亲人是与压力相关的抑郁性焦虑症发作的强烈预测因素。
Andrew Huberman:
安德鲁·休伯曼：
In terms of when and how oxytocin is released, you mentioned mother-infant bonding.
关于催产素何时以及如何释放，您提到了母婴关系。
I think you said, yes, that the infant is also releasing oxytocin, we think.
我想你说过，是的，我们认为婴儿也在释放催产素。
So it's bidirectional.
所以它是双向的。
Dr. Karen Parker:
凯伦·帕克博士：
We think.
我们认为。
I think most of the work has been done in mom.
我认为大部分工作都是妈妈完成的。
And again, this has not been really done well in primates, right?
再说一遍，这在灵长类动物身上并没有真正做得很好，对吗？
So we're extrapolating this information from species that have different evolutionary histories than us, right?
所以我们是从与我们有不同进化历史的物种中推断出这些信息的，对吗？
So it's goats, sheeps, prairie voles, mice, rats.
所以是山羊、绵羊、草原田鼠、老鼠。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
So what do we know about the role of oxytocin in humans?
那么我们对催产素对人类的作用了解多少呢？
We know it's there.
我们知道它就在那里。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
We presume, based on the animal models, that it's involved in mother-infant bonding, and presumably romantic partner bonding.
根据动物模型，我们推测它与母婴关系以及浪漫伴侣关系有关。
At least you hear that-
至少你听到的是——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a lot.
很多。
It was unfortunately nicknamed the love hormone.
不幸的是，它被昵称为“爱情荷尔蒙”。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And the reason it's unfortunate it was is that while that might cue attention to oxytocin, and I'm a big fan of people paying attention to biological phenomena, it discards the other and many roles of oxytocin.
不幸的是，虽然这可能会引起人们对催产素的关注，而且我是人们关注生物现象的忠实粉丝，但它放弃了催产素的其他许多作用。
But what can we say about oxytocin in humans, if anything?
但对于人类的催产素，我们能说些什么呢？
So we're assuming based on the animal models that it does something.
所以我们根据动物模型假设它有作用。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This is very different than dopamine, where there's tons of animal model data.
这与多巴胺有很大不同，多巴胺有大量的动物模型数据。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But there are brain imaging where we know where dopamine is expressed.
但通过大脑成像，我们可以知道多巴胺的表达位置。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And do we even know where oxytocin receptors are expressed in the human brain?
我们是否知道催产素受体在人脑中的何处表达？
Presumably, that information is out there.
据推测，这些信息就在那里。
Dr. Karen Parker:
凯伦·帕克博士：
Recently.
最近。
But again, there's a lot of specificity, and I think if you're thinking about disorders, you would then have to study those specific subpopulations.
但同样，有很多特殊性，我认为如果你正在考虑疾病，那么你就必须研究那些特定的亚群。
Right?
正确的？
A lot of this work has been done, so you have to think about how do we study it, right?
这方面的工作已经做了很多了，所以你要思考我们如何研究它，对吗？
So the best way to study it would be to have radiotracers, which we do have for dopamine and other compounds, where you would then go and see where after somebody's performed a task do we see activation, right, or uptake.
因此，研究它的最好方法是使用放射性示踪剂，我们确实有用于多巴胺和其他化合物的放射性示踪剂，然后你可以去看看某人执行任务后我们在哪里看到激活、正确或摄取。
There are some imaging studies.
有一些影像学研究。
They're usually done giving intranasal oxytocin, and then you basically ask questions about, okay, we give you oxytocin intranasally, which presumably enters the brain.
他们通常会鼻内注射催产素，然后你基本上会问一些问题，好吧，我们鼻内给你催产素，它可能会进入大脑。
We could talk about reasons why we think that.
我们可以谈谈我们这么认为的原因。
And then we have you perform on some task.
然后我们让你执行一些任务。
Right?
正确的？
And so there's evidence if you give oxytocin, it diminishes the amygdala's response to fearful stimuli, right?
因此，有证据表明，如果给予催产素，它会减弱杏仁核对可怕刺激的反应，对吗？
So that it might have this sort of prosocial effect.
所以它可能会产生这种亲社会效应。
And it was actually data like that that caused people to start thinking initially about oxytocin.
实际上正是这样的数据让人们最初开始考虑催产素。
Andrew Huberman:
安德鲁·休伯曼：
And those were data in humans.
这些是人类的数据。
That's right.
这是正确的。
It reminds me that there was this brief moment where oxytocin wasn't just being discussed as the love hormone.
它提醒我，有一个短暂的时刻，催产素不仅仅被讨论为爱情荷尔蒙。
It was being discussed as the trust hormone.
它被讨论为信任荷尔蒙。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Also, far too simple a heuristic.
而且，这种启发式方法太简单了。
But again, I think it's cool that the press picks up on these things and at least tells people about what's being discovered.
但我再次认为，媒体关注这些事情并至少告诉人们正在发现什么是很酷的。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And we just always have to be careful to not have it lead to the assumption that that's the only role of a given hormone.
我们必须始终小心，不要让它导致人们认为这是特定激素的唯一作用。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Apparently, it can reduce the output of the amygdala in some way-
显然，它可以通过某种方式减少杏仁核的输出——
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
this brain area associated with threat detection.
这个与威胁检测相关的大脑区域。
And so you could imagine how that would bias the person toward being more prosocial.
所以你可以想象这会让这个人变得更加亲社会。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Have there been studies exploring the role of oxytocin in making autistic children more prosocial?
是否有研究探索催产素在使自闭症儿童更加亲社会方面的作用？
And behind that question, I suppose, is the assumption, you can verify or not, that autistic children are less prosocial than other children.
我想，这个问题的背后是一个假设，你可以验证与否，自闭症儿童比其他孩子更不亲社会。
Is that true?
这是真的吗？
Or is it that autistic kids are just maybe more prosocial with the one friend they really, really like?
或者说，自闭症孩子可能只是更喜欢与他们真正喜欢的朋友交往？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I happen to know some kids with autism, or however you want to phrase it, and they have close friends And they seem to really like those specific friends a lot.
我碰巧认识一些患有自闭症的孩子，或者不管你怎么说，他们有亲密的朋友，而且他们似乎非常喜欢那些特定的朋友。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They seem very happy when they show up at the door, and all the hallmarks-
当他们出现在门口时，他们看起来很高兴，所有的标志——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
of healthy social mind, but it is true that they are uncomfortable in groups and where there's a lot of noise.
具有健康的社交心态，但他们确实在群体和噪音很大的地方感到不舒服。
A busy birthday party is overwhelming for them, but you see them playing with one or two friends, and you could see all that and assume, okay, it's just kind of an introverted kid.
忙碌的生日聚会对他们来说是难以承受的，但你看到他们和一两个朋友一起玩，你可以看到这一切，并假设，好吧，这只是一个内向的孩子。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Actually, it kind of reminds me of me .
事实上，这让我想起了我自己。
I don't have a problem with crowds, but I much prefer to be with a small group of friends-
我不介意人群拥挤，但我更喜欢和一小群朋友在一起——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
or one close friend.
或一位亲密的朋友。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So-
所以——
Dr. Karen Parker:
凯伦·帕克博士：
I hear you.
我听到了。
I'm that way, too.
我也是这样的
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
So, how do we think about this?
那么，我们如何看待这个问题呢？
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
Well, I would say the social features of autism are interesting.
嗯，我想说自闭症的社会特征很有趣。
There was an attempt a long time ago, like 1979.
很久以前就有人尝试过，比如1979年。
There was a woman named Lorna Wing who tried to subtype the social features of autism.
有一位名叫 Lorna Wing 的女士试图对自闭症的社会特征进行亚型分类。
And so there could be people that are socially avoidant and really just don't want to have social interactions.
因此，可能存在社交回避型的人，他们只是不想进行社交互动。
There could be kids that are active but odd, which means that they have an interest in being social, but maybe they don't read social cues right, and they interact in ways that other kids don't understand or could cause bullying.
可能有些孩子很活跃但很奇怪，这意味着他们对社交感兴趣，但也许他们没有正确解读社交线索，他们的互动方式其他孩子不理解或可能导致欺凌。
Andrew Huberman:
安德鲁·休伯曼：
Sounds like junior high school.
听起来像初中生。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah, exactly.
是的，完全正确。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And that's often why some autistic kids do better with adults.
这通常就是为什么一些自闭症儿童与成人相处得更好的原因。
Because adults know how to sort of channel discussions with somebody who might be a little socially awkward.
因为成年人知道如何与可能有点社交尴尬的人进行讨论。
But there's different phenotypes.
但有不同的表型。
People having a disinterest in social interactions could be that they're highly socially anxious.
对社交互动不感兴趣的人可能是因为他们高度社交焦虑。
That making eye contact makes them anxious.
目光接触会让他们感到焦虑。
You could have somebody who maybe is relatively, let's say, socially intact, if you will, but they have overwhelming sensory abnormalities that make it very difficult to interact with other people.
如果你愿意的话，你可能会遇到一个相对来说，比如说，在社交方面完好无损的人，但他们有压倒性的感官异常，这使得与其他人互动变得非常困难。
Again, that's another caveat.
再说一遍，这是另一个警告。
There have been some studies administering oxytocin to individuals with autism, and again, these are these single dose studies.
已经有一些研究对自闭症患者施用催产素，而且这些都是单剂量研究。
So, the first studies that were done were looking at single dose oxytocin in males, and we can talk a little bit about why oxytocin versus vasopressin, which vasopressin actually would have been my choice based on the animal literature, and we can talk about that.
因此，所做的第一项研究是针对男性的单剂量催产素，我们可以谈谈为什么催产素与加压素，根据动物文献，我实际上会选择加压素，我们可以讨论这一点。
But oxytocin was given to males, partly because the idea would be that the off-target effects in the peripheral nervous system, i.e. milk letdown, uterine contractions, are not going to happen in males.
但催产素被给予男性，部分原因是因为周围神经系统的脱靶效应，即泌乳、子宫收缩，不会发生在男性身上。
And so it was deemed that they might be safer subjects.
因此人们认为他们可能是更安全的受试者。
Males are often also the go-to for research studies, as you may have talked about on your podcast before, too.
男性通常也是研究的首选，正如您之前在播客中可能也谈到的那样。
Andrew Huberman:
安德鲁·休伯曼：
Yeah, something that fortunately is changing-
是的，幸运的是，一些事情正在改变——
Dr. Karen Parker:
凯伦·帕克博士：
Yes, absolutely
是的，绝对
Andrew Huberman:
安德鲁·休伯曼：
...
...
thanks to a mandate by the NIH.
感谢 NIH 的授权。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
I had to just kind of smile/raise my eyebrows a little bit at the idea that the assumption that oxytocin administered to males, yes, one can see why it wouldn't cause milk letdown- ...
我不得不微笑/扬起眉毛，因为假设催产素对男性使用，是的，人们可以明白为什么它不会导致泌乳——......
or uterine contractions.
或子宫收缩。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But, of course, there could be other peripheral effects of oxytocin-
但是，当然，催产素可能还有其他外周效应——
Dr. Karen Parker:
凯伦·帕克博士：
Of course.
当然。
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in males.
在男性中。
But they had to pick one, so they went with males.
但他们必须选择其中之一，所以他们选择了雄性。
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And there is this higher incidence of autism in males, so-
男性自闭症的发病率更高，所以——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
it's not a terrible place to start.
这并不是一个糟糕的开始。
You just would hope that they would also do the experiment on females.
你只是希望他们也能在女性身上做实验。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So they're doing this by nasal spray?
那么他们是通过鼻喷雾剂来做到这一点的吗？
Dr. Karen Parker:
凯伦·帕克博士：
So intranasal.
所以鼻内。
Andrew Huberman:
安德鲁·休伯曼：
One dose.
一剂。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
And for reasons that I don't understand, it's 24 international units, and I think maybe somebody did the first study using it, and this is how science happens.
出于我不明白的原因，它有 24 个国际单位，我想也许有人用它做了第一个研究，这就是科学发生的方式。
And it worked, and so then everyone uses that protocol.
它起作用了，所以每个人都使用该协议。
And so then there's been a lot of studies looking at, there's one reading the mind in the eyes.
因此，有很多研究正在研究，其中一项研究是从眼睛里读懂内心的。
So can you look at pictures of somebody's eyes and then ask what is the emotion that they're feeling?
那么你能看一下某人眼睛的照片，然后问他们感受到的情绪是什么吗？
Andrew Huberman:
安德鲁·休伯曼：
After receiving this intranasal-
接受鼻内注射后——
Dr. Karen Parker:
凯伦·帕克博士：
Oxytocin or a placebo.
催产素或安慰剂。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Karen Parker:
凯伦·帕克博士：
Where is your eye gaze going in a picture?
照片中你的目光投向哪里？
So one of the theories is that people with autism may, at least a subset of them, lack social motivation.
因此，其中一个理论是，自闭症患者（至少其中一部分人）可能缺乏社交动机。
So maybe they're not looking in the places like eyes where you receive a lot of social cues that are relevant to social communication.
所以也许他们没有看眼睛这样的地方，在那里你会收到很多与社交沟通相关的社交线索。
And so some of these early studies showed that a single dose of oxytocin in people that had high-functioning autism, so they were verbal, like you said, they could come in for studies, and that it looked like it had some potential effectiveness.
因此，其中一些早期研究表明，对于患有高功能自闭症的人来说，单剂催产素，所以他们是口头的，就像你说的那样，他们可以来参加研究，而且看起来它有一些潜在的效果。
And so there became a really strong interest in the field to think about oxytocin potentially as a therapy for autism.
因此，人们对催产素作为治疗自闭症的潜在疗法产生了浓厚的兴趣。
Andrew Huberman:
安德鲁·休伯曼：
And is oxytocin available over the counter, or does it require a prescription?
催产素可以在柜台购买吗，还是需要处方？
You see sites that are selling it, but that doesn't mean anything these days.
你会看到一些网站在出售它，但现在这已经没有任何意义了。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
There's gray market, there's all sorts of stuff-
那里有灰色市场，有各种各样的东西——
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
going on.
正在进行中。
But I know people that have used oxytocin.
但我知道有人使用过催产素。
There's actually a market for it.
其实是有市场的。
And by the way, folks, I'm not suggesting this, but someone the other day told me that they've been regularly taking oxytocin ketamine nasal inhalations as part of their work with their licensed therapist on PTSD-type stuff-
顺便说一句，各位，我并不是建议这样做，但前几天有人告诉我，他们一直在定期服用催产素氯胺酮鼻吸入剂，作为与有执照的治疗师一起治疗创伤后应激障碍（PTSD）类型的工作的一部分——
Dr. Karen Parker:
凯伦·帕克博士：
Okay
好的
Andrew Huberman:
安德鲁·休伯曼：
...
...
relating to, let's just call it relational trauma.
与，我们称之为关系创伤。
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
So that's happening.
所以事情就这样发生了。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But let's just think about oxytocin alone for the moment.
但我们暂时只考虑催产素。
Are parents of autistic kids able to buy oxytocin nasal spray?
自闭症孩子的家长可以购买催产素鼻喷雾剂吗？
Dr. Karen Parker:
凯伦·帕克博士：
No. So it would need to be written, the prescription would need to be written by a physician.
不，所以需要写，处方需要由医生写。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Karen Parker:
凯伦·帕克博士：
And it's not on the market.
而且市场上没有。
So there's one thing we should say, is there's only two drugs that are approved by the FDA to treat autism, and they're both antipsychotics, which they treat associated features like irritability, and they have off-target effects like weight gain, so we don't have any medications that are currently approved in the US, or anywhere else for that matter, to treat the core features of autism.
所以我们应该说的一件事是，只有两种药物被 FDA 批准用于治疗自闭症，它们都是抗精神病药物，它们治疗烦躁等相关特征，并且具有体重增加等脱靶效应，所以我们目前在美国或其他任何地方都没有批准任何药物来治疗自闭症的核心特征。
Andrew Huberman:
安德鲁·休伯曼：
Interesting and unfortunate.
有趣又不幸。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And hopefully, that will change in the not-too-distant future.
希望这会在不久的将来发生改变。
Do we know that children with autism, people with autism, because I'm going to just sort of-
我们是否知道患有自闭症的儿童、患有自闭症的人，因为我会-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
assume that autism is stable over the lifespan?
假设自闭症在一生中是稳定的？
Dr. Karen Parker:
凯伦·帕克博士：
Ooh.
哦。
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
If a child is diagnosed with autism, are they going to be an adolescent and adult with autism?
如果一个孩子被诊断出患有自闭症，他们会成为患有自闭症的青少年和成人吗？
Dr. Karen Parker:
凯伦·帕克博士：
So I would say that in a lot of cases, autism has lifelong impact, but there are people who outgrow their diagnosis.
所以我想说，在很多情况下，自闭症会产生终生影响，但有些人的诊断结果随着年龄的增长而不再适用。
There are people who respond well to behavioral therapy.
有些人对行为疗法反应良好。
Obviously, it's not the cure-all for everybody.
显然，这并不是解决所有人问题的灵丹妙药。
There's lots of people who go through intensive behavioral therapy and probably see minimal benefit.
有很多人接受了强化行为治疗，但可能收效甚微。
But it's certainly something that occurs in childhood, for the diagnosis occurs in childhood, and for most people, will then be present across the lifespan.
但这肯定是在童年时期发生的事情，因为诊断发生在童年时期，并且对于大多数人来说，然后将在整个一生中出现。
So we could say people with autism-
所以我们可以说患有自闭症的人——
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Karen Parker:
凯伦·帕克博士：
...
...
because each study sometimes will have adults, sometimes-
因为每项研究有时都会有成年人，有时-
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm
嗯嗯
Dr. Karen Parker:
凯伦·帕克博士：
...
...
you'll have teenagers, sometimes you'll have kids.
你会有青少年，有时你会有孩子。
Andrew Huberman:
安德鲁·休伯曼：
Is it known whether or not people with autism, assuming they meet the criteria for being autistic at that moment, have lower natural circulating or active levels of oxytocin?
假设患有自闭症的人当时符合自闭症的标准，是否知道他们的催产素自然循环或活跃水平是否较低？
Because it's one thing for a nasal spray of oxytocin to improve social functioning.
因为催产素鼻喷雾剂改善社会功能是一回事。
It's another to know that the effect is addressing an underlying biological deficit.
知道这种效应正在解决潜在的生物缺陷是另一回事。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
It's such a great question.
这是一个很好的问题。
Okay, so we should unpack that because there's been a lot of work in this area.
好的，我们应该将其解压，因为这方面已经做了很多工作。
So the first question is, where are we measuring the oxytocin, right?
所以第一个问题是，我们在哪里测量催产素，对吗？
So we mentioned oxytocin has all kinds of effects in the body as well as the brain.
所以我们提到催产素对身体和大脑都有各种影响。
And it's released into the blood, but it's also released directly into the brain.
它会释放到血液中，但也会直接释放到大脑中。
And there's variable evidence about if you measure it in blood, is it a readout of the brain or not, right?
有不同的证据表明，如果你在血液中测量它，它是否是大脑的读数，对吗？
Or should you be looking at something like spinal fluid that's maybe a better biochemical proxy of the brain?
或者你应该关注像脊髓液这样的东西，它可能是大脑更好的生化代表？
So what I will say is there's been a handful of small studies where there's been some benefit, maybe no benefit, small effects.
所以我要说的是，已经有一些小型研究取得了一些好处，也许没有好处，影响很小。
We did a study that was a small study at Stanford, and it was based on mouse genetic data, and I'll sort of walk you through what we did.
我们在斯坦福大学做了一项小型研究，它是基于小鼠遗传数据的，我将向您介绍我们所做的事情。
So there's multiple mouse models of these neurogenetic syndromes where people have social impairment, right?
因此，存在多种患有这些神经遗传综合征的小鼠模型，其中人们有社交障碍，对吗？
We can quibble about whether that's autism or not, but that they have social impairment.
我们可以争论这是否是自闭症，但他们有社交障碍。
And so that there are this fragile X mouse, there's a Prader-Willi syndrome mouse, which is the MAGEL2 gene that gets manipulated, and then there's a catenab 2 mouse.
因此，有这种脆弱的 X 小鼠，有一种 Prader-Willi 综合征小鼠，它是被操纵的 MAGEL2 基因，然后是一种 catenab 2 小鼠。
And in all of those instances, when you genetically modify those mice, you see a reduction of oxytocin in the hypothalamus.
在所有这些情况下，当你对这些小鼠进行基因改造时，你会看到下丘脑中催产素的减少。
And what's interesting is that in those instances where you see this genetic modification, you do see lower blood levels in these genetically defined models.
有趣的是，在您看到这种基因改造的情况下，您确实会在这些基因定义的模型中看到较低的血液水平。
What's really cool is you can give oxytocin across development in those models, and at least in the catenab 2 mouse, you can restore oxytocin neuron number to equivalent of control animals, suggesting that oxytocin is doing something in these oxytocin-deficient animals, right?
真正酷的是，你可以在这些模型的整个发育过程中给予催产素，至少在 Catenab 2 小鼠中，你可以将催产素神经元数量恢复到与对照动物相当，这表明催产素在这些缺乏催产素的动物中发挥了作用，对吗？
So these are not an oxytocin gene manipulation, but these are these syndromes where you see as a consequence of manipulating genes for these syndromes, that oxytocin gets knocked down, right?
所以这些不是催产素基因操纵，但这些是这些综合症，你认为操纵这些综合症的基因的结果是催产素被击倒，对吗？
And so our thinking when we went into our clinical trial was what if it's blood oxytocin levels, that there are going to be a subset of individuals that just make less oxytocin-
因此，当我们进行临床试验时，我们的想法是，如果是血液催产素水平，将会有一部分人产生的催产素较少——
Andrew Huberman:
安德鲁·休伯曼：
Humans
人类
Dr. Karen Parker:
凯伦·帕克博士：
...
...
humans.
人类。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And that maybe those are the individuals who stand to benefit the most from treatment.
也许这些人是从治疗中受益最大的人。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Karen Parker:
凯伦·帕克博士：
And so we were the first group to ask across this range of individuals who showed up, and we did in all the trials that we'll talk about today.
因此，我们是第一个对这一系列出现的个人进行询问的小组，我们在今天要讨论的所有试验中都这样做了。
These are done with my colleague Antonio Hardan at Stanford, who's a child psychiatrist.
这些是我和斯坦福大学的同事安东尼奥·哈丹一起完成的，他是一名儿童精神病学家。
And we always have double blind, meaning that the investigative team is blind or unaware, I should say.
我应该说，我们总是双盲，这意味着调查团队是盲目的或不知情的。
They're unaware of treatment, and then the families and the children are unaware.
他们不知道正在接受治疗，家人和孩子也不知道。
And then they're randomized, meaning there was an equal chance you could get either drug or placebo, and they're controlled, right?
然后它们是随机的，这意味着你有平等的机会获得药物或安慰剂，而且它们是受控制的，对吗？
Okay.
好的。
So we asked, "If we know what your pretreatment blood oxytocin level is, who's going to benefit from treatment?" And we found a couple of really interesting things.
所以我们问，“如果我们知道您治疗前的血液催产素水平是多少，谁将从治疗中受益？”我们发现了一些非常有趣的事情。
One was that the lower your baseline, so your pretreatment blood oxytocin level, you showed much greater benefit from the oxytocin intervention.
一是您的基线越低，治疗前的血液催产素水平越低，您从催产素干预中获得的益处就越大。
These are chil-
这些都是儿童——
Andrew Huberman:
安德鲁·休伯曼：
One intervention, one nasal spray?
一种干预，一种鼻喷雾剂？
Dr. Karen Parker:
凯伦·帕克博士：
This was four weeks.
这已经是四个星期了。
Sorry, I should have clarified.
抱歉，我应该澄清一下。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
This is four weeks of treatment being administered oxytocin twice a day.
这是为期四个星期的治疗，每天两次使用催产素。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
And so we saw effectiveness there.
所以我们看到了那里的有效性。
Andrew Huberman:
安德鲁·休伯曼：
May I...
我可以...
Sorry to interrupt so much.
抱歉打扰了这么多。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But just male and female subjects?
但只有男性和女性受试者？
Dr. Karen Parker:
凯伦·帕克博士：
We did, but again, because autism is male-biased in prevalence, even if you make this heroic effort to over-recruit, try to get more girls in, in the study, we usually try to aim for the prevalence rate because it's difficult to get girls just because there's fewer of them.
我们确实这样做了，但同样，因为自闭症的患病率偏向于男性，即使你做出了如此英勇的努力来过度招募，试图让更多的女孩参与进来，在研究中，我们通常会尝试以患病率为目标，因为很难仅仅因为女孩人数较少而吸引到女孩。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
Okay, but boys and girls were included.
好吧，但男孩和女孩都包括在内。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
They're taking oxytocin over the period of several-
他们在数年的时间里服用催产素——
Dr. Karen Parker:
凯伦·帕克博士：
Four weeks
四个星期
Andrew Huberman:
安德鲁·休伯曼：
...
...
four weeks.
四个星期。
And if they started off with lower baseline levels of oxytocin, you observed a benefit of the oxytocin treatment-
如果他们一开始的催产素基线水平较低，您就会观察到催产素治疗的好处-
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
in those individuals.
在那些人身上。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
What about the individuals who had normal to high levels?
那些水平正常到高的人呢？
Dr. Karen Parker:
凯伦·帕克博士：
You didn't see much benefit, right?
你没有看到太多好处，对吧？
And so that was a cue to me to think that there may be a subset of individuals that, for whatever reason, they have lower oxytocin, and that they may stand to benefit more from treatment.
因此，这提示我认为，可能有一部分人，无论出于何种原因，他们的催产素含量较低，并且他们可能会从治疗中受益更多。
And none of the prior studies had looked at blood oxytocin levels, and so what we had thought was that, well, maybe if everybody had measured baseline blood oxytocin levels, maybe there would have been more positive outcomes.
之前的研究都没有关注血液催产素水平，所以我们的想法是，如果每个人都测量基线血液催产素水平，也许会有更积极的结果。
But there's a lot of controversy in this field about whether oxytocin is a treatment for autism, right?
但关于催产素是否可以治疗自闭症，这个领域存在很多争议，对吗？
So after we completed that trial, there was a large multi-site, what's called a Phase 3 oxytocin treatment trial that was done at I think, five sites, and they gave oxytocin for an extended period of time, and they showed no benefit.
因此，在我们完成该试验后，进行了一项大型多站点，即所谓的三期催产素治疗试验，我认为是在五个站点进行的，他们长时间给予催产素，但没有显示出任何益处。
Andrew Huberman:
安德鲁·休伯曼：
Were they looking to see who started off with low levels of oxytocin at pre-treatment?
他们是否想看看谁在治疗前的催产素水平较低？
Dr. Karen Parker:
凯伦·帕克博士：
So what was interesting about that study, and there were a lot of issues with it, was that oxytocin is something where if you look at it, it degrades.
这项研究的有趣之处在于，它存在很多问题，那就是，如果你观察催产素，它就会降解。
That's kind of what I joke about.
我就是这么开玩笑的。
So you need to take it.
所以你需要接受它。
When we go in, we have these really intense protocols.
当我们进去时，我们有这些非常严格的协议。
So you go in, and we have vacutainer tubes that are cold, and we put them on ice, and then the phlebotomist takes the blood from the child.
所以你进去，我们有冷的真空采血管，我们把它们放在冰上，然后抽血医生从孩子身上抽取血液。
Andrew Huberman:
安德鲁·休伯曼：
So a lot of technical gymnastics.
所以有很多技术体操。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And then we make sure we spin it in a centrifuge cold, and then we pipette it onto dry ice, so we have very minimal loss of the signal.
然后我们确保将其在离心机中冷旋转，然后将其移至干冰上，这样我们的信号损失就非常小。
And so if you don't adhere to those rigid protocols, which is very difficult to do across multiple sites, it can be very difficult to get an accurate read of oxytocin.
因此，如果您不遵守这些严格的协议（这在多个站点上很难做到），那么就很难准确读取催产素。
And so I think for me, it's still an open question.
所以我认为对我来说，这仍然是一个悬而未决的问题。
They didn't see that blood oxytocin predicted response in that study.
他们在那项研究中没有发现血液催产素可以预测反应。
The data weren't provided in the paper.
论文中没有提供这些数据。
It was just said that they didn't.
只是据说他们没有。
But it's still an open question to me.
但这对我来说仍然是一个悬而未决的问题。
What if there was a group of children who had low oxytocin levels and they could benefit?
如果有一群儿童催产素水平较低并且他们可以受益怎么办？
There's other people where they'll say, "No, no, no, we don't think that chronic oxytocin's a good idea, that what you really should be doing is just giving it before a behavioral therapy session." And so maybe that is the way.
还有其他人会说，“不，不，不，我们认为慢性催产素不是一个好主意，你真正应该做的只是在行为治疗之前给予它。”也许就是这样。
So if you give it acutely, like in those early studies we talked about, that maybe oxytocin diminishes fear.
因此，如果你像我们谈到的那些早期研究那样敏锐地给予催产素，也许催产素会减少恐惧。
We know that oxytocin decreases the stress axis, the hypothalamic pituitary adrenal axis, and that it can diminish anxiety in animal models.
我们知道，催产素可以降低压力轴、下丘脑垂体肾上腺轴，并且可以减少动物模型中的焦虑。
So that's well established.
所以这是很确定的。
And in a former life, I was a stress researcher, so I've spent a lot of time thinking about this.
在前世，我是一名压力研究员，所以我花了很多时间思考这个问题。
But the sad thing is that once you have a negative trial, there isn't a lot of interest in funding the work going forward.
但可悲的是，一旦试验结果呈阴性，人们就没有太多兴趣为未来的工作提供资金。
And so I think it's still really an open question about if there is a subset of individuals that could benefit from oxytocin replacement therapy.
因此，我认为是否有一部分人可以从催产素替代疗法中受益仍然是一个悬而未决的问题。
And until there's money to do that work, we may not ever know the answer.
在有钱来做这项工作之前，我们可能永远不知道答案。
Andrew Huberman:
安德鲁·休伯曼：
Well, it will be important for that work to be done eventually.
嗯，最终完成这项工作非常重要。
Hopefully, the field will return to it despite whatever trends might be happening now.
希望无论现在发生什么趋势，该领域都会回归到原来的状态。
I think it's important to know for the parents of autistic children, whether or not there were any negative effects of oxytocin administration, in particular in the children that did not benefit from oxytocin treatment.
我认为对于自闭症儿童的父母来说，了解催产素的施用是否有任何负面影响非常重要，特别是对于那些没有从催产素治疗中受益的儿童。
The rationale is the following.
理由如下。
Well, of course, these things require a prescription.
嗯，当然，这些东西需要处方。
If a parent has a child with autism, especially if they're young enough that the behavioral interventions could possibly stand a good chance of inducing neuroplasticity, rewiring of the-
如果父母有一个患有自闭症的孩子，特别是如果他们足够年轻，行为干预很可能会诱发神经可塑性，重新布线-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
neural circuits that underlie social connection, well, then there's this time-limited window in which those parents presumably are willing to try most anything, provided it's safe.
社会联系背后的神经回路，好吧，然后有一个有时间限制的窗口，在这个窗口中，那些父母可能愿意尝试几乎任何事情，只要它是安全的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So let's assume, and I'm making up these numbers now because I haven't seen this study, but according to what you told me, that let's say a third of the autistic boys and girls that come in have low baseline levels of oxytocin.
所以让我们假设，我现在正在编造这些数字，因为我还没有看到这项研究，但根据你告诉我的情况，假设三分之一的自闭症男孩和女孩的催产素基线水平较低。
They're the ones that are going to benefit from this oxytocin intervention.
他们将从催产素干预中受益。
The other two-thirds don't.
另外三分之二的人则没有。
Well, given the difficulties of measuring baseline levels of oxytocin, most people don't have access to those kind of resources.
好吧，考虑到测量催产素基线水平的困难，大多数人无法获得此类资源。
If it's safe to give oxytocin no matter what, well, then if I were that parent, I'd be knocking on my physician's door saying, "Hey, give me an oxytocin spray because my kid might fall into that one-third category."
如果无论如何给予催产素是安全的，那么如果我是那个家长，我会敲我的医生的门说：“嘿，给我催产素喷雾剂，因为我的孩子可能属于那三分之一的类别。”
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
If and only if it turns out that oxytocin is safe to give.
当且仅当事实证明给予催产素是安全的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But if there's a risk profile that doesn't justify that kind of shotgun approach, well, then I wouldn't do that.
但如果风险状况无法证明这种霰弹枪方法的合理性，那么我就不会这样做。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So, is oxytocin spray safe?
那么，催产素喷雾安全吗？
And if so, why doesn't every physician who has a patient with autism give them oxytocin nasal spray?
如果是这样，为什么不是每个治疗自闭症患者的医生都给他们使用催产素鼻喷雾剂呢？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
It's a great question, and I know that I'm a parent of three children, and I know the sense of you would do anything to help your child, right?
这是一个很好的问题，我知道我是三个孩子的父母，我知道你会尽一切努力来帮助你的孩子，对吧？
And so I think the tricky part is that-- So one thing I will say is that all of the studies, and there's been many of them, have shown that oxytocin is relatively safe in a pediatric population.
所以我认为棘手的部分是 - 所以我要说的一件事是，所有研究（其中有很多研究）都表明催产素在儿科人群中相对安全。
The tricky part is I don't know, there's physicians that really pay attention to clinical trials, and if they don't see a benefit, they may not be willing to write the prescription.
棘手的是我不知道，有些医生真正关注临床试验，如果他们看不到好处，他们可能不愿意开处方。
So until we could identify a group of children that could benefit, we need to create the opportunity for physicians to recognize that this could potentially still be a treatment.
因此，在我们确定一组可以受益的儿童之前，我们需要为医生创造机会，让他们认识到这仍然可能是一种治疗方法。
But I think the tricky part, and what I will say is, and we can maybe talk a bit about vasopressin, which my feeling is that if I was placing bets and having to choose between these two, my money would be on vasopressin.
但我认为棘手的部分是，我要说的是，我们也许可以谈谈加压素，我的感觉是，如果我下注并必须在这两者之间进行选择，我的钱会花在加压素上。
Andrew Huberman:
安德鲁·休伯曼：
Well, we are definitely going to-
嗯，我们肯定会——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
talk about vasopressin in detail.
详细谈谈加压素。
The reason I mentioned that hypothetical scenario is just the sense of urgency and-
我之所以提到假设场景只是因为紧迫感以及——
Dr. Karen Parker:
凯伦·帕克博士：
Of course
当然
Andrew Huberman:
安德鲁·休伯曼：
...
...
in some cases, desperation that parents feel.
在某些情况下，父母会感到绝望。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And time's ticking, and if oxytocin's safe, then I guess I'll put in my vote that parents should at least talk to their physician, maybe even hand them the study to consider.
时间在流逝，如果催产素是安全的，那么我想我会投票赞成父母至少应该和他们的医生谈谈，甚至可能把研究交给他们考虑。
But I can also understand the perspective of a pediatrician who says, "Well, listen, it was a small number of kids that benefited.
但我也可以理解儿科医生的观点，他说：“好吧，听着，受益的是少数孩子。
You're welcome to try it, but it doesn't seem like the results are that impressive." But this gets to a bunch of larger issues about medical care and randomized controlled trials and the desperation of parents and kids to treat neurodevelopmental challenges.
欢迎你尝试一下，但看起来结果并不那么令人印象深刻。”但这涉及到一系列更大的问题，涉及医疗保健和随机对照试验，以及父母和孩子对治疗神经发育挑战的绝望。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
I just want to ask because it feels relevant in a real way.
我只是想问，因为它确实很相关。
If ultimately the goal of improving symptom profiles in autistic kids is about improving social cognition and social behavior And that process involves rewiring of brain circuits, neuroplasticity.
如果改善自闭症儿童症状的最终目标是改善社会认知和社会行为，那么这个过程涉及大脑回路的重新布线、神经可塑性。
Is there any reason to think that other approaches to inducing neuroplasticity would be beneficial, even if they're not in the biological pathways that are disrupted in autism?
有没有理由认为其他诱导神经可塑性的方法是有益的，即使它们不属于自闭症被破坏的生物途径？
I think, for instance, about the now extensive use of SSRIs-
例如，我认为现在广泛使用 SSRIs——
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
for the treatment of depression.
用于治疗抑郁症。
Some cases it works, in some cases it doesn't.
有些情况下它有效，有些情况下则无效。
Side effect profiles are a serious concern-
副作用概况是一个严重的问题 -
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
as I've discussed on this podcast before.
正如我之前在此播客中讨论过的那样。
But ultimately, we know that depression is not a serotonin deficiency in most cases.
但最终，我们知道在大多数情况下抑郁症并不是血清素缺乏。
SSRIs are atypical antidepressants like bupropion, Wellbutrin, and things of that sort.
SSRIs 是非典型抗抑郁药，如安非他酮、维布特林等。
When they work, they probably work because of their ability to induce or assist neuroplasticity.
当它们起作用时，它们起作用可能是因为它们能够诱导或协助神经可塑性。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Also, the trials on psilocybin are not really about psilocybin, they're about neuroplasticity.
此外，裸盖菇素的试验实际上并不是关于裸盖菇素，而是关于神经可塑性。
At least the trials for depression, right?
至少是针对抑郁症的试验，对吗？
There may be other uses of psilocybin-
裸盖菇素可能还有其他用途-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that relate more directly to the effects of psilocybin.
与裸盖菇素的作用更直接相关。
But ultimately, what we're talking about here is the attempt to rewire the brain in a specific way, whether or not it's assisted by oxytocin or some other mechanism.
但归根结底，我们在这里讨论的是尝试以特定方式重新连接大脑，无论是否有催产素或其他机制的帮助。
So the question is, are there trials happening where people are exploring, say, psilocybin, MDMA, which, by the way, we know increases oxytocin-
所以问题是，人们是否正在进行一些试验，比如探索裸盖菇素、MDMA，顺便说一下，我们知道它们会增加催产素——
Dr. Karen Parker:
凯伦·帕克博士：
I was going to mention that
我正想提一下
Andrew Huberman:
安德鲁·休伯曼：
...
...
and serotonin dramatically-
和血清素戏剧性地-
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
as well as things like atypical antidepressants in kids that have autism, not because we think that those autistic kids are deficient in any of the neurochemicals that these drugs would target, but that these drugs can help rewire the brain, and ultimately that's what these kids need.
以及自闭症儿童的非典型抗抑郁药之类的药物，并不是因为我们认为这些自闭症儿童缺乏这些药物所针对的任何神经化学物质，而是因为这些药物可以帮助重新连接大脑，而最终这正是这些孩子所需要的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
It's a really great point.
这真是一个伟大的观点。
And there might be subsets of kids, right?
可能还有一些孩子，对吧？
There might be kids where there would be a medication that would target other pathways, but that potently releases oxytocin, right?
可能有些孩子会有一种针对其他途径的药物，但会有效释放催产素，对吗？
But there might be kids that have an oxytocin deficiency, right?
但可能有些孩子缺乏催产素，对吧？
But I think that that circles back to your point at the beginning, or our point, is that autism is a very heterogeneous condition, and being able to know before you begin a trial, right, who am I going to put into it, and what is my primary outcome?
但我认为这又回到了你一开始的观点，或者我们的观点，那就是自闭症是一种非常异质的病症，在开始试验之前能够知道，对吧，我要把谁放进去，我的主要结果是什么？
One measure that I think is going to move the needle, right?
我认为一项措施将会起到推动作用，对吗？
It kind of requires a crystal ball.
这需要一个水晶球。
So there's a lot of guesswork that goes into this, but I would very much like to see.
所以这里面有很多猜测，但我非常想看到。
I will say one other thing.
我还要说一件事。
I have a colleague named Adam Guastella, who's at the University of Sydney, and he published a paper a year or two ago now suggesting that oxytocin may be most effective in kids at younger ages.
我有一位悉尼大学的同事 Adam Guastella，他在一两年前发表了一篇论文，表明催产素可能对年龄较小的孩子最有效。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Dr. Karen Parker:
凯伦·帕克博士：
And don't quote me, somewhere between two and five or three and six or something like that.
不要引用我的话，介于二到五或三到六之间或类似的东西。
Andrew Huberman:
安德鲁·休伯曼：
We'll find the paper and put it in the show notes.
我们会找到那张纸并将其放入演出笔记中。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
So it could be, to your point about neuroplasticity, that oxytocin may be maximally beneficial in younger ages, right?
因此，就您关于神经可塑性的观点而言，催产素可能在年轻时最有益，对吗？
And if these studies or these hodgepodges across ages and across sort of different social phenotypes, finding that signal is really important, right?
如果这些研究或这些跨年龄和跨不同社会表型的大杂烩，发现这个信号真的很重要，对吗？
And maybe age is a driver or maybe low blood oxytocin regardless of what age you are, or maybe in Adam's case, if you recruit really young children, you're likely to see a benefit just because the brain is wiring up and it's more plastic at younger ages.
也许年龄是一个驱动因素，或者可能是低血液催产素，无论你多大，或者在亚当的例子中，如果你招募非常小的孩子，你可能会看到一个好处，因为大脑正在连接并且在年轻时更具可塑性。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
That's also a vote, in my opinion, for early examination of kids.
在我看来，这也是对孩子进行早期检查的投票。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Parents really need to get autism screening, and perhaps maybe the most important thing is to make autism screening as available and as inexpensive as possible-
父母确实需要进行自闭症筛查，也许最重要的是让自闭症筛查尽可能可用且便宜 -
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
for everyone because of the importance of early intervention, even if it's purely behavioral intervention.
对每个人来说，因为早期干预的重要性，即使它纯粹是行为干预。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But certainly, if it's behavioral and drug intervention.
但当然，如果是行为和药物干预的话。
Dr. Karen Parker:
凯伦·帕克博士：
But the clinic wait times are really long, right?
但是诊所的等待时间真的很长，对吗？
So you have to have a specialist who's capable to diagnose autism, and so you could have a clinic where you're showing troublesome features and a parent wants to get their kid into a clinic, and you could have a 12-month or 18-month wait time, right?
所以你必须有一位能够诊断自闭症的专家，这样你就可以开一家诊所，在那里你表现出一些麻烦的特征，而家长想让他们的孩子去诊所，你可能需要 12 个月或 18 个月的等待时间，对吗？
And so there are a lot of people that are thinking about, are there laboratory-based tests that we can develop maybe either for detection or clinical referral, right?
因此，有很多人在考虑，我们是否可以开发基于实验室的测试来进行检测或临床转诊，对吗？
So could we come up with a biomarker panel, for instance, where we might be able to say, "Wow, here's a panel where we think this child is at reasonable risk for developing autism.
例如，我们是否可以提出一个生物标志物小组，我们可以说，“哇，这是一个小组，我们认为这个孩子有患自闭症的合理风险。
Can we make sure they're prioritized for getting a diagnosis," right?
我们能否确保他们优先获得诊断，”对吧？
So we can get them an early intervention.
这样我们就可以让他们尽早干预。
But right now, we don't have that, right?
但现在我们还没有这个，对吧？
So having some sort of laboratory-based test, whether it could be biological, or if we could do something with eye gaze.
因此，进行某种基于实验室的测试，无论它是生物学的，还是我们是否可以通过眼睛注视来做某事。
And there's a lot of companies working on these things now.
现在有很多公司正在研究这些事情。
And also, obviously, again, autism is always controversial in this field, right?
而且，显然，自闭症在这个领域总是存在争议，对吧？
There's so many different stakeholders.
有很多不同的利益相关者。
A lot of clinicians will say, "Well, I don't want a 30-second video clip replacing expert clinical opinion." There's good reasons for them to feel that way.
许多临床医生会说：“好吧，我不想让 30 秒的视频剪辑取代专家的临床意见。”他们有这样的感觉是有充分理由的。
But I think if there was a way to prioritize people that are in this line, we could get diagnoses faster.
但我认为，如果有一种方法可以优先考虑这一行的人，我们就可以更快地得到诊断。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Well, you wouldn't want false positives, but I would think that a 30-second-
好吧，你不会想要误报，但我认为 30 秒——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
video clip, provided it's of something useful, is going to be more valuable than nothing-
视频剪辑，只要有用，就比什么都没有更有价值-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
given the time sensitivity.
考虑到时间敏感性。
What are some of the barriers to getting this behavioral testing to be not just more prominent, but pervasive?
使这种行为测试不仅更加突出而且普遍存在的一些障碍是什么？
It seems to me that, well, I recall in school, they gave us the hearing test.
在我看来，嗯，我记得在学校时，他们给我们做了听力测试。
We all marched onto-
我们都迈进了——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
the bus.
公共汽车。
We get the beep test for hearing challenges.
我们进行了针对听力挑战的蜂鸣测试。
We get vision tests.
我们进行视力测试。
You get the Babinski reflex test, not the moment you come out of the womb, but-
你会接受巴宾斯基反射测试，不是在你离开子宫的那一刻，但是——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
pretty soon after.
不久之后。
Why isn't this stuff happening for autism- for every kid.
为什么这种事情没有发生在自闭症患者身上——每个孩子身上。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
It's not scalable, right?
它不可扩展，对吧？
So these interviews with parents and the tests that you do can take hours, right?
因此，与家长的面谈和所做的测试可能需要几个小时，对吧？
And any given clinician, even if they're working really long hours, there just aren't that many people that have the extensive training needed to make these expert diagnoses, right?
对于任何特定的临床医生，即使他们工作时间很长，也没有多少人接受过进行这些专家诊断所需的广泛培训，对吗？
And so I think that there's clinicians that are doing the absolute best they can, but they can only see a certain number of people a week, right?
所以我认为有些临床医生正在尽最大努力，但他们每周只能看一定数量的人，对吗？
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Does it have to be a physician?
一定是医生吗？
Sorry to interrupt.
抱歉打扰。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Or could a well-trained technician do this?
或者训练有素的技术人员可以做到这一点吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Well, I think technically it's a DSM diagnosis, right?
嗯，我认为从技术上来说这是 DSM 诊断，对吗？
So it's usually somebody with a clinical degree.
所以通常是拥有临床学位的人。
So it would be a clinical psychologist, it could be a behavioral pediatrician, it could be a child psychiatrist or child neurologist, but again, that requires years and years of training.
因此，这可能是一名临床心理学家，可能是一名行为儿科医生，可能是一名儿童精神病学家或儿童神经科医生，但这又需要多年的培训。
And if we look in areas where people have fewer access to resource, particularly in impoverished areas, the mean age of an autism diagnosis is years later than in wealthy areas where there's many different medical specialists with parents that aren't working three jobs and can sit waiting around, and really lobby and really advocate for their kids, right?
如果我们看看人们获得资源较少的地区，特别是贫困地区，那么自闭症诊断的平均年龄比富裕地区晚几年，富裕地区有许多不同的医学专家，他们的父母不做三份工作，可以坐着等待，真正为他们的孩子游说和倡导，对吗？
Because if they don't show up for work that day, they're not going to get fired from their job, right?
因为如果他们那天不去上班，他们就不会被解雇，对吗？
And so I think that if there's some sort of solution that allows there to be a more democratic approach to saying we need a really quick way, like you said, to be able to identify at-risk children, especially if it's a blood test or something like that, it could be incredibly impactful.
因此，我认为，如果有某种解决方案允许采用更民主的方法来表明我们需要一种非常快速的方法，就像您所说的那样，能够识别有风险的儿童，特别是如果是验血或类似的东西，那么它可能会产生难以置信的影响。
Andrew Huberman:
安德鲁·休伯曼：
Are there human trials exploring MDMA, methylenedioxymethamphetamine, also referred to as ecstasy, and/or psilocybin for treatment of autism?
是否有探索 MDMA、亚甲二氧基甲基苯丙胺（也称为摇头丸）和/或裸盖菇素治疗自闭症的人体试验？
Dr. Karen Parker:
凯伦·帕克博士：
So I was aware that MAPS had an MDMA trial in autism.
所以我知道 MAPS 正在进行一项治疗自闭症的 MDMA 试验。
I don't know what's happened with that.
我不知道这是怎么回事。
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Yeah.
是的。
Perhaps it's still ongoing.
也许它仍在继续。
I'll check the MAPS site.
我会检查一下 MAPS 网站。
I'm in communication with them from time to time.
我时不时地与他们沟通。
The reason for asking, of course you know, but maybe in case some of the listeners don't, is that MDMA causes these massive increases in serotonin.
你当然知道，问这个问题的原因是，摇头丸会导致血清素大量增加，以防万一有些听众不知道。
That seems to be the major source of the MDMA effect, so to speak, based on the work of our colleague, Rob Malenka, and at least one human study comparing MDMA to very high dose oxytocin treatment kind of ruled out the oxytocin spike that's induced by MDMA as the source or the only source, but of course, these chemicals can synergize.
可以这么说，这似乎是 MDMA 效应的主要来源，根据我们同事 Rob Malenka 的工作，至少一项将 MDMA 与极高剂量催产素治疗进行比较的人体研究排除了由 MDMA 引起的催产素峰值作为来源或唯一来源，但当然，这些化学物质可以协同作用。
But based on its chemical profile, oxytocin release, massive serotonin release, dopamine release, and a propensity to enhance neuroplasticity, assuming all the safety protocols were there, it seems like not the perfect drug, but not a bad choice, if, of course, it's inducing the kind of plasticity that someone with autism would be seeking.
但基于其化学特征、催产素释放、大量血清素释放、多巴胺释放以及增强神经可塑性的倾向，假设所有安全方案都存在，它似乎不是完美的药物，但也不是一个糟糕的选择，当然，如果它能诱导自闭症患者所寻求的那种可塑性的话。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
I think the tricky part, especially in children, right, is there's going to be a reluctance to potentially give them psychedelics, right?
我认为棘手的部分，尤其是对于儿童来说，是否会不愿意给他们服用迷幻药，对吗？
And so, is there a way to modify the chemical compound to be something that parents might be more willing to give to their children, right?
那么，有没有一种方法可以将化合物修改为父母可能更愿意给孩子的东西，对吗？
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
And I totally agree with that.
我完全同意这一点。
I guess to play devil's advocate-
我想扮演魔鬼代言人——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
not against you, but-
不是反对你，而是——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
well, I'll just state it very directly-
好吧，我就直接说吧——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and then I'll take the heat as necessary.
然后我会根据需要采取热量。
I've done two episodes about the drugs that millions, tens of millions, if not hundreds of millions of parents are already giving their kids for ADHD, which include amphetamines-
我已经制作了两集关于数百万、数千万甚至数亿父母已经给孩子服用治疗多动症的药物的故事，其中包括安非他明——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
including dioxin.
包括二恶英。
Methamphetamine is actually a prescription drug-
甲基苯丙胺实际上是一种处方药——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
for a very small subset of kids with ADHD.
对于一小部分患有多动症的孩子来说。
But things like Adderall, Vyvanse, even methylphenidate, Ritalin, these are amphetamines.
但像阿得拉（Adderall）、维凡斯（Vyvanse），甚至哌醋甲酯、利他林，这些都是安非他明。
They induce dopamine release and norepinephrine release.
它们诱导多巴胺释放和去甲肾上腺素释放。
And again, I'm not suggesting people give their kids MDMA to try and ameliorate symptoms of autism, but something chemically similar to it ought to be developed or at least explored in a human trial, in my opinion.
再说一遍，我并不是建议人们给孩子服用摇头丸来尝试改善自闭症症状，但我认为应该开发出化学成分类似的东西，或者至少在人体试验中进行探索。
Well, time will tell.
好吧，时间会证明一切。
I'll reach out to the MAPS group and see what's happening.
我将联系 MAPS 小组，看看发生了什么。
Let's talk about vasopressin-
我们来谈谈加压素——
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
because there's a lot to discuss there.
因为那里有很多东西要讨论。
So you told us this is a molecule that chemically is very similar to oxytocin.
所以你告诉我们这是一种化学成分与催产素非常相似的分子。
Is it manufactured in the human brain and body?
它是在人的大脑和身体中制造的吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Do we know a subset of the sites that it's known to be produced and where some of its actions are?
我们是否知道它所产生的网站的子集以及它的一些操作在哪里？
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
You mentioned the kidney and the antidiuretic hormone-
你提到了肾脏和抗利尿激素-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
roles, but within the brain, what brain areas have neurons that make vasopressin?
但在大脑中，哪些大脑区域具有产生加压素的神经元？
Dr. Karen Parker:
凯伦·帕克博士：
Well, so-
嗯，所以——
Andrew Huberman:
安德鲁·休伯曼：
Or have the receptors for vasopressin.
或者具有加压素受体。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
The receptors are all over the brain.
受体遍布大脑各处。
And again, it varies depending on the species and the way the receptors are measured are in postmortem tissue, right, which can be very difficult to get good samples, right?
再说一次，它根据物种的不同而有所不同，而且受体的测量方式是在死后组织中进行的，对吧，这可能很难获得好的样本，对吧？
And so we need to have that caveat going in.
所以我们需要注意这一点。
But yeah, it's made in the hypothalamus, and it's released all over the brain, and there's vasopressin receptors all over the brain, right?
但是，是的，它是在下丘脑中产生的，并且在整个大脑中释放，并且整个大脑都有加压素受体，对吧？
And what's really interesting about vasopressin, I always sort of joke that oxytocin always saw its day in the sun, if you will, and that vasopressin was sort of this stepchild that was left behind.
关于加压素，真正有趣的是，我总是开玩笑说，如果你愿意的话，催产素总是在阳光下看到它的日子，而加压素就像是被抛在后面的继子。
And the reason why I find this fascinating is, again, I think back to my My roots as a evolutionary biologist, behavioral neuroscientist.
我之所以觉得这很有趣，是因为我再次回想起我作为进化生物学家、行为神经科学家的根源。
And what was interesting is that there were studies in the early to mid 1990s showing that vasopressin was critical for male social behavior.
有趣的是，20 世纪 90 年代初至中期的研究表明，加压素对于男性社会行为至关重要。
And so, there was a variety of people, and I think Rob Malenka mentioned this on the podcast he did about there was a group of people like Sue Carter, Larry Young, Tom Insel, some of these early people, and they gave vasopressin to male prairie voles, and vasopressin was what induced pair bonding with a female mate, and also paternal care.
所以，有各种各样的人，我想罗布·马伦卡（Rob Malenka）在他做的播客中提到了这一点，有一群人，比如苏·卡特（Sue Carter）、拉里·杨（Larry Young）、汤姆·英塞尔（Tom Insel），其中一些是早期的人，他们给雄性草原田鼠注射加压素，加压素是诱导与雌性伴侣建立配偶关系以及父亲照顾的原因。
Andrew Huberman:
安德鲁·休伯曼：
And as I recall, those experiments were done in the context of looking at polygamy versus monogamy-
我记得，这些实验是在研究一夫多妻制与一夫一妻制的背景下进行的——
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
of these prairie voles.
这些草原田鼠。
Dr. Karen Parker:
凯伦·帕克博士：
Prairie voles versus a different species, so same genus, but a different species.
草原田鼠与不同的物种，所以相同的属，但不同的物种。
So it might be a montane vole or highly related, but these other species.
所以它可能是山地田鼠或高度相关的，但这些其他物种。
So prairie voles are monogamous.
所以草原田鼠是一夫一妻制的。
The males-
男性——
Andrew Huberman:
安德鲁·休伯曼：
For life?
为了一生？
Dr. Karen Parker:
凯伦·帕克博士：
Well, I mean, that was the mar-
嗯，我的意思是，那是市场-
Andrew Huberman:
安德鲁·休伯曼：
50% divorce rate.
离婚率50%。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
I don't think it's that bad, but I think the marketing-
我不认为这有那么糟糕，但我认为营销——
Andrew Huberman:
安德鲁·休伯曼：
Okay, they're doing better than we are as a species.
好吧，作为一个物种，他们比我们做得更好。
Dr. Karen Parker:
凯伦·帕克博士：
That's true.
确实如此。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
We should look to them for pointers.
我们应该向他们寻求指点。
Andrew Huberman:
安德鲁·休伯曼：
And all the divorced folks are saying, "Wait, why'd you say better?" I have some divorced friends that have said, "Divorce is like the greatest thing." So we always say like doing better, doing worse, right?
所有离婚的人都在说：“等等，你为什么说更好？”我有一些离婚的朋友说：“离婚是最伟大的事情。”所以我们总是说做得更好，做得更差，对吧？
Anyway, that's a whole other podcast.
不管怎样，那是另一个播客。
And certainly not the Huberman Lab Podcast, or maybe it is, or will be.
当然不是休伯曼实验室播客，或者也许是，或者将会是。
But yeah, my understanding is that you have certain voles that mate almost exclusively with one other vole for their entire lifespan, and then you have other voles located elsewhere, that in those colonies, they mate with lots of different voles.
但是，是的，我的理解是，某些田鼠在其整个一生中几乎只与另一只田鼠交配，然后还有位于其他地方的其他田鼠，在这些群体中，它们与许多不同的田鼠交配。
So the males and females have lots of different partners, raise young with lots of different partners, mating with lots of different partners, and that if you give vasopressin, then you can make the-- I always want to call them polyamorous, but I don't know- ...
所以雄性和雌性有很多不同的伴侣，与很多不同的伴侣一起养育后代，与很多不同的伴侣交配，如果你给予加压素，那么你可以让——我总是想称它们为多角恋，但我不知道——……
if they love each other.
如果他们彼此相爱。
I'm going to answer for more of fives and assume that they love each other.
我会回答更多的五人并假设他们彼此相爱。
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
The polygamous voles, not polyamorous, but polygamous voles then become monogamous.
一夫多妻制的田鼠，不是一夫多妻制的，而是一夫多妻制的田鼠，然后变成了一夫一妻制的。
Dr. Karen Parker:
凯伦·帕克博士：
Well, yeah.
嗯，是的。
I would say that is probably not the take-home message.
我想说这可能不是最重要的信息。
So the take-home message would be they had-- Let's say that there was the good voles, right, which are the prairie voles, and they were the ones that formed these monogamous pair bonds.
因此，带回家的信息是他们拥有——假设有好田鼠，对吧，就是草原田鼠，它们是形成这些一夫一妻制配对关系的田鼠。
Dad participates in paternal care with Mom.
爸爸和妈妈一起参与父亲的照顾。
They co-raise babies together.
他们共同抚养婴儿。
And then Dad chases off intruders, right?
然后爸爸会赶走入侵者，对吗？
And then there's the more asocial voles, and so these are like the montane voles.
然后还有更不合群的田鼠，所以它们就像山地田鼠。
And it's a complicated story, but there's these montane voles where males and females live separately.
这是一个复杂的故事，但这些山地田鼠是雄性和雌性分开生活的。
Females maybe live on the male's territory.
雌性可能生活在雄性的领地上。
The male mates with a few different females.
雄性与几只不同的雌性交配。
Absolutely doesn't provide any paternal care at all.
绝对不提供任何父亲般的照顾。
Mom raises babies by herself, right?
妈妈自己带孩子吧？
So these are really the two models.
所以这确实是两个模型。
Andrew Huberman:
安德鲁·休伯曼：
This is like 1950s versus 2020s.
这就像 20 世纪 50 年代与 2020 年代。
Dr. Karen Parker:
凯伦·帕克博士：
Yes, yes.
是的，是的。
Andrew Huberman:
安德鲁·休伯曼：
To broadly stereotype.
大致定型。
Dr. Karen Parker:
凯伦·帕克博士：
To broadly stereotype.
大致定型。
Okay, so for prairie voles, they're sort of primed to form bonds and the males to be good daddies, if you will.
好吧，对于草原田鼠来说，如果你愿意的话，它们已经准备好建立联系，而雄性则可以成为好爸爸。
And all you have to do is give them a single injection of vasopressin, or you can give an antagonist, and usually the way they form the bond is through mating, right?
你所要做的就是给它们注射一次加压素，或者你可以给它们注射拮抗剂，通常它们形成联系的方式是通过交配，对吗？
So you put them with a female.
所以你把它们和雌性放在一起。
They mate.
他们交配。
They cohabit for a bit.
他们同居了一段时间。
There's been all kinds of parametric studies.
有各种各样的参数研究。
I can't remember how many hours it takes to form a pair bond.
我不记得需要多少个小时才能形成情侣关系。
But then you can do these things called partner preference tests.
但是你可以做一些称为合作伙伴偏好测试的事情。
And then you can say, "Here's the guy that you mated with.
然后你可以说：“这就是和你交配的人。
Here's this guy you don't know." And you can do it for males, and you can do it for females, and they pick their partner, or they choose to go hang out with their partner.
这是一个你不认识的人。”你可以为男性这样做，也可以为女性这样做，他们会选择自己的伴侣，或者选择与伴侣一起出去玩。
The montane voles, either after mating with somebody may either be equal or maybe they'll even go spend time with a new individual.
山地田鼠在与某人交配后可能会变得平等，或者甚至可能会与新个体共度时光。
So the cleanest story was that prairie voles are monogamous.
所以最简单的说法是草原田鼠是一夫一妻制的。
Montane voles are not monogamous.
山地田鼠不是一夫一妻制的。
But in the prairie voles, you could give vasopressin instead of mated cohabitation, and you could turn on a bond with somebody after only living with them for a very short period of time, right?
但在草原田鼠中，你可以给予加压素而不是交配同居，并且你可以在与某人共同生活很短一段时间后与他们建立联系，对吗？
Or you could induce paternal behavior.
或者你可以诱导父亲的行为。
And I was working with a vole species in grad school.
我在研究生院时正在研究一种田鼠。
I think the most interesting scientific experience that I've ever had, right?
我认为这是我经历过的最有趣的科学经历，对吧？
And you and I both know this, right?
你和我都知道这一点，对吗？
When you're young, you're actually the person doing the work, right?
当你年轻的时候，你实际上是做工作的人，对吗？
As you become the head of your lab, you're mostly writing grants and giving talks, right?
当你成为实验室负责人时，你主要负责撰写资助金和发表演讲，对吧？
And then you get to hear about the super cool things that everybody in your lab is doing, right?
然后你就会听到实验室里的每个人都在做的超级酷的事情，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Eventually, the members of your laboratory kick you out of the lab.
最终，你实验室的成员把你踢出了实验室。
Dr. Karen Parker:
凯伦·帕克博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
They literally say like, "Get out of here.
他们的字面意思是：“离开这里。
You're leaving things in the wrong place." Whereas initially, you're telling them, "Hey, that's in the wrong place," within a year or two.
你把东西放在错误的地方了。”而一开始，你会在一两年内告诉他们，“嘿，那是在错误的地方”。
For me, I think it took about four or five years.
对我来说，我想大概花了四五年的时间。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
But by about year six-
但到了大约第六年——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
I was d- Demoted
我被降职了
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
To my office-
到我的办公室-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
to just write grants and write papers.
只是写补助金和写论文。
Dr. Karen Parker:
凯伦·帕克博士：
I was told that one time.
有一次有人告诉我。
I was back there, and I tried to weigh in.
我回到了那里，我试着权衡一下。
I was so excited about what they were working on, and they basically just said, "Go write grants and bring in more money." That was their attitude, like, "We get to be the ones who get to do the cool stuff." So back when I got to actually do the science, I remember I had this species where-- And again, I told you I came at this from an evolutionary perspective.
我对他们正在做的事情感到非常兴奋，他们基本上只是说，“去写赠款并带来更多的钱。”这就是他们的态度，比如“我们要做那些很酷的事情。”所以当我真正开始做科学研究时，我记得我有这个物种——而且，我再次告诉你我是从进化的角度来看待这个问题的。
So these were called meadow voles, and I found them very interesting.
所以这些被称为草地田鼠，我发现它们非常有趣。
So when I showed up in my thesis advisor's lab, I said, "I really want to study oxytocin and vasopressin, and I really want to study voles, and I know you have a vole species." And she said, "Well, I don't have prairie voles.
因此，当我出现在论文导师的实验室时，我说：“我真的很想研究催产素和加压素，我真的很想研究田鼠，而且我知道你们有一种田鼠。”她说：“好吧，我没有草原田鼠。
I have these meadow voles, and I'm studying them because they're so sensitive to light, and they change their behavior based on light." And she said, "Well, you can do what you want, but our grants basically have to have a circadian component." And so she said, "You got to work that in," but then we struck this deal.
我有这些草地田鼠，我正在研究它们，因为它们对光非常敏感，并且它们会根据光改变自己的行为。”她说：“好吧，你可以做你想做的事，但我们的资助基本上必须有昼夜节律组成部分。”所以她说，“你必须解决这个问题”，但后来我们达成了这笔交易。
So I was hanging out in the animal rooms, and I thought it was really fascinating.
所以我在动物房里闲逛，我觉得这真的很有趣。
So she had animals that were either on short day lengths or long day lengths, so they're mimicking summer and winter.
所以她的动物要么是短日照，要么是长日照，所以它们模仿夏天和冬天。
And I was noticing that on winter day lengths, the males were hanging out with the females, and when the female had a litter, he was participating.
我注意到，在冬天的白天，雄性会和雌性一起出去玩，而当雌性生下孩子时，他也会参与其中。
And I was like, "Whoa, these are not supposed to be monogamous animals." And so I went into the field research, and they were doing all these radio telemetry studies, and so if you need-
我当时想，“哇，这些不应该是一夫一妻制的动物。”所以我进入了实地研究，他们正在进行所有这些无线电遥测研究，所以如果你需要-
Andrew Huberman:
安德鲁·休伯曼：
We should probably explain what those are.
我们或许应该解释一下这些是什么。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Putting a little transmitter under the skin.
将一个小发射器放在皮下。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's painless for the animal, but that allows the researcher to monitor the behavior of the animal-
这对动物来说是无痛的，但这使得研究人员能够监测动物的行为——
Dr. Karen Parker:
凯伦·帕克博士：
In the field
在现场
Andrew Huberman:
安德鲁·休伯曼：
...
...
remotely without having to put them in cages and stuff.
远程，而不必将它们放入笼子之类的东西中。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
And so this is under field conditions.
这是在现场条件下进行的。
And voles are everybody's favorite snack, so they have a very limited lifespan in the wild, on the order of months.
田鼠是每个人最喜欢的零食，因此它们在野外的寿命非常有限，只有几个月。
And so if you have a short lifespan, you should just keep reproducing.
因此，如果你的寿命很短，你就应该继续繁殖。
And so what was interesting is, at the end of the summer days as you're going into winter, territories collapse and males are found with females, and they co-raise babies.
有趣的是，在夏季结束时，当你进入冬季时，领地崩溃，雄性与雌性一起被发现，他们共同抚养孩子。
It makes sense.
这是有道理的。
If you're going to have a litter and mom needs to get up to go eat, you need somebody to sit there and warm those babies, or they're going to die because they're going to freeze to death.
如果你要生一窝宝宝，而妈妈需要起床去吃饭，你需要有人坐在那里给这些婴儿取暖，否则他们就会死，因为他们会被冻死。
So I started saying, "Wow, I think these meadow voles are good dads.
所以我开始说：“哇，我认为这些草地田鼠是好爸爸。
I'm noticing this." And so I told my thesis advisor, "I want to study how oxytocin and vasopressin can-- Maybe this is involved in tracking these evolutionary mating strategies." And so again, the coolest experience I ever had was on these males that were housed under short day lengths, so they were winter males.
我注意到了这一点。”所以我告诉我的论文导师，“我想研究催产素和加压素如何——也许这与追踪这些进化交配策略有关。”再说一遍，我经历过的最酷的经历是在这些雄性身上，它们被安置在短日照下，所以它们是冬季雄性。
I was able to put vasopressin directly into their brains, and it was like turning on a light switch.
我能够将加压素直接注入他们的大脑中，就像打开电灯开关一样。
And they ran around the cage, picked up all these babies, put them in a nest, and huddled over them.
它们绕着笼子跑，把所有这些婴儿抱起来，把它们放进窝里，然后挤在它们身上。
And if you put a placebo into their brain, nothing happened.
如果你将安慰剂放入他们的大脑中，什么也不会发生。
And so to me, I always filed that away in the back of my mind of like, "Wow, vasopressin is this really interesting hormone, and maybe someday I will..." I did a postdoc on something else, but it was always in the back of my mind of, "I really want to return to this."
所以对我来说，我总是把它记在心里，“哇，加压素是一种非常有趣的激素，也许有一天我会……”我在其他方面做了博士后，但它总是在我的脑海深处，“我真的很想回到这个领域。”
Andrew Huberman:
安德鲁·休伯曼：
It's so incredible that an eight amino acid long peptide could basically turn these relatively negligent fathers into very attentive fathers.
令人难以置信的是，一个八个氨基酸长的肽基本上可以将这些相对疏忽的父亲变成非常细心的父亲。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Yeah, it was fascinating.
是的，这很有趣。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
It just speaks to the power of the peptide, vasopressin.
它只是说明了肽——加压素的力量。
It also speaks to the power of brain circuitry.
它还说明了大脑回路的力量。
It also speaks to the idea that brain circuitry is often sitting latent in the background-
它还说明了大脑电路经常隐藏在后台的想法——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
ready to be activated, that it's not just about neuroplasticity and building up a new circuit, that some forms of neuroplasticity are about unveiling what's-
准备好被激活，这不仅仅是神经可塑性和建立新的回路，某些形式的神经可塑性是为了揭示什么——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
already there.
已经在那里了。
Dr. Karen Parker:
凯伦·帕克博士：
Absolutely.
绝对的。
Andrew Huberman:
安德鲁·休伯曼：
And that peptides can act like switches.
肽可以像开关一样发挥作用。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Which makes sense on the one hand, but I've never heard of a result as dramatic as that.
一方面这是有道理的，但我从未听说过如此戏剧性的结果。
So I'm presuming you're going to tell us that that then led you to go back to vasopressin and explore its ability to induce good parenting in negligent fathers?
所以我猜你会告诉我们，这导致你回到加压素并探索它对疏忽的父亲产生良好养育作用的能力？
No.
不。
Dr. Karen Parker:
凯伦·帕克博士：
I haven't studied that yet.
我还没有研究过。
No. Well, so I think that my mom always says, "Chance favors the prepared mind." And so I was doing my postdoc at Stanford, and I got recruited to stay on the faculty.
不，嗯，所以我认为我妈妈总是说，“机会青睐有准备的头脑。”所以我在斯坦福大学做博士后，并被录用继续担任教职。
And I had been doing work in stress vulnerability and stress resilience, and I love doing that work.
我一直在从事压力脆弱性和压力恢复方面的工作，我喜欢做这项工作。
But I still felt this tug of, I had spent all this time in a psychiatry department where I was surrounded by clinicians, and I realized that a lot of the stuff that I was doing had clinical relevance.
但我仍然感受到这种拉力，我一直在精神病科度过，周围都是临床医生，我意识到我所做的很多事情都与临床相关。
And so sometimes you meet the moment.
所以有时你会遇到那个时刻。
And so right as I was transitioning to have my own lab in my department, there was a bunch of stuff going on.
当我过渡到在我的部门拥有自己的实验室时，发生了很多事情。
So there were a lot of very dedicated parents who were lobbying for funding for autism research because it was horrifically underfunded.
因此，有很多非常热心的家长正在游说为自闭症研究提供资金，因为该研究的资金严重不足。
Andrew Huberman:
安德鲁·休伯曼：
Really?
真的吗？
Dr. Karen Parker:
凯伦·帕克博士：
Horrifically underfunded.
资金严重不足。
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
At rates of 1 in 36 kids.
每 36 名儿童中就有 1 人患有此病。
Dr. Karen Parker:
凯伦·帕克博士：
Well, not at the time.
嗯，当时还没有。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Karen Parker:
凯伦·帕克博士：
So it was 1 in 150 or whatever it was back then.
所以当时的比例是 150 分之一或者其他什么。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Dr. Karen Parker:
凯伦·帕克博士：
But there were all these parents, and again, they're heroes in my eyes, that they advocated so much for their loved ones.
但还有所有这些父母，他们在我眼中都是英雄，他们为自己所爱的人提供了如此多的支持。
And so they started forming parent grassroots organizations that have culminated.
于是他们开始组建家长草根组织，并最终达到顶峰。
They all started joining together, which is now Autism Speaks.
他们开始联合起来，这就是现在的“自闭症之声”。
And then there was a man named Jim Simons, who runs one of the most successful hedge funds in the world, and he decided, "Wow, let's put money into autism." And so there was-
然后有一个名叫吉姆·西蒙斯（Jim Simons）的人，他经营着世界上最成功的对冲基金之一，他决定，“哇，让我们把钱投入到自闭症治疗上。”于是就有了——
Andrew Huberman:
安德鲁·休伯曼：
Does he have a personal link to autism?
他与自闭症有个人联系吗？
Dr. Karen Parker:
凯伦·帕克博士：
You'd have to ask him.
你得问他。
Andrew Huberman:
安德鲁·休伯曼：
Because oftentimes, not always, but oftentimes when you hear about wealthy donors-
因为很多时候，并非总是，但很多时候，当你听说富有的捐赠者时——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
devoting a lot of money to one area of science, there's a familial thing there.
为某一科学领域投入大量资金，这是一种家族性的事情。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That a member of their family or a close friend has this challenge, and they really want to see that challenge-
他们的家人或亲密朋友面临这个挑战，并且他们真的很想看到这个挑战 -
Dr. Karen Parker:
凯伦·帕克博士：
Absolutely
绝对
Andrew Huberman:
安德鲁·休伯曼：
...
...
overcome.
克服。
Dr. Karen Parker:
凯伦·帕克博士：
A lot of money I've gotten for my lab from philanthropists, and what I will say is the most impactful work I've ever done is through philanthropy, right?
我的实验室从慈善家那里得到了很多钱，我想说的是，我做过的最有影响力的工作就是通过慈善事业，对吗？
They're crazy ideas that no funding agency ever touches.
这些都是疯狂的想法，没有资助机构触及过。
But yeah, so they both put a lot-- There was a lot of emphasis.
但是，是的，所以他们都付出了很多——有很多强调。
And so because the Simons Foundation started issuing requests for applications, there was a group at Stanford that formed, and it was a clinician with a basic scientist.
因此，由于西蒙斯基金会开始发出申请请求，斯坦福大学成立了一个小组，其中包括一名临床医生和一名基础科学家。
And my chair at the time said, "Well, almost nothing is known about the biological basis of autism.
当时我的主席说：“嗯，人们对自闭症的生物学基础几乎一无所知。
Why don't you go-- I'm going to introduce you to the head of child psychiatry.
你为什么不去——我要向你介绍儿童精神病学的负责人。
You should go talk to this group." And so as I was preparing my slides and realizing that social interaction impairments were a core feature of autism, I thought, wow, these neuropeptides may really be a part of this puzzle.
你应该去和这个小组谈谈。”因此，当我准备幻灯片并意识到社交互动障碍是自闭症的核心特征时，我想，哇，这些神经肽可能真的是这个难题的一部分。
And so that's actually really how I got pulled into autism research was through that.
这实际上就是我进入自闭症研究的原因。
Everybody at the time was very interested in oxytocin.
当时每个人都对催产素非常感兴趣。
And I remember thinking, so we actually did probably the most definitive blood oxytocin study because there was this idea, again, this marketing campaign of the oxytocin deficit hypothesis of autism.
我记得当时想，所以我们实际上做了可能是最明确的血液催产素研究，因为有这个想法，再次，这是自闭症催产素缺乏假说的营销活动。
And given how clinically heterogeneous autism was, we got money actually from the Simons Foundation, and we did the first study with maybe 200 kids.
考虑到自闭症在临床上的异质性，我们实际上从西蒙斯基金会获得了资金，并且我们对大约 200 名孩子进行了第一项研究。
And what we were able to show was that blood oxytocin was not a marker of autism, right?
我们能够证明的是，血液催产素并不是自闭症的标志，对吧？
So it wasn't like there was a bimodal distribution, meaning two completely non-overlapping levels of oxytocin in people with autism, people without autism.
因此，这并不像是双峰分布，即自闭症患者和非自闭症患者的催产素水平完全不重叠。
So the lower your blood oxytocin levels, actually regardless of who you were, you could be a child with autism, you could be an unaffected sibling with autism, or you could be a unrelated control child, and it was the lower your blood oxytocin levels, the greater your sort of social difficulties.
因此，你的血液催产素水平越低，实际上无论你是谁，你都可能是一个患有自闭症的孩子，你可能是一个未受影响的自闭症兄弟姐妹，或者你可能是一个不相关的对照孩子，而且你的血液催产素水平越低，你的社交困难就越大。
And the slopes were different.
而且坡度也不同。
They started at different points because the behaviors were obviously different.
他们从不同的点开始，因为行为明显不同。
But that's what got us thinking about our clinical trial, which is that blood oxytocin level is not going to be this great differentiator between people with and without autism, right?
但这就是让我们思考我们的临床试验的原因，即血液催产素水平不会成为自闭症患者和非自闭症患者之间的巨大区别，对吗？
But we might be able to find a subgroup who could benefit from treatment.
但我们也许能够找到一个可以从治疗中受益的亚组。
Andrew Huberman:
安德鲁·休伯曼：
But what I like so much about your approach, the way you described it, is that it sets aside, we don't want to say discards, but it sets aside this thing that we call autism-
但我非常喜欢你的方法，你描述它的方式，是它搁置了，我们不想说丢弃，但它搁置了我们称之为自闭症的东西 -
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which is already hard to define and diagnose, and there's all these different spectrums, and you're trying to-- and just says, okay, children with autism have challenges in social cognition, social behavior, social bonding.
这已经很难定义和诊断，而且有所有这些不同的范围，你试图 - 只是说，好吧，自闭症儿童在社会认知、社会行为、社会联系方面面临挑战。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So do adults with autism, for that matter.
就此而言，患有自闭症的成年人也是如此。
Let's just focus on that-
我们只关注这一点——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and not worry so much about whether or not somebody is diagnosed as autistic or not, and just focus on what are some of the potential neuropeptide deficits or overexpression of neuropeptides that may in some way relate to those social challenges.
不要太担心某人是否被诊断为自闭症，而只需关注哪些潜在的神经肽缺陷或神经肽过度表达可能在某种程度上与这些社会挑战相关。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And then one can circle back to the question about autism in collecting those data.
然后，在收集这些数据时，我们可以回到关于自闭症的问题。
But it also points to this idea that when we go after a disease, like Alzheimer's, we can often miss the possibility that Alzheimer's, while it has deficits in cognition and memory, could also be a bunch of other things, like a metabolic disorder of the body.
但这也指出了这样一个观点，即当我们追寻一种疾病，比如阿尔茨海默氏症时，我们常常会忽略这样一种可能性：阿尔茨海默氏症虽然存在认知和记忆缺陷，但也可能是其他一些疾病，比如身体的代谢紊乱。
And so maybe you go after a particular symptomology-
所以也许你会追求一种特定的症状——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and try and attack that, and you might actually potentially treat or cure multiple diseases.
并尝试解决这个问题，你实际上可能会治疗或治愈多种疾病。
It's a very different approach, and I hope people are catching on to the subtlety, but also the potential impact of that.
这是一种非常不同的方法，我希望人们能够理解其中的微妙之处，以及它的潜在影响。
Because if I heard correctly, you said there are people who are not autistic who have social functioning deficits, and they too have less circulating oxytocin.
因为如果我没听错的话，你说有些人不是自闭症患者，但他们有社会功能缺陷，而且他们的催产素循环也较少。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So I would say we haven't studied people where we brought them in and characterized it, right?
所以我想说，我们还没有研究过我们引入的人并对其进行表征，对吗？
So these are typically developing kids, but what we did is in the abilities that are typical of a control child, we still saw that gradient, right?
所以这些都是典型的发育中的孩子，但我们所做的是控制儿童的典型能力，我们仍然看到了这种梯度，对吗？
And so I think it just sort of begs the question about what is oxytocin's role in human sociality, right?
所以我认为这只是回避了一个问题：催产素在人类社会中的作用是什么，对吗？
I think there's just so much that we don't understand about both of these molecules in terms of their disease liability if they're low or their healing potential if we are able to use them as modulators of other therapies.
我认为，我们对这两种分子的疾病责任性（如果它们较低）或治愈潜力（如果我们能够将它们用作其他疗法的调节剂）的了解太多了。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
So how did you move from oxytocin to vasopressin?
那么，您是如何从催产素转向加压素的呢？
You mentioned that everyone was all excited about oxytocin.
你提到每个人都对催产素感到兴奋。
Still the one that we hear the most about.
仍然是我们听到最多的一个。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Although after this podcast episode and when I start blabbing about vasopressin to everybody, maybe that'll change, but I think it's going to take a lot more than that.
尽管在这期播客之后，当我开始向每个人谈论加压素时，也许这种情况会改变，但我认为这需要的不仅仅是这些。
But maybe it's because the name isn't as-- There's something about oxytocin that kind of sounds like the love, looks like the love hormone.
但也许是因为这个名字并不像——催产素听起来像爱情，看起来像爱情荷尔蒙。
But vasopressin should be renamed.
但加压素应该重新命名。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Well, and also-
嗯，还有——
Andrew Huberman:
安德鲁·休伯曼：
It should be called something else.
它应该被称为别的东西。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Like not antidiuretic hormone, not vasopressin.
就像不是抗利尿激素，不是加压素。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
You're going to tell us how critically important it is, perhaps even more important than oxytocin, for autism and social functioning.
您将告诉我们它对于自闭症和社会功能有多么重要，甚至可能比催产素更重要。
So I don't know.
所以我不知道。
By the end of this podcast, we'll come up with a new name.
在本播客结束时，我们将想出一个新名称。
Dr. Karen Parker:
凯伦·帕克博士：
It's needed, right?
是需要的吧？
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Well, I'll put it out there.
好吧，我会把它放在那里。
Okay.
好的。
So how did you get to vasopressin?
那么您是如何获得加压素的呢？
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
So it was interesting with oxytocin because we didn't-- And again, I was skeptical that we would see these big group differences.
因此，催产素很有趣，因为我们没有——而且，我再次怀疑我们是否会看到这些巨大的群体差异。
But it was a little bit of like, okay, what everyone's saying, this is not going to be the big solution, right?
但这有点像，好吧，正如每个人所说，这不会是一个大的解决方案，对吧？
And so I actually came at it from the work that we did in monkeys.
所以我实际上是从我们在猴子身上所做的工作中得出这个结论的。
And so I think I mentioned previously at the beginning of the podcast that there were a lot of limitations that I saw.
因此，我想我之前在播客开头提到过，我看到了很多限制。
And then sometimes if you come into a field when you're a little bit of an outsider, right?
有时，当你进入一个领域时，你有点像个局外人，对吗？
I'm not a clinician, I don't see autism patients, but I also have this really strong interest in social behavior and the biology of it.
我不是临床医生，我不看自闭症患者，但我对社会行为及其生物学也有浓厚的兴趣。
And so I was thinking about what are things that we need to do to better address the challenges in autism?
所以我在想我们需要做哪些事情来更好地应对自闭症的挑战？
So one of them was, why are we looking in blood, right?
其中之一就是，我们为什么要寻找血液，对吗？
If you look at neurological conditions, there has been a lot of progress made by doing biomarker discovery in cerebral spinal fluid, right?
如果你观察神经系统疾病，就会发现在脑脊液中进行生物标志物发现已经取得了很多进展，对吧？
So the biological substrates or clues of markers of, say, various forms of dementia or MS were first found in spinal fluid, right?
那么，各种形式的痴呆症或多发性硬化症的生物底物或标记线索首先是在脊髓液中发现的，对吗？
Because it's the fluid that bathes the brain and the spinal column.
因为它是沐浴大脑和脊柱的液体。
And so if you're looking for the biochemistry of an illness, that's the closest fluid that you can get to the brain, right?
因此，如果您正在寻找某种疾病的生化特征，那是您可以到达大脑的最接近的液体，对吧？
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
A blood draw just won't do it
抽血是不行的
Dr. Karen Parker:
凯伦·帕克博士：
...
...
maybe, right?
也许吧？
So that was part of my thinking.
这就是我想法的一部分。
But then there was the issue of the animal models, right?
但接下来还有动物模型的问题，对吗？
So there was drug after drug after drug that was tested in mice, and they failed in human clinical trials.
因此，有一种又一种药物在小鼠身上进行了测试，但在人体临床试验中却失败了。
And so it made me start thinking, could we develop a primate model of naturally occurring social impairments, right?
所以这让我开始思考，我们是否可以开发出自然发生的社交障碍的灵长类动物模型，对吗？
Because in autism, these social impairments are, if you will, naturally occurring, right?
因为对于自闭症患者来说，如果你愿意的话，这些社交障碍是自然发生的，对吗？
And so these spontaneously occur in children.
因此，这些现象会自发地发生在儿童身上。
And so it made me wonder, could we identify monkeys in a large colony that have social impairments in-- And after talking to clinicians who treat these children, can I spend a lot of time validating a monkey model where there will be monkeys that have features that look like they have direct relevance to core autism symptoms?
所以这让我想知道，我们能否在一个大群体中识别出有社交障碍的猴子——在与治疗这些儿童的临床医生交谈后，我是否可以花大量时间验证猴子模型，其中会有一些猴子具有看起来与核心自闭症症状直接相关的特征？
And so what I did was, there's a primate center, the California National Primate Research Center, and so what we did is, so I think I mentioned earlier that there's these surveys that can be used to look at autistic traits in the general human population, right?
所以我所做的是，有一个灵长类动物中心，加州国家灵长类动物研究中心，所以我们所做的是，所以我想我之前提到过，这些调查可以用来观察一般人群的自闭症特征，对吗？
And so we refined one of these, and we did what we call back translate.
因此，我们改进了其中一项，并进行了所谓的“回译”。
So basically, it's an instrument that's used for humans, and then what we did is modified it to be able to use this rating scale in rhesus macaques, which are an Old World monkey, and I know you're familiar with them.
所以基本上，它是一种用于人类的仪器，然后我们所做的就是对其进行修改，以便能够在恒河猴（一种旧世界的猴子）中使用这个评级量表，我知道你对它们很熟悉。
And I was interested in looking at Old World monkeys because they're some of the closest relatives to human that are used in biomedical research.
我对观察旧大陆的猴子很感兴趣，因为它们是生物医学研究中与人类关系最近的猴子之一。
And as I mentioned previously, these autistic traits are continuously distributed across the general human population, and that this genetic, say, let's call it genetic liability, which is a fancy way of just saying that we think that there's a genetic risk that underlies this continuum of behavioral traits, right?
正如我之前提到的，这些自闭症特征持续分布在整个人类群体中，这种遗传，比如说，我们称之为遗传责任，这是一种奇特的方式，只是说我们认为这种行为特征的连续性背后存在遗传风险，对吗？
So if we think that that's true in humans and in one of our closest relatives, and we think that some of these genes create proteins that then are what sets up the developing brain to develop in the way that autistic brains develop, so let's just assume that that's the premise.
因此，如果我们认为这对于人类和我们的近亲来说是正确的，并且我们认为其中一些基因会产生蛋白质，那么这些蛋白质就会使正在发育的大脑以自闭症大脑的方式发育，那么我们就假设这就是前提。
That's what we went in with.
我们就是这样进去的。
Can we find rhesus macaques that are just living in large outdoor colonies and identify animals that might be good models for autism?
我们能否找到生活在大型户外群体中的恒河猴，并识别出可能成为自闭症良好模型的动物？
And the answer is yes.
答案是肯定的。
We could do this all kinds of different ways.
我们可以通过各种不同的方式来做到这一点。
One is we could just take people and score monkey behaviors outside their cages while they're interacting with their peers.
一是我们可以带人们对笼子外的猴子与同伴互动时的行为进行评分。
We can use rating scales, and again, the rating scale we used, it's called the Social Responsiveness Scale.
我们可以使用评级量表，我们使用的评级量表称为社会响应量表。
So this is called the Macaque Social Responsiveness Scale, revised.
所以这被称为猕猴社会反应量表，修订版。
It's a mouthful.
真是一口。
But what it allows us to do is measure autistic-like traits in monkeys.
但它让我们能够测量猴子的自闭症样特征。
And we can also bring monkeys in for experimental tests to see where their eyes look, or how do they perform, how do they respond to videos of other monkeys, if they're making affiliative overtures, do they do macaques go which is a-
我们还可以让猴子进行实验测试，看看它们的眼睛看向哪里，或者它们表现如何，它们对其他猴子的视频有何反应，如果它们做出亲和的举动，它们会做猕猴走吗？
Andrew Huberman:
安德鲁·休伯曼：
Yeah
是啊
Dr. Karen Parker:
凯伦·帕克博士：
...
...
a positive response.
积极回应。
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah.
哦，是的。
Dr. Karen Parker:
凯伦·帕克博士：
Well, they do that, right?
嗯，他们就是这么做的，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Well, I'm going to apologize for interrupting you again, but I just have to tell people this because I spent time up at the UC Davis Primate Center-
好吧，我要为再次打扰你而道歉，但我必须告诉人们这一点，因为我在加州大学戴维斯分校灵长类动物中心度过了时间-
Dr. Karen Parker:
凯伦·帕克博士：
Oh, yeah
哦，是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
as a graduate student.
作为一名研究生。
And by the way, what we're referring to here are non-invasive observational studies-
顺便说一下，我们这里指的是非侵入性观察研究——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at least thus far.
至少到目前为止。
So these are monkeys living in large exclosures
这些是生活在大围场中的猴子
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
not enclosures, large exclosures, forming colonies and social relationships.
不是圈地、大围场、形成群体和社会关系。
And I think anyone that sees monkeys at the zoo, and we all learn that monkeys go and they don't .
我想任何在动物园看到猴子的人都会知道猴子会去而它们不会。
If you want a monkey to like you, you learn this working with macaques.
如果你想让猴子喜欢你，你可以通过与猕猴一起学习这一点。
First of all, they don't .
首先，他们不这样做。
The affiliative call is a .
附属调用是 .
They do this really nice, and the little ones, the babies-
他们做得非常好，小孩子们、婴儿们——
Dr. Karen Parker:
凯伦·帕克博士：
You do that very well.
你做得很好。
Andrew Huberman:
安德鲁·休伯曼：
I spent a lot of time with these monkeys, and the little ones, they do this thing where they go-- I used to nurse the little ones every once in a while, and they go .
我花了很多时间和这些猴子以及小猴子们在一起，他们走到哪里都会做这种事——我以前每隔一段时间就照顾一下这些小猴子，然后他们就走了。
And it just makes your heart melt.
它只会让你的心融化。
I think there must've been an oxytocin dump at that moment- ...
我想那一刻一定有催产素倾倒——......
that's probably happening right now.
这可能正在发生。
But if you want the monkeys to like you, you have to give an affiliative facial gesture-
但如果你想让猴子喜欢你，你就必须做出亲和的面部表情——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
which is not a smile.
这不是微笑。
That's actually an aggressive gesture.
这实际上是一种攻击性的姿态。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So as Karen, Dr. Parker, just showed you-
正如凯伦·帕克博士刚刚向您展示的那样——
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
it's lip smacking.
这是咂嘴。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Which is .
这是 .
Dr. Karen Parker:
凯伦·帕克博士：
Yep.
是的。
Andrew Huberman:
安德鲁·休伯曼：
So if you see a monkey at the zoo and you want it to pay attention to you, you're going to have to lip smack.
因此，如果你在动物园看到一只猴子并且希望它注意到你，你就必须咂嘴。
And if it doesn't, either you're not doing it right, or it just doesn't like you.
如果没有，要么是你做得不对，要么是它不喜欢你。
Dr. Karen Parker:
凯伦·帕克博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Great.
伟大的。
All right, thanks.
好的，谢谢。
Now we'll go back to the study of or the establishment of this really key experiment.
现在我们将回到这个非常关键的实验的研究或建立上。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So then what we did is we identified these animals, and we spent a lot of time.
然后我们所做的就是识别这些动物，我们花了很多时间。
So one of the things that I do as one of my areas of expertise is validating animal models.
因此，作为我的专业领域之一，我所做的事情之一就是验证动物模型。
So like I mentioned, a lot of reason why pe- ...
就像我提到的，有很多原因为什么...
experiments fail is people will take an animal off the shelf and say, "Oh, I'm going to do this." But if you're studying a disorder that's characterized by visual issues, is it the best thing to do in a nocturnal species that has olfaction as its primary sensory modality?
实验失败的原因是人们将动物从架子上拿下来并说：“哦，我要做这个。”但是，如果您正在研究一种以视觉问题为特征的疾病，那么对于以嗅觉作为主要感觉方式的夜行性物种来说，这是最好的做法吗？
Or is it-
或者是——
Andrew Huberman:
安德鲁·休伯曼：
You're referring to mice.
你指的是老鼠。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
Or is it better-- And again, I will say all models have value.
还是更好——我再说一遍，所有模型都有价值。
There's reasons.
这是有原因的。
You basically have to stand by what you're modeling.
基本上你必须坚持你所建模的内容。
And so I think one of the biggest issues I have with this sort of mouse phenotyping mafia is that there's this group of tests that they use, and they use it in every single disorder, right?
所以我认为我对这种小鼠表型黑手党最大的问题之一是他们使用了这组测试，并且他们在每种疾病中都使用它，对吗？
And then if there's a positive hit, it's like, oh, this test is really for Parkinson's today, but it's for depression tomorrow.
然后，如果有积极的结果，就像，哦，这个测试今天确实是针对帕金森氏症，但明天是针对抑郁症。
And so my goal was to devise very specific tests that would allow us to evaluate core features of autism in this model.
因此，我的目标是设计非常具体的测试，使我们能够评估该模型中自闭症的核心特征。
And the answer is we found it, right?
答案是我们找到了，对吧？
So if you look at monkeys that spend a lot of time alone, they have a much greater burden of autistic-like traits measuring on this rating scale.
因此，如果你观察那些花大量时间独处的猴子，按照这个评分标准衡量，它们的自闭症样特征负担要大得多。
They have diminished social motivations, so other monkeys will come up and interact with them, but they don't engage in social overtures that much themselves.
它们的社交动机减弱，因此其他猴子会出现并与它们互动，但它们自己不会进行太多的社交示好。
They do less grooming, less affiliative behaviors.
他们更少梳理毛发，更少亲和行为。
In some of the work that we're doing, they don't lip smack back.
在我们正在做的一些工作中，他们不会回嘴。
And we can talk a little bit about that.
我们可以谈谈这个。
We did a pharmacological probe, and we can talk a bit about what vasopressin does to that, which is kind of exciting.
我们做了一个药理学探索，我们可以谈谈加压素对此的作用，这有点令人兴奋。
And so we spent a lot of time validating this behavioral phenotype, to say that we really feel like there are core aspects of it that are allowing us to model autism.
因此，我们花了很多时间来验证这种行为表型，说我们确实觉得它的核心方面可以让我们模拟自闭症。
And I have a paper, which if you want to put it in, it's all about creating this monkey model and the power of doing it and where it took us clinically.
我有一篇论文，如果你想把它放进去的话，它都是关于创建这个猴子模型以及这样做的力量以及它在临床上对我们的影响。
Andrew Huberman:
安德鲁·休伯曼：
We'll provide a link to that in the show note captions.
我们将在节目注释标题中提供指向该链接的链接。
I also just want to throw up my vote for the fact that you did this work, because, again, I don't disparage mouse model work, but we've just seen over and over again the incredibly small fraction of mouse models that lead to valid therapeutics in humans, and that there's just a lot of differences between primate brains and rodent brains.
我也只是想投票支持你所做的这项工作，因为我并没有贬低小鼠模型的工作，但我们只是一遍又一遍地看到，在人类中产生有效治疗的小鼠模型中的一小部分令人难以置信，而且灵长类动物的大脑和啮齿类动物的大脑之间存在很多差异。
And we have a very elaborate frontal cortex, a bunch of other circuitry that mice, if they have that, they probably use it for other things.
我们有一个非常复杂的额叶皮层，还有一堆其他的电路，如果它们有的话，它们可能会用它来做其他事情。
And it's just very hard to draw conclusions from those models.
很难从这些模型中得出结论。
And they're great for probing functions that are, let's just call them more autonomic-type functions, and for doing some of the initial investigations.
它们非常适合探测功能（我们将其称为更多自主类型功能），以及进行一些初步调查。
But I think while I don't want to see every research lab switch over to primates, I think one has to be really thoughtful about the kinds of experiments one does with primates at all.
但我认为，虽然我不想看到每个研究实验室都转向灵长类动物，但我认为人们必须认真考虑用灵长类动物进行的实验类型。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
This sort of behavioral assessment and the identification of a primate model for autism seems like a very good use-
这种行为评估和自闭症灵长类动物模型的识别似乎是一个非常好的用途——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
of human resources.
人力资源。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
Well, and the other thing I will say is that there were medications that were only tested in rodents that when they were tested in people, had really negative consequences.
好吧，我要说的另一件事是，有些药物只在啮齿类动物身上进行过测试，而当它们在人类身上进行测试时，却产生了真正的负面后果。
I can give you two examples.
我可以给你举两个例子。
So one is thalidomide, which was a morning sickness medication that was given to women that were pregnant.
其中一个是沙利度胺，这是一种给怀孕妇女服用的孕吐药物。
And the safety testing and toxicity testing was done only in mice.
并且安全性测试和毒性测试仅在小鼠中进行。
Andrew Huberman:
安德鲁·休伯曼：
I didn't know that.
我不知道。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
And that's why it went on the market.
这就是它上市的原因。
It went on the market in Europe, and there were all these children born with profound limb abnormalities.
它在欧洲上市，所有这些孩子出生时都患有严重的肢体畸形。
When they went back and tested the drug in marmosets, neither rhesus monkeys or cynomolgus monkeys and Old World monkey, they had the limb abnormalities.
当他们回去在狨猴身上测试这种药物时，无论是恒河猴、食蟹猴还是旧大陆猴，都出现了肢体异常。
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
So all they had to do-- And again, I as an animal lover treat the life of a single monkey or a single mouse for that matter, an individual monkey, excuse me, or individual mouse for that matter, as critical.
所以他们所要做的就是——再说一次，我作为一个动物爱好者，对待一只猴子或一只老鼠的生命，对不起，一只猴子或一只老鼠的生命是至关重要的。
I am a speciesist.
我是一个物种歧视者。
I do think there's a difference between their life and our lives when it comes to what study one does.
我确实认为，在学习方面，他们的生活和我们的生活是有区别的。
But just the idea that these severe developmental defects in humans could have been avoided by doing an experiment, perhaps even on one-
但只是认为人类这些严重的发育缺陷可以通过做实验来避免，甚至可能是一个实验——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
marmoset.
狨猴。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And again, I feel for the life of, discomfort of that marmoset, but the idea that that could have saved so many human lives-
再一次，我为那只狨猴的生命感到难过，但想到这可以拯救这么多人的生命——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is just striking.
真是引人注目。
Dr. Karen Parker:
凯伦·帕克博士：
Well, and there was also that street drug MPTP-
嗯，还有街头毒品 MPTP——
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah
哦，是的
Dr. Karen Parker:
凯伦·帕克博士：
...
...
that was a synthetic heroin that causes overnight Parkinsonism, when I think the dopamine cells were just ablated.
那是一种合成海洛因，会导致夜间帕金森症，当时我认为多巴胺细胞刚刚被消融。
But when you went and looked in mice, MPTP didn't have those effects.
但当你去观察老鼠时，你会发现 MPTP 并没有这些效果。
It was only in humans and other primates.
它只存在于人类和其他灵长类动物中。
And I agree with you.
我同意你的观点。
I am an animal lover.
我是一个动物爱好者。
I think that we have to be very careful whenever we do any animal experiments.
我认为我们在做任何动物实验时都必须非常小心。
And so you really need to have a good justification, I think, for any science that's done.
因此，我认为，对于任何已完成的科学研究，你确实需要有一个充分的理由。
I will say that upfront.
我会提前说这一点。
And we have this new generation of stem cell and organoid work, which I think is going to allow us to make all kinds of disease progress.
我们拥有新一代的干细胞和类器官工作，我认为这将使我们能够在各种疾病方面取得进展。
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Without having to study whole animal models
无需研究整个动物模型
Dr. Karen Parker:
凯伦·帕克博士：
Or in complementary, right?
或者是互补的，对吧？
But, again, I think we need to pick the model based on the question we're asking.
但是，我再次认为我们需要根据我们提出的问题来选择模型。
And so if you want to have a medication that's safe and well-tolerated in people or effective, and you want to move the needle on complex social cognition, you want to be testing it in a species that also has complex social cognition.
因此，如果你想要一种对人类安全、耐受性良好或有效的药物，并且你想在复杂的社会认知方面取得进展，你需要在同样具有复杂社会认知的物种中进行测试。
Andrew Huberman:
安德鲁·休伯曼：
Look at the Netflix show, "Chimp Empire."
看看 Netflix 的节目《黑猩猩帝国》。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
If people haven't seen it, they should watch it.
如果人们还没有看过，他们应该看一下。
When you watch it, you realize they're very much like us.
当你观看时，你会发现他们非常像我们。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And dare I say, we're very much like them.
我敢说，我们非常像他们。
Dr. Karen Parker:
凯伦·帕克博士：
Oh, yeah.
哦，是的。
Andrew Huberman:
安德鲁·休伯曼：
It's far and away different than watching a bunch of mice.
这与观察一群老鼠有很大不同。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I'm not being disparaging of mice.
我并不是在贬低老鼠。
I'm assuming that mice also have complex social cognition, voles also have complex social cognition, but it's of the mouse, vole type, and we don't know really even what to look for.
我假设老鼠也有复杂的社会认知，田鼠也有复杂的社会认知，但它是老鼠、田鼠类型的，我们甚至不知道要寻找什么。
But with primates, there's affiliative gaze, there's affiliative grooming, there's ostracization of individuals in a troop.
但对于灵长类动物来说，有亲和的目光，有亲和的梳理，有对群体中个体的排斥。
There's banding to- Taking care of other babies.
有责任——照顾其他婴儿。
There's all sorts of interesting dynamics that map so clearly onto human behavior-
有各种有趣的动态可以清晰地映射到人类行为——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and vice versa.
反之亦然。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So you established this colony up at Davis, at the Regional Primate Center-
所以你在戴维斯地区灵长类动物中心建立了这个殖民地-
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
where you identified some monkeys that we don't know if they have autism, but you could see that they were less socially affiliative.
您发现了一些猴子，我们不知道它们是否患有自闭症，但您可以看到它们的社会归属感较低。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
And I would never say they have autism.
我永远不会说他们患有自闭症。
I will say that upfront.
我会提前说这一点。
They have features that resemble human autism and that allow us to model this.
它们具有类似于人类自闭症的特征，这使我们能够对此进行建模。
So, we started studying those animals, and what we wanted to do was do some biomarker discovery.
因此，我们开始研究这些动物，我们想做的是发现一些生物标志物。
So what we wanted to ask was, are there any molecules that allow us to differentiate these, what we'll call them naturally low-social or low social monkeys, from socially competent high social monkeys?
所以我们想问的是，是否有任何分子可以让我们区分这些（我们称之为天生低社交或低社交猴子）和具有社交能力的高社交猴子？
And so we measured a bunch of different readouts of neurotransmitter systems that were either involved in mammalian social behavior, had been implicated in idiopathic, meaning autism that doesn't have a genetic cause, or these neurogenetic syndromes that we've been talking about, where there's pathways that are really associated with them.
因此，我们测量了一系列不同的神经递质系统读数，这些神经递质系统要么与哺乳动物的社会行为有关，要么与特发性自闭症有关，即没有遗传原因的自闭症，或者我们一直在谈论的这些神经遗传综合症，其中存在与它们真正相关的途径。
And so if we measured a bunch of these systems with 93% accuracy without even knowing who the monkey was, if they were low or high social, we could just put them in the low social or high social bucket.
因此，如果我们以 93% 的准确度测量一堆这样的系统，甚至不知道猴子是谁，如果它们是低社交性或高社交性，我们就可以将它们放入低社交性或高社交性类别中。
Andrew Huberman:
安德鲁·休伯曼：
And was this by blood draw or cerebral spinal fluid?
这是抽血还是脑脊液？
Dr. Karen Parker:
凯伦·帕克博士：
It was everything.
这就是一切。
We did blood, we did CSF, and we put all these measures into the hopper.
我们做了血液，我们做了脑脊液，我们将所有这些措施放入料斗中。
We did a discriminate statistical analysis, which was like a machine learning algorithm where we just said, "Here's all this information.
我们进行了区分统计分析，就像机器学习算法一样，我们只是说：“这是所有这些信息。
Help me classify if this individual is high or low social."
帮我判断这个人的社交程度是高还是低。”
Andrew Huberman:
安德鲁·休伯曼：
Cerebrospinal fluid is collected by spinal tap, correct?
脑脊液是通过脊椎穿刺收集的，对吗？
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
And my understanding, I've never had one, but that spinal tap is, of course, more invasive than a blood draw.
据我了解，我从来没有做过，但是脊椎穿刺当然比抽血更具侵入性。
But it still is done as an outpatient thing in humans.
但对于人类来说，这仍然是一种门诊治疗。
You can go in, get a needle inserted into the lower spine by an expert.
您可以进去，让专家将一根针插入下脊柱。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
They're going to draw cerebral spinal fluid.
他们要抽取脑脊液。
Not that much more invasive and time-consuming than getting a needle into your vein for a blood draw, right?
并不比将针插入静脉抽血更具侵入性和耗时，对吗？
We think of it as it's technically a little bit more challenging.
我们认为它在技术上更具挑战性。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But there's CSF draws in humans all the time.
但脑脊液一直对人类具有吸引力。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So in theory, this could map to a human study.
因此从理论上讲，这可以映射到人类研究。
Dr. Karen Parker:
凯伦·帕克博士：
And it did-
它确实——
Andrew Huberman:
安德鲁·休伯曼：
Right
右
Dr. Karen Parker:
凯伦·帕克博士：
...
...
which we'll talk about.
我们将讨论这一点。
Andrew Huberman:
安德鲁·休伯曼：
Very cool.
非常酷。
Dr. Karen Parker:
凯伦·帕克博士：
So we went out and we did this.
所以我们出去做了这个。
I have this spectacular statistician.
我有一位出色的统计学家。
We spend a lot of time together.
我们花了很多时间在一起。
His name's Joe Garner, and he is a statistical genius.
他的名字叫乔·加纳，是一位统计天才。
And so he developed this, and we do all of our work together, or I would say 95% of it.
所以他开发了这个，我们一起完成所有的工作，或者我会说 95%。
We just love working together.
我们只是喜欢一起工作。
And he developed a statistical winnowing strategy to identify what were the key drivers.
他制定了统计筛选策略来确定关键驱动因素。
And what was fascinating is in this first monkey cohort, it was the cerebral spinal fluid levels of vasopressin that were really what was driving this classification.
令人着迷的是，在第一个猴子群体中，脑脊液中加压素的水平真正推动了这种分类。
So if we just knew your levels of vasopressin in spinal fluid, but not in blood, interestingly, we could pretty closely to perfect classify you as high or low social.
因此，有趣的是，如果我们只知道您脊髓液中的加压素水平，而不是血液中的水平，我们就可以非常接近地完美地将您分类为高社交或低社交。
And so then we replicated that again in another monkey cohort, because obviously as a scientist, you always want to replicate your work.
然后我们在另一个猴子群体中再次复制了这一点，因为显然作为一名科学家，你总是想复制你的工作。
And then if it was really a biomarker, meaning it's a molecule in the body that gives us an indication of something, and in this case, it's an indication of your social functioning.
然后，如果它确实是一种生物标记物，意味着它是体内的一种分子，可以为我们提供某些信息的指示，在这种情况下，它可以指示您的社会功能。
We were able to look at monkeys, and we saw that the vasopressin was consistent across measurement time.
我们能够观察猴子，发现加压素在整个测量时间内保持一致。
So there was a wide variety of vasopressin levels, but within an individual monkey, it was pretty much the same.
因此，加压素水平存在多种差异，但在单个猴子体内，其水平几乎相同。
So that's what you want to see with a biomarker.
这就是您希望通过生物标志物看到的结果。
And then we showed that the vasopressin levels were closely linked to time spent in grooming.
然后我们发现加压素水平与梳理毛发的时间密切相关。
And as we mentioned, or I think we mentioned earlier, grooming is, in many monkey species, a critical behavior that solidifies social bonds and maintains them.
正如我们提到的，或者我想我们之前提到的，在许多猴子物种中，梳理毛发是一种巩固和维持社会联系的关键行为。
And so the individuals with the lowest CSF vasopressin levels had spent the least amount of time in grooming.
因此，脑脊液加压素水平最低的个体花在梳理毛发上的时间最少。
Andrew Huberman:
安德鲁·休伯曼：
Grooming other monkeys.
给其他猴子梳理毛发。
Dr. Karen Parker:
凯伦·帕克博士：
Other monkeys.
其他猴子。
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Yeah.
是的。
This allopathic grooming-
这种对抗疗法的美容——
Dr. Karen Parker:
凯伦·帕克博士：
And others.
还有其他人。
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is a very interesting behavior.
是一个非常有趣的行为。
And from watching "Chimp Empire," I can tell you that new relationships are established-
通过观看《黑猩猩帝国》，我可以告诉你，新的关系已经建立了——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
in many ways by monkeys, these chimpanzees, sort of offering their back for grooming.
在很多方面，猴子、这些黑猩猩都会用背部来梳理毛发。
And if another chimp elects to, yes, groom that chimp, then it establishes some form of trust.
如果另一只黑猩猩选择，是的，为那只黑猩猩梳理毛发，那么它就建立了某种形式的信任。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And it all seems to have to do with proximity, like how close are you going to let me get to you-
这一切似乎都与距离有关，比如你能让我离你有多近——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
vice versa.
反之亦然。
In humans, we talk about personal space, and-
在人类中，我们谈论个人空间，并且-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
there's a whole set of things related to consent in this whole allopathic grooming thing.
在整个对抗疗法美容过程中，有一整套与同意相关的事情。
And then if a chimp misbehaves on an outing, then they aren't groomed by others, and they can actually get parasitic infections-
然后，如果黑猩猩在郊游时行为不端，那么它们就不会被其他人梳理，而且它们实际上可能会感染寄生虫——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and it can be very costly.
而且成本可能会非常高。
It's very interesting to just think of allopathic grooming as not a primitive of language, but a whole language unto itself.
非常有趣的是，将对抗疗法梳理视为语言本身而不是一种原始语言。
Dr. Karen Parker:
凯伦·帕克博士：
Absolutely.
绝对的。
Yeah.
是的。
And also just critical for the species.
而且对于这个物种来说也至关重要。
So that was really interesting to me that we were seeing these hints that vasopressin could be really important.
所以这对我来说真的很有趣，我们看到这些暗示加压素可能非常重要。
But of course, somebody will say, and I will say upfront, monkeys don't have autism.
当然，有人会说，我会提前说，猴子没有自闭症。
So then the question becomes, does this have what's called translational value?
那么问题来了，这是否具有所谓的翻译价值？
So, can I see this observation in an animal model, and will it provide fundamental insights into humans?
那么，我可以在动物模型中看到这一观察结果吗？它会为人类提供基本的见解吗？
And so I wanted to get cerebral spinal fluid from people to test this hypothesis, because we had, in parallel, done a study looking at blood vasopressin levels in people without autism, and we didn't see a group difference there, unlike this really profound difference that we saw when we looked at spinal fluid in the monkeys.
所以我想从人们身上获取脑脊髓液来检验这个假设，因为我们同时进行了一项研究，观察非自闭症患者的血液加压素水平，我们没有看到组间差异，这与我们在观察猴子脊髓液时看到的这种真正深刻的差异不同。
And again, I think I mentioned the blood vasopressin levels were indistinguishable if you were high or low social monkeys.
再说一次，我想我提到过，如果你是高社交猴子或低社交猴子，血液加压素水平是无法区分的。
So there was something about looking more proximate to the brain that was giving us more information than, say, the blood alone.
因此，更接近大脑的观察可以为我们提供比单独的血液更多的信息。
And so I said I wanted to get spinal fluid.
所以我说我想要获取脊髓液。
And like you said, people do this all the time.
就像你说的，人们一直这样做。
But it's not going to be a first pass, especially when we don't really have any evidence in people, to go in for what we would call a research lumbar puncture.
但这不会是第一次进行我们所说的研究性腰椎穿刺，特别是当我们没有任何人体证据时。
And so I had to get really creative about how do I get spinal fluid from children.
因此，我必须在如何从儿童身上获取脊髓液方面发挥真正的创意。
And what we did was we piggybacked onto a clinical indication for a spinal fluid draw.
我们所做的是利用脊髓液抽取的临床指征。
And we did this, so I tried to get funding for this.
我们这样做了，所以我试图为此筹集资金。
Again, I think this is important for people to know how science is done.
再说一次，我认为这对于人们了解科学是如何进行的很重要。
And so I wrote all these grant applications.
所以我写了所有这些拨款申请。
Nobody would fund it.
没有人愿意资助它。
They said that this is really interesting.
他们说这真的很有趣。
It's too high risk.
风险太大了。
You won't be able to pull it off.
你将无法成功。
And I don't usually back down from a challenge.
我通常不会在挑战面前退缩。
If I think something's a good idea and I want to do it, I'm going to find a way to do it.
如果我认为某件事是个好主意并且我想做它，我就会找到一种方法来实现它。
If it's impossible, that's one thing.
如果这是不可能的，那是一回事。
But if it's hard to do, it doesn't mean you shouldn't do it.
但如果很难做到，并不意味着你不应该这样做。
You just have to figure out how to do it.
你只需要弄清楚如何去做。
And so I always try to see bridges where other people see barriers.
所以我总是试图在别人看到障碍的地方看到桥梁。
And so it's like, well, how can I access spinal fluid?
所以这就像是，我怎样才能获得脊髓液？
And so I went around talking to all my friends.
所以我到处和我所有的朋友交谈。
And Stanford's really wonderful because it's such a small school.
斯坦福大学真的很棒，因为它是一所很小的学校。
And so you're on all these different committees with all these different people, and so-
所以你和所有这些不同的人一起在所有这些不同的委员会中，所以-
Andrew Huberman:
安德鲁·休伯曼：
A lot of committees.
很多委员会。
Dr. Karen Parker:
凯伦·帕克博士：
Lots of committees.
很多委员会。
Andrew Huberman:
安德鲁·休伯曼：
I can attest.
我可以证明。
A lot of committees.
很多委员会。
Dr. Karen Parker:
凯伦·帕克博士：
Yes, exactly.
是的，完全正确。
But it's really cool because you're on them with people from all different departments.
但这真的很酷，因为你和来自不同部门的人一起工作。
Andrew Huberman:
安德鲁·休伯曼：
Oh, yeah.
哦，是的。
I know people in departments that I wouldn't otherwise know.
我认识一些我本来不会认识的部门的人。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And you get to know these people well-
你会很了解这些人——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
in these many committees.
在这么多的委员会中。
Dr. Karen Parker:
凯伦·帕克博士：
And where we live, it's a small community.
我们住的地方是一个小社区。
So like, I-
所以就像，我-
Andrew Huberman:
安德鲁·休伯曼：
Maybe we're the experiment, Karen.
也许我们就是实验品，凯伦。
I always wonder whether or not there's a larger experiment-
我总是想知道是否有更大的实验-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
not on monkeys, not on the ...
不是在猴子上，不是在...
the patients or the clinical trial, but maybe we're the experiment.
患者或临床试验，但也许我们就是实验。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
Dr. Karen Parker:
凯伦·帕克博士：
I mean, yeah.
我的意思是，是的。
Andrew Huberman:
安德鲁·休伯曼：
And they're looking at how we interact on committees.
他们正在研究我们如何在委员会中互动。
Anyway, please continue.
无论如何，请继续。
Dr. Karen Parker:
凯伦·帕克博士：
So I started going up to people that I knew and said, "Hey, if you're taking spinal fluid, can I get a little bit of extra?" Right?
所以我开始去找我认识的人说：“嘿，如果你要抽取脊髓液，我可以多拿一点吗？”正确的？
And of course, we got IRB approval, meaning we had ethics approval and all this.
当然，我们得到了 IRB 的批准，这意味着我们获得了道德批准等等。
Or you could get the remnant sample, and obviously again, get consent from the families.
或者你可以获取剩余的样本，显然，同样要征得家属的同意。
So we could either get a little bit extra when it was being drawn for a research indication.
因此，当它被用于研究指示时，我们可以得到一点额外的东西。
So they were getting a spinal tap no matter what, and then we were just either, we're getting a little bit extra, or we were going to get the remnant that they were going to throw out.
所以无论如何，他们都会接受脊椎穿刺，然后我们要么得到一点额外的东西，要么我们会得到他们要扔掉的残余物。
Right?
正确的？
So you usually take more than you need because you don't want to have to do another spinal tap.
因此，您通常会采取比您需要的更多的药物，因为您不想再进行一次脊椎穿刺。
Right?
正确的？
And so we were able to go around, and I hustled around and got all these people involved to help me.
所以我们能够四处走动，我四处奔走，让所有这些人都参与进来帮助我。
We put hot pink stickers on the lumbar puncture trays so that in the emergency room, so if somebody was doing a spinal tap, they would call us so we knew about it, and we could get samples, again, under people's consent.
我们在腰椎穿刺托盘上贴上亮粉色贴纸，以便在急诊室里，如果有人做脊椎穿刺，他们会打电话给我们，以便我们了解情况，并且在征得人们同意的情况下，我们可以再次获取样本。
So we got all these people involved, and we finally got samples from children with autism and children without autism.
所以我们让所有这些人都参与进来，最终我们获得了自闭症儿童和非自闭症儿童的样本。
And then we also made sure that whatever they were being worked up for was negative.
然后我们还确保他们所做的一切都是负面的。
Right?
正确的？
So we got the sort of healthiest people we could, given that everybody was coming in for a medical reason to have a lumbar puncture.
因此，考虑到每个人都是出于医疗原因来进行腰椎穿刺，我们尽可能地招募了最健康的人。
And in this first study, we had seven children with autism, seven children without autism, and we could nearly perfectly classify 13 out of 14 individuals by just knowing their CSF vasopressin level alone.
在第一项研究中，我们有 7 名患有自闭症的儿童，7 名没有自闭症的儿童，仅通过了解他们的脑脊液加压素水平，我们就可以几乎完美地对 14 个人中的 13 人进行分类。
Which is pretty remarkable given that there isn't a robust biological indicator that we know.
鉴于我们所知还没有可靠的生物指标，这是非常值得注意的。
Andrew Huberman:
安德鲁·休伯曼：
So basically, in this relatively small cohort-
所以基本上，在这个相对较小的群体中——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
having low vasopressin-
加压素水平低
Dr. Karen Parker:
凯伦·帕克博士：
Correct
正确
Andrew Huberman:
安德鲁·休伯曼：
...
...
is a biomarker of autism.
是自闭症的生物标志物。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
And again, and what I will say is in our monkey studies and in our human studies, CSF oxytocin level became our control.
再说一次，我要说的是，在我们的猴子研究和人类研究中，脑脊液催产素水平成为我们的对照。
Right?
正确的？
So in our monkeys, there were no difference in CSF oxytocin by group, and then in this first study, there were no differences in CSF oxytocin levels.
因此，在我们的猴子中，各组的脑脊液催产素没有差异，而在第一项研究中，脑脊液催产素水平也没有差异。
A sample size of 14 is intriguing, but given autism is so clinically heterogeneous, we want to replicate it.
14 个样本量很有趣，但鉴于自闭症在临床上的异质性如此之大，我们希望复制它。
And so I knew that there was a professor at the NIH named Sue Swedo who was collecting cerebral spinal fluid as part of a research study because she was interested in immune parameters and folate deficiency.
所以我知道美国国立卫生研究院有一位名叫 Sue Swedo 的教授，她正在收集脑脊髓液作为研究的一部分，因为她对免疫参数和叶酸缺乏症感兴趣。
So she had children that were medically healthy, and they were getting, just like at NIH, get these huge work-ups.
所以她的孩子们身体健康，他们就像在美国国立卫生研究院一样，接受了这些巨大的检查。
Right?
正确的？
So they were very well-characterized participants.
所以他们是非常有特点的参与者。
So we were able to look at, and again, this is the first time we were able to look at girls.
所以我们能够观察，这也是我们第一次能够观察女孩。
So we had a small sample of girls, and we had boys, and we basically just asked the question, can we replicate this?
所以我们有一小部分女孩样本，还有男孩，我们基本上只是问一个问题，我们可以复制这个吗？
And I was very interested in, well, will oxytocin be what's different in the girls?
我非常感兴趣的是，催产素对女孩来说会有什么不同吗？
Right?
正确的？
So maybe there will be some sex specificity here, and it will see low CSF vasopressin in the males and low CSF oxytocin in girls.
因此，这里可能存在一些性别特异性，男性的脑脊液加压素水平较低，而女孩的脑脊液催产素水平较低。
That was not the case.
事实并非如此。
What we found was that in the individuals with autism, regardless of their biological sex, that they all had lower CSF vasopressin levels than the individuals without autism.
我们发现，在自闭症患者中，无论其生物性别如何，他们的脑脊液加压素水平都低于非自闭症患者。
And because they were so well-characterized, we were also able to show on a gold standard research diagnostic assessment of autism, so it's an assessment that's used in a research situation to validate an autism diagnosis by an expert clinical opinion, that the lower your vasopressin levels in spinal fluid, the greater your social symptom severity, or your clinical symptom severity.
因为它们的特征如此明确，所以我们还能够展示自闭症的金标准研究诊断评估，因此这是一种在研究情况下使用的评估，以通过专家临床意见验证自闭症诊断，即脊髓液中的加压素水平越低，您的社会症状严重程度或临床症状严重程度就越高。
And then we asked, it's like, well, vasopressin's involved in social behavior, but it's not really that involved in restricted, repetitive behaviors, and that was actually the case.
然后我们问，这就像，嗯，加压素参与了社会行为，但它并不是真的参与了受限的、重复的行为，而事实确实如此。
So it was the CSF vasopressin tracked the social symptom severity, not the repetitive symptom severity, suggesting that there might be other biological measures that could be included as a way to have a more powerful way to differentiate people with and without autism.
因此，脑脊液加压素追踪的是社会症状的严重程度，而不是重复症状的严重程度，这表明可能还有其他生物学指标可以作为一种更有效的方法来区分患有自闭症和非自闭症的人。
So that was really exciting to replicate that.
所以复制它真的很令人兴奋。
And then I had a colleague named John Constantino, who is now at Emory, but he used to be at Wash U.
然后我有一位名叫约翰·康斯坦丁诺的同事，他现在在埃默里大学，但他曾经在华盛顿大学。
And I knew that John, I had been at a meeting in, I think it was 2010, and I found out that he had what I will call liquid gold.
我知道约翰，我参加过一次会议，我想那是 2010 年，我发现他拥有我所说的液态黄金。
So he had this minus 80 C freezer, that had a bunch of neonatal infant CSF samples that he had-
所以他有一个负80摄氏度的冰箱，里面有一堆新生儿脑脊液样本——
Andrew Huberman:
安德鲁·休伯曼：
From human
来自人类
Dr. Karen Parker:
凯伦·帕克博士：
...
...
from human infants.
来自人类婴儿。
And he had collected them, and again, this was under ethical approvals.
他收集了它们，而且这也是经过道德批准的。
And it was basically, these infants came in for something that needed to be worked up that was very rare, but if they had it, they could die, so they needed to get a medical treatment for it.
基本上，这些婴儿进来是为了接受一些非常罕见的治疗，但如果他们患有这种疾病，他们可能会死亡，所以他们需要接受治疗。
But the vast majority of these children ended up being healthy.
但这些孩子中的绝大多数最终都保持健康。
So it was a pretty healthy sample, if you will.
所以如果你愿意的话，这是一个非常健康的样本。
Right?
正确的？
And so I knew he had all these samples, and I said to him, "Wouldn't it be really interesting if we teamed up and we look at this CSF vasopressin finding in children before the period when behavioral symptoms first manifest?" Right?
所以我知道他有所有这些样本，我对他说，“如果我们合作，在行为症状首次出现之前观察儿童脑脊液加压素的发现，不是很有趣吗？”正确的？
And so-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
So sorry again to-
再次抱歉——
Dr. Karen Parker:
凯伦·帕克博士：
Sorry.
抱歉。
Am I getting too jargon-y?
我是不是太行话了？
Andrew Huberman:
安德鲁·休伯曼：
I'm going to apologize every time.
每次我都会道歉。
No, no. But I think it's important because this was a question that I was thinking about earlier, and I imagine many other people were, too.
不，不。但我认为这很重要，因为这是我之前考虑过的一个问题，我想很多其他人也是如此。
You find these monkeys that have social interaction deficits.
你会发现这些猴子有社交互动缺陷。
You find kids that have social interaction deficits, and you see that there's low vasopressin in both groups.
你会发现有社交互动缺陷的孩子，并且你会发现两组中的加压素都较低。
This extends to male and female children.
这也适用于男孩和女孩。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But then, of course, the question becomes, well, maybe they have low vasopressin because of so many years or even months of social interaction deficits.
但当然，问题就变成了，也许他们的加压素水平较低，因为多年来甚至几个月的社交互动不足。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
That the direction of causality isn't clear.
因果关系的方向并不明确。
And so-
所以——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
when you said liquid gold, Referring to the CSF from these infants, taken prior to any opportunity for social interaction beyond just whatever interaction they had with their mother up until the point the CSF draw was taken.
当你说液态金时，指的是这些婴儿的脑脊液，是在他们与母亲进行任何社交互动之前进行的任何社交互动之前采集的，直到采集脑脊液为止。
This really gets at the issue of causality.
这确实触及了因果关系的问题。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
正确的。
So it's a quasi perspective, because it was banked, and then a lot of time went by.
所以这是一个准视角，因为它被储存起来，然后很多时间就过去了。
Right?
正确的？
And so what we realized we could do was, and this was a heroic undertaking on John's part.
所以我们意识到我们可以做的是，这对约翰来说是一项英雄事业。
So these samples were collected back on paper medical records.
因此，这些样本被收集回纸质医疗记录中。
So he had to trace 2,000 paper med-
所以他必须追踪 2000 张纸质药物——
Andrew Huberman:
安德鲁·休伯曼：
Paper.
纸。
What's that?
那是什么？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah, exactly.
是的，完全正确。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
So he had to trace 2,000, I think, paper medical records to an electronic medical record.
所以我认为他必须将 2,000 份纸质病历追踪到电子病历。
And then what we did is he looked to see who went on to develop autism and who didn't.
然后我们所做的就是观察谁继续发展为自闭症，谁没有发展为自闭症。
Right?
正确的？
So then what we had was spinal fluid samples that have sort of been waiting in the freezer, if you will, and then we could ask, do individuals who later receive an autism diagnosis many months or even years later already have low vasopressin levels as infants?
So then what we had was spinal fluid samples that have sort of been waiting in the freezer, if you will, and then we could ask, do individuals who later receive an autism diagnosis many months or even years later already have low vasopressin levels as infants?
And the reason why this was a compelling question to ask is there's evidence to suggest that behavioral therapies are more effective the younger the child is.
And the reason why this was a compelling question to ask is there's evidence to suggest that behavioral therapies are more effective the younger the child is.
Right?
正确的？
And if you think about it, if behavioral characteristics of autism emerge across development, what if...
如果你想一想，如果自闭症的行为特征在发展过程中出现，如果......
We haven't substantiated this yet, but this is sort of my big question.
我们还没有证实这一点，但这是我的一个大问题。
What if all these autism susceptibility genes summon, interact, and converge upon a few common pathways in the brain, right?
如果所有这些自闭症易感基因在大脑中的一些常见通路上召唤、相互作用并汇聚，会怎么样，对吗？
And so for years, people have talked about this excitatory/inhibitory balance theory of autism.
因此多年来，人们一直在谈论自闭症的兴奋/抑制平衡理论。
But what if vasopressin is one of those pathways because it's so critically involved in social functioning?
但是，如果加压素是这些途径之一，因为它与社会功能密切相关，该怎么办？
And so what I was interested in, and so let's just say for a moment, your genes are set at birth.
所以我感兴趣的是，让我们暂时说一下，你的基因是在出生时就设定的。
What if the vasopressin is already low in the brains of these infants, and so it puts them on this very different trajectory, where you have this cumulative effect of they're maybe a little bit less socially interested, and maybe they're not making the eye contact, and if there was a way to intervene really early, even potentially with a vasopressin replacement therapy, that you might be able to put them on a different developmental trajectory.
What if the vasopressin is already low in the brains of these infants, and so it puts them on this very different trajectory, where you have this cumulative effect of they're maybe a little bit less socially interested, and maybe they're not making the eye contact, and if there was a way to intervene really early, even potentially with a vasopressin replacement therapy, that you might be able to put them on a different developmental trajectory.
So that was my big what if question.
这就是我最大的假设问题。
And what was really remarkable was, so I had been asking John, "Hey, can I have your spinal fluid samples?" And he finally agreed after he saw a couple of those papers.
真正值得注意的是，所以我一直问约翰，“嘿，我可以得到你的脊髓液样本吗？”在看到几篇这样的论文后，他终于同意了。
Understandably, he wanted to make sure that we already had shown something in people and animals that were sort of, if you will, symptomatic with social impairment.
可以理解的是，他想确保我们已经在人和动物身上展示了一些（如果你愿意的话）社交障碍症状的东西。
And what we found was, yes, this was the case.
我们发现，是的，情况确实如此。
So it was a small sample.
所以这是一个小样本。
It needs to be replicated.
它需要被复制。
But so infants that went on to have an autism diagnosis later in life already had low CSF vasopressin levels.
But so infants that went on to have an autism diagnosis later in life already had low CSF vasopressin levels.
Oxytocin levels did not differ between infants that received a subsequent autism diagnosis and those that didn't.
Oxytocin levels did not differ between infants that received a subsequent autism diagnosis and those that didn't.
So suggesting that we have a biomarker that might really be a good readout for clinical referral or risk management monitoring.
So suggesting that we have a biomarker that might really be a good readout for clinical referral or risk management monitoring.
Andrew Huberman:
安德鲁·休伯曼：
Incredible.
难以置信。
So you're telling us that levels of vasopressin correlate with social cognition deficits.
所以你告诉我们加压素水平与社会认知缺陷相关。
Is that right?
是这样吗？
I think that warrants a brief discussion about cerebral spinal fluid.
I think that warrants a brief discussion about cerebral spinal fluid.
I teach neuroanatomy to medical students, so forgive me for having to ask this, but I think of cerebral spinal fluid as the stuff that exists in the ventricles and down the central canal of the spinal cord, and provides essential nutrients for neurons and other cell types in the brain.
I teach neuroanatomy to medical students, so forgive me for having to ask this, but I think of cerebral spinal fluid as the stuff that exists in the ventricles and down the central canal of the spinal cord, and provides essential nutrients for neurons and other cell types in the brain.
But it's also a reservoir for chemicals coming from the brain-
但它也是来自大脑的化学物质的储存库——
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
which is why the spinal tap is useful.
这就是脊椎穿刺很有用的原因。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But in the context of a cerebral spinal tap, and you're measuring CSF, and you're seeing, okay, lower levels of vasopressin in these individuals with these challenges with social deficits, does that mean that they're making less vasopressin?
But in the context of a cerebral spinal tap, and you're measuring CSF, and you're seeing, okay, lower levels of vasopressin in these individuals with these challenges with social deficits, does that mean that they're making less vasopressin?
I mean, it could have gone the other way, too, like they're dumping too much vasopressin-
I mean, it could have gone the other way, too, like they're dumping too much vasopressin-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
into the CSF, and it's not able to function in the brain.
进入脑脊液，它无法在大脑中发挥作用。
What do we know about CSF, and what does it mean?
我们对 CSF 了解多少？它的含义是什么？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Well, it's a great question.
嗯，这是一个很好的问题。
So I think this is just the tip of the iceberg.
So I think this is just the tip of the iceberg.
Right?
正确的？
So I think of the CSF as sort of like the kitchen sink of the brain, right?
So I think of the CSF as sort of like the kitchen sink of the brain, right?
And what we need is real specificity.
我们需要的是真正的特异性。
And so, my working hypothesis, and we'll talk a little bit about pharmacology, is that there's a deficiency in vasopressin production in individuals with autism.
And so, my working hypothesis, and we'll talk a little bit about pharmacology, is that there's a deficiency in vasopressin production in individuals with autism.
But there's a lot of elegant experiments that need to be done to be able to answer this question.
但需要做很多优雅的实验才能回答这个问题。
So we have funding currently to look in postmortem human brain tissue, to look at in both blood, CSF, and hypothalamic tissue, where vasopressin is made, to look at interrelationships, which is very difficult to do, but also to see if there's a fewer number of vasopressin-producing cells, and if vasopressin gene expression is diminished.
因此，我们目前有资金来观察死后的人类脑组织，观察血液、脑脊液和产生加压素的下丘脑组织，观察相互关系，这是很难做到的，而且还要看看产生加压素的细胞数量是否减少，以及加压素基因表达是否减少。
Right?
正确的？
Because that would help us begin to answer, is this a production issue?
Because that would help us begin to answer, is this a production issue?
Right?
正确的？
So if you think back to the prairie voles, they're sort of primed to be parental.
So if you think back to the prairie voles, they're sort of primed to be parental.
Right?
正确的？
Or in my case, the meadow voles, right?
或者就我而言，是草地田鼠，对吗？
But you can do this in any vole species, or at least the two that I'm thinking of.
But you can do this in any vole species, or at least the two that I'm thinking of.
And you put vasopressin into the brain, and then all of a sudden it unlocks this behavior.
你将加压素注入大脑，然后突然它就解锁了这种行为。
Right?
正确的？
So is it possible that children with autism, or at least a subset of them, all you have to do is replace vasopressin, and that there might be a subset of these kids, minimally, that could benefit from vasopressin replacement, if you will?
So is it possible that children with autism, or at least a subset of them, all you have to do is replace vasopressin, and that there might be a subset of these kids, minimally, that could benefit from vasopressin replacement, if you will?
Andrew Huberman:
安德鲁·休伯曼：
Is there any evidence for excessive urination in kids with autism?
Is there any evidence for excessive urination in kids with autism?
Which if anyone's going, "What?
Which if anyone's going, "What?
Why is he asking that?" If you recall, vasopressin is also antidiuretic hormone.
他为什么这么问？”如果您还记得的话，加压素也是抗利尿激素。
I suppose the other question is, could you Has anyone looked at levels of vasopressin in the urine of autistic kids versus non-autistic kids?
I suppose the other question is, could you Has anyone looked at levels of vasopressin in the urine of autistic kids versus non-autistic kids?
Because it's acting peripherally, and you said blood draws don't reveal any differences-
因为它是外围作用的，而且你说抽血并不能显示出任何差异-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
in circulating blood.
在循环血液中。
We know that urine is filtered blood.
我们知道尿液是过滤后的血液。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Fair enough.
很公平。
But seems at least worth-
但似乎至少值得-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a look-see.
一看。
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
Okay, so I have this awesome medical student in my lab named Lauren Clark, and we, with three different physicians from different backgrounds, wrote a perspective piece that's currently under review, and it actually asked this question.
好吧，我的实验室里有一位很棒的医学生，名叫劳伦·克拉克（Lauren Clark），我们与来自不同背景的三位不同的医生一起写了一篇目前正在审查的观点文章，它实际上提出了这个问题。
So given all these weird medical naming conventions, it's possible that this information is existing in information silos in different disciplines.
因此，鉴于所有这些奇怪的医学命名约定，这些信息可能存在于不同学科的信息孤岛中。
Right?
正确的？
So it raises this idea of if you have low vasopressin, if you're not making vasopressin, you have a disorder called central diabetes insipidus, right, which is characterized by excessive thirst, lots of urination, and bedwetting potentially.
因此，这就提出了这样的想法：如果你的加压素水平较低，如果你不产生加压素，你就会患上一种称为中枢性尿崩症的疾病，对吧，其特征是过度口渴、大量排尿和可能尿床。
And so what we wanted to do was ask, has this been missed?
And so what we wanted to do was ask, has this been missed?
Right?
正确的？
So shouldn't there be a subset of kids with autism where we might be able to look at these other physiological features and say, "Yeah, this is the subset we want to be giving vasopressin to." And so she wrote this perspective where we did a little bit of a review, and the answer is there's some intriguing studies that we reviewed in this paper where it looks like...
因此，难道不应该有一个自闭症儿童的子集，我们可以通过观察这些其他生理特征并说：“是的，这就是我们想要给予加压素的子集。” And so she wrote this perspective where we did a little bit of a review, and the answer is there's some intriguing studies that we reviewed in this paper where it looks like...
And what's funny is when you read the discussion section, it'll be like, wow, there's all these kids with autism that are drinking lots of water, and we don't know why.
有趣的是，当你阅读讨论部分时，你会觉得，哇，所有这些患有自闭症的孩子都喝了大量的水，而我们不知道为什么。
Or wow, there's a lot of bedwetting, but it's not tied to intellectual disability, where you might see a lot of bedwetting or something.
或者哇，尿床很多，但这与智力障碍无关，你可能会看到很多尿床之类的。
So all of these studies kind of raise this point of like, wow, this is really interesting.
So all of these studies kind of raise this point of like, wow, this is really interesting.
And there's been no big epidemiological study done on this, and certainly not any study where people who come at it from brain science and then the practitioners who are like an endocrinologist, for instance, which is where some of these people could show up, are really connecting the dots.
And there's been no big epidemiological study done on this, and certainly not any study where people who come at it from brain science and then the practitioners who are like an endocrinologist, for instance, which is where some of these people could show up, are really connecting the dots.
So I think that remains to be determined, but we are actually about to launch a study to investigate this.
So I think that remains to be determined, but we are actually about to launch a study to investigate this.
Right?
正确的？
I was meeting with Lauren yesterday about it.
昨天我和劳伦会面讨论这件事。
So, it's a really good question, and I hope to have information on it in the not-too-distant future.
所以，这是一个非常好的问题，我希望在不久的将来能够获得有关它的信息。
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
As I recall, alcohol is an antagonist of vasopressin.
As I recall, alcohol is an antagonist of vasopressin.
Dr. Karen Parker:
凯伦·帕克博士：
So there's a lot of different drugs that could interact with vasopressin.
So there's a lot of different drugs that could interact with vasopressin.
And so one thing I'm interested in is, are there any drugs that release vasopressin as a side effect, and could some of them be mobilized to treat autism?
所以我感兴趣的一件事是，是否有任何药物会释放加压素作为副作用，并且其中一些药物可以用来治疗自闭症？
We also know that acupuncture can release vasopressin.
We also know that acupuncture can release vasopressin.
There's been some studies done in rats on that.
已经在老鼠身上进行了一些研究。
And so one question would just be, are there any alternative therapies where we can be releasing vasopressin naturally, or do we need to do a replacement study where we give intranasal vasopressin to children with autism?
所以一个问题是，是否有任何替代疗法可以让我们自然释放加压素，或者我们是否需要进行一项替代研究，为自闭症儿童鼻内加压素？
Right.
正确的。
And of course, I want to say I'm not advocating that people go out and do this on their own.
And of course, I want to say I'm not advocating that people go out and do this on their own.
Right?
正确的？
I'm a big proponent of randomized clinical trials where you assess safety, right, and efficacy.
我是随机临床试验的大力支持者，在随机临床试验中评估安全性、正确性和有效性。
Andrew Huberman:
安德鲁·休伯曼：
Science.
科学。
Dr. Karen Parker:
凯伦·帕克博士：
Yes, science.
是的，科学。
Andrew Huberman:
安德鲁·休伯曼：
It's the science of medicine.
这是医学科学。
Right.
正确的。
But I appreciate you saying that.
但我很欣赏你这么说。
Yeah, some years ago, so this would be mid-'90s, there was a small but very active subculture that I was not a part of-
是的，几年前，所以那是 90 年代中期，有一个小但非常活跃的亚文化，我不属于其中 -
Dr. Karen Parker:
凯伦·帕克博士：
Okay
好的
Andrew Huberman:
安德鲁·休伯曼：
...
...
I swear, that were combining GHB, gamma-hydroxybutyrate, and vasopressin as combination quote-unquote sex drugs.
我发誓，那是 GHB、γ-羟基丁酸和加压素的组合，作为性药物的组合。
Dr. Karen Parker:
凯伦·帕克博士：
Really?
真的吗？
Andrew Huberman:
安德鲁·休伯曼：
Yes.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
Huh.
呵呵。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
And I don't know what the rationale for including vasopressin was.
我不知道加入加压素的理由是什么。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
In any case, whether or not that's by way of enhancing social bonding or a direct effect on sexual arousal itself-
无论如何，无论是通过增强社会联系还是对性唤起本身产生直接影响——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
is still unclear.
目前还不清楚。
But in any event, since we're talking about vasopressin, maybe you should tell us about the actual science of vasopressin.
但无论如何，既然我们谈论的是加压素，也许你应该告诉我们加压素的实际科学知识。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
Sorry, maybe I should allow you to tell us about the actual scientific study of vasopressin.
抱歉，也许我应该允许您告诉我们有关加压素的实际科学研究。
In other words, what happens if you give people vasopressin in a controlled environment?
换句话说，如果在受控环境下给予人们加压素，会发生什么？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Exactly.
确切地。
Andrew Huberman:
安德鲁·休伯曼：
Not the sort of environment I'm talking about.
不是我所说的那种环境。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But a controlled environment.
但受控环境。
Dr. Karen Parker:
凯伦·帕克博士：
And the one thing I will say, because I have people contact us all the time saying, "Where can I get vasopressin?" And what I would say is vasopressin means you're having effects on blood pressure.
我要说的一件事是，因为有人一直联系我们说：“我在哪里可以获得加压素？”我想说的是，加压素意味着你会对血压产生影响。
You're having effects on really important-
你对非常重要的事情产生了影响-
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Vaso-
瓦索-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
means vasculature.
指脉管系统。
Yep
是的
Dr. Karen Parker:
凯伦·帕克博士：
...
...
and the dosing has to be appropriate.
并且剂量必须适当。
You don't want people just going and trying this because there could be really severe adverse effects.
你不希望人们只是去尝试这个，因为这可能会产生非常严重的副作用。
Right?
正确的？
So that's why we've been studying this in a controlled clinical trial.
这就是我们一直在对照临床试验中研究这一点的原因。
Right?
正确的？
So, I teamed up with Antonio Hardan, who's the child psychiatrist that I've been working with for years, and we did the first in class vasopressin treatment trial in children with autism.
因此，我与安东尼奥·哈丹（Antonio Hardan）合作，他是我合作多年的儿童精神病学家，我们对自闭症儿童进行了首个班级加压素治疗试验。
So again, everyone was unaware of who was on vasopressin, whether it was the family or the clinician who was doing the evaluation.
同样，每个人都不知道谁在服用加压素，无论是家人还是进行评估的临床医生。
And then it was randomized, placebo-controlled, and then we basically gave vasopressin, again, twice a day for four weeks, to children.
然后是随机的、安慰剂对照的，然后我们基本上再次给儿童注射加压素，每天两次，持续四个星期。
They were about 6 to 12 years of age.
They were about 6 to 12 years of age.
And then we had a primary outcome measure, which was the social responsiveness scale.
然后我们有一个主要的结果衡量标准，即社会反应量表。
We could get into discussions about what a primary outcome measure should be.
我们可以讨论主要结果指标应该是什么。
Wouldn't it be great if there was a biological measure?
如果有一种生物措施不是很好吗？
But this is sort of what had been used in the past and something that the FDA approved us using.
But this is sort of what had been used in the past and something that the FDA approved us using.
I was partly interested in using the SRS because we had used it in monkeys, right, and we had shown, at least in monkeys, we've never looked at this in people because of the lack of available samples, but that in monkeys, in this general population that we've looked at, there's a continuous distribution of these SRS scores that relate to the CSF vasopressin levels.
我对使用 SRS 感兴趣，部分原因是我们在猴子身上使用过它，对吧，我们已经证明，至少在猴子身上，由于缺乏可用的样本，我们从未在人类中观察过这一点，但在猴子中，在我们观察的这个一般人群中，这些 SRS 分数存在与脑脊液加压素水平相关的连续分布。
And so I wanted to know if we use the SRS as an outcome measure and we're administering vasopressin, can we change the scoring on this instrument based on our animal data?
所以我想知道如果我们使用 SRS 作为结果测量并且我们正在施用加压素，我们可以根据我们的动物数据改变该仪器的评分吗？
Andrew Huberman:
安德鲁·休伯曼：
So SRS is social responsiveness scale.
所以SRS是社会反应量表。
Dr. Karen Parker:
凯伦·帕克博士：
Correct.
正确。
Andrew Huberman:
安德鲁·休伯曼：
Without going into a lot of detail, because we can always refer people to the paper-
无需讨论太多细节，因为我们总是可以向人们推荐这篇论文——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and I think most people just want to understand the top contour, the SRS presumably has to do with how often the kid interacts with another kid, how often they initiate that interaction-
我认为大多数人只是想了解顶部轮廓，SRS 可能与孩子与另一个孩子互动的频率以及他们发起互动的频率有关 -
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
versus on the receiving end, things like affiliative play, how often they look at one another-
与接收端相比，诸如附属游戏之类的事情，他们互相看一眼的频率——
Dr. Karen Parker:
凯伦·帕克博士：
Yep
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
versus averting gaze These kinds of things?
versus averting gaze These kinds of things?
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
And then there's also a little bit about restrictive repetitive behaviors.
还有一些关于限制性重复行为的内容。
So even though it's called the social responsiveness scale, there's also an assessment of other features of autism in it.
因此，尽管它被称为社会反应量表，但它也评估了自闭症的其他特征。
But you can sort of think about it as a quantitative way to assess features of interest in autism, and this was related to our biology in the monkeys, and so then we use this as this outcome measure in our trial.
But you can sort of think about it as a quantitative way to assess features of interest in autism, and this was related to our biology in the monkeys, and so then we use this as this outcome measure in our trial.
And as an experimentalist, I have this sort of trust but verify, right?
And as an experimentalist, I have this sort of trust but verify, right?
So you want to see the same thing over and over and over again, right?
所以你想一遍又一遍地看到同样的事情，对吧？
Scientists like repetition.
科学家喜欢重复。
And so we had parents fill out their impressions of what the child's behavior was before and after being on the medication.
因此，我们让父母填写他们对孩子在服药前后行为的印象。
We also had a clinician make an evaluation, but we also had the kids perform laboratory-based tests where they would see, like I mentioned, the reading the mind in the eyes test, or we would show them a picture of a face and say, "What emotion is this?" And so we were able to have what's called convergent validity, right?
我们还请了一名临床医生进行评估，但我们也让孩子们进行基于实验室的测试，就像我提到的那样，他们会看到“从眼睛里读懂思想”测试，或者我们会给他们看一张脸的照片并说，“这是什么情绪？” And so we were able to have what's called convergent validity, right?
So it's a fancy scientific term to say, do all these measures that we think should be related, are they related, and are we seeing the same thing?
So it's a fancy scientific term to say, do all these measures that we think should be related, are they related, and are we seeing the same thing?
And the answer was yes.
答案是肯定的。
So that when we gave children with autism vasopressin versus kids with autism a placebo, the kids who were treated with vasopressin showed increases in social abilities on parent report, clinician evaluation, and child performance on laboratory-based tests.
So that when we gave children with autism vasopressin versus kids with autism a placebo, the kids who were treated with vasopressin showed increases in social abilities on parent report, clinician evaluation, and child performance on laboratory-based tests.
Andrew Huberman:
安德鲁·休伯曼：
Wow.
哇。
Dr. Karen Parker:
凯伦·帕克博士：
And-
还有——
Andrew Huberman:
安德鲁·休伯曼：
Was that immediate?
那是立即的吗？
Like they did the nasal spray and they immediately started receiving and initiating more social engagement or was this a buildup over time?
就像他们使用鼻喷雾剂一样，他们立即开始接受并发起更多的社交活动，或者这是随着时间的推移而积累的？
And what I'm getting at here is whether or not this is the reflection of a short-
我在这里要了解的是，这是否是短期的反映——
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
or longer-term neuroplasticity.
or longer-term neuroplasticity.
Were there structural changes in the brain or-
Were there structural changes in the brain or-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
is this something that was more acute?
is this something that was more acute?
Dr. Karen Parker:
凯伦·帕克博士：
We don't know the answer to that.
We don't know the answer to that.
So we basically looked at dosing with the idea that we would-- And again, I think we've mentioned this about limitations on, there's so many things that a scientist would like to do, but you are always limited by a budget, right?
So we basically looked at dosing with the idea that we would-- And again, I think we've mentioned this about limitations on, there's so many things that a scientist would like to do, but you are always limited by a budget, right?
And so when we started this work, again, it was like philanthropic shoestring budgets, right?
因此，当我们再次开始这项工作时，这就像慈善事业的小额预算，对吧？
And so you had to really be laser-focused on what are the things that we can do on the budget at hand.
And so you had to really be laser-focused on what are the things that we can do on the budget at hand.
So unfortunately, we didn't do EEG or brain imaging or other things that would be, I think, potentially very interesting to do because you might be able to see an early signature of response, right?
不幸的是，我们没有做脑电图或脑成像或其他我认为可能非常有趣的事情，因为你可能能够看到反应的早期特征，对吗？
So maybe after the first dose, let's say, wow, there's some interesting changes that are predictive of somebody who would be a responder to the medication, and we don't know that yet.
因此，也许在第一次服药后，哇，有一些有趣的变化预示着某人会对药物有反应，但我们还不知道。
But we do know after this four-week period that we saw these changes.
But we do know after this four-week period that we saw these changes.
And then in a subset of kids, we actually saw diminished anxiety and also diminished restricted repetitive behaviors.
And then in a subset of kids, we actually saw diminished anxiety and also diminished restricted repetitive behaviors.
So suggesting that the vasopressin effect may not only be on social behavior.
因此表明加压素的作用可能不仅限于社会行为。
Andrew Huberman:
安德鲁·休伯曼：
Have you ever just wanted to try or try vasopressin?
您是否曾经只是想尝试或尝试加压素？
Dr. Karen Parker:
凯伦·帕克博士：
I haven't, but I think-
我没有，但我想——
Andrew Huberman:
安德鲁·休伯曼：
You're in a psychiatry department after all.
You're in a psychiatry department after all.
And I'm not suggesting that members of the psychiatry department are constantly testing the drugs that they use on their patients with themselves.
And I'm not suggesting that members of the psychiatry department are constantly testing the drugs that they use on their patients with themselves.
But I've had several members of this department, of which I'm a courtesy member-
但我这个部门有好几个成员，我是其中的礼节性成员——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
member by courtesy.
会员有礼貌。
Any event, and we'll see if I still am after what I'm about to say.
Any event, and we'll see if I still am after what I'm about to say.
Dr. Carl Dice Roth, who's a clinician-
Dr. Carl Dice Roth, who's a clinician-
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
our first guest on the Huberman Lab podcast, also a phenomenal neurobiology researcher, David Spiegel-
our first guest on the Huberman Lab podcast, also a phenomenal neurobiology researcher, David Spiegel-
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
Rob Malenka, and others that I've spoken to.
Rob Malenka, and others that I've spoken to.
I think all of whom said that they felt as clinicians, Rob's not a clinician anymore, right?
I think all of whom said that they felt as clinicians, Rob's not a clinician anymore, right?
But as a clinician, that they felt almost a responsibility to understand the effects and side effect profiles of the drugs that they were giving their patients, which I saw not as renegade or experimental-
But as a clinician, that they felt almost a responsibility to understand the effects and side effect profiles of the drugs that they were giving their patients, which I saw not as renegade or experimental-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but rather as very compassionate-
but rather as very compassionate-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
like seeking empathy.
就像寻求同理心一样。
So I'm curious, have you ever just snuck a little?
So I'm curious, have you ever just snuck a little?
No?
不？
Dr. Karen Parker:
凯伦·帕克博士：
No, I never have.
不，我从来没有。
Andrew Huberman:
安德鲁·休伯曼：
No?
没有？
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
But there is a long history in medicine of people trying out, they believe so much in their solution that they go and vaccinate their family with the new vaccine that they've created or they try the medication themselves, right?
But there is a long history in medicine of people trying out, they believe so much in their solution that they go and vaccinate their family with the new vaccine that they've created or they try the medication themselves, right?
So I don't-
所以我不-
Andrew Huberman:
安德鲁·休伯曼：
Well, MDMA was developed by Sasha Colgan in a laboratory in the East Bay, first by a pharmaceutical company in the early 1900s-
Well, MDMA was developed by Sasha Colgan in a laboratory in the East Bay, first by a pharmaceutical company in the early 1900s-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
but then kind of disappeared.
but then kind of disappeared.
It did disappear, and then it was resurrected independently in the 19-, I think '70s and '80s, and then now it's one of the sort of hot topic items for the treatment of PTSD.
It did disappear, and then it was resurrected independently in the 19-, I think '70s and '80s, and then now it's one of the sort of hot topic items for the treatment of PTSD.
Still in late-phase clinical trials, still illegal, but self-experimentation is one of the central themes of psychiatry-
Still in late-phase clinical trials, still illegal, but self-experimentation is one of the central themes of psychiatry-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
frankly.
坦白说。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
I guess I got in trouble in class for being too social, right?
I guess I got in trouble in class for being too social, right?
So I guess I've never-
所以我想我从来没有-
Andrew Huberman:
安德鲁·休伯曼：
They might send you over to the other side.
They might send you over to the other side.
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Exactly.
确切地。
Who knows?
谁知道？
But no, I never...
但不，我从来没有...
No, and the thing is that these oxytocin vasopressin, and again, these are done, and this is something that I think we've hit on over and over again in the podcast, is you need to know who you're studying, right?
No, and the thing is that these oxytocin vasopressin, and again, these are done, and this is something that I think we've hit on over and over again in the podcast, is you need to know who you're studying, right?
What's the species?
品种是什么？
Who's the individual?
个人是谁？
Most of these have been done in neuro-- A lot of the oxytocin and a little bit of the vasopressin work, the single dose work, was mostly done in what we'll call neurotypical people, right?
Most of these have been done in neuro-- A lot of the oxytocin and a little bit of the vasopressin work, the single dose work, was mostly done in what we'll call neurotypical people, right?
Just asking can we move around social behavior by just giving this single drug administration.
Just asking can we move around social behavior by just giving this single drug administration.
Most people that are neurotypical didn't say that they could tell if they were on the drug or the placebo, right?
Most people that are neurotypical didn't say that they could tell if they were on the drug or the placebo, right?
Andrew Huberman:
安德鲁·休伯曼：
Hmm.
嗯。
Interesting.
有趣的。
Dr. Karen Parker:
凯伦·帕克博士：
So I think the question really becomes, drugs work differently based on the individual who's taking them.
So I think the question really becomes, drugs work differently based on the individual who's taking them.
So if you have a neurotypical individual and you give them vasopressin, maybe they'll self-report that they don't see a difference.
So if you have a neurotypical individual and you give them vasopressin, maybe they'll self-report that they don't see a difference.
But if you had somebody who isn't producing enough vasopressin, maybe they would self-report after a period of time, or maybe even after the first dose, "Wow, I really see something different," right?
But if you had somebody who isn't producing enough vasopressin, maybe they would self-report after a period of time, or maybe even after the first dose, "Wow, I really see something different," right?
Andrew Huberman:
安德鲁·休伯曼：
Did any of the kids report how they felt?
Did any of the kids report how they felt?
They just said, "Wow, I-" I like playing with other kids more?
They just said, "Wow, I-" I like playing with other kids more?
Were they self-aware in that way?
Were they self-aware in that way?
And also feel free to mention if it feels right to you, let's consider two outlier cases.
And also feel free to mention if it feels right to you, let's consider two outlier cases.
One spectacular result-
一个惊人的结果——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
a kid that went from very socially isolated-
一个从社会上非常孤立的孩子——
Dr. Karen Parker:
凯伦·帕克博士：
Mm-hmm
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
to maybe very gregarious and-
也许非常合群并且-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but let's also balance that with another outlier, the kid with low vasopressin who took vasopressin, for whom there was no significant shift.
but let's also balance that with another outlier, the kid with low vasopressin who took vasopressin, for whom there was no significant shift.
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I'm presuming that within the data set, you probably observed something like each of those.
我假设在数据集中，您可能观察到类似的情况。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
What I'll say is that there were definitely kids who didn't respond to the medication.
我要说的是，肯定有一些孩子对药物没有反应。
One thing I think it's important to say, and again, this was a small pilot trial.
我认为有一点很重要，再说一遍，这是一个小型试点。
We're in the process of replicating this in a much larger sample.
我们正在更大的样本中复制这一点。
So as a scientist, again, you want to say, "Okay, this is really intriguing and interesting, and I've invested a lot in this monkey model, and then doing all the CSF work in patients to suggest that there may be a there there here, but I want to see it replicate." We did have an article, that Stanford Medicine, I can send you the link.
因此，作为一名科学家，你想说，“好吧，这真的很有趣，我在这个猴子模型上投入了很多，然后在患者身上进行了所有脑脊液工作，以表明这里可能存在一个那里，但我希望看到它复制。”我们确实有一篇文章，斯坦福大学医学院，我可以给你发送链接。
They were able to, I think, interview a family that had been in the trial.
我认为他们能够采访一个参与审判的家庭。
And so obviously there's patient privacy and they have to say it's okay to talk about it.
很明显，这是患者隐私，他们必须说可以谈论它。
But this is a family that was contacted, and I think they were anonymous, but this is in this report.
但我们联系的是一个家庭，我认为他们是匿名的，但这在这份报告中。
And they basically said, the dad said that he was on vasopressin, and his son was walking around a grocery store, and he was looking for him, and he turned around and he said he was gobsmacked because his child was just making chit-chat with somebody in an aisle, and he said he had never seen that happen before.
他们基本上说，父亲说他正在服用加压素，他的儿子正在一家杂货店里走来走去，他正在寻找他，他转过身来，他说他大吃一惊，因为他的孩子只是在过道上与某人闲聊，他说他以前从未见过这种情况发生。
And so, we do have anecdotal reports like that, and I think, the tricky part is we didn't stratify anyone going into this trial.
因此，我们确实有类似的轶事报告，我认为，棘手的部分是我们没有对参与这项试验的任何人进行分层。
And so the concern always is, did we get really lucky in the first trial and we somehow got the "right people" that entered the trial that were going to be the ones who would respond to the medication, or is this a medication that has sort of broad use in this population and the second trial will be positive?
因此，人们总是担心，我们在第一次试验中是否真的很幸运，并且以某种方式找到了进入试验的“合适的人”，这些人将对药物产生反应，或者这是一种在该人群中广泛使用的药物，并且第二次试验将是积极的？
Andrew Huberman:
安德鲁·休伯曼：
You used nasal spray-
你用过鼻喷雾剂-
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
to deliver the vasopressin, and presumably that gets into the blood circulation of the brain, and supplies neurons with vasopressin.
输送加压素，可能会进入大脑的血液循环，并为神经元提供加压素。
But it's very nonspecific, and I'm not criticizing it, but if you think about it, you're just putting a bunch of vasopressin into the brain.
但这是非常不具体的，我并不是在批评它，但如果你仔细想想，你只是将一堆加压素放入大脑中。
And if people wonder why this is, that it's because basically you have neurons of your central nervous system, are part of your olfactory system, and believe it or not, right behind where your nose meets your forehead, the brain is right there.
如果人们想知道这是为什么，那是因为基本上你有中枢神经系统的神经元，是嗅觉系统的一部分，不管你信不信，在你的鼻子与前额相接的地方，大脑就在那里。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
There's a little bit of bone, and then the brain is right there.
有一点骨头，然后大脑就在那里。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So, one of the reasons you can get in there, and it's easier than an ocular injection or something, that wouldn't be a good approach.
所以，你可以进入那里的原因之一，它比眼部注射或其他东西更容易，这不是一个好方法。
And it's easier than peripheral injection into the vein.
而且比外周静脉注射更容易。
But at the same time, I have to presume that this, I'm imagining this vasopressin just kind of permeating through the brain, binding to whatever receptors happen to be there.
但与此同时，我必须假设，我想象这种加压素会渗透到大脑中，与碰巧存在的任何受体结合。
You said the receptors are everywhere, and then this significant improvement in social cognition.
你说受体无处不在，然后社会认知的显着改善。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So that raises all sorts of interesting questions about what relevant circuits are impacted.
因此，这就提出了各种有趣的问题，即哪些相关电路受到了影响。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Or could it be some global increase in awareness of surroundings?
或者可能是全球对周围环境的认识有所提高？
Although some autistic kids are overwhelmed by their awareness of surroundings.
尽管一些自闭症孩子对周围环境的意识不知所措。
So, what are some thoughts about how vasopressin might be working to exert this really impressive and frankly, important effect?
那么，对于加压素如何发挥这种令人印象深刻且坦率地说重要的作用，有哪些想法呢？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So could it increase social motivation?
那么它可以增加社会动力吗？
So let's talk about how complexity of social sensory processing.
那么我们来谈谈社会感觉处理的复杂性如何。
Is it that we're directing attention to social cues where there wouldn't have necessarily been as much attentiveness?
是不是我们将注意力集中在社交线索上，而这些线索不一定有那么多的关注？
Are we increasing social motivation, which would suggest from some of the animal studies may actually be happening?
我们是否正在增加社会动机，这从一些动物研究中可以看出，这实际上可能正在发生？
We don't know.
我们不知道。
And I think that's partly when you have other models or if you're able to do imaging studies.
我认为这在一定程度上是因为你有其他模型或者你能够进行成像研究。
One thing that's been a little bit of a holy grail in this field is that if we could get tracers that are basically a molecule that would allow us to inject it into somebody and then visualize the brain, like if I'm thinking about a PET tracer or a radioligand, where you could then ask questions about what's happening in the brain.
在这个领域有一点点圣杯的是，如果我们能够获得基本上是一种分子的示踪剂，我们可以将其注射到某人体内，然后可视化大脑，就像我正在考虑 PET 示踪剂或放射性配体一样，然后你可以询问有关大脑中发生的情况的问题。
Can we give vasopressin in the context of a functional brain imaging scan and ask where is the vasopressin binding?
我们能否在功能性脑成像扫描的背景下给予加压素并询问加压素结合在哪里？
What kind of circuits are involved?
涉及哪些电路？
That needs to be the next step of the work to know where our targets are.
这需要成为下一步工作，以了解我们的目标在哪里。
And you can do something like functional proteomics, where if you know where vasopressin receptors are, you can overlay that with studies of functional brain imaging.
你可以做一些类似功能蛋白质组学的事情，如果你知道加压素受体在哪里，你可以将其与功能性脑成像研究相结合。
And that would allow you to say, these areas are dense in vasopressin receptors, and do we see similar responses in what we call bold signal on a brain scan?
这会让你说，这些区域的加压素受体密集，我们在大脑扫描中所谓的“大胆信号”中是否看到了类似的反应？
So let's be more colloquial about this.
所以让我们用更口语化的方式来讨论这个问题。
Do certain areas of the brain light up, if you will, where we know vasopressin receptors are densely distributed, in ways that we know are tied to social motivation or social salience or other things that we think could be moving the needle here in the trial.
如果你愿意的话，大脑的某些区域是否会亮起来，我们知道加压素受体在这些区域密集分布，我们知道这些区域与社会动机或社会显着性或我们认为可能在试验中发挥作用的其他因素有关。
How is this happening?
这是怎么发生的？
And I think, the reason why we did this work is, and I think it speaks to what you said earlier, is there is an urgency on the part of parents to say, "My child's brain is developing." And there's a sense of that the Western model has failed a lot of people.
我认为，我们做这项工作的原因是，我认为这符合你之前所说的，是父母迫切需要说：“我孩子的大脑正在发育。”人们感觉西方模式让很多人失望了。
They look to doctors and say, "What are the solutions?" And doctors will say, "Well, we have a limited number of tools in the toolkit here.
他们向医生询问：“解决方案是什么？”医生会说：“好吧，我们这里的工具箱中的工具数量有限。
We just don't know." And so, one of the reasons why they did that big oxytocin study was that people were trying to get the oxytocin anyway.
我们只是不知道。”因此，他们进行大规模催产素研究的原因之一是人们无论如何都想获得催产素。
So it was like, let's just make sure that this is safe.
所以就像，让我们确保这是安全的。
Let's see if it's effective.
让我们看看是否有效。
And so some of our thinking was as soon as some of this work hits- ...
因此，一旦这项工作完成，我们的一些想法是——......
and some of the work has been covered by the media.
部分作品被媒体报道。
And so our feeling was we can give this intranasally, and we can do it under safe monitoring ways.
所以我们的感觉是我们可以通过鼻内给药，并且我们可以在安全的监测方式下进行。
And so people are going to think about doing these things anyway, so let's just make sure that this is safe, and let's test this in a rigorous way.
因此人们无论如何都会考虑做这些事情，所以让我们确保这是安全的，并以严格的方式进行测试。
So we don't know the mode of action, but then our feeling is that, at least from the initial safety data, it looks pretty safe.
所以我们不知道作用方式，但我们的感觉是，至少从最初的安全数据来看，它看起来相当安全。
And so the idea would be, and there's a long tradition in psychiatry of we don't know the mechanism of action, but if we have a medication that can be impactful and improve the lives of people with autism, and we can diminish suffering, and people can more readily reach their full potential, to me, it actually seems unethical not to move forward in a way that's scientifically sound.
所以这个想法是，精神病学有一个悠久的传统，我们不知道作用机制，但如果我们有一种药物可以有效并改善自闭症患者的生活，我们可以减少痛苦，人们可以更容易地充分发挥潜力，对我来说，不以科学合理的方式前进实际上似乎是不道德的。
Andrew Huberman:
安德鲁·休伯曼：
All right.
好吧。
Amen to that.
阿门。
This seems like a good time to raise the topic of the microbiome, and not as an unrelated topic, and here's why.
这似乎是提出微生物组主题的好时机，而不是作为一个不相关的主题，原因如下。
I've seen a fair number of studies in mouse models arguing that in a mouse model of autism, which now, frankly, I have to wonder about the power of that model.
我已经看到相当多的小鼠模型研究表明，在自闭症小鼠模型中，现在，坦率地说，我不得不怀疑该模型的力量。
But anyway, the models are out there in the field.
但无论如何，模型已经在现场了。
One can take the microbiome, basically, let's be direct, fecal transplants from a, and here I'm using air quotes, non-autistic mouse, or a mouse that doesn't have social interaction deficits, and put that fecal transplant into a host that does have social deficits and rescue some degree of social deficits.
基本上，我们可以直接将微生物组从非自闭症小鼠或没有社交互动缺陷的小鼠中进行粪便移植，然后将粪便移植到确实有社交缺陷的宿主中，并挽救一定程度的社交缺陷。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I don't know if this has actually been done in humans as well.
我不知道这是否真的在人类身上也发生过。
And for those of you that are cringing, yes, they do fecal transplants in humans for treatment of obesity and a bunch of other things.
对于那些感到畏缩的人来说，是的，他们对人类进行粪便移植以治疗肥胖和其他一些疾病。
This isn't because scientists are obsessed with fecal matter.
这并不是因为科学家们痴迷于粪便。
It's because fecal matter contains a lot of the microbiome elements, so the microbacteria of the gut.
这是因为粪便中含有大量微生物组元素，即肠道微生物。
And the reason I'm raising this now is one possibility, and it's not mutually exclusive with a brain mechanism, is that the administration of vasopressin somehow rescued a vasopressin deficiency in the gut.
我现在提出这个问题的原因是一种可能性，并且它与大脑机制并不相互排斥，是加压素的施用以某种方式挽救了肠道中的加压素缺乏。
So the questions are as follows: Is there any evidence that vasopressin is manufactured in or impacted by the gut microbiome of humans?
因此，问题如下：是否有任何证据表明加压素是在人类肠道微生物群中产生或受其影响的？
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
Andrew Huberman:
安德鲁·休伯曼：
We'll just start with humans-
我们先从人类开始——
Dr. Karen Parker:
凯伦·帕克博士：
Okay
好的
Andrew Huberman:
安德鲁·休伯曼：
...
...
since I think most-- And because that wouldn't be a smoking gun, but it'd be an interesting-
因为我认为大多数——而且因为这不是铁证，但它会是一个有趣的——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
detective story.
侦探故事。
Dr. Karen Parker:
凯伦·帕克博士：
Well, okay, so the one piece of evidence that I will say that I find provocative and fascinating, and one thing I want to say is I think there's really great work done in mice.
好吧，好吧，所以我要说的一个证据是我觉得具有挑战性和令人着迷的，我想说的一件事是我认为在老鼠身上做了非常伟大的工作。
I don't want to be a mouse basher.
我不想成为一个打老鼠的人。
So I want to just go on the record that I'm not bashing other models.
所以我想郑重声明一下，我并不是在抨击其他模特。
If it's a conserve-- So I think about everything from an evolutionary perspective.
如果它是一个保护区——那么我从进化的角度思考一切。
If a mouse shares a brain structure with a human and it's highly conserved, mouse work can be incredibly important and very impactful, right?
如果老鼠与人类共享大脑结构并且高度保守，那么老鼠的工作就会非常重要并且非常有影响力，对吗？
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
My lab did years of mouse work-
我的实验室做了多年的小鼠研究-
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
some primate work where necessary.
必要时进行一些灵长类工作。
Now I only work on humans.
现在我只研究人类。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But absolutely.
但绝对是。
It has its uses.
它有它的用途。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
But clearly, the primate model for social deficits as it relates to autism, you at least have me convinced that that one has a lot of power.
但显然，与自闭症相关的社会缺陷灵长类动物模型，你至少让我相信这个模型拥有很大的力量。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Let's just say that.
就这么说吧。
Dr. Karen Parker:
凯伦·帕克博士：
Exactly.
正是如此。
Okay, but I'm going to now say there is a really cool mouse study that was done that I found, and there's been lots of different studies.
好吧，但我现在要说的是，我发现了一项非常酷的小鼠研究，并且有很多不同的研究。
So there's been mice, so there's these, like I said, these genetically modified mice that have genetic syndromes where the individuals have social impairments.
所以有老鼠，所以有这些，就像我说的，这些转基因老鼠患有遗传综合症，个体有社交障碍。
And some of these individuals, and again, here's a problem with the field.
其中一些人，再次，这是该领域的问题。
Often, they will measure oxytocin but not vasopressin.
通常，他们会测量催产素，但不会测量加压素。
So, they're not often both measured together, which I always do now.
因此，它们通常不会一起测量，而我现在总是这样做。
But there's been some really interesting evidence that in these mouse models that, and again, multiple studies, but certainly low blood oxytocin levels in these mouse models, and with a sense that maybe they have some sort of abnormal gut microbiome.
但有一些非常有趣的证据表明，在这些小鼠模型中，再次进行多项研究，但这些小鼠模型中的血液催产素水平肯定较低，并且感觉它们可能具有某种异常的肠道微生物组。
And then what they've done is they've given a probiotic to these mice, normalized their social functioning, and there was an increase in oxytocin, and in a recent study, also vasopressin, at the level of the hypothalamus.
然后他们所做的是给这些小鼠服用益生菌，使它们的社会功能正常化，催产素有所增加，在最近的一项研究中，下丘脑水平的加压素也有所增加。
So by giving a probiotic, I believe the oxytocin levels were increased in the blood.
因此，通过给予益生菌，我相信血液中的催产素水平会增加。
You saw more species-typical social behavior, and this was all driven by this upregulation of oxytocin gene expression, and also vasopressin in this very recent study.
你看到了更多物种典型的社会行为，这都是由催产素基因表达的上调以及最近这项研究中的加压素驱动的。
And what's interesting is there's this nerve called the vagus nerve, which is, I think, it means the wandering nerve.
有趣的是有一种神经叫做迷走神经，我认为它的意思是游走神经。
Andrew Huberman:
安德鲁·休伯曼：
It's for vagabond.
是给流浪汉用的
Dr. Karen Parker:
凯伦·帕克博士：
Yeah, exactly.
是的，完全正确。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And it's in the gut, but it actually has a direct projection to the nuclei in the hypothalamus where oxytocin and vasopressin are made.
它在肠道中，但实际上它直接投射到产生催产素和加压素的下丘脑的细胞核。
Andrew Huberman:
安德鲁·休伯曼：
Oh, interesting.
哦，有趣。
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
And so when you sever the vagus, you then in this one study, it's a neuron paper, I think it's like 2020.
所以当你切断迷走神经时，你在这项研究中，这是一篇神经元论文，我认为这就像 2020 年。
It's a super cool paper.
这是一张超级酷的纸。
And then what you do is you decrease the gene expression, and you don't see the rescue of the oxytocin levels or the social behavior in this model.
然后你所做的就是降低基因表达，并且在这个模型中你看不到催产素水平或社会行为的拯救。
Andrew Huberman:
安德鲁·休伯曼：
So, in other words, if I interpret this correctly, and I'll go look up the paper-
所以，换句话说，如果我解释正确的话，我会去查一下论文——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and provide a link to it.
并提供一个链接。
By increasing the diversity of gut microbiota, because that's really what a probiotic does-
通过增加肠道微生物群的多样性，因为这确实是益生菌的作用——
Dr. Karen Parker:
凯伦·帕克博士：
Exactly
正是如此
Andrew Huberman:
安德鲁·休伯曼：
...
...
sort of across the board increases the diversity of gut microbiota, no one specific alis, as I always say, because they all seem to end in alis.
某种程度上全面增加了肠道微生物群的多样性，正如我常说的，没有特定的 alis，因为它们似乎都以 alis 结尾。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Multiple alises.
多个别名。
Alises?
艾莉丝？
Alisae.
艾莉萨。
Here we go again.
又来了。
You upregulate gene expression and thereby action of oxytocin and vasopressin in the hypothalamus.
您上调基因表达，从而上调下丘脑中催产素和加压素的作用。
But that's a neural mediated thing.
但这是神经介导的事情。
It's not as if the microbiota travel to the brain.
微生物群并没有进入大脑。
Something changes in the gut, which activates the vagal pathway from gut to the specific nucleus in the brain.
肠道发生了一些变化，激活了从肠道到大脑特定核的迷走神经通路。
And we know that the vagal pathway is involved because it seems at least partially necessary.
我们知道迷走神经通路参与其中，因为它似乎至少部分是必要的。
If you sever that, you give a vagotomy, then-
如果你切断它，你就会进行迷走神经切断术，然后-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
this effect is blunted-
这种效果被削弱了——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
or eliminated.
或被淘汰。
That's very interesting and ties the microbiome to oxytocin vasopressin production in a neural and somewhat causal way, and makes the data on fecal transplants make a lot of more sense.
这非常有趣，并且以神经和某种程度上因果的方式将微生物组与催产素加压素的产生联系起来，并使粪便移植的数据更有意义。
Because I always wondered, okay, so taking the microbiota from one animal and putting them into another animal-
因为我总是想知道，好吧，所以从一只动物身上取出微生物群并将其放入另一只动物体内 -
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
you're transferring the milieu of the gut.
你正在转移肠道环境。
But it doesn't say anything about mechanism.
但它没有提及任何有关机制的内容。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So this is a really cool paper.
所以这是一篇非常酷的论文。
Dr. Karen Parker:
凯伦·帕克博士：
It's fascinating.
这很有趣。
And there's also a study I've always wanted to do, is you can get a vagal nerve stimulator.
还有一项我一直想做的研究，就是你可以获得迷走神经刺激器。
They used to do them as implants, right?
他们过去常常把它们当作植入物，对吗？
But you can also get one that you sort of clip onto the ear.
但你也可以买一个夹在耳朵上的。
And I've always wanted to ask, if we use this in autistic individuals, could we increase, can we alter social behavior, right?
我一直想问，如果我们在自闭症患者身上使用它，我们是否可以增加、改变社会行为，对吧？
And would that be something that we could actually measure in the blood, especially if we're seeing this change in these blood levels, right?
这是否是我们可以在血液中实际测量的东西，特别是如果我们看到这些血液水平的变化，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Are you doing that experiment?
你在做那个实验吗？
Dr. Karen Parker:
凯伦·帕克博士：
No. But I've always said it would be so cool.
不，但我一直说那会很酷。
Andrew Huberman:
安德鲁·休伯曼：
We have to get you the funding to do that experiment.
我们必须为你提供资金来进行该实验。
And I know a few times you've raised the issue of funding.
我知道您曾多次提出资金问题。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
It's not something we spend a lot of time discussing on this podcast, but I think what should be abundantly clear to the listeners throughout the course of this episode, as you mentioned earlier, you're very determined to get work done.
这不是我们在这个播客上花费大量时间讨论的事情，但我认为在整个过程中听众应该非常清楚，正如您之前提到的，您非常决心完成工作。
You'll figure out a way.
你一定会想出办法的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But the way I describe finances and research is that it's absolutely necessary, but it's not sufficient.
但我描述财务和研究的方式是，它是绝对必要的，但还不够。
You, of course, have to have the right people and the right lab head directing the work, but no money, no project.
当然，你必须有合适的人和合适的实验室负责人来指导工作，但没有钱，没有项目。
And it is disappointing to see that despite the federal budget for research being still reasonable, it's not what we would like it to be, it's still very hard for amazing world-class labs like yours to say, "Hey, listen, there's this vagal thing," and clearly there's a rationale.
令人失望的是，尽管联邦研究预算仍然合理，但这并不是我们希望的那样，对于像你们这样令人惊叹的世界级实验室来说，仍然很难说，“嘿，听着，有这种迷走神经的东西”，而且显然这是有道理的。
It's not like you're pulling this out of nowhere.
这并不是说你凭空把它拉出来。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And you want to go do this study, but what we're really talking about is three to five years of grant writing before you could even initiate that study.
你想做这项研究，但我们真正讨论的是在你开始这项研究之前需要三到五年的拨款写作。
Dr. Karen Parker:
凯伦·帕克博士：
Exactly.
正是如此。
Andrew Huberman:
安德鲁·休伯曼：
Meanwhile, autistic kids are going from age two to five to six.
与此同时，自闭症儿童的年龄从两岁到五岁到六岁。
These are critical windows, so if ever there was a rationale for moving a lot of funding to, I don't even call it high risk, but logically sound hypothesis testing for the treatment of autism, it's now.
这些是关键的窗口，所以如果有理由将大量资金转移到，我什至不称其为高风险，而是逻辑上合理的自闭症治疗假设检验，那就是现在。
So I'm going to get active on this front.
所以我将在这方面积极行动。
So I won't get into how, but when I get something in my neural circuits for talking, they tend to not shut down for a while, so.
所以我不会讨论如何进行，但是当我的神经回路中有一些东西可以说话时，它们往往不会关闭一段时间，所以。
Dr. Karen Parker:
凯伦·帕克博士：
Well, there will be a community that is going to be immensely grateful.
好吧，将会有一个社区会非常感激。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Well, it seems like the parents of these kids and the kids themselves could greatly benefit.
嗯，看来这些孩子的父母和孩子们自己都会受益匪浅。
So you mentioned that the first study on vasopressin administration that saw these improvements in social functioning, you said a small cohort.
所以你提到第一个关于加压素管理的研究看到了社会功能的这些改善，你说的是一小群人。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
How many kids was it ultimately that you could use data from?
您最终可以使用多少个孩子的数据？
Dr. Karen Parker:
凯伦·帕克博士：
Okay.
好的。
You screen a lot, because we had very rigid criteria, so we ended up with 17 kids that were on active drug and 13 that were on placebo.
你进行了很多筛选，因为我们有非常严格的标准，所以我们最终选出了 17 名服用活性药物的孩子和 13 名服用安慰剂的孩子。
And then-
然后——
Andrew Huberman:
安德鲁·休伯曼：
So not a tiny study.
所以这不是一个小研究。
Dr. Karen Parker:
凯伦·帕克博士：
No. And we always have a humanitarian open label extension arm, which allows for anybody who is in placebo can get access to the drug.
不会。我们始终有一个人道主义开放标签延伸臂，允许任何服用安慰剂的人都可以获得该药物。
So both Antonio and I feel very strongly about making sure that if we're doing a medication trial, everybody can benefit from it, right?
因此，安东尼奥和我都强烈希望确保如果我们正在进行药物试验，每个人都能从中受益，对吧？
So-
所以——
Andrew Huberman:
安德鲁·休伯曼：
Afterwards, if they say, "Okay, I was in the placebo group-
之后，如果他们说：“好吧，我在安慰剂组中——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
but I really want the chance to try this thing-"
但我真的很想有机会尝试这个东西——”
Dr. Karen Parker:
凯伦·帕克博士：
Yes
是的
Andrew Huberman:
安德鲁·休伯曼：
...
...
they can.
他们可以。
But then you also get more data.
但随后您还会获得更多数据。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So I think when the families are now aware that their child is on vasopressin and the clinicians are aware, there's a huge placebo response rate, right?
所以我认为，当家庭现在意识到他们的孩子正在服用加压素并且临床医生也意识到时，安慰剂反应率很高，对吗？
And so, it's not a placebo response rate here, but we really would want to make sure that our evaluation of the social behavior is done unaware to the medication.
因此，这不是安慰剂反应率，但我们确实希望确保我们对社会行为的评估是在不了解药物的情况下进行的。
But you can get good safety data, right?
但你可以获得良好的安全数据，对吗？
So you can have those 13 children who were on placebo.
所以你可以生下那 13 个服用安慰剂的孩子。
We can then also make sure that their blood chemistry labs look good, that their electrocardiograms look good, right?
然后我们还可以确保他们的血液化学实验室看起来不错，他们的心电图看起来不错，对吧？
And so that also allows us to assess safety parameters in a greater number of children.
因此，这也使我们能够评估更多儿童的安全参数。
Andrew Huberman:
安德鲁·休伯曼：
In a fairly broad literature search, I was able to find, okay, microbiome, so fecal transplant-
在相当广泛的文献检索中，我能够找到，好吧，微生物组，所以粪便移植-
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh
嗯嗯
Andrew Huberman:
安德鲁·休伯曼：
...
...
is something that people are excited about, as weird as it-
是人们感到兴奋的事情，尽管很奇怪-
Dr. Karen Parker:
凯伦·帕克博士：
And there are trials in people with autism ongoing.
针对自闭症患者的试验正在进行中。
Andrew Huberman:
安德鲁·休伯曼：
Using fecal transplants?
使用粪便移植吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yes.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Oxytocin nasal spray, presumably still being investigated by some groups, or it's been abandoned?
催产素鼻喷雾剂，大概仍在被某些团体研究，或者已经被放弃了？
Dr. Karen Parker:
凯伦·帕克博士：
Well, I think it's mostly been abandoned because there's no funding priorities for it, right?
嗯，我认为它大部分被放弃了，因为它没有资金优先事项，对吗？
So I know that maybe in Australia, because of Adam's positive findings, that I don't know what his plans are, but maybe he's doing work there.
所以我知道也许在澳大利亚，由于亚当的积极发现，我不知道他的计划是什么，但也许他正在那里工作。
There might be a little bit of work with behavioral therapy and oxytocin, but this is the problem.
行为疗法和催产素可能会起到一些作用，但这就是问题所在。
When there's one big trial that fails, the funding just completely dries up.
当一项大型试验失败时，资金就会完全枯竭。
So even if there's promise, I don't know a single funding agency that's going to touch it.
因此，即使有希望，我也不知道有哪个资助机构会这么做。
Andrew Huberman:
安德鲁·休伯曼：
Got it.
明白了。
And then there's the vasopressin administration work that you're doing.
然后是您正在做的加压素管理工作。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
I think it's worth contrasting that work with the fairly large trial that was done by a major pharmaceutical company exploring the role of vasopressin for the treatment of autism.
我认为值得将这项工作与一家大型制药公司进行的相当大的试验进行对比，该试验探索加压素在治疗自闭症方面的作用。
You could tell us what they did, because it's basically the opposite of what you did.
你可以告诉我们他们做了什么，因为这基本上与你所做的相反。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And you can tell us the outcome.
你可以告诉我们结果。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Because I think that if anything, that study inadvertently provides support for the results that you observed, which is that administering, let's say, increasing vasopressin levels in the brain seems to ameliorate some of the social deficits-
因为我认为，如果有的话，这项研究无意中为你观察到的结果提供了支持，也就是说，增加大脑中的加压素水平似乎可以改善一些社交缺陷——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
of autism.
自闭症。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
So, Roche had a compound called balovaptan, which was a vasopressin V1a receptor antagonist, which basically means, I think I mentioned there's these four neuropeptide receptors, and oxytocin vasopressin bind to each other's receptors.
所以，罗氏有一种叫做 balovaptan 的化合物，它是一种加压素 V1a 受体拮抗剂，这基本上意味着，我想我提到过有这四种神经肽受体，催产素加压素与彼此的受体结合。
But the V1a receptor is the one that is most implicated in social behavior.
但 V1a 受体是与社会行为关系最密切的受体。
And this is the tricky part about when medications are developed in pharma versus in academics, right?
这是制药公司和学术界何时开发药物的棘手部分，对吗？
In academics, there's definitely this transparency.
在学术界，绝对存在这种透明度。
We write grants.
我们写赠款。
The abstracts are publicly available.
摘要是公开的。
We register our trials.
我们登记我们的试验。
They do, too.
他们也这样做。
But a lot of the, shall we say, early development is all put out in publications, right?
但是，我们可以说，早期开发的很多内容都发表在出版物中，对吧？
And then it's also peer-reviewed.
然后它也会经过同行评审。
And there's an open trail of why we're doing what we're doing.
关于我们为什么要做我们正在做的事情，有一个公开的线索。
But in a pharmaceutical company, they have the ability, because also they have all the funding, to be able to do all kinds of development that may never see the light of day because of the proprietary basis of it, right?
但在一家制药公司，他们有能力，因为他们也有所有的资金，能够进行各种可能因为专有基础而永远不会见光的开发，对吗？
And so when you go back to-- So it still is not clear to me why they took the approach of using an antagonist to the main vasopressin receptor in the brain.
所以当你回到——所以我仍然不清楚为什么他们采取使用大脑主要加压素受体拮抗剂的方法。
What's interesting is if you go back and you look at the animal literature, there are hamsters that if you give them vasopressin, they become aggressive, right?
有趣的是，如果你回顾一下动物文献，就会发现有些仓鼠，如果你给它们加压素，它们就会变得具有攻击性，对吗？
And if you give male prairie voles vasopressin, they can become aggressive.
如果给雄性草原田鼠注射加压素，它们就会变得具有攻击性。
But let's think about the context that they're doing this in.
但让我们考虑一下他们这样做的背景。
These hamsters that show aggression are asocial.
这些表现出攻击性的仓鼠是不合群的。
They live by themselves.
他们自己生活。
If you give them vasopressin and the only social repertoire they have is to have sex with a female or to fight a male that they see, they have a very limited social repertoire, right?
如果你给它们加压素，而它们唯一的社交技能就是与女性发生性关系或与他们看到的男性打斗，那么它们的社交技能就非常有限，对吗？
And when the prairie vole male is being given vasopressin, it's often in the context of protecting his mate and his offspring, and so then it's actually species appropriate for him to attack a marauding male on his territory who's going to kill his babies, right?
当雄性草原田鼠被给予加压素时，通常是为了保护他的配偶和后代，所以实际上这是适合他攻击其领地内的掠夺性雄性并杀死他的孩子的物种，对吗？
And so my thinking in reading the preclinical literature, the animal literature, was that, all right, that makes a lot of sense in the context of those species, but we've never seen any evidence in our trial.
因此，我在阅读临床前文献、动物文献时的想法是，好吧，这在这些物种的背景下很有意义，但我们在试验中从未看到任何证据。
Aggression didn't change.
攻击性没有改变。
We also have an aggression measure in the current trial as well.
在当前的试验中我们也有一个攻击措施。
But for me, the vast majority of evidence from the animal literature suggested that vasopressin was pro-social, and that especially given our CSF findings, like over and over, across species, across studies, across ages, that we should be giving vasopressin, especially given the correlations between vasopressin in CSF and symptom severity and autistic traits, the former in people and the latter in the monkeys.
但对我来说，来自动物文献的绝大多数证据表明，加压素是有利于社会的，特别是考虑到我们的脑脊液发现，比如一遍又一遍、跨物种、跨研究、跨年龄，我们应该给予加压素，特别是考虑到脑脊液中的加压素与症状严重程度和自闭症特征之间的相关性，前者在人类中，后者在猴子中。
And so they had some preliminary studies that I believe were maybe single dose, one that they published.
因此，他们进行了一些初步研究，我认为这些研究可能是单剂量的，他们发表了一项研究。
But then they had a trial where the primary outcome measure, the social responsiveness scale, was negative.
但随后他们进行了一项试验，主要结果指标——社会反应量表——为负。
And then they had some secondary measures that maybe showed some promise.
然后他们采取了一些可能显示出一些希望的次要措施。
And then they were conducting another trial, and then they did a futility analysis, and I know they stopped the trial.
然后他们进行了另一项试验，然后他们进行了无效分析，我知道他们停止了试验。
And I don't think it was for safety reasons, but again, a lot of this isn't made public, right, because it's a pharmaceutical company.
我不认为这是出于安全原因，但同样，其中很多内容都没有公开，对吧，因为它是一家制药公司。
So we will see, because we are going to be completing our larger trial this year, and as they say, the proof is in the pudding, so we will see if we can replicate our initial pilot findings.
所以我们会看到，因为我们今年将完成更大规模的试验，正如他们所说，证据就在布丁中，所以我们将看看是否可以复制我们最初的试点结果。
Andrew Huberman:
安德鲁·休伯曼：
Well, it sounds like they got it backwards, that blocking vasopressin pathways would just make things worse, and that augmenting vasopressin makes things better, although that last statement needs to be supported by this more extensive-
好吧，听起来他们好像搞反了，阻断加压素通路只会让事情变得更糟，而增加加压素会让事情变得更好，尽管最后一个说法需要得到更广泛的支持——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
population.
人口。
Dr. Karen Parker:
凯伦·帕克博士：
Well, I think there's been a lot of speculation, and maybe there are people closer to the trial than me who might be able to speak to mechanism.
嗯，我认为有很多猜测，也许还有比我更了解审判的人可能能够谈论机制。
But I would meet the Roche people at conferences, and they would come to my talks, and I would always ask them, "What's the mechanism of action?
但我会在会议上见到罗氏的人，他们会来参加我的演讲，我总是会问他们，“作用机制是什么？
Why are you antagonizing the system when we're giving a vasopressin agonist," if you will.
当我们给予加压素激动剂时，你为什么要对抗系统呢？”如果你愿意的话。
And some people had said, well, maybe by blocking the vasopressin receptor, there's a way to have oxytocin be more bioavailable.
有些人说，好吧，也许通过阻断加压素受体，有一种方法可以提高催产素的生物利用度。
Andrew Huberman:
安德鲁·休伯曼：
That sounds like some gymnastics to me.
对我来说，这听起来像是体操。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah, I totally agree.
是的，我完全同意。
Andrew Huberman:
安德鲁·休伯曼：
Yeah.
是的。
Dr. Karen Parker:
凯伦·帕克博士：
And so I've never received a compelling response from anybody about why they did their trial and then the differences.
因此，我从未收到任何人关于他们为何进行试验以及差异的令人信服的回应。
When this was ongoing and there was potentially room for both, right?
当这种情况持续进行并且两者都有潜在的空间时，对吗？
I thought that maybe there's some optimal band of vasopressin signaling in the brain, right?
我想大脑中可能存在一些最佳的加压素信号带，对吗？
And so maybe there's some people where they have too much vasopressin and some who have too little, right?
所以也许有些人的加压素过多，有些人的加压素太少，对吗？
And so this was a lot of maybes, but it doesn't, to me, seem like that's the case, especially if our current trial has a positive readout.
所以这有很多可能，但对我来说，情况似乎并非如此，特别是如果我们当前的试验有积极的结果的话。
Andrew Huberman:
安德鲁·休伯曼：
I'd be remiss if I didn't ask for your stance and read of the landscape on the data about vaccines and autism.
如果我没有询问您的立场并阅读有关疫苗和自闭症的数据情况，那就是我的失职。
I'm not talking about COVID vaccines here.
我不是在这里谈论新冠疫苗。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
I want to be really clear about that.
我想澄清这一点。
But there was a theory running about, not just in the press, but in scientific literature for a while, that vaccines could cause autism.
但有一种理论不仅在媒体上流传，而且在科学文献中也流行了一段时间，即疫苗可能会导致自闭症。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
That was proposed.
这是有人提议的。
My understanding is that was debunked.
我的理解是，这已经被揭穿了。
That idea still lives on the internet.
这个想法仍然存在于互联网上。
But what is the evidence?
但证据是什么？
Or let's go through this sequentially.
或者让我们依次讨论一下。
What was the idea?
有什么想法吗？
What was the evidence for that idea?
这个想法的证据是什么？
And then What caused the demise of the-
然后是什么导致了——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
at least the scientific support for that idea?
至少这个想法有科学支持吗？
Leaving open, of course, that new data may come.
当然，保持开放状态，新数据可能会出现。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
But let's talk about what is known now.
但让我们谈谈现在已知的事情。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
And I think what I will say is being evidence-based is sort of something that all scientists should strive for, right?
我认为我要说的是基于证据是所有科学家都应该努力的目标，对吗？
And so the backstory on this is there was a guy named Andrew Wakefield who published a paper, and he basically said that preservatives in vaccines are causing autism.
背后的故事是，有一个名叫安德鲁·韦克菲尔德（Andrew Wakefield）的人发表了一篇论文，他基本上说疫苗中的防腐剂会导致自闭症。
Andrew Huberman:
安德鲁·休伯曼：
So not the specific vaccine, but the adjuvant, the stuff that's preserving-
所以不是特定的疫苗，而是佐剂，保存的东西-
Dr. Karen Parker:
凯伦·帕克博士：
Like mercury was one of them
就像水银就是其中之一一样
Andrew Huberman:
安德鲁·休伯曼：
...
...
the stuff that's keeping the vaccines bio-effective.
保持疫苗生物有效性的物质。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
At least that was my understanding, right?
至少这是我的理解，对吧？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Yeah, that's mine as well.
是的，那也是我的。
Dr. Karen Parker:
凯伦·帕克博士：
And so, and then it turned-
所以，然后事情就变成了——
Andrew Huberman:
安德鲁·休伯曼：
But I want to be clear because the internet is a cruel and- ...
但我想澄清一下，因为互联网是残酷的......
diabolical place.
恶魔般的地方。
My stance is that that was the hypothesis.
我的立场是，这就是假设。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
I don't agree with that stance.
我不同意这个立场。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
And so or if we want to just back up a little bit broader, there was this idea that something about vaccines were causing autism, but the study was debunked.
因此，或者如果我们想支持得更广泛一些，有一种观点认为疫苗会导致自闭症，但这项研究被揭穿了。
He lost his medical license, and the paper was retracted, right?
他失去了行医执照，论文也被撤回了，对吗？
Andrew Huberman:
安德鲁·休伯曼：
Well, he lost his medical license on the basis of the fact that the study was wrong, or was there ev-
好吧，他被吊销了行医执照，因为这项研究是错误的，或者是——
Dr. Karen Parker:
凯伦·帕克博士：
I think he faked the data
我认为他伪造了数据
Andrew Huberman:
安德鲁·休伯曼：
...
...
there were...
有……
That's what I recall as well-
我也是这样回忆的——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
that there was evidence of him literally making up the data.
有证据表明他确实捏造了这些数据。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Right.
对。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
So it wasn't a case of sloppy technique, it was a case of-
所以这不是技术马虎的问题，而是——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
of intentional fraud.
的故意欺诈。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
That's my understanding.
这是我的理解。
Again-
再说一遍——
Andrew Huberman:
安德鲁·休伯曼：
What was the...
那是什么...
Does anyone ever look into what his motivation for what it was?
有没有人调查过他这样做的动机是什么？
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Like why someone would...
就像为什么有人会...
I mean, he threw away his whole career.
我的意思是，他放弃了自己的整个职业生涯。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Yeah, I don't know.
是的，我不知道。
But I think the hard part about that is understandably, people got very frightened, right, that we're doing something to our children that could have unanticipated consequences.
但我认为其中最困难的部分是可以理解的，人们非常害怕，对吧，我们正在对我们的孩子做一些可能会产生意想不到的后果的事情。
And when something like that happens, then we dump a...
当类似的事情发生时，我们就会抛弃......
We spend a lot of money investigating it.
我们花了很多钱来调查它。
And so the good news is at this point, there have been multiple, multiple studies that haven't shown a correlation between vaccines and autism.
因此，目前的好消息是，已有多项研究尚未表明疫苗与自闭症之间存在相关性。
I do believe the preservatives have been changed as a result, so that's something we should check.
我确实相信防腐剂因此发生了变化，所以这是我们应该检查的事情。
That might be something where there's been a public health change on preservatives that are in vaccines.
这可能与疫苗中防腐剂的公共卫生变化有关。
Andrew Huberman:
安德鲁·休伯曼：
That's interesting in its own right.
这本身就很有趣。
We don't want to cause alarm, but that's interesting, that in this data fraud case, it might have cued people to the idea that certain things might have been needing change, even though it wasn't the specific issue that this-
我们不想引起恐慌，但有趣的是，在这个数据欺诈案例中，它可能会提示人们认为某些事情可能需要改变，尽管这不是具体问题——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
fraudulent researcher was focused on.
欺诈性研究人员受到关注。
Dr. Karen Parker:
凯伦·帕克博士：
Or the change was made to make sure people would vaccinate their children, right?
或者做出改变是为了确保人们为他们的孩子接种疫苗，对吗？
So this is something-
所以这就是——
Andrew Huberman:
安德鲁·休伯曼：
I see
我明白了
Dr. Karen Parker:
凯伦·帕克博士：
...
...
that I think we should have lots of caveats here, like post the studies, make sure that what we're saying is accurate, right?
我认为我们应该在这里有很多警告，比如发布研究，确保我们所说的是准确的，对吗？
Andrew Huberman:
安德鲁·休伯曼：
Mm-hmm.
嗯嗯。
Of course.
当然。
Dr. Karen Parker:
凯伦·帕克博士：
But I think that my concern is that we've spent...
但我认为我担心的是我们已经花了......
So the good news is that every single study that I'm aware of does not show a relationship between vaccination and autism, right?
所以好消息是，据我所知，每一项研究都没有表明疫苗接种和自闭症之间存在关系，对吧？
And so I think that most scientists and medical doctors that I know that are part of the standard biomedical research community do not believe that vaccines cause autism.
因此，我认为我认识的大多数属于标准生物医学研究界的科学家和医生都不相信疫苗会导致自闭症。
They vaccinate their own children, they recommend vaccinations to other people's children, and so I think that's where we are.
他们为自己的孩子接种疫苗，他们建议其他人的孩子接种疫苗，所以我认为这就是我们的处境。
Andrew Huberman:
安德鲁·休伯曼：
Could I just ask a question?
我可以问一个问题吗？
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I feel more than obligated to do this because I think I have a pretty good finger on the pulse of the listenership of this podcast, but I think there's a range of stances on this, where some people have a lot of trust in the standard medical establishment, others have less-
我觉得自己有义务这样做，因为我认为我对这个播客听众的脉搏有很好的把握，但我认为对此有多种立场，有些人对标准医疗机构有很大的信任，而另一些人则不太信任——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
trust in the standard medical establishment, and I wouldn't be doing my job if I didn't try and represent-
相信标准的医疗机构，如果我不尝试代表，我就无法完成我的工作-
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
all those sides.
所有这些方面。
And one thing that I've heard, okay, is that over the last 20 or 30 years, there's been a dramatic increase in the number of vaccinations that kids get, and I don't know if that's true, but when we say vaccinations, we could be talking about measles, mumps, rubella-
我听说的一件事是，在过去的 20 或 30 年里，孩子们接种疫苗的数量急剧增加，我不知道这是否属实，但当我们说疫苗接种时，我们可能谈论的是麻疹、腮腺炎、风疹——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
polio.
小儿麻痹症。
We could also be talking about measles, mumps, rubella, polio, flu shots every year-
我们还可以每年谈论麻疹、腮腺炎、风疹、脊髓灰质炎、流感疫苗——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
rabies vaccine, tetanus vaccine.
狂犬病疫苗、破伤风疫苗。
Dr. Karen Parker:
凯伦·帕克博士：
HPV.
HPV。
Andrew Huberman:
安德鲁·休伯曼：
HPV, right, one that wasn't even available when I was in college-
HPV，对吧，我上大学的时候还没有的——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
as everyone in college was well aware, there wasn't an HPV vaccine.
正如大学里的每个人都清楚的那样，当时还没有 HPV 疫苗。
Didn't change people's behavior a whole lot, but there's a vaccine, there's multiple vaccines, and then there's all the vaccines.
并没有彻底改变人们的行为，但有一种疫苗，有多种疫苗，还有所有的疫苗。
Dr. Karen Parker:
凯伦·帕克博士：
Yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
Right?
对吗？
And I think that one of the concerns that I hear about is the idea that, okay, there are some critical vaccines, but then which ones are perhaps less critical, if any?
我认为我听到的担忧之一是这样的想法，好吧，有一些关键的疫苗，但哪些疫苗可能不那么重要（如果有的话）？
And these are the kinds of discussions that are starting to surface-
这些是开始浮出水面的讨论——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
and that have parents and potential parents rightfully thinking about this stuff.
这让父母和潜在的父母正确地思考这个问题。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And no one really knows where to get the information, right?
没有人真正知道从哪里获取信息，对吧？
I've tried, and I can't find a pediatrician that says, "Hey, listen, these but not those," or you can certainly find board-certified physicians that say many and certain board-certified physicians that say none.
我已经尝试过，但我找不到一位儿科医生会说：“嘿，听着，是这些，但不是那些。”或者你当然可以找到许多委员会认证的医生说，而某些委员会认证的医生却什么也不说。
You actually can find those.
你实际上可以找到那些。
Dr. Karen Parker:
凯伦·帕克博士：
Uh-huh.
嗯嗯。
Andrew Huberman:
安德鲁·休伯曼：
The none category tend to hide themselves a little bit more than others, for obvious reasons.
出于显而易见的原因，无类别往往比其他类别更隐藏自己。
But it's hard to get a sense of which vaccines are critical and which ones aren't if you're a parent and you're not versed in this stuff.
但是，如果您是父母并且不熟悉这些东西，则很难了解哪些疫苗至关重要，哪些疫苗不是。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
And so you could imagine that kids are taking many more vaccines, and only some of those are critical, or maybe all of them are critical.
所以你可以想象孩子们正在接种更多的疫苗，但只有其中一些是至关重要的，或者也许所有疫苗都是至关重要的。
Dr. Karen Parker:
凯伦·帕克博士：
Well, I think, I guess the way I would maybe turn it on its head is that because of this study that did, in some ways, so much harm, right, like we spent-
好吧，我想，我想我可能会扭转它的方式是因为这项研究在某些方面确实造成了很大的伤害，对吧，就像我们花了-
Andrew Huberman:
安德鲁·休伯曼：
The Wakefield study
韦克菲尔德研究
Dr. Karen Parker:
凯伦·帕克博士：
...
...
we spent...
我们花了...
I don't even want to hazard a guess about how much money worldwide went into studying vaccines and autism based on fraudulent data, right?
我什至不想冒险猜测全世界有多少钱用于基于欺诈性数据研究疫苗和自闭症，对吗？
That's, to me, a real tragedy because-
对我来说，这是一场真正的悲剧，因为——
Andrew Huberman:
安德鲁·休伯曼：
But at the time, they didn't know it was fraudulent, right?
但当时他们并不知道这是欺诈，对吧？
Dr. Karen Parker:
凯伦·帕克博士：
No, right, exactly.
不，对，完全正确。
Andrew Huberman:
安德鲁·休伯曼：
So they went after this thinking it was true.
所以他们认为这是真的。
Dr. Karen Parker:
凯伦·帕克博士：
Right.
对。
Andrew Huberman:
安德鲁·休伯曼：
Okay.
好的。
Dr. Karen Parker:
凯伦·帕克博士：
But I think the consequence of all this that I think is also extremely sad is that everybody Because everyone got so riled up and so fearful, there has been historically, until recently, many researchers who are like, "Oh, man, I don't want to touch immunology and autism with a 10-foot pole." Right?
但我认为这一切的后果也是极其悲伤的，因为每个人都变得如此愤怒和恐惧，从历史上看，直到最近，许多研究人员都在说，“哦，伙计，我不想用一根 10 英尺长的杆子来触及免疫学和自闭症。”正确的？
And yeah.
是的。
Andrew Huberman:
安德鲁·休伯曼：
And I wouldn't consider myself fearless, but my lab never had any reason to work on those-
我不会认为自己无所畏惧，但我的实验室从来没有任何理由去研究这些——
Dr. Karen Parker:
凯伦·帕克博士：
Yeah
是啊
Andrew Huberman:
安德鲁·休伯曼：
...
...
on those important problems.
关于那些重要的问题。
But I'll tell you, it seems like it's not a kettle of fish, it's a ball of barbed wire-
但我告诉你，看起来这不是一壶鱼，而是一团铁丝网——
Dr. Karen Parker:
凯伦·帕克博士：
Right
右
Andrew Huberman:
安德鲁·休伯曼：
...
...
with a bunch of napalm burning around it.
周围燃烧着一堆凝固汽油弹。
Dr. Karen Parker:
凯伦·帕克博士：
Totally.
完全可以。
Andrew Huberman:
安德鲁·休伯曼：
When you say one thing, your career's ending.
当你说出一件事时，你的职业生涯就结束了。
You say the opposite thing, your career is also ending.
你说反了，你的职业生涯也结束了。
It's a mess.
真是一团糟。
Dr. Karen Parker:
凯伦·帕克博士：
But I think this highlights that there are so many parents, again, and I think we need to listen to parent stakeholders, right?
但我认为这再次凸显了有这么多家长，我认为我们需要倾听家长利益相关者的意见，对吗？
There needs to be a dialogue whenever anybody's studying any illness, to talk to the people who are involved, right?
每当有人研究任何疾病时，就需要与相关人员进行对话，对吗？
And I think that there are parents who will report, "Wow, there is immune system dysregulation in my child." But because of this historical issue with vaccines, it's only been very recently that I think people, scientists, medical doctors, have said, "Okay, we're hearing a lot about this from parents, and are there a group of individuals who have immune issues that could be driving their autism?" Right?
我认为有些家长会报告，“哇，我的孩子有免疫系统失调。”但由于疫苗的历史问题，我认为人们、科学家、医生直到最近才说：“好吧，我们从父母那里听到了很多关于这个问题的信息，是否有一群人存在免疫问题，可能会导致他们患上自闭症？”正确的？
We don't know, and everything should be evidence-based.
我们不知道，一切都应该以证据为基础。
But I think that, like you said, with this cancel culture and all this fear, scientists sometimes will pick topics very judiciously based on, "Hey, I just want to be left in peace, and I'm trying to help this community." And if there is areas of the enterprise that you think are going to cause all kinds of grief, then people are going to be less reluctant to study them, even if it's critically needed.
但我认为，正如你所说，在这种取消文化和所有这些恐惧的情况下，科学家有时会非常明智地选择主题，基于“嘿，我只是想保持平静，我正在努力帮助这个社区。”如果你认为企业的某些领域会引起各种痛苦，那么人们就不会那么不愿意研究它们，即使它是迫切需要的。
Andrew Huberman:
安德鲁·休伯曼：
Well, that's a perfect place to say thank you.
嗯，这是表达谢意的最佳场所。
I realize you're not addressing the vaccine autism issue directly, but you're so clearly going after the target, trying to figure out what are the biological mechanisms that are disrupted in autism, and by extension, other deficits of social function in kids and adults.
我意识到你并没有直接解决疫苗自闭症问题，但你显然是在追求目标，试图找出自闭症中被破坏的生物机制是什么，进而找出儿童和成人社会功能的其他缺陷。
You've identified this incredible relationship between vasopressin, which should have more prominence, in my opinion, than oxytocin, its lesser cousin.
您已经发现了加压素之间的这种令人难以置信的关系，在我看来，加压素应该比它的小表亲催产素更重要。
Just kidding oxytocin lovers.
只是在开玩笑催产素爱好者。
But also have shown, yes, in a small study, but you're now extending this to a larger cohort, as you mentioned, a causal relationship when vasopressin is administered to these low vasopressin/low social functioning kids, their symptoms improve.
但也已经表明，是的，在一项小型研究中，但正如您所提到的，您现在将其扩展到更大的队列，当对这些低加压素/低社会功能的孩子施用加压素时，他们的症状会改善，这是一种因果关系。
So I know I speak for many people when I say that I truly appreciate your doggedness in going after this problem, especially on the complicated landscape of lack of funding for doing novel and truly high-risk work, especially on the backdrop of the sociopolitical landscape around autism.
所以我知道，当我说我真的很欣赏你们在解决这个问题时的顽强精神时，我代表了很多人，特别是在缺乏资金进行新颖和真正高风险工作的复杂情况下，特别是在自闭症的社会政治格局的背景下。
It's a complicated thing even to discuss.
即使讨论起来也是一件复杂的事情。
As I mentioned in the introduction, we had to have some fluency around autism, so we sometimes said autistic, sometimes we said people with autism.
正如我在介绍中提到的，我们必须对自闭症有一定的了解，所以我们有时说自闭症，有时我们说患有自闭症的人。
It's a tough one, but in order to make progress, real progress in this area, we need people like you.
这是一项艰巨的任务，但为了在这一领域取得真正的进步，我们需要像你这样的人。
We need you, and you're doing it, to get in there and just go, "Okay, let's get at the biological functions.
我们需要你，你正在这样做，进入那里，然后说：“好吧，让我们了解生物学功能。
Let's get at the novel treatments." And you're making amazing progress.
让我们来看看新的治疗方法。”你正在取得惊人的进步。
So I'm so grateful that you're doing it, and that you'll continue to do it, and that you came here today to teach us what you've been up to.
所以我非常感谢你正在这样做，并且你将继续这样做，并且你今天来到这里告诉我们你一直在做什么。
I'm oh, so grateful, and I just want to say thank you for that, and that we absolutely have to get you back here to give us an update on your progress really soon.
我哦，非常感激，我只是想说谢谢你，我们绝对必须让你回到这里，尽快向我们通报你的进展情况。
Dr. Karen Parker:
凯伦·帕克博士：
Awesome.
太棒了。
Andrew Huberman:
安德鲁·休伯曼：
And again, and again, and again.
一次又一次，一次又一次。
Dr. Karen Parker:
凯伦·帕克博士：
Thank you so much.
非常感谢。
I love being here.
我喜欢呆在这里。
Andrew Huberman:
安德鲁·休伯曼：
All right.
好吧。
Well, I've loved this conversation, and I'll sign off by saying, folks, this is how diseases are cured.
嗯，我很喜欢这次谈话，最后我会说，伙计们，这就是治愈疾病的方法。
Thank you for joining me for today's discussion with Dr. Karen Parker about the biological basis of social functioning and autism.
感谢您今天与我一起与凯伦·帕克博士讨论社会功能和自闭症的生物学基础。
To learn more about Dr. Parker's research, please see the links in our show note captions.
要了解有关帕克博士研究的更多信息，请参阅我们的节目注释标题中的链接。
If you're learning from and/or enjoying this podcast, please subscribe to our YouTube channel.
如果您正在学习和/或喜欢此播客，请订阅我们的 YouTube 频道。
That's a terrific zero-cost way to support us.
这是支持我们的绝佳零成本方式。
In addition, please subscribe to the podcast on both Spotify and Apple.
此外，请在 Spotify 和 Apple 上订阅该播客。
And on both Spotify and Apple, you can leave us up to a five-star review.
在 Spotify 和 Apple 上，您都可以给我们五星级的评价。
If you have questions for me or comments about the podcast or guests you'd like me to consider on the Huberman Lab Podcast, please put those in the comments section on YouTube.
如果您对我有疑问或对播客或您希望我在 Huberman 实验室播客上考虑的嘉宾有意见，请在 YouTube 的评论部分中提出。
I do read all the comments.
我确实阅读了所有评论。
Please also check out the sponsors mentioned at the beginning and throughout today's episode.
另请查看今天节目开头和整个节目中提到的赞助商。
That's the best way to support this podcast.
这是支持这个播客的最佳方式。
Not so much on today's episode, but on many previous episodes of the Huberman Lab Podcast, we discuss supplements.
今天的节目不多，但在休伯曼实验室播客的许多以前的节目中，我们讨论了补充剂。
While supplements aren't necessary for everybody, many people derive tremendous benefit from them, for things like improving sleep, for hormone support, and for improving focus.
虽然补充剂并不是每个人都需要的，但许多人都从它们中获得了巨大的好处，例如改善睡眠、支持激素和提高注意力。
To learn more about the supplements discussed on the Huberman Lab Podcast, go to Live Momentous, spelled O-U-S, so livemomentous.com/huberman.
要了解有关 Huberman 实验室播客中讨论的补充剂的更多信息，请访问 Live Momentous，拼写为 O-U-S，即 livemomentous.com/huberman。
If you're not already following me on social media, I am hubermanlab on Instagram, X, formerly called Twitter, LinkedIn, Facebook, and Threads.
如果您还没有在社交媒体上关注我，我是 Instagram、X（以前称为 Twitter、LinkedIn、Facebook 和 Threads）上的 hubermanlab。
And at all of those places, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab Podcast, but much of which is distinct from the content covered on the Huberman Lab Podcast.
在所有这些地方，我讨论了科学和与科学相关的工具，其中一些与胡伯曼实验室播客的内容重叠，但其中大部分与胡伯曼实验室播客涵盖的内容不同。
So again, it's hubermanlab on all social media channels.
再说一次，所有社交媒体渠道上都是 hubermanlab。
If you haven't already subscribed to our Neural Network Newsletter, our Neural Network Newsletter is a zero-cost newsletter that comes out every month.
如果您还没有订阅我们的神经网络时事通讯，我们的神经网络时事通讯是每月发布的零成本时事通讯。
It includes podcast summaries, as well as protocols in the form of short PDFs of maybe just one to three pages, where I list out the specific protocols, for instance, for improving dopamine functioning, or for improving your sleep, or for deliberate cold exposure, deliberate heat exposure, or fitness protocols, and on and on.
它包括播客摘要，以及可能只有一到三页的简短 PDF 形式的协议，其中我列出了具体协议，例如，用于改善多巴胺功能、或改善睡眠、或有意冷暴露、有意热暴露或健身协议，等等。
All of which are presented in brief fashion, very direct, just the protocols listed out.
所有这些都以简短、非常直接的方式呈现，只是列出了协议。
Again, completely zero cost.
再次强调，完全零成本。
To sign up, you simply go to hubermanlab.com, go to the menu function, scroll down to Newsletter, and enter your email.
要注册，您只需访问 hubermanlab.com，转到菜单功能，向下滚动到新闻通讯，然后输入您的电子邮件。
And I should point out that we do not share your email with anybody.
我应该指出，我们不会与任何人分享您的电子邮件。
Thank you once again for joining me for today's discussion with Dr. Karen Parker.
再次感谢您参加今天与凯伦·帕克博士的讨论。
And last but certainly not least, thank you for your interest in science.
最后但并非最不重要的一点是，感谢您对科学的兴趣。