Understanding & Conquering Depression

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。

Andrew Huberman:

安德鲁·休伯曼：

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。

This month we're talking all about disorders of the mind, things like depression, attention deficit disorders, eating disorders, schizophrenia and bipolar disorder.

这个月我们谈论的都是精神疾病，比如抑郁症、注意力缺陷障碍、饮食失调、精神分裂症和双相情感障碍。

During the course of this month, we are going to discuss the psychological and biological underpinnings of mood disorders of all kinds.

在这个月里，我们将讨论各种情绪障碍的心理和生物学基础。

You'll learn a lot of science.

你会学到很多科学知识。

You'll also learn a lot about the various treatments that exist and that are in development for these various mood disorders.

您还将了解很多关于针对这些不同情绪障碍的现有和正在开发的各种治疗方法。

We will talk about behavioral tools, things like exercise, meditation, breath work, but also prescription drugs, supplements and novel compounds that are now being tested in various clinical trials.

我们将讨论行为工具，例如锻炼、冥想、呼吸工作，还有处方药、补充剂和目前正在各种临床试验中测试的新型化合物。

Across the month, I think you'll start to realize that there are common pathways underlying many mood disorders.

在这个月里，我想你会开始意识到许多情绪障碍背后都有共同的途径。

In fact, mood disorders that look quite different from one another often depend on the action of the same neurochemicals or neurocircuits in the brain and body.

事实上，看起来彼此截然不同的情绪障碍通常取决于大脑和身体中相同神经化学物质或神经回路的作用。

Andrew Huberman:

安德鲁·休伯曼：

That actually should be a point of great relief because what it means is that by understanding the biology of one mood disorder or understanding how one treatment or behavioral intervention can impact a mood disorder, we gain insight into other mood disorders as well.

这实际上应该是一个很大的缓解点，因为它意味着通过了解一种情绪障碍的生物学原理或了解一种治疗或行为干预如何影响情绪障碍，我们也可以深入了解其他情绪障碍。

As always, we will discuss science and science-related tools that people could implement, should they choose.

与往常一样，我们将讨论人们可以选择使用的科学和与科学相关的工具。

Before we dive into today's topic, I'd like to discuss a very particular set of scientific findings that relate to today's topic and that are important for understanding all mood disorders and all states of motivation, happiness and sadness, as well as depression.

在我们深入讨论今天的主题之前，我想讨论一组非常特别的科学发现，这些发现与今天的主题相关，对于理解所有情绪障碍以及所有动机、快乐和悲伤以及抑郁状态非常重要。

Basically, I'm going to paraphrase a brief segment of my discussion with Dr. Anna Lemke, who I sat down with to discuss addiction and the biological basis of addiction and addiction treatment.

基本上，我将转述我与安娜·莱姆克博士讨论的一小段内容，我和她坐下来讨论了成瘾以及成瘾和成瘾治疗的生物学基础。

A very important aspect of that discussion was when Dr. Lemke described the pleasure-pain balance, literally the circuits in our brains that control our sense of pleasure and pain and ultimately whether or not we remain happy in our pursuit of pleasure or not.

这次讨论的一个非常重要的方面是莱姆克博士描述了快乐与痛苦的平衡，即我们大脑中控制我们的快乐和痛苦感的回路，以及最终我们在追求快乐时是否保持快乐。

Andrew Huberman:

安德鲁·休伯曼：

This is an absolutely crucial aspect to the way that we function in everyday life, and especially under conditions of mood disorders.

这对于我们日常生活中的运作方式来说绝对至关重要，尤其是在情绪障碍的情况下。

The pathway that she was describing is the so-called pleasure system.

她所描述的途径就是所谓的快乐系统。

However, what most people don't realize is that the pleasure system is also directly associated with and in fact is the very same system that modulates mental or psychological anguish and pain.

然而，大多数人没有意识到，快乐系统也与调节精神或心理痛苦和痛苦直接相关，而且实际上是同一个系统。

Essentially what she described is that whenever we pursue something that we think will bring us pleasure, and that could be anything that we think will bring us pleasure from food, to video games, to sex, to a particular job or goal, short-term or long-term, that we experience release of the neuromodulator dopamine.

她所描述的本质上是，每当我们追求一些我们认为会给我们带来快乐的东西时，这可能是任何我们认为会给我们带来快乐的东西，从食物、电子游戏、性、特定的工作或目标，无论是短期还是长期，我们都会经历神经调节剂多巴胺的释放。

Now, dopamine is associated with increased levels of motivation and drive.

现在，多巴胺与动机和动力水平的提高有关。

It is not the molecule of reward.

它不是奖励的分子。

It is the molecule of craving, motivation and drive.

它是渴望、动机和动力的分子。

Andrew Huberman:

安德鲁·休伯曼：

However, as Dr. Lemke pointed out, when we are in pursuit of something, there is a release of dopamine in our brain.

然而，正如莱姆克博士指出的那样，当我们追求某样东西时，我们的大脑就会释放多巴胺。

That makes us feel motivated, and in general it makes us feel good.

这让我们感到有动力，总的来说，这让我们感觉良好。

But very shortly thereafter and beneath our conscious awareness, there is a tilt of the pleasure-plain balance in the brain.

但此后不久，在我们的意识之下，大脑中的快乐与平淡的平衡发生了倾斜。

Literally a shift in the neural circuits that underlie pleasure and pain, such that every bit of pleasure or pleasure-seeking that causes release of dopamine will be balanced out by a little bit of pain.

从字面上看，构成快乐和痛苦的神经回路发生了变化，导致多巴胺释放的每一点快乐或寻求快乐都会被一点点痛苦所平衡。

And we don't experience this as physical pain, at least not at first.

我们不会将其视为身体上的疼痛，至少一开始不会。

We experience it as craving for more of the thing that brought us pleasure.

我们将其体验为渴望更多给我们带来快乐的事物。

Now that sounds pretty good.

现在听起来不错。

You get pleasure and then you get a little bit of pain to balance it out.

你会得到快乐，然后你会得到一点痛苦来平衡它。

It's subconscious and you experience it as the desire to seek out more pleasure.

它是潜意识的，你将其体验为寻求更多快乐的欲望。

Andrew Huberman:

安德鲁·休伯曼：

However, it's actually more diabolical than that.

然而，实际上比这更邪恶。

And we really need to keep an eye on this if we are to remain happy, if we are to remain in pursuit of our goals.

如果我们要保持快乐，如果我们要继续追求我们的目标，我们确实需要密切关注这一点。

The crucial thing to understand is that if we remain in constant pursuit of pleasure, the pain side of the balance tips, so that each time we are in pursuit of that pleasureful thing, activity or substance, we are going to experience, we literally achieve less dopamine release each subsequent time, so we get less pleasure, and the amount of craving increases.

需要理解的关键一点是，如果我们持续不断地追求快乐，平衡中痛苦的一面就会倾斜，因此每次我们追求快乐的事情、活动或物质时，我们都会体验到，我们随后每次释放的多巴胺实际上会减少，因此我们获得的快乐会减少，渴望的数量也会增加。

Now after a certain point or threshold, we call that addiction.

现在，在某个点或阈值之后，我们称之为成瘾。

And the way to reset the balance, and this is very important, the way to reset the balance is actually to enter into states in which we are not in pursuit of pleasure, to literally enter states in which we are bored, maybe even a little bored and anxious.

重置平衡的方法，这一点非常重要，重置平衡的方法实际上是进入我们不追求快乐的状态，真正进入我们感到无聊的状态，甚至可能有点无聊和焦虑。

And that resets the pleasure-plain balance so that we can return to our pursuit of pleasure in a way that's healthy, and that in an ongoing way, won't lead to this over-tipping, or this increase, in the amount of pain or addiction.

这会重置快乐与普通的平衡，这样我们就可以以一种健康的方式回归对快乐的追求，并且以一种持续的方式，不会导致这种过度倾斜，或者这种痛苦或成瘾程度的增加。

Andrew Huberman:

安德鲁·休伯曼：

So this is very important, and if this seemed vague, what this means is we should always be cautious of any state of mind or body, or any pursuit, that leads to very large increases in dopamine.

所以这非常重要，如果这看起来很模糊，那么这意味着我们应该始终对任何导致多巴胺大幅增加的精神或身体状态或任何追求保持警惕。

And if it does, we should be very careful to not pursue that repeatedly over time.

如果确实如此，我们应该非常小心，不要随着时间的推移反复追求这一点。

During today's episode, I'm going to give an example, a real-life example of a discussion that I've been in with a young man who's 21 years old who's dealing with a disruption in this pleasure-plain balance.

在今天的节目中，我将举一个例子，一个现实生活中的例子，我曾与一位 21 岁的年轻人进行过讨论，他正在处理这种快乐与平淡的平衡被破坏的问题。

He is essentially depressed, and he's depressed because of his ongoing pursuit of a particular activity that initially led to a lot of dopamine, but over time has led to less and less dopamine and more and more of this pain side of the balance.

他本质上是抑郁的，他之所以抑郁，是因为他不断追求某种特定的活动，最初会产生大量的多巴胺，但随着时间的推移，导致多巴胺越来越少，这种平衡的痛苦一侧越来越多。

We could call him addicted to that particular activity.

我们可以说他对这项特定的活动上瘾了。

Whether or not he's addicted by clinical standards or not really isn't important.

按照临床标准，他是否上瘾并不重要。

What is important is that he experiences this as depression, as low affect, as it's called, or anhedonia, an inability to experience pleasure from that thing or from anything else.

重要的是，他将这种体验视为抑郁，即所谓的低情感，或快感缺乏，即无法从那件事或其他任何事情中体验到快乐。

Andrew Huberman:

安德鲁·休伯曼：

And he's currently undergoing treatment through a rebalancing of this pleasure-plain pathway.

他目前正在接受重新平衡这条快乐-平淡途径的治疗。

So while I can't reveal his identity to you, that wouldn't be appropriate, he did give me permission to reveal the general architecture of what he's coping with, and I spent some hours with him on the phone this week talking to him as well as to the various people that he's working with to really understand what's going on here.

因此，虽然我不能向你透露他的身份，但这并不合适，但他确实允许我透露他正在应对的总体架构，本周我花了几个小时与他通电话，与他以及与他一起工作的各个人交谈，以真正了解这里发生的事情。

Because I think it can illustrate the relationship between dopamine, pleasure and pain, for sake of addiction, but also for understanding how to avoid depressive states, how to remove ourselves from depressive states.

因为我认为它可以说明多巴胺、快乐和痛苦之间的关系，为了成瘾，也为了了解如何避免抑郁状态，如何使自己摆脱抑郁状态。

And as you'll see today, as we discuss depression, many of the molecules and neural pathways and biological mechanisms that we know can be used to counter depression feed back onto this pleasure-plain balance.

正如您今天将看到的，当我们讨论抑郁症时，我们知道的许多分子、神经通路和生物机制可用于对抗抑郁症，这些分子、神经通路和生物机制都会反馈到这种快乐与平淡的平衡。

Andrew Huberman:

安德鲁·休伯曼：

Before we begin, I'd like to say that this podcast is separate from my teaching and research roles at Stanford.

在开始之前，我想说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将有关科学和科学相关工具的零成本消费者信息带给公众。

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。

Today we're discussing depression.

今天我们讨论的是抑郁症。

In particular, we're going to talk about major depression.

特别是，我们要讨论重度抑郁症。

The phrase "major depression" is used to distinguish one form of depression from the other, the other one being bipolar depression.

“重度抑郁症”一词用于区分一种形式的抑郁症和另一种形式的抑郁症，另一种是双相抑郁症。

Bipolar depression, sometimes called bipolar disorder, is really characterized by manic highs — so where people aren't sleeping, and they're talking very fast, and they're buying things and pursuing resources that they can't afford; they're starting relationships left and right; they're manic — followed by periods of crashes of feeling very low lethargic, and so on.

双相抑郁症，有时也称为双相情感障碍，其真正的特征是躁狂高潮——人们不睡觉，语速很快，买东西、追求自己买不起的资源；他们开始左右建立关系；他们很躁狂——然后是一段时间的极度昏昏欲睡的崩溃，等等。

Andrew Huberman:

安德鲁·休伯曼：

Bipolar depression is an absolutely crucial thing for us to discuss, and therefore we are going to have an entire separate episode related to bipolar depression.

双相抑郁症对我们来说绝对是至关重要的事情，因此我们将有一个与双相抑郁症相关的完整单独的事件。

Today we're going to talk about major depression, also sometimes called unipolar depression just because it doesn't have the highs and lows.

今天我们要讨论的是重度抑郁症，有时也称为单相抑郁症，因为它没有高潮和低谷。

It's more characterized by the lows.

它的特点是低点。

We're going to talk about the biology, the psychology and the various treatments: behavioral drugs, supplementation, diet, exercise, all of that.

我们将讨论生物学、心理学和各种治疗方法：行为药物、补充剂、饮食、运动等等。

Before we go forward into the material, I just want to emphasize that any discussion about mood disorders carries with it a particular sensitivity.

在我们继续讨论材料之前，我只想强调，任何有关情绪障碍的讨论都具有特殊的敏感性。

And that sensitivity is one related to self-diagnosis.

这种敏感性与自我诊断有关。

Today's episode, and indeed in the future episodes for this month on mood disorders, you're going to hear various symptomatology that are used to diagnose and characterize these disorders.

今天的节目，甚至在本月关于情绪障碍的未来节目中，您将听到用于诊断和表征这些疾病的各种症状。

If you recognize some of these symptomologies in yourself or in others that you know, that's an important thing to take note of.

如果您在自己或您认识的其他人身上发现了其中一些症状，那么这是需要注意的重要事项。

Andrew Huberman:

安德鲁·休伯曼：

However, accurate diagnosis really should be done by a qualified healthcare professional.

然而，准确的诊断确实应该由合格的医疗保健专业人员进行。

So at once I'm saying keep your eyes and your ears up for things that sound familiar to you, that might be of concern.

因此，我要立即说，请留意那些听起来熟悉、可能令人担忧的事情。

And at the same time I'm saying don't necessarily leap to conclusions.

同时我想说的是，不必急于下结论。

Take those flags of concern, if they're there, and bring them to a qualified healthcare professional, and they'll be able to properly diagnose you as having a particular mood disorder, or diagnose somebody as having a particular mood disorder, or not.

如果有这些值得关注的标志，请将其带给合格的医疗保健专业人员，他们将能够正确诊断您是否患有特定的情绪障碍，或诊断某人是否患有特定的情绪障碍。

And that's an essential step.

这是至关重要的一步。

I don't say this to protect us.

我这么说并不是为了保护我们。

I say this really to protect you.

我说这些，其实是为了保护你。

Okay, let's have a fact-based discussion about depression.

好吧，让我们就抑郁症进行基于事实的讨论。

And I promise you that where we don't know certain things about depression, I will be clear to tell you.

我向你保证，如果我们不知道有关抑郁症的某些事情，我会明确地告诉你。

In fact, we are going talk about some treatments for depression that are looking very promising and that right now are actually being used more and more.

事实上，我们将讨论一些看起来非常有前途的抑郁症治疗方法，而且现在实际上正在越来越多地使用。

Andrew Huberman:

安德鲁·休伯曼：

And from my read of the mechanistic literature, we're still a bit in the dark as to how these work.

从我对机械论文献的阅读来看，我们对它们的工作原理仍然一无所知。

That's actually a common theme of medicine.

这实际上是医学的一个共同主题。

Many times there are treatments that seem promising or that look really terrific, and there isn't a lot of understanding about mechanism.

很多时候，有些治疗方法看起来很有希望，或者看起来真的很棒，但人们对机制的了解却很少。

However, any good discussion about neuroscience and in particular about mood disorders has to get into mechanisms.

然而，任何关于神经科学，特别是情绪障碍的好的讨论都必须涉及机制。

So we're going to do that.

所以我们要这么做。

And in doing that, we're going to frame the discussion for the tools of how to keep depression at bay and how to deal with it if you happen to find yourself depressed, or if you know somebody else who's depressed.

在此过程中，我们将讨论如何预防抑郁症，以及如果您碰巧发现自己抑郁或您认识其他人患有抑郁症，如何应对抑郁症。

Andrew Huberman:

安德鲁·休伯曼：

What is this thing we call depression?

我们所说的抑郁症到底是什么？

As I mentioned before, it has two forms, bipolar depression, which we're not talking about today, and major depression, also called unipolar depression, is the other.

正如我之前提到的，它有两种形式，一种是双相抑郁症，我们今天不讨论这种抑郁症，另一种是重度抑郁症，也称为单相抑郁症。

Major depression impacts five percent of the population.

重度抑郁症影响百分之五的人口。

That is an enormous number.

这是一个巨大的数字。

That means if you're in a class of a hundred people, five of them are dealing with major depression or have at some point.

这意味着，如果你在一个一百人的班级中，其中有五个人正在应对严重抑郁症或在某个时候患有抑郁症。

Look around you in any environment, and you can be sure that a good portion of the people that you're surrounded by is impacted by depression or will be at some point.

在任何环境中环顾四周，您都可以确定您周围的人中有很大一部分受到抑郁症的影响或将在某个时候受到抑郁症的影响。

So this is something we really have to take seriously, and that we want to understand.

所以这是我们必须认真对待、我们想要理解的事情。

It is the number four cause of disability.

它是导致残疾的第四大原因。

A lot of people miss work, miss school, and before then, likely perform poorly in work or school due to major depression.

许多人错过了工作、错过了学校，在此之前，可能会因为重度抑郁症而在工作或学习中表现不佳。

Andrew Huberman:

安德鲁·休伯曼：

Now, there's a very serious challenge in having a discussion about depression, and it relates directly to the challenges in diagnosing depression.

现在，讨论抑郁症是一个非常严峻的挑战，它与诊断抑郁症的挑战直接相关。

Earlier I did an episode with Dr. Karl Deisseroth, who is indeed a medical doctor and a PhD.

早些时候，我和 Karl Deisseroth 博士一起做了一集，他确实是一名医生和博士学位。

He's a psychiatrist.

他是一名精神科医生。

And he made a very important point, which is that the field of psychiatry and psychology are confronted with a challenge, which is they're trying to understand what's going on within the stuff that's in our brains, that's deep to our skulls.

他提出了一个非常重要的观点，那就是精神病学和心理学领域面临着一个挑战，他们试图了解我们大脑中、我们头骨深处的东西正在发生什么。

We don't have access to that without brain imaging and electrodes and things like that.

如果没有大脑成像和电极之类的东西，我们就无法获得这一点。

Someone just comes into the office and the dissection tool for depression, so to speak, is language.

有人刚进办公室，抑郁症的剖析工具可以说是语言。

In order to determine if somebody has depression or not, we have to use language, how they talk about things, also how they carry their body, also some general patterns of health.

为了确定某人是否患有抑郁症，我们必须使用语言、他们如何谈论事物、他们的身体如何以及一些一般的健康模式。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk about depression the way that clinicians talk about depression.

因此，让我们以临床医生谈论抑郁症的方式来谈论抑郁症。

Because one of the issues is that we use the word depression loosely.

因为问题之一是我们宽松地使用“抑郁症”这个词。

A lot of people say, "Oh, I'm so depressed.

很多人说：“哦，我很沮丧。

I didn't get this job." Or, "I'm so depressed.

我没有得到这份工作。”或者，“我很沮丧。

I had a really rough week." Or, "I'm exhausted.

我度过了非常艰难的一周。”或者，“我累坏了。

I'm so depressed." Or, "I'm so depressed.

我很沮丧。”或者，“我很沮丧。

I thought I was going to go on vacation, and then they canceled the flight." That is not clinical depression.

我以为我要去度假，然后他们取消了航班。”这不是临床抑郁症。

That's called being bummed out, being sad or disappointed.

这就是所谓的沮丧、悲伤或失望。

Now, that person might be depressed, but clinical depression actually has some very specific criteria.

现在，那个人可能患有抑郁症，但临床抑郁症实际上有一些非常具体的标准。

And those criteria are mainly characterized by the presence of certain things and the absence of a few particular things.

这些标准的主要特征是某些事物的存在和某些特定事物的不存在。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk about the things that are present in somebody that has major depression.

那么让我们来谈谈患有重度抑郁症的人身上出现的事情。

First of all, there tends to be a lot of grief.

首先，往往会有很多悲伤。

There tends to be a lot of sadness.

往往会有很多悲伤。

That's no surprise.

这并不奇怪。

The threshold to cry is often a signature of depression.

哭泣的阈值通常是抑郁症的标志。

Now, that doesn't mean that if you cry easily that you're depressed.

现在，这并不意味着如果您容易哭泣就表示您患有抑郁症。

Some people cry more easily than others.

有些人比其他人更容易哭泣。

But if you're somebody who typically didn't cry easily and suddenly you find yourself crying very easily, that could be a sign of depression.

但如果你是一个平时不轻易哭泣的人，突然发现自己很容易哭泣，这可能是抑郁症的征兆。

And I want to emphasize could.

我想强调可以。

There's also this thing that we call anhedonia, a general lack of ability to enjoy things, things that typically or previously we enjoyed, things like food, things like sex, things like exercise, things like social gatherings, a kind of lack of enjoyment from those things.

还有一种我们称之为快感缺失的东西，即普遍缺乏享受事物的能力，通常或以前我们喜欢的事物，比如食物，比如性，比如运动，比如社交聚会，缺乏对这些事物的享受。

Andrew Huberman:

安德鲁·休伯曼：

Sometimes that lack of enjoyment is sad, and sometimes it's just flat.

有时，缺乏乐趣是令人悲伤的，有时则只是平淡无奇。

It's just kind of neutral.

这只是一种中立的态度。

It doesn't feel good because there's nothing there.

感觉不太好，因为那里什么都没有。

It's like bland food.

就像清淡的食物一样。

It's like these experiences are analogous to biting into your favorite article of food and it just not tasting very good.

就好像这些体验类似于咬你最喜欢的食物，但味道不太好。

It just doesn't taste like anything at all.

它的味道一点也不像。

And that's a common symptom of major depression.

这是重度抑郁症的常见症状。

The other one is guilt.

另一种是内疚。

Oftentimes people with depression will feel very guilty about things they have done in the past, or they'll just generally feel badly about themselves.

通常，患有抑郁症的人会对自己过去所做的事情感到非常内疚，或者他们只是对自己感觉很糟糕。

And we're going to talk about this because it relates to some of the more serious symptomology seen in depression, sometimes things like self-harm, mutilation or even suicide.

我们之所以要讨论这个，是因为它与抑郁症中出现的一些更严重的症状有关，有时是自残、残害甚至自杀。

But for the time being, we want to frame up anhedonia, this lack of ability to achieve or experience pleasure, kind of a flat affect, as it's called sometimes, even delusional thinking, negative delusional thinking, and in particular, anti-self confabulation.

但目前，我们想要构建快感缺失，即缺乏获得或体验快乐的能力，有时被称为一种平淡的情感，甚至是妄想思维、消极妄想思维，尤其是反自我虚构。

Andrew Huberman:

安德鲁·休伯曼：

What is anti-self confabulation?

什么是反自我虚构？

Well, first of all, confabulation is an incredible aspect of our mind and our nervous system.

嗯，首先，虚构是我们的思想和神经系统的一个令人难以置信的方面。

You sometimes see other forms of confabulation in people who have memory deficits, either because they have brain damage or they have age-related dementia.

有时，你会在有记忆缺陷的人身上看到其他形式的闲聊，要么是因为他们有脑损伤，要么是因为患有与年龄相关的痴呆症。

A good example of this would be someone with age-related dementia sometimes will find themselves in a location in the house and not know how they got there.

一个很好的例子是，患有与年龄有关的痴呆症的人有时会发现自己处于房子的某个位置，但不知道自己是如何到达那里的。

And if you ask them, "Oh, what are you doing here?" they will create these elaborate stories.

如果你问他们：“哦，你在这里做什么？”他们将创造这些精心设计的故事。

"I was thinking about going to shopping today, and I was going to take the bus, and then I was going to do ...

“我本来想今天去购物，然后我打算坐公共汽车，然后我想做......

" They create these elaborate stories.

“他们创造了这些精心设计的故事。

They confabulate.

他们闲聊。

And yet that person hasn't left the house in weeks, and that person doesn't have a driver's license.

然而那个人已经好几个星期没有离开过家了，而且那个人没有驾照。

And so they're really just creating this stuff.

所以他们实际上只是在创造这些东西。

They're not lying to get out of anything.

他们撒谎并不是为了摆脱任何事情。

They're confabulating.

他们正在闲聊。

It's as if a brain circuit that writes stories just starts generating content.

就好像编写故事的大脑回路刚刚开始生成内容一样。

Andrew Huberman:

安德鲁·休伯曼：

In major depression, there's often a state of delusional anti-self confabulation, where the confabulations are not directly or completely linked to reality, but they are ones that make the self, the person describing them, seem sick or in some way not well.

在重度抑郁症中，常常会出现一种妄想性的反自我虚构的状态，其中的虚构与现实没有直接或完全的联系，但它们会让自我、描述它们的人看起来生病或在某种程度上不太好。

A good example would be somebody who experiences a physical injury, perhaps maybe they break their ankle; maybe it's an athlete, and they also happen to become depressed.

一个很好的例子是某人遭受了身体伤害，也许他们的脚踝骨折了；也许是一名运动员，他们也恰好变得抑郁。

And you'll talk to them, you say, "How are things going?

你会和他们交谈，你说：“事情进展得怎么样？

How's your rehab?" And they'll go, "Oh, it's okay.

你的康复情况怎么样？”他们会说：“哦，没关系。

And I don't know, I feel like I'm getting weaker and weaker by the day.

我不知道，我感觉自己一天天变得越来越虚弱。

I'm just not performing well." And then you'll talk to the person that they're working with, their kinesiologist or whoever the physical therapist is, and they'll say, "No, they're actually really improving.

我只是表现得不好。”然后你会和他们一起工作的人、他们的运动学家或物理治疗师交谈，他们会说：“不，他们实际上真的在进步。

And I tell them they're improving, but somehow they're not seeing that improvement.

我告诉他们他们正在进步，但不知何故他们没有看到这种进步。

They're not registering that improvement."

他们没有注意到这种改进。”

Andrew Huberman:

安德鲁·休伯曼：

And you notice that sometimes it's subtle, and sometimes it's severe, but they'll start confabulating.

你会注意到，有时很微妙，有时很严重，但他们会开始闲聊。

You'll say, "I actually heard you're doing much better, getting better.

你会说：“我实际上听说你做得好多了，越来越好。

You're taking multiple trips around the building now; before you could barely get out of bed." And they'll say, "Yeah, well basically they changed some things about the parking lot that make it easier to move around.

您现在正在大楼周围进行多次旅行；在你几乎无法起床之前。”他们会说，“是的，基本上他们改变了停车场的一些东西，让人们更容易走动。

So it's not really me." And these aren't people that are just explaining away their accomplishments because they're trying to brush off praise.

所以这不是真正的我。”这些人并不是因为试图拒绝赞扬而只是为了解释自己的成就。

They are viewing themselves, and they're confabulating according to a view that is very self-deprecating to the point where it doesn't match up with reality.

他们在看待自己，他们在根据一种非常自嘲的观点进行闲聊，以至于与现实不符。

It's not what other people see, and it's actually not matched up with reality.

这不是别人看到的，实际上也不符合现实。

And that's a symptom of depression that I think we don't often think about or conceptualize enough.

我认为这是抑郁症的一种症状，我们经常思考或概念化得不够。

Andrew Huberman:

安德鲁·休伯曼：

So it's not just telling people, "Oh yeah, it's not as good as it seems.

所以它不仅仅是告诉人们，“哦，是的，它并不像看起来那么好。

Everything's bad." These people really believe that, and it becomes disconnected from reality.

一切都很糟糕。”这些人确实相信这一点，但它与现实脱节了。

So if they're sort of sinking into a pit, and they're losing touch with the realities of the world, including data about themselves, their ability to move and get around, for example, in the particular instance that I used as an example, but there are others as well.

因此，如果他们有点陷入困境，并且他们正在与世界的现实失去联系，包括关于他们自己的数据，他们移动和四处走动的能力，例如，在我用作示例的特定情况下，但也有其他情况。

The other common symptomology of major depression is what they call vegetative symptoms.

重度抑郁症的另一个常见症状是所谓的植物人症状。

So vegetative symptoms are symptoms that occur without any thinking, without any doing or without any confabulation.

因此，植物人症状是在没有任何思考、没有任何行动或没有任何虚构的情况下出现的症状。

These are things that are related to our core physiology.

这些都是与我们的核心生理有关的事情。

The word "vegetative" you might know; it sounds like vegetable.

“植物人”这个词你可能知道；听起来像蔬菜。

It actually relates to what a system in the body that nowadays is more commonly called the autonomic nervous system.

它实际上与身体中的一个系统有关，现在更常称为自主神经系统。

The vegetative nervous system and the autonomic nervous system historically where considered sort of one in the same.

植物神经系统和自主神经系统在历史上被认为是一体的。

And it relates to things like the stress response or to our ability to sleep.

它与压力反应或我们的睡眠能力等因素有关。

Andrew Huberman:

安德鲁·休伯曼：

So vegetative symptoms would be things like constantly being exhausted.

所以植物人的症状就是经常感到精疲力竭。

The person just feels exhausted.

这个人只是感到筋疲力尽。

It's not because they exercise too much.

这并不是因为他们运动太多。

It's not necessarily because of a life event.

这不一定是因为生活事件。

It could be.

可能是。

But they're just worn out.

但他们只是疲惫不堪。

They don't have the energy they once had.

他们不再拥有曾经拥有的能量。

So it's not in their heads.

所以这不在他们的脑海里。

It's probably, and now I think we have good data to support the fact, that there's something off.

现在我认为我们有足够的数据来支持这样一个事实：有可能是有问题的。

Something is disrupted in the autonomic or so-called vegetative nervous system.

自主神经系统或所谓的植物神经系统出现了紊乱。

And one of the most common symptoms of people with major depression, one of the signs of major depression is early waking and not being able to fall back asleep despite being exhausted.

重度抑郁症患者最常见的症状之一，重度抑郁症的症状之一就是早醒，尽管精疲力竭却无法重新入睡。

So waking up at 3:00 a.m.

于是凌晨 3:00 起床。

or 4:00 a.m.

或凌晨 4:00

or 5:00 a.m., just spontaneously, and not being able to go back to sleep.

或凌晨 5:00，只是自发地，无法再入睡。

Now I want to emphasize that that could happen for other reasons as well, but it is a common symptom or warning sign of major depression.

现在我想强调的是，这种情况也可能因其他原因而发生，但这是重度抑郁症的常见症状或警告信号。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk more about sleep and depression.

那么让我们更多地谈谈睡眠和抑郁。

It's well-known that the architecture of sleep is disrupted in depression.

众所周知，抑郁症会破坏睡眠结构。

What's the architecture of sleep?

睡眠的架构是怎样的？

I've done entire episodes about this, but very briefly in two sentences, although they'll probably be run-on sentences, early in the night, you tend to have slow wave sleep more than REM sleep or rapid eye movement sleep.

我已经完成了关于此的整个剧集，但非常简短地用两句话来描述，尽管它们可能是连续的句子，但在深夜，你往往会比快速眼动睡眠或快速眼动睡眠更多地进行慢波睡眠。

As the night goes on, you tend to have more rapid eye movement sleep.

随着夜晚的推移，您的眼动睡眠往往会更加快速。

That architecture of slow wave sleep preceding rapid eye movement sleep is radically disrupted in major depression.

在重度抑郁症中，快速眼动睡眠之前的慢波睡眠结构被彻底破坏。

In addition, the pattern of activity in the brain during particular phases of sleep is disrupted.

此外，大脑在特定睡眠阶段的活动模式也会被打乱。

Now this is during sleep, so this can't be that people are creating this situation for themselves.

现在是在睡觉的时候，所以这不可能是人给自己造成的。

These are real physiological signs that something is off in this so-called autonomic or vegetative nervous system.

这些是真实的生理迹象，表明所谓的自主神经或植物神经系统出现了问题。

Andrew Huberman:

安德鲁·休伯曼：

And then there are some other things that relate to the autonomic nervous system, but that we normally think of as more voluntary in nature.

还有一些其他与自主神经系统有关的事情，但我们通常认为本质上更自愿。

And these are things like decreased appetite.

这些都是食欲下降之类的事情。

So you could imagine that one could have decreased appetite because of the anhedonia, the lack of pleasure from food.

所以你可以想象，一个人可能会因为快感缺乏（缺乏食物带来的乐趣）而食欲下降。

If you don't enjoy food, then you might be less motivated to eat it.

如果你不喜欢食物，那么你可能就没有动力去吃它。

That makes sense.

这是有道理的。

As well, because of these disruptions in the autonomic nervous system, these vegetative symptoms, as they're called, you can imagine that someone would have decreased appetite because some of the hormones associated with appetite, hypocretin/orexin and things of that sort, grehlin, that those would be disrupted.

同样，由于自主神经系统的这些破坏，这些所谓的植物人症状，你可以想象有人会食欲下降，因为一些与食欲相关的激素，下丘脑分泌素/食欲素和类似的东西，胃饥饿素，这些都会被破坏。

And if those names of hypocretin/orexin and ghrelin don't make any sense to you, don't worry about it.

如果下丘脑分泌素/食欲素和生长素释放肽这些名称对您来说没有任何意义，请不要担心。

What those are, just hormones that impact when we eat, when we feel hungry, and when we crave food more, as well as when we feel full — we have enough so-called satiety.

这些是什么，只是影响我们何时进食、何时感到饥饿、何时更渴望食物以及何时感到饱的荷尔蒙——我们有足够的所谓饱腹感。

If you want to learn more about those, we did entire episodes on eating and metabolism.

如果你想了解更多，我们做了关于饮食和新陈代谢的整集。

Andrew Huberman:

安德鲁·休伯曼：

So you can see that the symptomology of major depression impacts us at multiple levels.

所以你可以看到重度抑郁症的症状在多个层面上影响着我们。

There's the conscious level of how excited we are generally.

我们通常有多么兴奋是有意识的。

Well, that's reduced.

嗯，减少了。

There's grief.

有悲伤。

There's guilt.

有罪恶感。

There's crying.

有哭声。

But then there's also these vegetative things.

但也有这些植物性的东西。

There's disruptions in sleep, which of course make everything more challenging when we're awake.

睡眠受到干扰，这当然会让我们清醒时的一切变得更具挑战性。

We know that.

我们知道这一点。

Sleep is so vital for resetting.

睡眠对于恢复至关重要。

You're waking up early.

你起得很早。

You can't get back to sleep.

你无法再入睡。

That's going to adjust your affect, your emotions, in negative ways.

这将以消极的方式调整你的影响、你的情绪。

We know this.

我们知道这一点。

And appetite is off.

而且食欲不振。

And there are hormones that get disrupted.

还有一些荷尔蒙会受到干扰。

So cortisol levels are increased.

因此皮质醇水平会增加。

In particular, there's a signature pattern of depression whereby cortisol, the stress hormone that normally is released in a healthy way only in the early part of the day, is shifted to late in the day.

特别是，抑郁症有一个标志性模式，即皮质醇（一种压力荷尔蒙）通常只在一天的早些时候以健康的方式释放，但会转移到一天的晚些时候。

In fact, a 9:00 p.m.

事实上，晚上 9:00

peak in cortisol is one of the physiological signatures of depressive-like states.

皮质醇的峰值是抑郁样状态的生理特征之一。

It's not the only one, but it is an important one.

它不是唯一的一个，但却是一个重要的。

Andrew Huberman:

安德鲁·休伯曼：

So there are a lot of things going on in major depression.

所以重度抑郁症会发生很多事情。

And by now you're probably thinking, "Oh goodness, this is dreadful.

现在你可能会想：“天哪，这太可怕了。

Like there's all this terrible stuff." And indeed it is terrible.

就像有这么多可怕的东西一样。”确实，这很可怕。

It is a terrible thing to find oneself in a mode where things feel sad, you feel guilty, you're exhausted.

发现自己处于一种感到悲伤、感到内疚、精疲力竭的状态是一件可怕的事情。

And oftentimes there's also an association with the anxiety system.

通常也与焦虑系统有关。

So just because people are exhausted and lethargic and they don't enjoy things doesn't necessarily mean that there's an absence of anxiety.

因此，仅仅因为人们疲惫不堪、昏昏欲睡、不喜欢事情，并不一定意味着不存在焦虑。

There can also be a lot of anxiety about, what's going to happen to me?

也可能会有很多焦虑，我会发生什么？

Am I going to be able to achieve my goals in life?

我能够实现我的人生目标吗？

Will I ever get out of this state?

我能摆脱这种状态吗？

And so things really start to layer on.

所以事情真的开始分层了。

And if this sounds depressing to you, it is indeed depressing.

如果这听起来让你感到沮丧，那么它确实令人沮丧。

This is really the place that many people find themselves, and it's a pit that they just don't know how to climb out of.

这确实是很多人发现自己的地方，这是一个他们不知道如何爬出来的坑。

Andrew Huberman:

安德鲁·休伯曼：

So let's just take a few minutes and talk about some of the underlying biology that creates this cloud, or this constellation, of symptomology.

因此，让我们花几分钟时间来讨论一下产生这种症状学云或症状群的一些基础生物学。

I think that's really important to do because if we want to understand the various treatments, how they work and why they work and how to implement them, we have to understand some of the underlying biology.

我认为这非常重要，因为如果我们想了解各种治疗方法、它们如何起作用、为什么起作用以及如何实施它们，我们必须了解一些基础生物学。

So let's spend a few minutes talking about the biology of depression.

让我们花几分钟讨论一下抑郁症的生物学原理。

What's known?

已知什么？

What's not known?

什么是不知道的？

Because in doing that, I think you'll get a much clearer picture about why certain tools work to relieve depression, and why others might not.

因为这样做，我认为你会更清楚地了解为什么某些工具可以缓解抑郁症，而其他工具则不能。

So one of the most important early findings in the search for a biological basis of depression was this finding that there are drugs that relieve some of the symptoms of depression.

因此，在寻找抑郁症生物学基础的过程中，最重要的早期发现之一就是发现有药物可以缓解抑郁症的某些症状。

Andrew Huberman:

安德鲁·休伯曼：

Those drugs generally fall into three major categories.

这些药物通常分为三大类。

But the first set of ones that were discovered were the so-called tricyclic antidepressants and the MAO inhibitors, the monoamine oxidase inhibitors.

但第一批被发现的是所谓的三环类抗抑郁药和 MAO 抑制剂，即单胺氧化酶抑制剂。

You don't need to understand that nomenclature, but I'm going to give you a little bit of detail, so that if you want to understand it, you can.

你不需要理解这个术语，但我会给你一些细节，这样如果你想理解它，你就能理解。

Most of this work took place in the late 1950s and in the 1960s and continued well until the 1980s when new classes of drugs were discovered.

大部分工作发生在 20 世纪 50 年代末和 1960 年代，一直持续到 1980 年代发现新类别的药物。

And these tricyclic antidepressants and the MAO inhibitors largely worked by increasing levels of norepinephrine in the brain, as well as in the body in some cases.

这些三环类抗抑郁药和单胺氧化酶抑制剂主要是通过增加大脑中去甲肾上腺素的水平来发挥作用，在某些情况下还可以增加体内的去甲肾上腺素水平。

And they were discovered through a kind of odd set of circumstances.

他们是在一系列奇怪的情况下被发现的。

We don't have time to go into all the history, but suffice to say that they were discovered because of the exploration for drugs that alter blood pressure.

我们没有时间详细了解所有历史，但足以说明它们是由于探索改变血压的药物而被发现的。

Norepinephrine impacts blood pressure, and drugs that lower blood pressure reduce levels of norepinephrine.

去甲肾上腺素会影响血压，而降低血压的药物会降低去甲肾上腺素的水平。

And that in many cases was shown to lead to depression or depressive-like symptoms.

在许多情况下，这被证明会导致抑郁或抑郁样症状。

Andrew Huberman:

安德鲁·休伯曼：

And so these drugs, these tricyclic drugs and the MAO inhibitors, actually increase norepinephrine.

所以这些药物，这些三环类药物和 MAO 抑制剂，实际上会增加去甲肾上腺素。

And frankly, they do quite a good job of relieving some, if not all of the symptoms of major depression.

坦率地说，它们在缓解部分（如果不是全部）重度抑郁症症状方面做得相当好。

However, they carry with them many side effects.

然而，它们也带来许多副作用。

Some of those side effects are side effects related to blood pressure itself.

其中一些副作用是与血压本身相关的副作用。

By increasing noradrenaline, norepinephrine as it's called, you raise blood pressure.

通过增加去甲肾上腺素（所谓的去甲肾上腺素），血压就会升高。

That can be dangerous.

这可能很危险。

That can be uncomfortable.

这可能会让人不舒服。

But they also have a lot of other side effects.

但它们也有很多其他副作用。

The reason they have other side effects is because they impact systems in the brain, and in the body, that impact things like libido, appetite, digestion and others.

它们之所以有其他副作用，是因为它们会影响大脑和身体的系统，从而影响性欲、食欲、消化等。

And we'll talk about each of those in sequence.

我们将按顺序讨论其中的每一个。

Andrew Huberman:

安德鲁·休伯曼：

Okay, so the experience that clinicians had of observing some relief for depression with the tricyclic antidepressants and with MAO inhibitors was terrific.

好吧，临床医生观察到三环类抗抑郁药和 MAO 抑制剂对抑郁症有所缓解的经验是非常棒的。

But there were all these side effects, side effects that people really did not like.

但所有这些副作用都是人们真正不喜欢的。

They didn't like these drugs at all.

他们根本不喜欢这些药物。

A lot of people would get dry mouth.

很多人都会口干舌燥。

I mentioned the low libido.

我提到了性欲低下。

They'd have sleep issues, appetite issues, weight gain.

他们会有睡眠问题、食欲问题、体重增加。

They made some people so uncomfortable that they preferred not to take them, even though when they didn't take them, they had a worsening or a maintenance of their depressive symptoms.

它们让一些人感到非常不舒服，以至于他们宁愿不服用它们，即使当他们不服用它们时，他们的抑郁症状会恶化或持续。

Andrew Huberman:

安德鲁·休伯曼：

A decade or so later, there was the discovery of the so-called pleasure pathways in the brain.

大约十年后，人们发现了大脑中所谓的快乐通路。

These are pathways, literally groups of neurons that reside in different locations in the brain but connect to one another, so it's a circuit.

这些是通路，实际上是一组神经元，它们位于大脑的不同位置，但彼此连接，所以它是一个电路。

And when you stimulate these neurons with certain behaviors or with electrical stimulation in an experiment; believe it or not, that's been done in both animals and humans; animals and humans become very, very motivated to get more stimulation of these pathways.

当你在实验中用某些行为或电刺激刺激这些神经元时；不管你信不信，这在动物和人类身上都曾发生过。动物和人类变得非常非常有动力去获得这些途径的更多刺激。

So this pleasure pathway, or these circuits for pleasure, are very what we call reinforcing.

因此，这种快乐途径，或者这些快乐回路，正是我们所说的强化。

In fact, animals and humans will work hard to get stimulation of these brain areas even more than they will work to obtain sex, drugs.

事实上，动物和人类为了获得这些大脑区域的刺激而付出的努力甚至比为了获得性和毒品而付出的努力还要多。

Or even if they are addicted to a particular drug and they are in a state of withdrawal, the ultimate state of craving, if given a choice, a person or an animal will select to have stimulation of this pleasure pathway instead of the drug itself.

或者，即使他们对某种药物上瘾，并且处于戒断状态，即渴望的最终状态，如果有选择，人或动物会选择刺激这种快乐途径而不是药物本身。

Andrew Huberman:

安德鲁·休伯曼：

And that is a major and significant finding.

这是一个重大且意义重大的发现。

This pleasure pathway, as it's sometimes called, involves areas like the nucleus accumbens and the ventral tegmental area.

这种快乐通路有时被称为伏隔核和腹侧被盖区等区域。

These are areas of the brain that are rich with neurons that make dopamine.

这些大脑区域富含产生多巴胺的神经元。

And if you think to the symptoms of depression, of anhedonia, lack of pleasure, a lack of ability to experience pleasure, well that was a smoking gun that there's something wrong with the dopamine pathway in depression.

如果你想到抑郁症、快感缺失、缺乏快乐、缺乏体验快乐的能力等症状，那么这确实是抑郁症中多巴胺通路出现问题的证据。

And indeed that's the case.

事实确实如此。

So it's not just norepinephrine, it's also the dopamine, or pleasure pathway is somehow disrupted.

因此，不仅仅是去甲肾上腺素，多巴胺或快乐通路也受到了某种程度的破坏。

And then in the 1980s, there was the discovery of the so-called SSRIs.

然后在 20 世纪 80 年代，发现了所谓的 SSRI。

Most people are now familiar with the SSRIs, the selective serotonin reuptake inhibitors.

现在大多数人都熟悉 SSRIs，即选择性血清素再摄取抑制剂。

The SSRIs worked by distinct mechanisms from the tricyclic antidepressants and the MAO inhibitors.

SSRIs 的作用机制与三环类抗抑郁药和 MAO 抑制剂不同。

As their name suggests, SSRI, selective serotonin reuptake inhibitors, prevent serotonin from being wiped up from the synapse after two neurons talk to one another.

顾名思义，SSRI（选择性血清素再摄取抑制剂）可防止两个神经元相互交谈后突触中的血清素被清除。

Andrew Huberman:

安德鲁·休伯曼：

What do I mean by that?

我这么说是什么意思？

Well, here's some very basic Neurobiology 101.

嗯，这是一些非常基础的神经生物学 101。

If you don't know any neurobiology, you're going to know some in about 15 seconds.

如果您不懂任何神经生物学，大约 15 秒后您就会了解一些。

Neurons communicate with one another by spitting out chemicals into the little gap between them.

神经元通过向它们之间的小间隙喷出化学物质来相互交流。

The little gap between them is called the synapse or by the Brits, the synapse.

它们之间的小间隙称为突触，或者英国人称为突触。

Those chemicals bind to the neuron on the opposite side and cause changes in the electrical activity of that neuron on the other side of the synapse.

这些化学物质与另一侧的神经元结合，导致突触另一侧神经元的电活动发生变化。

Serotonin is one such neurotransmitter, or more specifically, it's a neuromodulator.

血清素就是这样一种神经递质，或更具体地说，它是一种神经调节剂。

It can change the activity of large groups of neurons in very meaningful ways.

它可以以非常有意义的方式改变大量神经元的活动。

Selective serotonin reuptake inhibitor means when a person takes this drug, some of those drugs include things like Prozac or Zoloft.

选择性血清素再摄取抑制剂意味着当一个人服用这种药物时，其中一些药物包括百忧解或左洛复等药物。

The more typical names, or more generic names, are things like Fluoxetine.

更典型的名称，或更通用的名称是氟西汀之类的东西。

Andrew Huberman:

安德鲁·休伯曼：

When people take those, more serotonin hangs out in the synapse and is able to be taken up by the neuron on the opposite side because of this selective reuptake inhibition.

当人们服用这些药物时，更多的血清素会滞留在突触中，并且由于这种选择性再摄取抑制，能够被另一侧的神经元吸收。

It prevents the clearance of serotonin from the synapse, and thereby more serotonin can have an effect.

它阻止血清素从突触中清除，从而更多的血清素可以发挥作用。

So SSRIs don't increase the total amount of serotonin in the brain.

因此，SSRIs 不会增加大脑中血清素的总量。

They change how effective the serotonin that's already in the brain is at changing the activity of neurons.

它们改变了大脑中已有的血清素在改变神经元活动方面的效果。

So they don't increase serotonin.

所以它们不会增加血清素。

They increase the efficacy, or the function of serotonin in the way that I just described.

它们以我刚才描述的方式增加血清素的功效或功能。

So that was more than 15 seconds, but now you understand how SSRIs work.

时间超过 15 秒，但现在您已经了解 SSRI 的工作原理了。

Andrew Huberman:

安德鲁·休伯曼：

So that was more than 15 seconds.

所以这已经超过 15 秒了。

But now you understand how SSRIs work, and I wouldn't be talking about SSRIs if they didn't in fact work.

但现在您了解了 SSRI 的工作原理，如果 SSRI 确实不起作用，我就不会谈论它们。

Yes, there are many problems with SSRIs.

是的，SSRIs 存在很多问题。

They do carry certain side effects in many individuals.

它们确实对许多人有一定的副作用。

Also, about a third of people that take SSRIs don't derive any benefit.

此外，大约三分之一服用 SSRI 的人没有获得任何益处。

It doesn't relieve their symptoms of depression.

它并不能缓解他们的抑郁症状。

However, for the other two-thirds, there's often a relief of some, if not all of the symptoms of major depression.

然而，对于另外三分之二的人来说，重度抑郁症的部分症状（如果不是全部的话）通常会得到缓解。

The problem is the side effects that accompany those SSRIs.

问题是这些 SSRI 药物伴随而来的副作用。

Andrew Huberman:

安德鲁·休伯曼：

And so these days, SSRIs are a complicated topic.

因此，如今，SSRIs 是一个复杂的话题。

It's sort of what I would call a barbed wire topic because we often hear about all the problems with them.

这有点像我所说的带刺铁丝网主题，因为我们经常听到它们的所有问题。

But these drugs also have saved a lot of lives.

但这些药物也挽救了很多生命。

They've also improved a lot of lives.

他们还改善了很多生活。

The issue is that they tend to have varying effects on different individuals and sometimes varying effects over time.

问题是它们往往对不同的人产生不同的影响，有时甚至随着时间的推移产生不同的影响。

So they'll work for a while, then they won't work for a while.

所以他们会工作一段时间，然后他们就不会工作一段时间。

There're also a lot of mysteries about the SSRIs, and those mysteries bother people.

关于SSRIs也有很多谜团，这些谜团让人们感到困扰。

What mysteries am I referring to?

我指的是什么奥秘？

Well, SSRIs increase the amount of serotonin, or more specifically, they increase the efficacy of serotonin at the synapse.

SSRIs 会增加血清素的量，或者更具体地说，它们会增加突触处血清素的功效。

That happens immediately or very soon after people start taking SSRIs.

当人们开始服用 SSRIs 后，这种情况会立即或很快发生。

But people generally don't start experiencing any relief from their symptoms of depression, if they're going to experience them at all, until about two weeks after they start taking these drugs.

但人们通常要到开始服用这些药物大约两周后，他们的抑郁症状才会开始得到任何缓解（如果他们真的要经历的话）。

So there's something going on there that's not clear.

所以那里发生了一些尚不清楚的事情。

Andrew Huberman:

安德鲁·休伯曼：

One idea is that the SSRIs actually can improve symptoms of depression or even remove symptoms of depression through so-called neuroplasticity, by changing the way that neural circuits function.

一种观点认为，SSRIs 实际上可以通过所谓的神经可塑性（通过改变神经回路的功能方式）改善抑郁症状，甚至消除抑郁症状。

And there are many studies on this, but the main categories of studies on SSRIs that relate to neuroplasticity fall into two camps.

这方面的研究有很多，但与神经可塑性相关的 SSRIs 研究主要分为两大类。

One is that the ways in which SSRIs might, and I want to emphasize might, be able to trigger the production of more neurons in the brain, in particular areas of the hippocampus called the dentate gyrus and others that impact memory.

一是 SSRIs 可能（我想强调的是）能够触发大脑中产生更多神经元，特别是海马体中称为齿状回的区域和其他影响记忆的区域。

This is important.

这很重要。

And we're going to come back to memory.

我们将回到记忆中。

Andrew Huberman:

安德鲁·休伯曼：

The other is that the SSRIs have been shown in various scientific studies to reopen critical periods of plasticity.

另一个是，各种科学研究表明，SSRIs 可以重新开启可塑性的关键时期。

I'll just briefly describe one of those studies.

我将简要描述其中一项研究。

It was a study done by Lamberto Maffei's group in Pisa that explored brain plasticity that's known to be present in young animals and disappear in older animals.

这是兰贝托·马菲 (Lamberto Maffei) 比萨研究小组进行的一项研究，旨在探索大脑可塑性，这种可塑性已知存在于年轻动物中，而在老年动物中消失。

And this is also true in humans, that younger humans have a far more plastic brain that can change in many more ways more easily than can the older brain.

对于人类来说也是如此，年轻人的大脑可塑性更强，比年长的大脑更容易以多种方式发生变化。

And what they showed was that fluoxetine, Prozac, given to adult animals can reopen this incredible period of plasticity, can allow more plasticity to occur.

他们证明，给成年动物服用氟西汀、百忧解可以重新开启这段令人难以置信的可塑性时期，可以让更多的可塑性发生。

That was interesting.

这很有趣。

I mean, it's purely through increases in serotonin transmission.

我的意思是，这纯粹是通过增加血清素传输来实现的。

And there are other studies showing that fluoxetine can increase the number of new neurons that are born into the adult brain, so-called neurogenesis, the production of new neurons.

还有其他研究表明，氟西汀可以增加成人大脑中新生神经元的数量，即所谓的神经发生，即新神经元的产生。

Andrew Huberman:

安德鲁·休伯曼：

So it's very clear that there are at least three major chemical systems in the brain, norepinephrine, dopamine and serotonin, that relate to and can adjust the symptoms of depression.

因此，很明显，大脑中至少存在三种主要化学系统：去甲肾上腺素、多巴胺和血清素，它们与抑郁症症状相关并可以调节抑郁症症状。

And those actually can be divided into separate categories.

这些实际上可以分为不同的类别。

So for instance epinephrine, or norepinephrine, is thought to relate to the so-called psychomotor defects, sometimes called psychomotor retardation.

例如，肾上腺素或去甲肾上腺素被认为与所谓的精神运动缺陷（有时称为精神运动迟缓）有关。

This is the lethargy; this is the exhaustion.

这就是昏睡；这就是疲惫。

This is the inability to get out of bed in the morning.

这是早上起不来床的表现。

Dopamine is thought to relate to the anhedonia, or I should say lack of dopamine in depressive patients is thought to lead to the anhedonia.

多巴胺被认为与快感缺乏有关，或者我应该说抑郁症患者缺乏多巴胺被认为导致快感缺乏。

The lack of ability to experience pleasure.

缺乏体验快乐的能力。

And serotonin is thought to relate to the grief, the guilt, some of the more cognitive or more emotional aspects of depression.

血清素被认为与悲伤、内疚以及抑郁症的一些认知性或情感性方面有关。

So we've got the norepinephrine system related to activity and alertness, the dopamine system relating to motivation — pleasure and the ability to seek and experience pleasure — and then the serotonin system that's related to grief.

因此，我们有与活动和警觉性相关的去甲肾上腺素系统，与动机（快乐以及寻求和体验快乐的能力）相关的多巴胺系统，以及与悲伤相关的血清素系统。

Andrew Huberman:

安德鲁·休伯曼：

And unfortunately, brains and organisms don't work in a simple mathematical way, where you just say, "Oh, well this person's experiencing a lot of grief, but they don't have any problems with lethargy.

不幸的是，大脑和有机体并不是以简单的数学方式工作，你只需说，“哦，这个人经历了很多悲伤，但他们没有任何嗜睡的问题。

And so let's just boost up their serotonin." On paper it works, but oftentimes it doesn't work clinically.

因此，让我们提高他们的血清素水平。”在纸面上它是有效的，但在临床上通常不起作用。

And in another patient, you might get somebody who can't experience pleasure, but they're kind of anxious.

在另一个病人身上，你可能会遇到一些无法体验快乐的人，但他们有点焦虑。

They don't have any trouble sleeping, but they're just much more anxious and frustrated than they normally are, and they meet the symptoms of depression.

他们没有任何睡眠问题，但他们只是比平时更加​​焦虑和沮丧，并且出现了抑郁症的症状。

Well, you might think, "Oh, well, you just give that person some drug to increase dopamine and everything will be better."

好吧，你可能会想，“哦，好吧，你只要给那个人一些药物来增加多巴胺，一切都会好起来的。”

Andrew Huberman:

安德鲁·休伯曼：

And indeed, in some cases that's true.

事实上，在某些情况下确实如此。

There are drugs like Wellbutrin, which function more specifically on the dopamine system to increase dopamine, and they also increase norepinephrine.

有些药物如维布特林（Wellbutrin），其作用更具体地作用于多巴胺系统以增加多巴胺，并且它们还增加去甲肾上腺素。

Many people get great relief from things like Wellbutrin.

许多人从像维布特林这样的药物中得到很大的缓解。

They don't really impact the serotonin system so much, and therefore you don't get a lot of the serotonergic, or serotonin-related, side effects.

它们对血清素系统的影响并不大，因此您不会产生很多血清素能或与血清素相关的副作用。

However, some people feel far too anxious on those drugs.

然而，有些人对这些药物感到过于焦虑。

Some people get addicted to those drugs, in a way, because a lot of those drugs that increase dopamine make you want more of those drugs.

在某种程度上，有些人对这些药物上瘾，因为许多会增加多巴胺的药物会让你想要更多这些药物。

So you start to realize that what makes sense on paper doesn't always make sense clinically.

所以你开始意识到，纸面上有意义的东西在临床上并不总是有意义。

And this is why it's complicated.

这就是为什么它很复杂。

And a really good psychologist and a really good psychiatrist will work with someone to try and pull and push on these various systems to find the combination of drugs that may be or may not be correct for them.

一位真正优秀的心理学家和一位真正优秀的精神病学家将与某人合作，尝试推动这些不同的系统，以找到可能适合或不适合他们的药物组合。

Andrew Huberman:

安德鲁·休伯曼：

There's a fourth aspect of the chemistry of depression that's really important to understand, and that's pain.

抑郁症的第四个化学性质非常重要，那就是疼痛。

We've talked about pain on this podcast before, but even if you didn't hear the episode on pleasure and pain, I just want to emphasize that pain is something that we experience in our body, no surprise there, an injury, a cut, et cetera, but that we also experience emotional pain.

我们之前在这个播客上讨论过疼痛，但即使你没有听过关于快乐和疼痛的那一集，我只是想强调，疼痛是我们在身体中经历的事情，毫不奇怪，受伤、割伤等等，但我们也会经历情感上的痛苦。

And those systems are linked in very intricate ways.

这些系统以非常复杂的方式联系在一起。

There's actually some data showing that pain relievers, Tylenol, aspirin, these sorts of things, can help certain people with emotional pain.

实际上有一些数据表明，止痛药、泰诺、阿司匹林之类的东西可以帮助某些患有情绪痛苦的人。

Andrew Huberman:

安德鲁·休伯曼：

Now, I'm not recommending people run out and take those things for emotional pain, but actually, if you think about it, that shouldn't come as any surprise, given the enormous number of people that take painkillers, opioids and things like them, to try and relieve their psychological pain.

现在，我并不是建议人们为了情感上的痛苦而服用这些药物，但事实上，如果你仔细想想，考虑到有大量的人服用止痛药、阿片类药物和类似药物来试图缓解他们的心理痛苦，这应该不足为奇。

And as we know, those drugs are very, very problematic for many individuals.

正如我们所知，这些药物对许多人来说是非常非常有问题的。

They can help certain individuals, but they are very prone to abuse, and they can induce addiction very easily in a number of people.

它们可以帮助某些人，但很容易被滥用，并且很容易使许多人上瘾。

Andrew Huberman:

安德鲁·休伯曼：

There's a substance that's literally called substance P, the letter P, that's manufactured by neurons in our brain and body, which underlies our sensation of pain.

有一种物质的字面意思是 P 物质，字母 P，是由我们大脑和身体中的神经元产生的，它是我们疼痛感的基础。

And indeed, substance P inhibitors have been used to treat depression and, in some cases, works.

事实上，P 物质抑制剂已被用于治疗抑郁症，并且在某些情况下确实有效。

A lot of people with depression are hypersensitive to pain.

许多抑郁症患者对疼痛非常敏感。

And of course they could have multiple things going on.

当然，他们可能会发生多种事情。

They could have chronic pain or chronic injury and major depression.

他们可能患有慢性疼痛或慢性损伤以及重度抑郁症。

So you start to get the constellation of the many things that could happen.

所以你开始了解可能发生的许多事情。

Andrew Huberman:

安德鲁·休伯曼：

So that's all I want to say today about the chemistry underlying depression or major depression.

这就是我今天要说的关于抑郁症或重度抑郁症背后的化学原理。

There's a lot more there, but I think if you understand the norepinephrine system and that it relates to some of these things like lethargy, the psychomotor defects as they're called; dopamine, and how it relates to motivation and lack of motivation; and lack of dopamine and depression; and serotonin and its relationship to grief, and that low serotonin can lead to extreme grief and shame, and higher serotonin levels can sometimes restore a sense of wellbeing and safety and feeling good about oneself.

还有更多，但我想如果你了解去甲肾上腺素系统并且它与其中一些事情有关，例如嗜睡，即所谓的精神运动缺陷；多巴胺，以及它与动机和缺乏动机的关系；以及缺乏多巴胺和抑郁症；血清素及其与悲伤的关系，低血清素会导致极度悲伤和羞耻，而较高的血清素水平有时可以恢复幸福感、安全感和自我感觉良好。

If you understand that, and you understand that physical pain is somehow involved in certain cases, I think you will know more about depression and its underlying chemistry than most all people out there.

如果你明白这一点，并且你明白身体疼痛在某种程度上与某些情况有关，我想你会比大多数人更了解抑郁症及其潜在的化学反应。

And if you'd like to learn more, I invite you to pursue searching those terms further on the Internet, and we'll certainly go into them in more depth, but that really sets the stage for where we're headed next.

如果您想了解更多信息，我邀请您在互联网上进一步搜索这些术语，我们肯定会更深入地研究它们，但这确实为我们下一步的发展奠定了基础。

Andrew Huberman:

安德鲁·休伯曼：

So next I'd like to talk about hormones and how they relate to depression.

接下来我想谈谈激素以及它们与抑郁症的关系。

And I'd also like to talk about stress and how it relates to depression, as well as talk about some of the genetics, or the predispositions to depression.

我还想谈谈压力以及它与抑郁症的关系，以及一些遗传学或抑郁症的倾向。

And for those of you that are thinking, "Hey, I want the tools, I want to know how to fix depression," I understand the desire for that.

对于那些想“嘿，我想要这些工具，我想知道如何治疗抑郁症”的人来说，我理解他们的愿望。

I will just ask, if you hang in here with me a little bit longer, not only will you learn a lot more about how this complicated mood disorder works, some of the more interesting things about it, but it will also position you to get a lot more out of the tools that we will describe.

我只想问，如果你和我一起坚持一会儿，你不仅会更多地了解这种复杂的情绪障碍是如何运作的，一些更有趣的事情，而且还会让你从我们将描述的工具中获得更多的东西。

You always have the option to skip forward, of course, but I think it's important to understand some of the hormonal and stress-related aspects of depression.

当然，你总是可以选择跳过，但我认为了解抑郁症的一些荷尔蒙和压力相关方面很重要。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk about hormones.

那么我们来谈谈荷尔蒙。

20% of people that have major depression have low thyroid hormone.

20% 的重度抑郁症患者甲状腺激素水平较低。

Thyroid hormone is related to metabolism.

甲状腺激素与新陈代谢有关。

Oftentimes we think about thyroid as only related to having a fast metabolism, but thyroid is related to all forms of metabolism, including our ability to synthesize new tissues like protein, and repair injuries.

通常我们认为甲状腺只与快速新陈代谢有关，但甲状腺与所有形式的新陈代谢有关，包括我们合成蛋白质等新组织和修复损伤的能力。

I did a whole episode on thyroid and growth hormone if you want to check that out.

如果你想看的话，我做了一整集关于甲状腺和生长激素的内容。

All of that is archived at hubermanlab.com.

所有这些都存档在 hubermanlab.com 上。

It's all timestamped, et cetera.

一切都带有时间戳，等等。

You can find on YouTube, Apple, Spotify, all those places.

您可以在 YouTube、Apple、Spotify 等所有这些地方找到。

So if you're curious about thyroid hormone and growth hormone, and you want to do the deep dive on those, and you want to learn how to alter their levels using various approaches, check that out.

因此，如果您对甲状腺激素和生长激素感到好奇，并且想要深入研究它们，并且想要了解如何使用各种方法改变它们的水平，请检查一下。

Andrew Huberman:

安德鲁·休伯曼：

But 20% of people with major depression are hypothyroidal.

但 20% 的重度抑郁症患者患有甲状腺功能减退症。

They don't make enough thyroid.

他们不能产生足够的甲状腺。

And that leads to low energy, low metabolism in the brain and body.

这会导致大脑和身体能量低、新陈代谢低。

And there's a condition called Hashimoto's, which is essentially low thyroid output.

还有一种叫做桥本氏症的病症，本质上是甲状腺分泌量低。

And again, I don't want to get into all the tools related to thyroid.

再说一遍，我不想讨论所有与甲状腺相关的工具。

Sometimes a psychiatrist will prescribe thyroid medication to increase thyroid output in people that are depressed, and that will work to relieve the symptoms.

有时，精神科医生会开甲状腺药物来增加抑郁症患者的甲状腺输出，这将有助于缓解症状。

So there isn't necessarily a direct problem with serotonin, dopamine and norepinephrine or substance P; sometimes it's a thyroid problem.

因此，血清素、多巴胺、去甲肾上腺素或 P 物质不一定存在直接问题；有时是甲状腺问题。

Andrew Huberman:

安德鲁·休伯曼：

So there are certain situations or conditions that can impact the thyroid hormone system and make people more susceptible to depression, or make a preexisting depression worse.

因此，某些情况或条件可能会影响甲状腺激素系统，使人们更容易患抑郁症，或使已有的抑郁症恶化。

And those are things like childbirth.

这些都是像分娩这样的事情。

So it's well-known that women who give birth can often undergo what's called postpartum depression.

众所周知，分娩的女性经常会患上所谓的产后抑郁症。

It actually comes from the word post-parturition depression.

它实际上来自产后抑郁症这个词。

They give birth.

他们生孩子。

What's happier, what's more joyful than the birth of a new healthy child?

还有什么比一个健康的新孩子的诞生更幸福、更快乐的呢？

And they will lapse into a depression.

他们会陷入抑郁。

And that's thought to be hormonally related, either directly to the thyroid system or perhaps to the cortisol system as well.

这被认为与激素有关，要么直接与甲状腺系统有关，要么也与皮质醇系统有关。

We'll talk about cortisol in a moment.

我们稍后会讨论皮质醇。

As well, certain women during certain phases of their menstrual cycle experience symptoms that are very much like clinical depression and oftentimes are diagnosed with clinical depression appropriately.

此外，某些女性在月经周期的某些阶段会经历与临床抑郁症非常相似的症状，并且通常会被适当地诊断为临床抑郁症。

And of course the menstrual cycle is associated with shifts in hormone levels.

当然，月经周期与激素水平的变化有关。

As well, menopause and postmenopausal women are more susceptible to major depression, regardless of whether or not they've had that major depression earlier in their life.

此外，更年期和绝经后女性更容易患重度抑郁症，无论她们在生命早期是否患有重度抑郁症。

Andrew Huberman:

安德鲁·休伯曼：

So these are things to be on the lookout for and to definitely talk to a doctor and get a blood panel that hopefully includes measures of thyroid hormone and cortisol hormone.

因此，这些都是需要注意的事情，并且一定要咨询医生并进行血液检查，希望包括甲状腺激素和皮质醇激素的测量。

Why cortisol hormone?

为什么是皮质醇激素？

Well, more stress is correlated with more bouts of major depression across the lifespan.

嗯，更大的压力与一生中更多的重度抑郁症相关。

How many bouts?

几回合？

Well, it turns out that as you go from having one to two to three, well, when you hit four to five bouts of really intense, stressful episodes in life — these tend to be long-term, stressful episodes — your risk for major depression goes way up.

好吧，事实证明，当你从一次到两次再到三次，好吧，当你在生活中经历四到五次真正强烈、有压力的发作时——这些往往是长期的、有压力的发作——你患重度抑郁症的风险就会上升。

Andrew Huberman:

安德鲁·休伯曼：

So whether or not you have a genetic predisposition to depression or not, one of the best things you can do to try and avoid getting depressed is to learn to control your stress system, to not go from short-term stress, which everybody experiences — we all have short-term stressors — to medium-term stress, to long-term stress, and to not have too many bouts of long-term stress, because that probability of getting depressed goes way, way up.

因此，无论你是否有抑郁症的遗传倾向，为了避免抑郁，你能做的最好的事情之一就是学会控制你的压力系统，不要从每个人都会经历的短期压力（我们都有短期压力源）转变为中期压力，再到长期压力，并且不要承受太多的长期压力，因为患抑郁症的可能性会大大增加。

And this is something I've seen over and over again, not just in my scientific career but just throughout life, people in all sorts of domains, young and old.

这是我一遍又一遍地看到的事情，不仅在我的科学生涯中，而且在一生中，各个领域的人们，无论年轻还是年老。

I've seen that people will go through a very intense relationship, a breakup.

我见过人们会经历一段非常紧张的关系，甚至分手。

Sometimes it's the staying together that's stressful.

有时，在一起会带来压力。

Sometimes it's graduate school that can be stressful.

有时研究生院可能会带来压力。

Sometimes it's some other event.

有时是其他事件。

And then some months later, they become depressed.

几个月后，他们变得沮丧。

And that's because the stress system is associated with the release of cortisol.

这是因为压力系统与皮质醇的释放有关。

The cortisol system can dramatically impact the way that these different neuromodulators, dopamine, norepinephrine and serotonin function.

皮质醇系统可以极大地影响这些不同的神经调节剂、多巴胺、去甲肾上腺素和血清素的功能方式。

And so there's this kind of latent or longer-lasting impact on the systems that impact mood and wellbeing.

因此，对影响情绪和健康的系统存在这种潜在或更持久的影响。

Andrew Huberman:

安德鲁·休伯曼：

So learning how to control your stress is really key.

因此，学习如何控制压力非常关键。

If you're not depressed, or you're somebody that has not lapsed into a depression recently, take control of your stress system.

如果您没有抑郁，或者您最近没有陷入抑郁，请控制您的压力系统。

And we did an entire episode on how to conquer stress, and that involves dealing with stress in the short term, the medium term, and in the long term.

我们做了一整集关于如何克服压力的内容，其中涉及处理短期、中期和长期的压力。

And there are a lot of different ways to do that.

有很多不同的方法可以做到这一点。

Andrew Huberman:

安德鲁·休伯曼：

One of the more important reasons for learning how to counter stress in order to offset depression, is that there is a genetic predisposition that certain people carry to become depressed.

学习如何应对压力以抵消抑郁症的更重要原因之一是，某些人具有抑郁的遗传倾向。

There are these studies now of many, many thousands of individuals — these were mainly done in New Zealand, but these studies have now been done elsewhere — looking at many tens of thousands of individuals who carry particular copies of genes, they're called polymorphisms, in particular of a gene called 5-HTTLPR, which is a serotonin transporter.

现在有针对成千上万个体的研究——这些研究主要是在新西兰进行的，但这些研究现在也在其他地方进行——观察了成千上万携带特定基因拷贝的个体，它们被称为多态性，特别是一种名为 5-HTTLPR 的基因，它是一种血清素转运蛋白。

So this is a gene that controls or regulates how much serotonin is available in the brain.

所以这是一个控制或调节大脑中可用血清素含量的基因。

If you have this gene, this polymorphism, it doesn't necessarily mean that you will be depressed, but it greatly shifts your susceptibility to depression under conditions of stress.

如果你有这个基因，这种多态性，并不一定意味着你会抑郁，但它极大地改变了你在压力条件下患抑郁症的易感性。

Andrew Huberman:

安德鲁·休伯曼：

So I realize some people are listening to this, and some people are watching it on YouTube.

所以我意识到有些人正在听这个，有些人正在 YouTube 上观看。

So I'm going to describe this in a way that doesn't require looking at any graphs.

所以我将以一种不需要查看任何图表的方式来描述这一点。

What I want you to imagine is a very shallow hill, like a very mellow hill.

我想让你想象的是一座非常浅的山，就像一座非常柔和的山。

It's just a ramp set at about 10 or 15 degrees.

这只是一个大约 10 或 15 度的坡道。

What we're plotting there in your mind is that with each bout of serious stress — so that could be trying to finish a degree, or a relationship breakup, or a family member that's sick, or the loss of a loved one or a pet — with each bout of stress, the probability that you'll experience a major depression goes up.

我们在你脑海中描绘的是，随着每一次严重的压力——可能是试图完成学位，或者关系破裂，或者家庭成员生病，或者失去亲人或宠物——每一次压力，你经历严重抑郁症的可能性都会上升。

However, if you carry this gene, this HTTLPR gene, the steepness of that curve goes way, way up, where it's actually more like a line, such that you need far fewer bouts of stress in order to lapse into a major depression.

然而，如果你携带这个基因，这个 HTTLPR 基因，那条曲线的陡度就会大大上升，实际上更像是一条线，这样你就需要更少的压力才能陷入严重的抑郁症。

So if the typical person who doesn't carry this polymorphism has to experience two or three or four or five bouts of stress before they lapse into a depression, somebody with this gene is susceptible to getting depression after just one bout or two bouts of intense stress.

因此，如果不携带这种多态性的典型人在陷入抑郁症之前必须经历两次或三次或四次或五次压力，那么携带这种基因的人在经历一两次强烈压力后就很容易患上抑郁症。

Andrew Huberman:

安德鲁·休伯曼：

So, that's how these genes work.

这就是这些基因的工作原理。

They don't preordain or determine you to be depressed.

它们不会注定或决定你会抑郁。

They raise a susceptibility, and many genes, many things related to heritability in general work in that way.

它们提高了易感性，许多基因、许多与遗传性相关的事物通常都以这种方式起作用。

And we know there's a strong genetic component to depression.

我们知道抑郁症有很强的遗传因素。

How do we know?

我们怎么知道？

Well, in what are called concordant monozygotic twins, so these will be identical twins.

嗯，在所谓的一致同卵双胞胎中，所以这些将是同卵双胞胎。

And they can either be in one biological sac or two biological sacs while in utero, what's called monochorionic or dichorionic.

在子宫内时，它们可以位于一个生物囊中，也可以位于两个生物囊中，即所谓的单绒毛膜或双绒毛膜。

Well, typically it's monochorionic.

嗯，通常是单绒毛膜的。

And identical twins for which one of those twins goes on to have major depression, there's a 50% probability that the other one will have major depression.

对于同卵双胞胎来说，如果其中一个患有重度抑郁症，那么另一个也有 50% 的可能性会患上重度抑郁症。

So it's not 100%; it's not 100% inherited it's not 100% genetic, as you might say, but there's a much higher predisposition for depression.

所以这不是100%；它不是 100% 遗传的，正如你可能会说的，它不是 100% 遗传的，但抑郁症的易感性要高得多。

Whereas in fraternal twins, that number drops.

而在异卵双胞胎中，这个数字却下降了。

And in siblings, that number drops to about 25%.

而在兄弟姐妹中，这个数字下降到 25% 左右。

And in half siblings it's about 10%.

在同父异母的兄弟姐妹中，这一比例约为 10%。

The numbers vary from study to study.

这些数字因研究而异。

But basically, the more closely related you are to somebody who has major depression, the more likely it is that you will also get major depression.

但基本上，您与患有重度抑郁症的人关系越密切，您也患上重度抑郁症的可能性就越大。

And therefore, if you haven't gotten major depression, the more likely it is that you should take steps to learn to mitigate stress, because stress is the major factor that can trigger one of these depressive episodes.

因此，如果您没有患上重度抑郁症，您更有可能应该采取措施学习减轻压力，因为压力是引发这些抑郁发作的主要因素。

Andrew Huberman:

安德鲁·休伯曼：

So we covered a lot related to the stress and the hormones and the neurochemistry of depression.

所以我们讨论了很多与压力、激素以及抑郁症的神经化学有关的内容。

In fact, I think this is probably the deepest I've ever gone into the biology of any topic on this podcast before getting to any specific tools.

事实上，我认为这可能是我在使用任何特定工具之前对本播客中任何主题的生物学最深入的了解。

I mentioned that learning how to mitigate stress and deal with stress, learning how to measure and adjust your thyroid hormone, those might be useful.

我提到学习如何减轻压力和应对压力，学习如何测量和调整甲状腺激素，这些可能会有用。

But next I'd like to turn to some very specific tools that people who both have depression or who are prone to depression, as well as people who don't have depression and simply want to maintain a good mood, who want to maintain a positive affect and pursuit of things in life, what are the things that you can do?

但接下来我想谈谈一些非常具体的工具，对于那些患有抑郁症或容易患抑郁症的人，以及那些没有抑郁症但只想保持好心情的人，想要对生活中的事物保持积极的影响和追求的人，你可以做哪些事情？

Turns out there are things that you can do.

事实证明，有些事情是你可以做的。

And all of the biology that underlies the utility of those things, meaning the reasons those things work, will now make sense to you, because they adjust things like serotonin and dopamine, and they adjust them through very specific pathways.

所有这些东西的效用背后的生物学，意味着这些东西起作用的原因，现在对你来说都是有意义的，因为它们调整血清素和多巴胺等东西，并且通过非常特定的途径来调整它们。

Andrew Huberman:

安德鲁·休伯曼：

I know for many people, learning about mechanism is kind of grueling.

我知道对很多人来说，学习机制是一件很辛苦的事。

I realize this podcast isn't necessarily one that you can listen to passively while doing other things, although I would hope that you could do that and still enjoy it and extract the information.

我意识到这个播客不一定是您可以在做其他事情时被动收听的播客，尽管我希望您可以这样做并且仍然喜欢它并提取信息。

Why mechanism?

为什么机制？

Mechanism is so key, Because mechanism is a little bit like understanding some of the chemistry of cooking.

机制是如此关键，因为机制有点像理解烹饪的一些化学成分。

If you read a recipe, and you can follow a recipe — you often hear people say, "Oh, I can follow a recipe." That means that if you have every ingredient in that recipe, you're good.

如果你读过食谱，并且可以遵循食谱 - 你经常会听到人们说，“哦，我可以遵循食谱。”这意味着，如果您拥有该食谱中的所有成分，那么您就可以了。

You likely can make that dish, you can make that meal.

你可能可以做那道菜，你可以做那顿饭。

However, if you understand a little bit of the chemistry of why salt has to be added third and not first, or why the heat has to be adjusted at a particular time, well then not only can you follow a recipe, but that also gives you flexibility for when salt isn't available, or when you want to adjust the flavor of the dish, or when you want to try a new dish or you want to get experimental.

然而，如果您了解为什么必须第三次而不是首先添加盐，或者为什么必须在特定时间调整热量的一些化学原理，那么您不仅可以遵循食谱，而且还可以在没有盐的情况下，或者当您想要调整菜肴的味道时，或者当您想尝试新菜肴或想要进行实验时提供灵活性。

Andrew Huberman:

安德鲁·休伯曼：

So when you understand mechanism, it puts you in a tremendous place of power to work with your system.

因此，当您了解机制时，您就会拥有使用系统的巨大能力。

So it's not just plug and chug, like take 12 milligrams of this, you either feel better or you don't.

所以，这不仅仅是塞下就喝的问题，比如服用 12 毫克，你要么感觉好点，要么感觉不好。

You can really start to understand how prescription drugs, supplements, nutrition, behavioral tools, how those things weave together to either work for you or not work for you, and get you to paths of healthy mind and body.

你可以真正开始了解处方药、补充剂、营养、行为工具，这些东西如何交织在一起，对你有效或无效，并让你走上健康的身心之路。

Andrew Huberman:

安德鲁·休伯曼：

So let's think about why any tool would work to relieve depression.

因此，让我们思考一下为什么任何工具都可以缓解抑郁症。

We've talked about how some of the drugs that impact these different chemical systems might work, and why they create some of the problems they create.

我们已经讨论了一些影响这些不同化学系统的药物如何发挥作用，以及为什么它们会产生一些问题。

Problems are mainly created by the fact that they impact lots of systems in the brain and body.

问题主要是由于它们影响大脑和身体的许多系统而产生的。

So you take a drug to increase serotonin, but that serotonin is also related not just to mood, but to things related to libido and appetite.

所以你服用药物来增加血清素，但血清素不仅与情绪有关，还与性欲和食欲有关。

And so you start disrupting multiple systems.

于是你开始扰乱多个系统。

Andrew Huberman:

安德鲁·休伯曼：

The same could be said for behavioral tools, right, that any behavioral tool that adjusts the levels of a particular chemical ought to, perhaps, provide some relief for some of the symptoms of major depression.

对于行为工具来说也是如此，对吧，任何调整特定化学物质水平的行为工具也许应该为重度抑郁症的某些症状提供一些缓解。

Let's take an example that I've talked about before on the podcast, which is if you get into a very cold shower, you take an ice bath, you will release norepinephrine and epinephrine in your brain and body.

让我们举一个我之前在播客上讲过的例子，如果你洗个很冷的澡，洗个冰浴，你的大脑和身体就会释放去甲肾上腺素和肾上腺素。

There's no question about that.

毫无疑问。

I don't think anyone can really escape that.

我认为没有人能够真正逃脱这一点。

It's a kind of universal response to being in cold water.

这是身处冷水中的一种普遍反应。

Well, if some aspects of depression are related to low levels of norepinephrine, will taking cold showers relieve your depression?

那么，如果抑郁症的某些方面与去甲肾上腺素水平低有关，那么洗冷水澡会缓解你的抑郁症吗？

Perhaps.

也许。

It might even relieve certain aspects of that depression.

它甚至可能缓解抑郁症的某些方面。

Is it a cure?

这是一种治疗方法吗？

Well, that's going to depend on the individual.

嗯，这取决于个人。

Andrew Huberman:

安德鲁·休伯曼：

Will exercise help?

运动会有帮助吗？

Well, if you go out for a run, you're going to increase the amount of norepinephrine in your body.

好吧，如果你出去跑步，你体内去甲肾上腺素的含量就会增加。

If you enjoy that run, it's likely that you'll increase the levels of dopamine and probably serotonin in your brain and body as well.

如果您喜欢跑步，很可能会增加大脑和身体中多巴胺以及血清素的水平。

Will that cure your depression?

这能治愈你的抑郁症吗？

Well, there are a lot of studies exploring how exercise can impact depression.

嗯，有很多研究探索运动如何影响抑郁症。

And indeed, regular exercise is known to be a protective behavior against depression, but it also can help relieve some of the symptoms of depression.

事实上，众所周知，定期锻炼是预防抑郁症的一种保护行为，但它也可以帮助缓解抑郁症的一些症状。

Andrew Huberman:

安德鲁·休伯曼：

So you may ask yourself, why would you need drugs at all?

所以你可能会问自己，为什么你需要药物？

Why would there be prescription drugs or the need for supplementation or other things to alleviate the symptoms of depression?

为什么会有处方药或需要补充剂或其他东西来缓解抑郁症状？

Well, that's the diabolical nature of depression, which is if people are far enough along in this thing, this sometimes called disease, sometimes called disorder, but major depression, oftentimes they can't get the energy to even get up and take a bath or a shower.

嗯，这就是抑郁症的恶魔本质，如果人们在这件事上走得足够远，这有时被称为疾病，有时被称为障碍，但重度抑郁症，通常他们甚至没有力气站起来洗澡或淋浴。

They have no motivation to do it.

他们没有动力这样做。

They have no desire to go for a run.

他们不想去跑步。

Andrew Huberman:

安德鲁·休伯曼：

So you say, "Come on, let's go.

所以你说：“来吧，我们走吧。

You'll feel better.

你会感觉好多了。

I know you'll feel better.

我知道你会感觉好一些。

It generates all these chemicals.

它产生所有这些化学物质。

I heard on the whatever podcast, Huberman Lab podcast or another podcast, that getting into action does all these things," and they just don't want to do it.

我在任何播客、胡伯曼实验室播客或其他播客上听说，采取行动可以做到所有这些事情，”但他们只是不想这样做。

And to you, a person who's not experiencing depression, that perhaps could just seem like the most frustrating and confusing thing in the world.

对于你来说，一个没有经历过抑郁症的人，这也许看起来是世界上最令人沮丧和困惑的事情。

But it's very important to highlight the fact that these circuits that are accessible to some of us, the circuits for happiness, for pursuit of pleasure, for exercise, for getting in a cold shower if that's your thing, that those circuits are present in all people, but for certain people that are experiencing major depression and are really in the depths of their depression, they can't really access those circuits in the same way that people who are not suffering from depression can.

但重要的是要强调这样一个事实，即我们中的一些人可以使用这些回路，这些回路是为了幸福、为了追求快乐、为了锻炼、为了洗冷水澡（如果这是你的事），这些回路存在于所有人身上，但对于某些正在经历严重抑郁症并且真正处于抑郁症深处的人来说，他们无法像没有患有抑郁症的人那样真正地使用这些回路。

So I hope that makes it clear it's not offering any excuses for them.

所以我希望这能够表明，这并不是为他们提供任何借口。

And indeed, I think those behaviors would help jolt them out of some of the symptomology of depression, but they're just not accessible to everybody.

事实上，我认为这些行为可以帮助他们摆脱抑郁症的一些症状，但并不是每个人都能做到。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk about the things that people can do to deal with depression.

那么让我们来谈谈人们可以采取哪些措施来应对抑郁症。

And again, any time you add a behavior or a tool or a supplement or subtract a behavior, tool, supplement drug, et cetera, you absolutely should talk to your physician, especially if you're somebody that's dealing with major depression.

再说一次，任何时候你添加一种行为、一种工具或一种补充剂，或者减少一种行为、工具、补充剂药物等，你绝对应该咨询你的医生，特别是如果你是一个患有重度抑郁症的人。

I want to focus on the stress system, and I'm not just going to tell you to get sunlight in your eyes and to get a good night's sleep, although I think everybody should do that on a regular basis.

我想关注压力系统，我不只是告诉你要让阳光照射到眼睛里并睡个好觉，尽管我认为每个人都应该定期这样做。

Ideally, every day.

理想情况下，每天。

Talked about those at nauseam on this podcast.

在这个播客上谈论了那些令人恶心的人。

They will help your sleep.

它们会帮助你的睡眠。

They will help you alleviate stress.

他们将帮助您减轻压力。

I think you should have tools to deal with stress in real time, et cetera.

我认为你应该拥有实时应对压力的工具，等等。

Andrew Huberman:

安德鲁·休伯曼：

But let's look at depression from the standpoint of a deeper biological phenomenon, which is inflammation and the immune system.

但让我们从更深层次的生物现象——炎症和免疫系统——的角度来看待抑郁症。

There's growing evidence now that many forms of major depression, if not all of them, relate to excessive inflammation.

现在有越来越多的证据表明，许多形式的重度抑郁症（如果不是全部）都与过度炎症有关。

Now, inflammation plays an important role in wound healing.

现在，炎症在伤口愈合中发挥着重要作用。

It is a positive aspect of our immune system, our ability to combat wounds, combat illnesses, et cetera.

这是我们的免疫系统、我们对抗伤口、对抗疾病等能力的积极方面。

But inflammation gone unchecked, inflammation that lasts too long or is of too high amplitude, meaning too many anti-inflammatory or inflammatory cytokines and things of that sort in the body, is bad.

但如果炎症不受控制，炎症持续时间过长或幅度过高，意味着体内有过多的抗炎或炎症细胞因子等类似物质，那就不好了。

And there's decent evidence now that inflammation can lead to or exacerbate depression, and that if we want to control depression or limit or eliminate depression, that focusing on reducing inflammation and its associated pathways is a really good thing to do.

现在有充分的证据表明炎症会导致或加剧抑郁症，如果我们想控制抑郁症或限制或消除抑郁症，那么专注于减少炎症及其相关途径确实是一件好事。

And I think this is a really good thing for everybody to do regardless of whether or not you suffer from depression or not.

我认为这对每个人来说都是一件非常好的事情，无论你是否患有抑郁症。

And today we're going to talk about exactly how depression comes about through the inflammation pathway.

今天我们将讨论抑郁症是如何通过炎症途径产生的。

Andrew Huberman:

安德鲁·休伯曼：

Okay, so first of all, who are the major players in creating chronic inflammation in the brain and body?

好的，首先，谁是造成大脑和身体慢性炎症的主要因素？

They are the inflammatory cytokines, things like IL-6, interleukin six, things like tumor necrosis alpha, TNF alpha, things like C-reactive protein.

它们是炎症细胞因子，例如 IL-6、白细胞介素 6、肿瘤坏死 α、TNF α 等，以及 C 反应蛋白等。

All right?

好的？

Not all of these are cytokines.

并非所有这些都是细胞因子。

You have interferons and your prostaglandins and a lot of these things.

你有干扰素和前列腺素以及很多这样的东西。

But when we are stressed, chronically stressed, we get inflamed.

但当我们承受压力时，长期承受压力，我们就会发炎。

Our brain and various locations in the brain become inflamed, because certain classes of cells, in particular those glial cells, the cells that are typically thought to just be support cells, those cells and their biochemistry and their dialogue with the neurons of the brain and body starts to become disrupted.

我们的大脑和大脑中的各个部位会发炎，因为某些类型的细胞，特别是那些神经胶质细胞，通常被认为只是支持细胞的细胞，这些细胞及其生物化学以及它们与大脑和身体神经元的对话开始被破坏。

Andrew Huberman:

安德鲁·休伯曼：

I may have mentioned it earlier, I don't recall, but I certainly mentioned it in an earlier podcast, that adrenaline, epinephrine, when it's released in the body, it doesn't cross the blood-brain barrier.

我可能之前提到过，我不记得了，但我确实在之前的播客中提到过，肾上腺素、肾上腺素在体内释放时，不会穿过血脑屏障。

But there are certain things that are able to cross the blood-brain barrier when we are stressed, things like the E2 prostaglandins; those cross the blood-brain barrier, and our blood and our brain, therefore, our brain and our body can communicate because certain things can pass through this barrier we call the BBB, or the blood-brain barrier, and also we have something called the glymphatic system, which is really a plumbing system that links the brain and body.

但当我们感到压力时，有些物质能够穿过血脑屏障，例如 E2 前列腺素；它们穿过血脑屏障，我们的血液和大脑，因此，我们的大脑和我们的身体可以交流，因为某些东西可以穿过这个我们称之为BBB或血脑屏障的屏障，而且我们还有一种叫做类淋巴系统的东西，它实际上是一个连接大脑和身体的管道系统。

It's the link between the immune system and the brain.

它是免疫系统和大脑之间的联系。

Well, there is a set of actions that we can take in order to limit inflammation.

那么，我们可以采取一系列行动来限制炎症。

And this has been shown in several quality peer-reviewed studies now to reduce inflammation and to relieve some, and in some cases, all of the symptoms of major depression.

现在几项高质量的同行评审研究表明，这一点可以减少炎症并缓解部分（在​​某些情况下）重度抑郁症的全部症状。

Andrew Huberman:

安德鲁·休伯曼：

One of those approaches is to increase our intake of so-called EPAs, or essential fatty acids.

其中一种方法是增加我们所谓的 EPA（必需脂肪酸）的摄入量。

There's now a very long list of papers in quality peer-review journals showing that when people ingest a certain level of EPA omega-3 fatty acids, the relief from depressive symptoms matches the SSRIs.

现在，高质量同行评审期刊上有一长串论文表明，当人们摄入一定水平的 EPA omega-3 脂肪酸时，抑郁症状的缓解效果与 SSRI 相当。

That's incredible, right?

这太不可思议了，对吧？

That essential fatty acids could relieve symptoms of depression as well as some of the prescription antidepressants.

这种必需脂肪酸可以像某些处方抗抑郁药一样缓解抑郁症状。

Now, this doesn't necessarily mean you run off and stop taking your antidepressants if you've been prescribed them.

现在，这并不一定意味着如果您服用了抗抑郁药，您就可以逃跑并停止服用。

Please don't do that.

请不要这样做。

Please talk to your physician.

请咨询您的医生。

And I should mention that some of these same studies have shown that increasing our intake of these essential fatty acids, in particular the EPA variety of omega-3s, can lower the effective dose of things like SSRIs.

我应该提到的是，其中一些研究表明，增加这些必需脂肪酸的摄入量，特别是 EPA 中的 omega-3 脂肪酸，可以降低 SSRI 等物质的有效剂量。

Meaning if we required a 50 milligram or 40 milligram dose of fluoxetine, that one can get by on a lower dose and, thereby, perhaps not experience as many or as severe side effects by taking or supplementing with EPAs.

这意味着，如果我们需要 50 毫克或 40 毫克剂量的氟西汀，则可以使用较低剂量，因此，也许不会因服用或补充 EPA 而经历那么多或那么严重的副作用。

Andrew Huberman:

安德鲁·休伯曼：

Now, the threshold level seems to be about one gram, 1000 milligrams, of EPA.

现在，EPA 的阈值水平似乎约为 1 克（1000 毫克）。

So you will sometimes see on a bottle of krill oil or fish oil or any other source, even plant source or other source of EPA, that it's 1000 milligrams or 1200 milligrams.

因此，有时您会在一瓶磷虾油或鱼油或任何其他来源（甚至植物来源或其他来源的 EPA）上看到 EPA 含量为 1000 毫克或 1200 毫克。

But what's really important to look at is whether or not there's more than a thousand milligrams of EPA, because the EPA, in particular, is what's important here.

但真正重要的是要看看其中的 EPA 含量是否超过一千毫克，因为 EPA 在这里尤其重要。

And actually, in exploring some of the literature on the effects of EPAs on cardiovascular health, as well as their effects on depression, there's some interesting dose-dependent responses, such that people who took anywhere from 400 milligrams to 5,000 milligrams of EPAs achieved a variety of different benefits, and in some cases some side effects.

事实上，在探讨 EPA 对心血管健康的影响以及对抑郁症的影响的一些文献时，发现了一些有趣的剂量依赖性反应，例如服用 400 毫克到 5,000 毫克 EPA 的人获得了各种不同的益处，在某些情况下还产生了一些副作用。

We'll talk about those.

我们会讨论这些。

And it does seem that this 1000 milligrams is the critical threshold for benefiting or getting some relief from depressive symptoms.

这 1000 毫克似乎确实是使抑郁症状受益或得到一定程度缓解的关键阈值。

Andrew Huberman:

安德鲁·休伯曼：

But people who took two grams seemed to do better.

但服用两克的人似乎表现更好。

And in the cardiovascular health realm there, it's a little more complicated.

在心血管健康领域，情况要复杂一些。

Some studies point to a very positive effect on cardiovascular health by taking increasing amounts of EPA, others not so much.

一些研究表明，增加 EPA 摄入量对心血管健康有非常积极的影响，但其他研究则不然。

The current data point to the fact that for every gram of EPA that one ingests, there's about a nine percent improvement in cardiovascular health.

目前的数据表明，每摄入一克 EPA，心血管健康就会改善约 9%。

The same dose-dependent improvement on psychological health, in combating depression, can't really be stated.

在对抗抑郁症方面，对心理健康的同样剂量依赖性改善是无法真正说明的。

I wouldn't say that the more EPA you take, the better you're going to feel, so to speak.

可以这么说，我并不是说您服用的 EPA 越多，您的感觉就越好。

I don't think the data point to that.

我不认为数据表明这一点。

However, it does seem that if you take a gram, 1000 milligrams, or 2000 milligrams of EPA, there does seem to be some substantial relief for many people; I should emphasize many, not all, for many people, in major depressive symptoms.

然而，如果您服用 1 克、1000 毫克或 2000 毫克 EPA，对许多人来说似乎确实会得到一些实质性的缓解；对于很多人来说，我应该强调许多重度抑郁症状，而不是全部。

Andrew Huberman:

安德鲁·休伯曼：

So how would this work?

那么这将如何运作呢？

Well, turns out that these inflammatory cytokines, they impact neurons and the circuits of the brain that relate to things like serotonin, dopamine and norepinephrine.

事实证明，这些炎症细胞因子会影响神经元和与血清素、多巴胺和去甲肾上腺素等物质相关的大脑回路。

These inflammatory cytokines act in a variety of different ways, but they mainly act to inhibit the release of serotonin, norepinephrine and dopamine, or the synthesis of serotonin, norepinephrine and dopamine.

这些炎性细胞因子以多种不同的方式发挥作用，但主要作用是抑制血清素、去甲肾上腺素和多巴胺的释放，或抑制血清素、去甲肾上腺素和多巴胺的合成。

And I'll give you one example of how EPAs can positively impact this process.

我将举一个例子来说明 EPA 如何对这一过程产生积极影响。

And then it points to a second tool, which is the proper utilization of exercise to offset the effects of depression.

然后它指出了第二个工具，那就是适当利用运动来抵消抑郁症的影响。

Andrew Huberman:

安德鲁·休伯曼：

So now you should understand why having healthy levels of serotonin is important for maintaining healthy mood.

所以现在您应该明白为什么拥有健康的血清素水平对于保持健康的情绪很重要。

It's not responsible for all the aspects of having a healthy mood; there's also dopamine and norepinephrine, but it is a very important one.

它并不负责拥有健康情绪的所有方面；还有多巴胺和去甲肾上腺素，但它是非常重要的一种。

Dopamine, also called 5-HT, essentially derives from a precursor called tryptophan.

多巴胺，也称为 5-HT，本质上源自一种称为色氨酸的前体。

Tryptophan arrives into our system through our diet.

色氨酸通过我们的饮食进入我们的系统。

PART 1 OF 3 ENDS Andrew Huberman:

第 1 部分（共 3 部分）结束 Andrew Huberman：

Tryptophan arrives into our system through our diet.

色氨酸通过我们的饮食进入我们的系统。

Okay, tryptophan is an amino acid.

好吧，色氨酸是一种氨基酸。

Tryptophan is found in turkey, it's found in carbohydrates, and that should therefore raise the idea of, Hmmm, I wonder if one of the reasons why people who are depressed have such an appetite for carbohydrate-laden foods is because they're trying to get more tryptophan and therefore more serotonin.

色氨酸存在于火鸡中，存在于碳水化合物中，因此应该提出这样的想法：嗯，我想知道抑郁症患者对富含碳水化合物的食物如此感兴趣的原因之一是否是因为他们试图获得更多的色氨酸，从而获得更多的血清素。

And indeed that's the case.

事实确实如此。

Tryptophan is eventually converted into serotonin.

色氨酸最终转化为血清素。

However, if there's excessive amounts of inflammation, these inflammatory cytokines cause tryptophan to not be converted so much into serotonin, but to be diverted down a different pathway.

然而，如果炎症过多，这些炎症细胞因子会导致色氨酸不会大量转化为血清素，而是会转移到不同的途径。

The pathway involves something called IDO indoleamine, which converts tryptophan into kynurenine.

该途径涉及一种叫做 IDO 吲哚胺的物质，它将色氨酸转化为犬尿氨酸。

Okay?

好的？

Kynurenine actually acts as a neurotoxin by way of converting into something called quinolinic acid.

犬尿氨酸实际上通过转化为喹啉酸而充当神经毒素。

Okay?

好的？

And quinolinic acid is prodepressive.

喹啉酸具有抑制作用。

Andrew Huberman:

安德鲁·休伯曼：

So if that seems like a complicated biochemical pathway, what's basically happening here is that the tryptophan that normally would be made into serotonin, under conditions of inflammation is being diverted into a neurotoxic pathway, and ingestion of EPAs, because it limits these inflammatory cytokines, things like IL-6 C, reactive protein, et cetera, can cause more of the tryptophan that one ingests or has in their body to be diverted towards the serotonergic pathway.

因此，如果这看起来像是一个复杂的生化途径，那么这里基本上发生的事情是，在炎症条件下通常会被制成血清素的色氨酸被转移到神经毒性途径，而摄入 EPA，因为它限制了这些炎症细胞因子，如 IL-6 C、反应蛋白等，可能会导致一个人摄入或体内含有的更多色氨酸被转移到血清素能途径。途径。

Exercise, it turns out, also has a positive effect on the tryptophan-to-serotonin conversion pathway.

事实证明，运动对色氨酸到血清素的转化途径也有积极的影响。

Andrew Huberman:

安德鲁·休伯曼：

And the way it does it is really interesting.

它的做法真的很有趣。

You now know that tryptophan can either be converted into serotonin or it can be converted into this neurotoxin, which is a bad thing.

您现在知道色氨酸可以转化为血清素，也可以转化为这种神经毒素，这是一件坏事。

Exercise, the activation of the muscles through rhythmic repeated use, in particular aerobic exercise, but also resistance training has been shown to do this to some extent, tends to sequester or shuttle the kynurenine into the muscle, so that it isn't converted into this neurotoxin that is pro depression, okay?

锻炼，通过有节奏的重复使用来激活肌肉，特别是有氧运动，而且阻力训练已被证明可以在某种程度上做到这一点，往往会将犬尿氨酸隔离或输送到肌肉中，这样它就不会转化为这种导致抑郁的神经毒素，好吗？

There are a lot of steps in the pathway leading to depression, but what this essentially means is that hitting a certain threshold level of EPA intake, whether by supplementation with fish oil, krill oil, or through some plant source, if you're not into ingesting fish or krill, or trying to get up above that 1000 milligram threshold for EPA by ingesting particular food sources, you certainly can do it through food; you don't have to supplement, but it's easier to do with supplements.

导致抑郁症的途径有很多步骤，但这本质上意味着，无论是通过补充鱼油、磷虾油还是通过某些植物来源，达到 EPA 摄入量的某个阈值水平，如果您不喜欢摄入鱼或磷虾，或者试图通过摄入特定食物来源来提高 EPA 的 1000 毫克阈值，那么您当然可以通过食物来做到这一点；你不必补充，但补充更容易。

Andrew Huberman:

安德鲁·休伯曼：

That doing that will limit the inflammation that diverts tryptophan into this neurotoxic pathway.

这样做将限制将色氨酸转移到这种神经毒性途径的炎症。

And exercise, as well, augments this conversion of tryptophan into serotonin, because it takes this thing that would potentially be a neurotoxin, and it sequesters, it pulls it away so that it can't actually go have its prodepressive effects.

运动也会增强色氨酸向血清素的转化，因为它吸收了这种可能是神经毒素的物质，并将其隔离，将其拉走，使其实际上无法发挥其抑制作用。

So you've got multiple steps here.

所以你这里有多个步骤。

We're describing two tools, increasing EPA and regular exercise, as a way of increasing serotonin, somewhat indirectly, right?

我们描述了两种工具，增加 EPA 和定期锻炼，作为增加血清素的一种方式，某种程度上是间接的，对吗？

It's by limiting this bad pathway to promote the activity of a good pathway.

它是通过限制这种不良途径来促进良好途径的活性。

But from the data that are published in quality peer-review journals, it really appears that this inflammation pathway does function to increase depression through these pathways.

但从高质量同行评审期刊上发表的数据来看，这种炎症途径确实可以通过这些途径增加抑郁症。

And so knowing that there are behavioral steps and supplementation-based steps, or if you prefer getting your EPAs from typical food — from nutritional approaches — I find that very reassuring that the mechanisms all converge on a common pathway, serotonin.

因此，知道有行为步骤和基于补充的步骤，或者如果您更喜欢从典型食物（从营养方法）中获取 EPA，我发现这些机制都集中在一个共同的途径（血清素）上，这非常令人放心。

Andrew Huberman:

安德鲁·休伯曼：

That gives me great peace of mind that when people say, "Hey, go out and go for a run," or "You should get outdoors, exercise," or you know, "You should take fish oil," or like the Scandinavians do — I have Scandinavian family members.

当人们说，“嘿，出去跑步”，或者“你应该去户外锻炼，”或者你知道，“你应该服用鱼油”，或者像斯堪的纳维亚人那样——我有斯堪的纳维亚家庭成员时，这让我内心非常平静。

And they are known to, or I should say they are quite open about the fact that during the winter months, in particular, when depression is more likely, but throughout the year really, they make an effort to regularly ingest high levels of EPA, either through ingesting fatty fish and its skin — I'm not a particular fan of ingesting the skin of fatty fish — or by supplementing with cod liver oil or other types of fish oil, sardines and things of that sort, sardine oils.

众所周知，或者我应该说，他们对这样一个事实相当开放：在冬季，特别是抑郁症更容易出现的时候，但实际上全年，他们都在努力定期摄入高含量的EPA，要么通过摄入富含脂肪的鱼及其鱼皮——我不太喜欢摄入富含脂肪的鱼皮——要么通过补充鱼肝油或其他类型的鱼油、沙丁鱼和类似的东西，沙丁鱼油。

There are a number of different things out there that one could use.

人们可以使用许多不同的东西。

So I find it very, very reassuring that there's a common biochemical pathway that can explain why these things not just work, but why they should work.

所以我觉得非常非常放心，有一个共同的生化途径可以解释为什么这些东西不仅起作用，而且为什么它们应该起作用。

Andrew Huberman:

安德鲁·休伯曼：

They should work because they operate in the very same biochemical pathways that antidepressants that are prescribed to people do.

它们应该有效，因为它们的生化途径与开给人们的抗抑郁药完全相同。

So what does this mean for you?

那么这对你来说意味着什么？

Well, if you're somebody who suffers from major depression, again, don't stop taking your prescribed medication — talk to your doctor, but talk to them perhaps about the EPAs and exercise and how these things can impinge on the same biochemical pathways.

好吧，如果您患有重度抑郁症，请再次强调，不要停止服用处方药物 - 与您的医生交谈，但也许可以与他们讨论 EPA 和锻炼以及这些东西如何影响相同的生化途径。

If you're somebody who's not suffering from major depression, I still think these pathways are really important to understand.

如果您没有患有重度抑郁症，我仍然认为了解这些途径非常重要。

And actually knowing these pathways is additional motivation to get regular exercise.

实际上了解这些途径是定期锻炼的额外动力。

I think we all know that we should be getting anywhere from 150 minutes to 180 minutes per week of so-called Zone 2 cardio for cardiovascular effects.

我想我们都知道，我们应该每周进行 150 分钟到 180 分钟的所谓 2 区有氧运动，以达到对心血管的影响。

Zone 2 is the kind of mellowish cardio where you can sort of hold a conversation if you needed to, but it's a little bit tough; you're kind of sucking for air a little bit.

2区是一种柔和的有氧运动，如果需要的话你可以在那里进行对话，但这有点困难；你有点吸空气了。

Andrew Huberman:

安德鲁·休伯曼：

And that's going to limit these depressive-like symptoms.

这将限制这些类似抑郁的症状。

I think in all of us.

我认为我们所有人都有。

I don't think that we should think of depression as a strict threshold.

我认为我们不应该将抑郁症视为一个严格的门槛。

I'm somebody who personally has made the choice to take 1000 milligrams of EPA per day.

我个人选择每天服用 1000 毫克 EPA。

I do that by supplementing fish oil.

我通过补充鱼油来做到这一点。

There's debate out there as to whether or not it's better to take EPA and DHA in particular ratios, and whether or not DHA can impact the LDL, which is the so-called bad cholesterol.

关于以特定比例服用 EPA 和 DHA 是否更好，以及 DHA 是否会影响 LDL（即所谓的坏胆固醇），存在争议。

That's getting really down into the weeds, and we can talk about that in a future episode.

这真的很深入，我们可以在以后的剧集中讨论这个问题。

But for myself, I notice a pretty substantial positive effect of taking anywhere from 1000 milligrams to 2000 milligrams of EPA per day.

但就我自己而言，我注意到每天服用 1000 毫克到 2000 毫克 EPA 会产生相当大的积极效果。

I do that through supplementation, and I do strive to try and eat some fish, even though, frankly, I've never liked the taste of fish.

我通过补充来做到这一点，并且我确实努力尝试吃一些鱼，尽管坦率地说，我从来不喜欢鱼的味道。

Andrew Huberman:

安德鲁·休伯曼：

For those of you that would like a little more detail, or perhaps a lot more detail into the effects of EPA on depression and in relieving depressive symptoms, and if you want to get into the nitty gritty of it, I invite you to go to examine.com, put in Depression EPA.

对于那些想要更详细地了解 EPA 对抑郁症和缓解抑郁症状的影响的人，如果您想了解其实质内容，我邀请您访问 exam.com，输入 Depression EPA。

They list off and have links to 28 studies on the effects of EPA on major depression.

他们列出了 28 项关于 EPA 对重度抑郁症影响的研究并提供了链接。

If you go to PubMed, there are many, many studies on this now that date back several decades, really.

如果你去 PubMed，你会发现现在有很多很多关于这个问题的研究，可以追溯到几十年前。

If you're interested in the specific effects of EPA, as opposed to DHA, I want to point you towards a particular study entitled, not surprisingly, "EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized control trials." This is a really wonderful paper.

如果您对 EPA（而不是 DHA）的具体作用感兴趣，我想向您介绍一项名为“EPA 而不是 DHA 似乎是 omega-3 长链多不饱和脂肪酸补充剂治疗抑郁症功效的原因：来自随机对照试验荟萃分析的证据”的特定研究，这并不奇怪。这是一篇非常精彩的论文。

The author is Julian Martins, M-A-R-T-I-N-S.

作者是朱利安·马丁斯 (Julian Martins)，M-A-R-T-I-N-S。

Andrew Huberman:

安德鲁·休伯曼：

It was published in 2009.

它于 2009 年出版。

We will provide a link to this study in the caption.

我们将在标题中提供这项研究的链接。

And that study is really the one that, at least to me, points to why EPA in particular is what's effective, and that whether or not DHA is problematic or not is a separate issue, but it's really the EPA that one wants to hit a certain threshold level of if one's goal is to get relief from depression or to keep depression at bay by keeping mood elevated, which is why I take high dose EPA.

至少对我来说，这项研究确实指出了为什么 EPA 特别有效，而 DHA 是否有问题是一个单独的问题，但如果一个人的目标是缓解抑郁症或通过保持情绪高涨来控制抑郁症，那么人们真正想要达到某个阈值水平的就是 EPA，这就是我服用高剂量 EPA 的原因。

So we've got EPA, we've got exercise.

所以我们有EPA，我们有锻炼。

Now you understand how they work to adjust mood.

现在您了解它们如何调节情绪了。

Now I want to talk about something that at least for me was quite surprising when I first learned about it for sake of treatment of mood disorders, and that's creatine.

现在我想谈谈一些东西，至少对我来说，当我第一次了解到它用于治疗情绪障碍时，它是相当令人惊讶的，那就是肌酸。

Creatine has a number of very important functions throughout the body.

肌酸在全身具有许多非常重要的功能。

Andrew Huberman:

安德鲁·休伯曼：

For those of you that are into resistance training, and actually for those of you that are into endurance training as well, creatine has achieved a lot of popularity in recent years because supplementation with creatine can draw more water into muscles and can increase power output from muscles.

对于那些热衷于阻力训练的人来说，实际上对于那些热衷于耐力训练的人来说，肌酸近年来非常受欢迎，因为补充肌酸可以将更多的水分吸入肌肉，并可以增加肌肉的功率输出。

So it's something that does indeed work.

所以这是确实有效的东西。

There have been debates about whether or not it's unhealthy for the kidneys to take long-term creatine supplementation at high doses, and I invite you to go down that rabbit hole.

关于长期服用高剂量肌酸补充剂是否对肾脏不健康存在争议，我邀请您走进这个兔子洞。

I think most people now accept the idea that for most people, not all, but for most people, low-dose creatine supplementation of anywhere from one gram to five grams per day can have a number of positive effects on physical performance.

我认为大多数人现在都接受这样的想法：对于大多数人来说，不是所有人，但对于大多数人来说，每天补充一克到五克的低剂量肌酸可以对身体表现产生许多积极影响。

People with kidney issues, et cetera, need to be especially cautious.

有肾脏问题等的人需要特别小心。

But creatine is interesting for that purpose.

但肌酸对于这个目的很有趣。

However, there's also a so-called phosphocreatine system in the brain, and that phosphocreatine system has everything to do with the dialogue between neurons and these other cell types called glia.

然而，大脑中还有一个所谓的磷酸肌酸系统，该磷酸肌酸系统与神经元和称为神经胶质细胞的其他细胞类型之间的对话密切相关。

Andrew Huberman:

安德鲁·休伯曼：

And glia comprise several cell types: microglia, astrocytes, et cetera.

神经胶质细胞包含多种细胞类型：小胶质细胞、星形胶质细胞等。

But the phosphocreatine system in the forebrain, in particular in the front of our brain, has been shown to be involved in regulation of mood and some of the reward pathways, as well as in depression.

但前脑中的磷酸肌酸系统，特别是我们大脑前部的磷酸肌酸系统已被证明参与情绪调节和一些奖励途径，以及抑郁症。

And there are now several studies, at least three, although there are probably more by time this comes out because they're coming out very quickly now, at least three quality studies pointing to the fact that creatine supplementation doesn't just have these positive effects on physical performance, but can also be used as a way to increase mood and to improve the symptoms of major depression.

现在有几项研究，至少三项，尽管到时候可能会有更多，因为它们现在出来得很快，至少三项高质量的研究指出，肌酸补充剂不仅对身体表现有这些积极影响，而且还可以用作改善情绪和改善重度抑郁症症状的一种方法。

This has been now done in several double-blind, placebo-controlled studies.

目前，这已在几项双盲、安慰剂对照研究中完成。

These studies have looked at women.

这些研究着眼于女性。

have looked at men, have looked at adolescents, some of whom were taking SSRIs, some of whom were not.

研究人员对男性和青少年进行了研究，其中一些人服用了 SSRI，另一些则没有。

Andrew Huberman:

安德鲁·休伯曼：

They've done magnetic resonance spectroscopy.

他们做了磁共振波谱分析。

So spectroscopy is a way that you can look at the concentrations of particular compounds in the brain in real time in humans.

因此，光谱学是一种可以实时观察人类大脑中特定化合物浓度的方法。

It can be used for other things as well, of course.

当然，它也可以用于其他事情。

And basically what's been observed is that increasing the activity of the phosphocreatine system in the forebrain can be beneficial, or at least is correlated with improvements in mood.

基本上观察到的是，增加前脑磷酸肌酸系统的活性可能是有益的，或者至少与情绪的改善相关。

So let's just talk for a moment about what's involved with using or supplementing creatine in order to improve mood and perhaps even treat depression.

因此，让我们暂时讨论一下使用或补充肌酸以改善情绪甚至治疗抑郁症的相关内容。

First of all, when I talk about creatine, I'm talking about creatine monohydrate.

首先，当我谈论肌酸时，我指的是一水肌酸。

There are a number of different forms of creatine.

肌酸有多种不同形式。

Here I'm talking about creatine monohydrate.

这里我说的是一水肌酸。

The American Journal of Psychiatry in 2012 published a study which was a randomized double-blind, placebo-controlled trial of oral creatine monohydrate.

2012 年《美国精神病学杂志》发表了一项研究，该研究是口服一水肌酸的随机双盲、安慰剂对照试验。

And what it found is that it could augment or enhance the response to a selective serotonin reuptake inhibitor, in particular in women with major depressive disorder.

研究发现，它可以增强或增强对选择性血清素再摄取抑制剂的反应，特别是对于患有重度抑郁症的女性。

Andrew Huberman:

安德鲁·休伯曼：

So, like EPA, creatine supplementation seems to either lower the required dose of SSRI that's required to treat depression or can improve the effectiveness of a given dose of SSRI.

因此，与 EPA 一样，补充肌酸似乎可以降低治疗抑郁症所需的 SSRI 剂量，或者可以提高给定剂量 SSRI 的有效性。

However, there are other studies that have looked directly at creatine supplementation in the absence of SSRI, and those are interesting as well.

然而，还有其他研究直接研究了在缺乏 SSRI 的情况下补充肌酸的情况，这些研究也很有趣。

There's a wonderful and very comprehensive review on creatine for the treatment of major depression that includes beautiful tables of all the subjects and the dosages, et cetera.

有一篇关于肌酸治疗重度抑郁症的精彩且非常全面的评论，其中包括所有受试者和剂量等的漂亮表格。

I'm not going to read off every line and every column in that review, but we will provide a link to that review as well.

我不会读出该评论中的每一行和每一列，但我们也会提供该评论的链接。

One of the things that's really striking about the lists of studies that they include is that most of them used dosages that are pretty reasonable for most people, anywhere from three grams to five grams, sometimes up to as many 10 grams per day of creatine.

他们所包含的研究清单中真正引人注目的一件事是，大多数研究使用的肌酸剂量对大多数人来说都相当合理，从 3 克到 5 克，有时高达每天 10 克肌酸。

Andrew Huberman:

安德鲁·休伯曼：

Many of these also were shown to increase activity of this phosphocreatine system in the forebrain, and some show a relationship between that phosphocreatine system and a particular category of receptors in the brain called the NMDA receptor, N-methyl-D-aspartate receptor.

其中许多还被证明可以增加前脑中磷酸肌酸系统的活性，并且一些显示出磷酸肌酸系统与大脑中称为 NMDA 受体（N-甲基-D-天冬氨酸受体）的特定受体类别之间的关系。

The NMDA receptor is one of the first things that every budding neuroscientist learns about, because it is the receptor that has particular electrical and chemical properties that make it a critical gate for so-called neuroplasticity.

NMDA 受体是每个崭露头角的神经科学家首先要了解的东西之一，因为它具有特殊的电学和化学特性，使其成为所谓神经可塑性的关键大门。

So it's not a receptor that's activated in the brain typically for just the functioning of the brain on a day-to-day basis.

因此，它并不是一种在大脑中被激活的受体，通常只是为了大脑的日常功能。

It's a receptor that's activated when circuits are going to change, when they are inspired to change by some very strong stimulus, meaning some experience, or in some cases a drug, or in some cases something else.

它是一种受体，当电路将要改变时，当它们受到一些非常强烈的刺激（意味着某种经验，或者在某些情况下是药物，或者在某些情况下是其他东西）的启发而改变时，就会被激活。

Andrew Huberman:

安德鲁·休伯曼：

But the NMDA receptor is a kind of a key node for shifting brain circuitry, and so while the details aren't entirely clear, it seems that creatine supplementation leads to increases in the phosphocreatine system in the forebrain, and that increases in the activity of the forebrain phosphocreatine system relate to changes in the way that NMDA receptors function and may lead to some of the plasticity, the changes in neural circuits that underlie the shift from negative mood and affect to positive mood.

但 NMDA 受体是改变大脑回路的关键节点，因此虽然细节尚不完全清楚，但肌酸补充似乎会导致前脑磷酸肌酸系统的增加，而前脑磷酸肌酸系统活动的增加与 NMDA 受体功能方式的变化有关，并可能导致一些可塑性，即神经回路的变化，这些变化是从消极情绪转变为积极情绪的基础。

Now, there are a lot of gaps.

现在，有很多差距。

Those are a lot of little boxes or bins in the diagram I just laid out for you, and some of them are still truly black boxes, as we say, meaning we don't really know what's in them yet, and more mechanistic data are coming.

在我刚刚为您展示的图表中，有很多小盒子或箱子，正如我们所说，其中一些仍然是真正的黑盒子，这意味着我们还不知道它们里面有什么，更多的机械数据即将到来。

However, when you look over the data in this review, or when I look over the data in this review, what you find is that there're pretty striking positive effects of creatine.

然而，当你查看这篇评论中的数据时，或者当我查看这篇评论中的数据时，你会发现肌酸具有相当惊人的积极作用。

Andrew Huberman:

安德鲁·休伯曼：

And one of the more interesting effects is that creatine has actually been shown to increase mania in people that are already manic.

更有趣的作用之一是，肌酸实际上已被证明会加剧已经躁狂的人的躁狂。

And that's interesting.

这很有趣。

We're not talking about bipolar depression today, but it seems that creatine elevates levels of activation and kind of mood overall.

我们今天讨论的不是双相抑郁症，但肌酸似乎可以提高整体的激活水平和情绪。

And you could see why that would be a problem for somebody that's already in a manic phase, but it actually might be beneficial for somebody who is very low affect and has major depression.

你会明白为什么这对于已经处于躁狂阶段的人来说是一个问题，但实际上它可能对那些情绪低落且患有严重抑郁症的人有益。

So should you supplement with creatine?

那么你应该补充肌酸吗？

Well as always, talk to your healthcare provider.

一如既往，请咨询您的医疗保健提供者。

But if you're somebody who is thinking about things that you can do and things that you can take in order to improve your mood, keep depression at bay, maybe even support other treatments for major depression, the creatine system seems like a logical one.

但是，如果您正在考虑可以做哪些事情或可以采取哪些措施来改善情绪、远离抑郁症，甚至可能支持其他治疗重度抑郁症的方法，那么肌酸系统似乎是一个合乎逻辑的系统。

There's at least strong studies and a good number of them to look to determine whether or not that's right for you.

至少有大量的研究可以确定这是否适合您。

Andrew Huberman:

安德鲁·休伯曼：

I personally take five grams of creatine for other reasons.

我个人因其他原因服用五克肌酸。

I take it for the physical performance-enhancing effects, but it's kind of nice to think that perhaps it's also helping me improve my mood.

我认为它具有增强身体表现的作用，但想到它也许还能帮助我改善情绪，这真是太好了。

That's a choice that I've made for me, it is within the margins of safety for me in my life.

这是我为自己做出的选择，它在我人生的安全范围之内。

I don't know that it's right for everybody, but I find it very interesting.

我不知道它是否适合每个人，但我觉得它很有趣。

And again, I find it particularly interesting because there's a logical biochemical pathway to support the finding that it improves mood and can offset the effects of major depression in some cases, or can improve the effects of antidepressant medication in many cases.

再说一遍，我发现它特别有趣，因为有一个合乎逻辑的生化途径支持这一发现，即它可以改善情绪，在某些情况下可以抵消重度抑郁症的影响，或者可以在许多情况下改善抗抑郁药物的效果。

When I see mechanism, and I see effectiveness and the mechanism and the effectiveness map to a lot of the same mechanisms that are involved in prescription drugs, that gives me great reassurance that this isn't just some sort of mysterious pathway or mysterious compound by which creatine might be working.

当我看到机制时，我看到有效性，而机制和有效性映射到处方药中涉及的许多相同机制，这让我非常放心，这不仅仅是肌酸可能发挥作用的某种神秘途径或神秘化合物。

Andrew Huberman:

安德鲁·休伯曼：

So now we've clustered together EPAs, exercise and their relationship to inflammation; creatine, and its relationship to forebrain function; and the phosphocreatine system and this NMDA receptor.

现在我们将 EPA、运动及其与炎症的关系聚集在一起；肌酸及其与前脑功能的关系；以及磷酸肌酸系统和 NMDA 受体。

And as you'll see in a few minutes, that NMDA receptor turns out to be vitally important and is actually one of the main nodes of action for some of the more novel and exciting therapeutics that are being explored now in psychiatric clinics.

几分钟后您就会看到，NMDA 受体非常重要，实际上是精神科诊所目前正在探索的一些更新颖、更令人兴奋的疗法的主要作用节点之一。

Andrew Huberman:

安德鲁·休伯曼：

So let's talk a little bit more about this NMDA receptor and how it relates to some of the more experimental or novel therapeutic compounds for the treatment of major depression.

因此，让我们更多地讨论一下这种 NMDA 受体，以及它如何与一些用于治疗重度抑郁症的更具实验性或新颖的治疗化合物相关。

And the compounds that we're going to be talking about you may have heard of before.

我们将要讨论的化合物您可能以前听说过。

One is ketamine, which is getting increasing interest in psychiatric clinics and in various experimental and clinical studies.

其中之一是氯胺酮，它越来越受到精神病诊所以及各种实验和临床研究的关注。

And the other is PCP.

另一个是PCP。

Both ketamine and PCP are known drugs of abuse.

氯胺酮和五氯苯酚都是已知的滥用药物。

For many years people have abused these drugs, go by the street name Special K, et cetera, and they create dissociative, anesthetic states.

多年来，人们一直在滥用这些药物，这些药物的街道名称为“Special K”等等，它们会造成分离、麻醉状态。

So dissociative states, where people don't feel as closely meshed with their emotions and their perceptions.

在这种分离的状态下，人们感觉自己的情绪和感知不再紧密相连。

It's an odd state, I hear, and it's an odd state that clinicians are now leveraging for the treatment of depression.

我听说这是一种奇怪的状态，临床医生现在正在利用这种奇怪的状态来治疗抑郁症。

We'll talk about why that is, but let's talk a little bit about this NMDA receptor and why ketamine and PCP might work for the treatment of depression, or how they even could work.

我们将讨论其中的原因，但让我们稍微讨论一下这种 NMDA 受体，以及为什么氯胺酮和 PCP 可能有助于治疗抑郁症，或者它们是如何发挥作用的。

I want to be very direct that this is an area that still needs a lot of data.

我想非常直接地说，这是一个仍然需要大量数据的领域。

Andrew Huberman:

安德鲁·休伯曼：

There are, however, some excellent papers from really terrific groups.

然而，也有一些来自非常出色的团队的优秀论文。

One of them is a paper that was published in Nature last year, 2020.

其中一篇是去年2020年发表在《自然》杂志上的一篇论文。

First author is Vesuna, Sam Vesuna, V-E-S-U-N-A, and the last author, and the lead on the study, was Dr. Karl Deisseroth, who was a guest on the Huberman Lab podcast a few months ago — world expert in neuroscience — he's a psychiatrist.

第一作者是 Vesuna，Sam Vesuna，V-E-S-U-N-A，最后一位作者，也是这项研究的领导者，是 Karl Deisseroth 博士，他是几个月前 Huberman Lab 播客的嘉宾——神经科学领域的世界专家——他是一名精神病学家。

And this paper from Sam Vesuna and Carl and colleagues explored how these dissociate states come about, and they looked at this both in animals and in humans, and found that there was essentially a common mechanism whereby a particular layer of cortex; so your brain has this outer shell of tissue that is called the neocortex.

Sam Vesuna 和 Carl 及其同事的这篇论文探讨了这些分离状态是如何产生的，他们在动物和人类中都观察了这一点，发现本质上存在一种共同的机制，即特定的皮层层；所以你的大脑有一个叫做新皮质的外壳组织。

It's where our perceptions lie.

这就是我们的看法所在。

It's where our associations lie.

这就是我们的协会所在。

It's a very important area for processing decision-making and planning, et cetera.

这是处理决策和规划等的非常重要的领域。

It's literally stacks of cells.

它实际上是一堆细胞。

And one of those layers in the stack of cells is layer V.

电池堆中的其中一层是第五层。

And the layer V neurons in particular went into a particular rhythm of electrical activity, this one-to-three hertz rhythm after mice or humans were administered ketamine or PCP.

在小鼠或人类服用氯胺酮或五氯苯酚后，第五层神经元特别进入一种特定的电活动节律，即一到三赫兹的节律。

Andrew Huberman:

安德鲁·休伯曼：

There was activation of a particular area of the brain, this retrosplenial cortex, as it's called, and the dissociative state that emerged was an interesting one.

大脑的一个特定区域，即所谓的压后皮层被激活，出现的解离状态是一个有趣的状态。

And clinically what's described in the trials for ketamine, and things like it, that people who are depressed will take ketamine, will experience a kind of separateness from their grief and from their emotions.

在临床上，氯胺酮试验中所描述的以及类似的情况是，抑郁症患者服用氯胺酮，会体验到一种与悲伤和情绪的分离。

And that possibly there's plasticity.

这可能存在可塑性。

There are actually shifts in the neural circuitry such that their emotions don't weigh on them so heavily.

实际上，神经回路发生了变化，因此他们的情绪不会对他们产生如此沉重的压力。

I'm using very loose language here, but that they don't feel as overridden or as burdened by their own emotions as they did previously to the ketamine therapy.

我在这里使用了非常宽松的语言，但他们并不像以前接受氯胺酮治疗时那样感到被自己的情绪压倒或负担。

Now absolutely in no way, shape or form am I suggesting that people run out and take ketamine in order to treat their own depression.

现在，我绝不建议人们跑出去服用氯胺酮来治疗自己的抑郁症。

These drugs are still very much experimental, although they are approved in certain contexts, at least in the U.S., by prescription for the treatment of depression.

这些药物仍然处于实验阶段，尽管它们在某些情况下（至少在美国）被批准作为治疗抑郁症的处方。

Andrew Huberman:

安德鲁·休伯曼：

What's interesting to me is that these dissociative states sound, at least at the outset, to be more of a separateness from everything.

对我来说有趣的是，这些分离状态听起来更像是与一切事物的分离，至少在一开始是这样。

It sounds a little bit like depression itself.

这听起来有点像抑郁症本身。

It's sort of like anhedonia and inability to experience pleasure, and then one takes a dissociative anesthetic and somehow is able to get relief by getting even further away from an experience.

这有点像快感缺乏和无法体验快乐，然后一个人接受解离麻醉剂，并以某种方式能够通过远离某种体验来获得缓解。

To me, that doesn't make sense, but that just speaks to the fact that these drugs and these receptors and these pathways operate through very cryptic means, and we really don't understand all the pathways in the brain that relate to motivation and mood, and so forth.

对我来说，这没有意义，但这只是说明了这样一个事实：这些药物、这些受体和这些通路通过非常神秘的方式运作，而我们真的不了解大脑中与动机和情绪等相关的所有通路。

And the results with these ketamine trials are looking very promising.

这些氯胺酮试验的结果看起来非常有希望。

In fact, there are a number of trials that show that a fair number of people that take ketamine in a therapeutic setting legally with a psychiatrist guiding the experience are able to get relief from their symptoms without the need from many, many treatments with the drug.

事实上，许多试验表明，相当多的人在精神科医生的指导下合法地在治疗环境中服用氯胺酮，他们的症状能够得到缓解，而不需要进行很多很多的药物治疗。

Andrew Huberman:

安德鲁·休伯曼：

Just how many treatments varies from individual to individual, but it's not like people have to take this stuff ongoing.

治疗次数因人而异，但人们并不需要持续接受这些治疗。

This is really an attempt to tap into this NMDA receptor that is related to neuroplasticity.

这实际上是一次利用与神经可塑性相关的 NMDA 受体的尝试。

Both ketamine and PCP essentially act as antagonists, which means they block the NMDA receptor.

氯胺酮和 PCP 本质上都是拮抗剂，这意味着它们会阻断 NMDA 受体。

They do it through different methods, noncompetitive and competitive, for you chemists and pharmacologists out there.

对于化学家和药理学家来说，他们通过不同的方法（非竞争性和竞争性）来做到这一点。

You can look it up if you like, but what's therefore even more surprising is that every neuroscientist learns that activation of the NMDA receptor, not antagonism or blocking of the NMDA receptor, leads to changes in neurocircuitry in very profound ways.

如果你愿意，你可以查一下，但更令人惊讶的是，每个神经科学家都知道，NMDA 受体的激活，而不是 NMDA 受体的拮抗或阻断，会以非常深刻的方式导致神经回路的变化。

In fact, experimentally, and I've done these experiments myself, if you want to prevent plasticity, you want to prevent an experience from reshaping neurocircuitry, you give an NMDA receptor blocker.

事实上，在实验上，我自己也做过这些实验，如果你想阻止可塑性，你想阻止重塑神经回路的经历，你可以给予 NMDA 受体阻滞剂。

I've done that many times in the course of my experimental neuroscience career, not to myself obviously, but in the course of doing experiments.

在我的实验神经科学生涯中，我已经这样做过很多次了，显然不是对我自己，而是在做实验的过程中。

Andrew Huberman:

安德鲁·休伯曼：

So it's still a bit mysterious to me how this could work.

所以这对我来说仍然有点神秘，这是如何运作的。

A couple things.

有几件事。

One is this layer V activation is pretty interesting.

一是第五层激活非常有趣。

We're going to come back to layer V when we talk about yet another emerging treatment for depression, which is psilocybin, so-called magic mushrooms, and the effects of psilocybin on layer V neurons in the cortex.

当我们谈论另一种新兴的抑郁症治疗方法时，我们将回到第五层，即裸盖菇素，即所谓的迷幻蘑菇，以及裸盖菇素对皮质中第五层神经元的影响。

So there's a common theme emerging here, which is that layer V activity in the cortex may be important for rewiring the brain in certain ways that can lead to recovery or to an alleviation of some of the symptoms of major depression.

因此，这里出现了一个共同的主题，即皮质中的 V 层活动可能对于以某些方式重新连接大脑很重要，从而可以导致恢复或减轻重度抑郁症的某些症状。

So if this is sounding a little bit vague to you, it's because this is still truly experimental and new and still very much on the cutting edge of what's happening now.

因此，如果这对您来说听起来有点模糊，那是因为这仍然是真正的实验性和新事物，并且仍然处于当前正在发生的事情的最前沿。

We don't have all the answers.

我们没有所有的答案。

So if it sounds like I'm moving slowly through this and I'm being extra careful about what I say, you are correct; your antennae are correct in this case.

因此，如果听起来我正在缓慢地处理这件事并且我对我所说的话格外小心，那么你是对的；在这种情况下你的天线是正确的。

Andrew Huberman:

安德鲁·休伯曼：

I never want to misstep and say something that's not true.

我不想犯错，说出一些不真实的话。

But that's especially the case when we're talking about experimental therapies and drugs which formally were taken as drugs of abuse, which are now being used as drugs for therapeutic treatment in the clinic.

但当我们谈论实验疗法和正式被视为滥用药物的药物时尤其如此，这些药物现在被用作临床治疗药物。

There is a very interesting study.

有一项非常有趣的研究。

This was published in Science in 2019, so these are very recent studies.

该研究发表于 2019 年的《科学》杂志上，因此这些都是最近的研究。

The last author on this is Liston, L-I-S-T-O-N.

最后一位作者是 Liston, L-I-S-T-O-N。

The title of the paper is "Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation." And here, when we hear spine, we're not referring to spine as in your vertebrae, running down your spinal column.

论文的标题是“通过抗抑郁药诱导脊柱形成持续挽救前额回路功能障碍”。在这里，当我们听到脊柱时，我们指的不是脊椎骨，沿着脊柱延伸。

We're talking about the spines, which are these little protrusions on neurons.

我们谈论的是刺，它们是神经元上的小突起。

Neurons are not smooth by any stretch.

神经元无论如何拉伸都不是光滑的。

If you zoom in on a neuron, if you were to come to my lab and look down the microscope at a neuron and zoom in on it, you'd find that some neurons are smooth.

如果你放大一个神经元，如果你来到我的实验室，用显微镜观察一个神经元，然后放大它，你会发现一些神经元是光滑的。

Andrew Huberman:

安德鲁·休伯曼：

But most neurons have these little protrusions, and those little protrusions are called spines.

但大多数神经元都有这些小突起，这些小突起被称为棘。

And those little spiny protrusions are little sites where neurons can reach out and form and receive new synapses from neighboring neurons.

这些小刺状突起是神经元可以伸出并形成并接收来自邻近神经元的新突触的小部位。

So they increase the surface area of a neuron and allow new connections to be formed.

因此它们增加了神经元的表面积并允许形成新的连接。

And so spine formation is synonymous with neuroplasticity, which is synonymous with changes in circuit function, which is synonymous with changes in the ways that we think we feel and we behave.

因此，脊柱的形成与神经可塑性同义，神经可塑性与回路功能的变化同义，与我们认为、感觉和行为方式的变化同义。

And what was shown in this study is really interesting.

这项研究显示的内容非常有趣。

What they showed is that ketamine can relieve depressive symptoms rapidly, by changing or increasing, in this case, the spines on these neurons in the prefrontal cortex.

他们的研究表明，氯胺酮可以通过改变或增加前额皮质神经元的棘来快速缓解抑郁症状。

And if that word prefrontal rings a bell, well now you remember the phosphocreatine system, the ingestion of creatine monohydrate and the forebrain, activation of the forebrain, were related to in some way or another to relief or improvement of major depressive symptoms.

如果前额叶这个词听起来很熟悉，那么现在您还记得磷酸肌酸系统、一水肌酸的摄入和前脑、前脑的激活以某种方式与重度抑郁症状的缓解或改善有关。

Andrew Huberman:

安德鲁·休伯曼：

So we're starting to converge on a picture here whereby these drugs, ketamine, PCP, used in a therapeutic context, may be increasing neuroplasticity, literally the changing of neural circuits in the forebrain somehow through dissociative states.

因此，我们开始集中在这样一个画面上，即这些药物，氯胺酮，五氯苯酚，在治疗环境中使用，可能会增加神经可塑性，实际上是通过解离状态以某种方式改变前脑中的神经回路。

And I don't want to speculate too much about how that might come about, but one of the things that's such a resounding or repeating theme of major depression is that when you talk to somebody who has major depression, it is a real downer, and I'm not being disparaging of those people, but if you've ever had a conversation with someone who's depressed, they're always talking about how exhausted they are, or in really severe cases, they're not even responsive at all.

我不想过多猜测这可能会如何发生，但重度抑郁症如此响亮或重复的主题之一是，当你与患有重度抑郁症的人交谈时，他真的很沮丧，我并不是在贬低这些人，但如果你曾经与抑郁症的人交谈过，他们总是在谈论他们是多么疲惫，或者在真正严重的情况下，他们甚至根本没有反应。

They just kind of stand stare at you blankly, or they fall asleep.

他们只是站在那里茫然地盯着你，或者睡着了。

I mean, they're truly depressed; their system is lowered in terms of its activation state.

我的意思是，他们真的很沮丧；他们真的很沮丧。他们的系统的激活状态降低了。

So I think that it's interesting that the application of drugs that allow people to separate from that state of not caring, or being uninterested or unwilling to do anything is actually one of the paths to treatment.

所以我认为有趣的是，应用药物让人们摆脱不关心、不感兴趣或不愿意做任何事情的状态实际上是治疗的途径之一。

Andrew Huberman:

安德鲁·休伯曼：

It's not always about just getting people peppy and excited and happy.

它并不总是只是让人们充满活力、兴奋和快乐。

There also seems to be a requirement for getting them distanced from their own grief.

似乎还需要让他们远离自己的悲伤。

And this brings us back to something that we talked about way back at the beginning of this episode, which was this particular feature of the anti-self confabulation, that everything that happens is a reflection that, I should say for the depressed person, that everything that happens is a reflection of how life is bad, and their experiences just point to the fact that nothing is going to get better.

这让我们回到了我们在本集开始时讨论过的事情，这是反自我虚构的一个特殊特征，发生的一切都是一种反映，我应该对抑郁的人说，发生的一切都是生活如何糟糕的反映，而他们的经历只是指向这样一个事实：没有什么会变得更好。

This is the common language of depression.

这是抑郁症的共同语言。

If this is very depressing to hear me talk about it, it is heavy, and that's what it's like to hear these things.

如果听到我谈论这件事让人感到非常沮丧，那就很沉重，这就是听到这些事情的感觉。

It's even heavier, of course, for somebody to experience them.

当然，对于有人体验它们的人来说，它甚至更重。

And those beliefs, those patterns of guilt and grief and anhedonia and delusional anti-self confabulation, those are the things that eventually, if they get severe enough, start to convert into things like self-harm, mutilation and in the most tragic of cases, of course, suicide.

那些信念，那些内疚、悲伤、快感缺失和妄想性反自我虚构的模式，如果它们变得足够严重，最终就会开始转化为自残、残害，当然，在最悲惨的情况下，会转化为自杀。

Andrew Huberman:

安德鲁·休伯曼：

And so I think we can look to these treatments such as ketamine and PCP, but in particular ketamine and its use in the clinic, as ways for people to get distanced from the negative effect that they feel isn't just inside them or overwhelms them, but that for the very severely depressed person they feel is them.

因此，我认为我们可以关注氯胺酮和五氯苯酚等治疗方法，特别是氯胺酮及其在临床中的使用，作为人们远离负面影响的方法，他们认为这些负面影响不仅存在于他们内部或压倒他们，而且对于他们认为是他们自己的非常严重抑郁的人来说。

And we hear this sometimes: "You are not your emotions." That's a statement that I've always been a little bit challenged by.

我们有时会听到这样的话：“你的情绪不是你的。”我一直对这句话感到有点挑战。

I mean, yes, indeed, emotions are not who we are.

我的意思是，是的，确实，情绪并不是我们的本质。

They are states that we go into and out of, including happiness and sadness, but they are very much a part of us when we experience them.

它们是我们进入和退出的状态，包括快乐和悲伤，但当我们经历它们时，它们就成为我们的一部分。

We don't experience them as next to us or behind us or across the room from us.

我们不会感觉到它们就在我们旁边、在我们后面或在我们房间的另一边。

We experience them as our emotions.

我们将它们视为我们的情感。

Andrew Huberman:

安德鲁·休伯曼：

They are so much part and parcel with our experience of ourself that a statement like we aren't our emotions is a very hard statement to digest, especially for the depressed person.

它们与我们的自我体验息息相关，以至于像“我们不是我们的情绪”这样的说法是很难消化的，尤其是对于抑郁的人来说。

And so I think that the NMDA receptor and its capacity to induce neuroplasticity, circuit changes, the fact that PCP and ketamine are both showing activation of neural circuits by way of suppressing activity, the NMDA receptor, and some of the positive or exciting therapeutic outcomes that are coming from this really point to the fact that ketamine and PCP, and removal of negative experiences, or the experience of a negative experience — sort of getting meta there — but the experience of a negative experience may be an important path by which people treat their depression, especially in its most severe forms where people are veering towards self-harm, mutilation and suicide.

因此，我认为 NMDA 受体及其诱导神经可塑性、回路变化的能力，PCP 和氯胺酮都通过抑制活动而显示出神经回路的激活，NMDA 受体以及由此产生的一些积极或令人兴奋的治疗结果确实表明了这样一个事实：氯胺酮和 PCP，以及消除负面经历或负面经历的经历 - 有点在那里 - 但负面经历的经历可能是人们治疗抑郁症的重要途径，尤其是在最严重的形式下，人们倾向于自残、残害和自杀。

Andrew Huberman:

安德鲁·休伯曼：

So you may have noticed a theme, which is that certain categories of approaches that we've been discussing for offsetting the symptoms of depression, such as exercise, ingesting EPAs, reducing inflammation, or even the SSRIs for increasing serotonin, focus on changing some core biological function, like raising the amount of a chemical, serotonin, or reducing the amount of inflammatory cytokines in the brain and body.

因此，您可能已经注意到一个主题，即我们一直在讨论的用于抵消抑郁症状的某些方法，例如锻炼、摄入 EPA、减少炎症，甚至用于增加血清素的 SSRI，重点是改变一些核心生物功能，例如提高化学物质、血清素的含量，或减少大脑和身体中炎症细胞因子的含量。

And yet things like ketamine focus more on rewiring circuitry, changing neural circuitry so that it functions better in the immediate and, hopefully, in the long term as well, and keep people with major depression in what they call remission, away from major depression.

然而，像氯胺酮这样的药物更注重重新布线、改变神经回路，使其在短期内以及长期内都能更好地发挥作用，并使重度抑郁症患者处于所谓的缓解状态，远离重度抑郁症。

Another category of treatments that's being-

另一类治疗方法是——

PART 2 OF 3 ENDS Andrew Huberman:

第 2 部分（共 3 部分）结束 Andrew Huberman：

Another category of treatments that's being actively explored now in laboratories and in the psychiatry realm are the psychedelics, and that's a huge category of compounds.

目前实验室和精神病学领域正在积极探索的另一类治疗方法是致幻剂，这是一大类化合物。

However, one in particular, psilocybin, is one that's being most intensely and actively pursued for its capacity to treat major depressive disorder.

然而，其中一种特别是裸盖菇素，因其治疗重度抑郁症的能力而受到最强烈和积极的研究。

I want to be very clear that the work that I'm going to describe is work that's being done in university settings, university hospitals, by scientists and psychiatrists, and these are clinical studies, clinical trials leading to peer-reviewed data, and those are the data that we'll be discussing.

我想非常明确的是，我要描述的工作是由科学家和精神病学家在大学环境、大学医院所做的工作，这些是临床研究、临床试验，得出同行评审的数据，这些就是我们将要讨论的数据。

Some of the major luminaries in this area include, of course aren't limited to, but include people like Matthew Johnson, who's at Johns Hopkins; we'll discuss some of his work now, and fortunate to say that he will be coming on the podcast as a guest to describe the studies in a variety of laboratories working on a variety of different psychedelic compounds.

当然，该领域的一些主要杰出人物包括但不限于约翰·霍普金斯大学的马修·约翰逊 (Matthew Johnson) 等人；我们现在将讨论他的一些工作，幸运的是，他将作为嘉宾出现在播客中，描述各个实验室对各种不同迷幻化合物的研究。

Andrew Huberman:

安德鲁·休伯曼：

But let's focus on psilocybin for its capacity to rewire neural circuits and alleviate depression.

但让我们重点关注裸盖菇素，因为它具有重新连接神经回路和缓解抑郁症的能力。

There have been anecdotal data, or evidence over the years, that psilocybin has this capacity.

多年来有传闻数据或证据表明裸盖菇素具有这种能力。

How does psilocybin work?

裸盖菇素如何发挥作用？

Well, psilocybin, magic mushrooms as it's sometimes called, mainly works on what's called the serotonin 5-H2A receptor with some affinity for the 5-HT1 receptor.

裸盖菇素，有时也被称为迷幻蘑菇，主要作用于所谓的血清素 5-H2A 受体，对 5-HT1 受体有一定的亲和力。

What does that mean?

这意味着什么？

Well, basically you've got a lot of different kinds of serotonin receptors, just as you have a lot of different kinds of dopamine receptors, or other types of receptors.

嗯，基本上你有很多不同类型的血清素受体，就像你有很多不同类型的多巴胺受体或其他类型的受体一样。

Andrew Huberman:

安德鲁·休伯曼：

The advantage of having different receptors expressed in different parts of the brain and body, even on different parts of individual cells in the brain and body, is that the same compound, serotonin, can have a diverse set of effects on different cells and tissues.

在大脑和身体的不同部位，甚至在大脑和身体的单个细胞的不同部位表达不同的受体的优点是，同一种化合物——血清素——可以对不同的细胞和组织产生不同的影响。

This is also the basis of some of the side-effect profiles of SSRIs, because maybe, for instance, we know that taking Prozac, fluoxetine, will increase serotonin in one area but also in another area.

这也是 SSRI 的一些副作用的基础，因为也许，例如，我们知道服用百忧解、氟西汀会增加一个区域的血清素，但也会增加另一个区域的血清素。

And then they will go have diverse effects on different brain circuits because of the variety of receptors.

然后，由于受体的多样性，它们会对不同的大脑回路产生不同的影响。

Receptors are just like parking slots where the molecule serotonin parks and has different effects.

受体就像停车位，血清素分子停泊在那里，并具有不同的作用。

Andrew Huberman:

安德鲁·休伯曼：

Well, psilocybin engages, or increases, serotonin transmission, meaning it increases the amount of serotonin, mainly by acting at these 5-H2A receptors.

裸盖菇素参与或增加血清素传输，这意味着它主要通过作用于这些 5-H2A 受体来增加血清素的量。

But where in the brain does it happen, and what are the major effects?

但它发生在大脑的哪个部位，主要影响是什么？

First, let's talk about the major effects because I think that's what people are interested in.

首先，我们来谈谈主要影响，因为我认为这是人们感兴趣的。

The study that I'd like to highlight is a fairly recent one.

我想强调的一项研究是最近的一项研究。

It was published in May of 2021 in Journal of the American Medical Association Psychiatry, so JAMA Psychiatry, and it's entitled, "Effects of psilocybin-assisted therapy on major depressive disorder, a randomized clinical trial." It's an absolutely beautiful study, a very important study.

该研究于 2021 年 5 月发表在《美国医学会精神病学杂志》（JAMA Psychiatry）上，标题为“裸盖菇素辅助治疗对重度抑郁症的影响，一项随机临床试验”。这是一项绝对美丽的研究，一项非常重要的研究。

It includes some of the luminaries in this area like Matthew Johnson, Patrick Finan, Roland Griffiths and others.

其中包括该领域的一些杰出人物，如马修·约翰逊、帕特里克·费南、罗兰·格里菲斯等。

We will provide a link to this study.

我们将提供该研究的链接。

It is available in its full form at zero cost if you want to read it.

如果您想阅读它，可以以零成本获得完整版本。

Andrew Huberman:

安德鲁·休伯曼：

It's got a lot of details, so I'm just going to summarize a few things.

里面有很多细节，所以我简单总结一下。

But basically what they did was they screened for patients to come into the clinic, these were people that suffered from major depressive disorder, and administered either one or two rounds of psilocybin.

但基本上他们所做的是筛选进入诊所的患者，这些患者患有严重抑郁症，并注射一到两轮裸盖菇素。

They used particular dosages that are listed in the study, so you can look it up if you're really interested in that level of detail.

他们使用了研究中列出的特定剂量，因此如果您确实对详细程度感兴趣，可以查阅。

Typically, it was 20 milligrams per kilogram of body weight, so it depends on body weight or 30 milligrams of psilocybin per 70 kilograms of body weight.

通常情况下，它是每公斤体重 20 毫克，因此它取决于体重或每 70 公斤体重 30 毫克裸盖菇素。

They were given in capsule form, so people weren't eating the mushrooms.

它们以胶囊形式提供，因此人们不会吃蘑菇。

This is obviously a very controlled study, and they want to control the dosages appropriately.

这显然是一项非常对照的研究，他们希望适当地控制剂量。

They were randomized to begin the treatment immediately or after an eight-week delay.

他们被随机分配立即开始治疗或延迟八周后开始治疗。

They had all the appropriate control groups that one would like to see.

他们拥有人们希望看到的所有适当的对照组。

Andrew Huberman:

安德鲁·休伯曼：

What's really striking about this study is that there was a very significant improvement in mood and affect and relief from depressive symptoms in anywhere from 50 to 70% of the people that were subjects in the study who received the psilocybin treatment and whether or not it was 50 or whether or not it was 71% varied according to how long after the study they maintain these antidepressant effects, whether or not they stayed in remission from the depression.

这项研究真正引人注目的是，接受裸盖菇素治疗的研究对象中有 50% 至 70% 的人的情绪和情感得到了非常显着的改善，抑郁症状得到缓解，无论是 50% 还是 71%，都根据研究后他们维持这些抗抑郁效果的时间长短而变化，无论他们是否处于抑郁缓解状态。

But these are really enormous and significant effects, very exciting and are pointing in the direction of psilocybin very soon becoming a treatment for various forms of depression, including major depression.

但这些确实是巨大而显着的效果，非常令人兴奋，并表明裸盖菇素很快就会成为治疗各种形式抑郁症（包括重度抑郁症）的药物。

Andrew Huberman:

安德鲁·休伯曼：

Now of course, this is limited to the laboratory at present.

当然，目前这仅限于实验室。

There are a number of elements of these studies that are important to take into consideration too, which is that there are highly trained guides, meaning people to direct people through the experience.

这些研究中还有一些重要的因素需要考虑，那就是有训练有素的导游，这意味着人们可以指导人们进行体验。

As Matthew Johnson has told me, there is the occurrence from time to time of people having so-called bad trips, of having anxiety attacks during the hallucinations, and all that, and they have ways to mitigate that and deal with that because the guides are trained.

正如马修·约翰逊告诉我的那样，人们时不时会发生所谓的糟糕旅行，在幻觉期间出现焦虑症等等，他们有办法减轻和处理这种情况，因为导游受过培训。

They have all the sorts of medical monitoring devices for heart rate and temperature and things that one would like to see for a study like this, because these are very powerful compounds.

他们拥有各种各样的心率和体温医疗监测设备以及人们希望在这样的研​​究中看到的东西，因为这些都是非常强大的化合物。

Andrew Huberman:

安德鲁·休伯曼：

I don't want to give away any elements of the discussion with Matthew Johnson because it will be released in podcast form reasonably soon here, at the Huberman Lab podcast.

我不想泄露与 Matthew Johnson 讨论的任何内容，因为它将很快以播客形式在 Huberman 实验室播客上发布。

But one of the things that came up and is a fundamental question that I had that I think probably many of you are asking is, does the experience that one has on these compounds make a difference for whether or not somebody gains relief from depression from these psilocybin journeys or not?

但出现的一件事也是我提出的一个基本问题，我想你们中的许多人可能都在问，一个人对这些化合物的体验是否会对某人是否从这些裸盖菇素之旅中获得抑郁症的缓解产生影响？

In other words, does it matter what they talk about?

换句话说，他们谈论什么重要吗？

Does it matter what they think about?

他们的想法重要吗？

Does it matter if they have a good trip or a bad trip?

他们的旅行愉快还是糟糕有什么关系吗？

And I don't want to hold you in too much suspense; I'll let Matthew provide the more thorough answer.

我不想让你有太多的悬念；我会让马修提供更彻底的答案。

Andrew Huberman:

安德鲁·休伯曼：

But what's really interesting is there are some common themes to psilocybin administration and experience that lead to relief from depressive symptoms.

但真正有趣的是，裸盖菇素的给药和体验有一些共同的主题，可以缓解抑郁症状。

But they are subjectively very varied, meaning that whether or not people feel they had a good experience or a bad experience, whether or not people thought about their parents or thought about the color of the ceiling doesn't seem to have too much of an impact on whether or not they received relief during these studies, in these clinical studies.

但主观上它们是非常不同的，这意味着人们是否觉得自己有好的经历或不好的经历，人们是否想到了他们的父母或想到了天花板的颜色，似乎对他们在这些临床研究中是否得到缓解没有太大影响。

It seems like different people can have lots of different experiences and still receive benefit, and that points to something deeper.

似乎不同的人可以有很多不同的经历，但仍然受益匪浅，这指向了更深层次的东西。

Andrew Huberman:

安德鲁·休伯曼：

It points to the fact that these drugs, which is really what they are, are rewiring neural circuitry in a common way despite a diversity of experience while on the drug.

它指出了这样一个事实，即这些药物实际上正在以一种共同的方式重新连接神经回路，尽管人们在使用药物时有不同的经验。

And that itself is really interesting, and it takes us back to a place that we've been before in this discussion, which is layer V of the cortex, this area that ketamine seems to impact as well by generating rhythms of the ...

这本身就很有趣，它让我们回到了之前讨论过的地方，即皮质的第五层，氯胺酮似乎也通过产生……的节律来影响这个区域。

I mentioned one-to-three-hertz activity in layer V of certain areas of the cortex.

我提到了皮质某些区域的第五层的一到三赫兹的活动。

Well, the 5-HT1A receptor is known to be enriched in layer V of the cortex.

众所周知，5-HT1A 受体富含于皮质的 V 层。

And layer V of the cortex is a very interesting area because it's an area in which there's a lot of lateral connectivity.

皮质的第五层是一个非常有趣的区域，因为它是一个有很多横向连接的区域。

So connections between different brain areas laterally generally is what allows us to merge different senses.

因此，不同大脑区域之间的横向连接通常使我们能够融合不同的感官。

So for instance, when we hear a sound off to our right over here, and we turn to our right, there's a very hardwired response, and typically we hear something off to our right, we don't look to our left.

举例来说，当我们听到右边有声音，然后我们转向右边时，就会有一个非常固定的反应，通常我们听到右边有声音，我们不会看左边。

That's how hardwired some of these circuits are.

这就是其中一些电路的硬连线方式。

Andrew Huberman:

安德鲁·休伯曼：

What appears to be happening is that the activation of the serotonin system in 5-HT1A receptor in layer V is offering up, or providing an experience, whereby the lateral connections are able to engage much more broadly than they would normally.

似乎正在发生的事情是，V 层 5-HT1A 受体中的血清素系统的激活正在提供或提供一种体验，从而使横向连接能够比正常情况下更广泛地参与。

Now, that also could be a bad thing.

现在，这也可能是一件坏事。

And I asked Matt about this.

我向马特询问了此事。

That sounds kind of spooky.

这听起来有点怪异。

I don't know that when I hear something off to my right that I want to look off to my left; that could be highly maladaptive, especially if it's a car coming at me from my right.

我不知道当我听到右边有什么声音时我会想看向左边；这可能是非常不适应的，特别是如果有一辆汽车从我右边向我驶来。

That doesn't seem to be what's happening.

事情似乎并非如此。

It's not really rewiring these deeply reflexive circuits.

它并没有真正重新连接这些深度反射电路。

It's somehow rewiring associations between events, emotional events, past events, current events and future events in ways that allow people to get some sort of relief or distance from these narratives, these depressive stories about their past and present, and allow them to see new opportunity and optimism in the future.

它以某种方式重新连接事件、情感事件、过去事件、当前事件和未来事件之间的关联，让人们从这些叙述、这些关于他们过去和现在的抑郁故事中获得某种解脱或距离，并让他们看到未来的新机会和乐观情绪。

Andrew Huberman:

安德鲁·休伯曼：

That's really a fascinating thing if you really think about it, because I would've thought that simply by ramping up laterality of connections, meaning the cross associations, that things could either be rewired randomly in ways that don't serve us or would perhaps just cause no effect at all.

如果你认真思考的话，这确实是一件令人着迷的事情，因为我会认为，简单地通过增加连接的横向性（即交叉关联），事物要么以不适合我们的方式随机重新连接，要么根本不会产生任何影响。

So it's either going to be bad or neutral, but that's not really the way things are turning out.

所以它要么是坏的，要么是中性的，但事情的发展并不是这样的。

Again, these are highly controlled studies.

同样，这些都是高度对照的研究。

I do want to emphasize that ketamine, psilocybin, these things are still illegal, most all places.

我确实想强调，氯胺酮、裸盖菇素这些东西在大多数地方仍然是非法的。

There are some regions and cities in the United States where they are locally decriminalized, but they are not legal; they're still illegal.

美国有一些地区和城市在当地将其合法化，但并不合法；他们仍然是非法的。

So what we're referring to here are indeed clinical studies in which people are taking them legally.

所以我们这里指的确实是人们合法服用它们的临床研究。

I think it's very likely we will see a shift in the legislature around psychedelics, and in particular psilocybin, in the not-too-distant future.

我认为在不久的将来，我们很可能会看到立法机构围绕迷幻药，特别是裸盖菇素发生转变。

Andrew Huberman:

安德鲁·休伯曼：

And I think that for now, what we should know is what Matt told me, and what you'll hear far more about, which is that psilocybin, this one, or in most cases two-dose treatments done in a highly clinical setting, controlled setting, with patients that are carefully selected, can ...

我认为现在我们应该知道的是马特告诉我的，以及你会听到的更多信息，那就是裸盖菇素，这一种，或者在大多数情况下，在高度临床环境、受控环境中，对经过精心挑选的患者进行的两剂治疗，可以......

in many cases the majority of people receive and maintain relief from their depressive symptoms simply through the experience of this psychedelic journey.

在许多情况下，大多数人仅仅通过这种迷幻之旅的经历就可以缓解并维持抑郁症状。

I did ask him about microdosing.

我确实问过他有关微剂量的问题。

I made it sound as if I'd never heard about it before.

我说得好像我以前从未听说过一样。

Microdosing, not microdosing — microdosing.

微剂量，不是微剂量——微剂量。

And his answer was interesting.

他的回答很有趣。

His answer was that the microdosing effects don't seem to be nearly as impactful as some of these, well, let's just call them what they are, these kind of high-amplitude sessions that there are just one or two.

他的回答是，微剂量效应似乎并不像其中一些效应那么有影响力，好吧，我们就这样称呼它们吧，这些高幅度的治疗只有一两次。

There are some studies ongoing where there's more than two, but that the microdosing doesn't seem to compare to these macrodosing.

有一些研究正在进行，其中有两种以上，但微剂量似乎无法与这些大剂量相比。

Andrew Huberman:

安德鲁·休伯曼：

I mentioned the dosages before, this 20 milligrams per 70 kilograms or 30 milligrams per 70 kilograms dosages given several weeks apart.

我之前提到过剂量，每70公斤20毫克或每70公斤30毫克，间隔几周服用。

So you'll hear more about microdosing and other psychedelics and their impact on depressive states and major depression in the episode with Matt.

因此，您将在马特的这一集中听到更多有关微剂量和其他迷幻药及其对抑郁状态和重度抑郁症的影响的信息。

But for the time being, it really seems as if, again, we're looking at neuroplasticity, we're coming back to layer V.

但就目前而言，我们似乎再次关注神经可塑性，我们又回到了第五层。

Just like with ketamine and PCP, we're hearing about layer V, we're hearing about rewiring of circuitry, we're hearing about a dissociation, or a distancing of oneself from these negative moods and affects and narratives.

就像氯胺酮和五氯苯酚一样，我们听到第五层，我们听到电路的重新布线，我们听到分离，或者远离这些负面情绪、情感和叙述。

Andrew Huberman:

安德鲁·休伯曼：

But there's a key distinction between the ketamine work and the psilocybin work, which is that in the ketamine work, it really is about dissociating from experience during the session with the psychiatrist.

但氯胺酮工作和裸盖菇素工作之间有一个关键区别，那就是在氯胺酮工作中，它实际上是与精神科医生就诊期间的经验脱离。

Whereas during the psilocybin journey, it's really about immersing oneself in the experience and being fully present to that experience.

而在裸盖菇素之旅中，真正重要的是让自己沉浸在体验中并完全投入到这种体验中。

That does seem to be an important component, and what the difference is there and why they both seem to provide some relief from major depression isn't clear.

这似乎确实是一个重要的组成部分，但其中有何区别以及为什么它们似乎都能在一定程度上缓解重度抑郁症，目前尚不清楚。

I think most likely it takes us back to the fact that this thing we call major depression clearly involves serotonin, dopamine and norepinephrine.

我认为这很可能让我们回到这样一个事实：我们称之为重度抑郁症的东西显然涉及血清素、多巴胺和去甲肾上腺素。

And in some individuals, they may be more deficient in one or several of those, or all of those, whereas in other individuals it might be a different collection of chemicals.

在某些个体中，他们可能更缺乏其中的一种或几种，或全部，而在其他个体中，可能是不同的化学物质集合。

Andrew Huberman:

安德鲁·休伯曼：

And of course there are a tremendous number of other psychedelic compounds that people are exploring for treatment of major depression.

当然，人们正在探索大量其他迷幻化合物来治疗重度抑郁症。

But really, psilocybin is the one that we have the most data on.

但实际上，裸盖菇素是我们拥有最多数据的一种。

MDMA has mainly been explored in the clinical realm for treatment of trauma.

MDMA 主要在临床领域探索用于治疗创伤。

There are some trials ongoing for treatment of depression, but the big breakthroughs seem to be happening in the realm of trauma treatment, the so-called MAPS group that's doing this, again legally, in a clinical setting.

目前正在进行一些治疗抑郁症的试验，但重大突破似乎发生在创伤治疗领域，即所谓的 MAPS 小组，他们正在临床环境中合法地进行这项工作。

And there are other groups that are starting to do it as well.

还有其他团体也开始这样做。

We are going to do an entire podcast episode about MDMA and some related compounds.

我们将制作一整集关于 MDMA 和一些相关化合物的播客。

So I'll save that discussion for then.

所以我会留到那时再讨论。

Andrew Huberman:

安德鲁·休伯曼：

One of the most common questions I get for this podcast is about different diets, different regimes, different nutritional plans, things like keto, ketogenic diet, or vegan diets, or intermittent fasting, or the all-meat diet, the so-called lion diet, et cetera.

我在这个播客中收到的最常见的问题之一是关于不同的饮食、不同的饮食习惯、不同的营养计划，比如酮、生酮饮食、纯素饮食、间歇性禁食、全肉饮食、所谓的狮子饮食等等。

There are actually really interesting data relating nutrition and diet to major depressive disorder.

实际上有一些非常有趣的数据将营养和饮食与重度抑郁症相关。

And I think we just need to frame this by returning to something that was said earlier, which is that the ingestion of carbohydrates, in particular carbohydrates, and some meats, like turkey, that are rich in tryptophan, this precursor to serotonin, are in many ways the self-medicating version of depression treatment.

我认为我们只需要回到之前说过的内容来框架这一点，那就是摄入碳水化合物，特别是碳水化合物，以及一些富含色氨酸（血清素前体）的肉类，如火鸡，在很多方面都是抑郁症治疗的自我治疗版本。

Andrew Huberman:

安德鲁·休伯曼：

Now, to be clear, I'm not saying that people should use food to medicate their depression.

现在，需要澄清的是，我并不是说人们应该用食物来治疗抑郁症。

Many people do that reflexively, however; they reach for carbohydrate-rich foods to blunt their cortisol, because that's indeed what it does.

然而，很多人都会本能地这么做。他们寻求富含碳水化合物的食物来减弱皮质醇，因为这确实是它的作用。

It blunts cortisol when you ingest high-carbohydrate foods, in particular starchy foods, and it does increase serotonin, in particular if those foods are rich in the amino acid tryptophan.

当你摄入高碳水化合物食物，特别是淀粉类食物时，它会减弱皮质醇，并且它确实会增加血清素，特别是当这些食物富含氨基酸色氨酸时。

Now, ingesting food is wonderful and important and great, but ingesting excessive foods of any kinds, carbohydrate or otherwise, is not healthy, of course.

现在，摄入食物是美妙、重要和伟大的，但摄入过量的任何种类的食物，无论是碳水化合物还是其他食物，当然都是不健康的。

Andrew Huberman:

安德鲁·休伯曼：

There have been some explorations of whether or not a vegan diet can improve symptoms of depression.

关于纯素饮食是否可以改善抑郁症症状已经进行了一些探索。

Not a lot of data, not impressive data.

数据不多，也没有令人印象深刻的数据。

There have been very few controlled studies looking at the carnivore, all-meat diet; on that I think there are now some that are starting to spin up, meaning there are studies that are starting to spin up.

针对肉食动物、全肉饮食的对照研究很少。在这一点上，我认为现在有些研究正在开始启动，这意味着有些研究正在开始启动。

However, the ketogenic diet has been explored for its ability to relieve certain symptoms of depression, in particular to, what's called maintain euthymia.

然而，生酮饮食因其缓解某些抑郁症症状的能力而被探索，特别是所谓的维持正常情绪。

Euthymia is the kind of state of equilibrium between a manic episode and a depressive episode in a manic-bipolar person.

情绪愉悦是躁狂双相情感障碍者躁狂发作和抑郁发作之间的一种平衡状态。

We'll return to this more in a future episode, but it basically ...

我们将在以后的剧集中更多地讨论这一点，但基本上......

Manics have highs and they have lows, bipolars either cycle back and forth really quickly — so rapid cycling bipolars or slow.

躁狂症有高潮，也有低谷，双相情感障碍要么快速循环，要么快速循环，要么缓慢循环。

Some people ...

有些人...

so really quickly, it can be day-to-day.

所以真的很快，它可以是日常的。

Other people, it's month-to-month or week-to-week they're going highs and lows.

其他人则每个月或每周都会经历高潮和低谷。

Andrew Huberman:

安德鲁·休伯曼：

And you hear about mania, and you hear about dysphoria.

你听说过躁狂症，也听说过烦躁症。

Euthymia is that kind of place in the middle where people feel neither too high nor too low.

Euthymia 是一种介于中间的位置，人们感觉既不太高也不太低。

And there are some interesting studies looking at the ketogenic diet for maintaining euthymia in manic depressives, but also in people with major depressive disorder.

还有一些有趣的研究着眼于生酮饮食对于躁狂抑郁症患者以及重度抑郁症患者维持正常情绪的作用。

Why would this work?

为什么这会起作用？

Well, we have to remember that the ketogenic diet wasn't discovered so that self-appointed nutrition gurus could talk about it online, or so that people could make money selling anything related to ketosis.

好吧，我们必须记住，生酮饮食的发现并不是为了让自封的营养专家可以在网上谈论它，或者为了让人们可以通过出售与酮症相关的任何东西来赚钱。

And here I'm not disparaging of the ketogenic diet; it's helped a lot of people.

在这里，我并不是贬低生酮饮食；而是要贬低生酮饮食。它帮助了很多人。

The ketogenic diet was actually shown to be medically relevant for its use to treat epilepsy.

生酮饮食实际上被证明在医学上与治疗癫痫有关。

It turns out that in epilepsy, or in particular, pediatric epilepsy, that a ketogenic diet and the shift of brain metabolism to predominantly one in which ketones are being metabolized rather than more standard glucose-type metabolism, can greatly reduce the number of epileptic seizures that these children experience.

事实证明，在癫痫症，特别是小儿癫痫症中，生酮饮食和脑代谢转变为主要是酮类代谢而不是更标准的葡萄糖型代谢，可以大大减少这些儿童癫痫发作的次数。

It's not always the case, but it's often the case.

情况并非总是如此，但经常如此。

Andrew Huberman:

安德鲁·休伯曼：

And so you talk to a neurologist or a neurosurgeon who's specialized in epilepsy, in particular pediatric epilepsy, and they'll tell you this, "Oh yeah, the ketogenic diet in many cases, not all, can be very effective for this treatment." How?

因此，您与专门研究癫痫（尤其是小儿癫痫）的神经科医生或神经外科医生交谈，他们会告诉您，“哦，是的，生酮饮食在很多情况下（并非全部）对于这种治疗非常有效。”如何？

How is it that a ketogenic diet reduces seizures?

生酮饮食如何减少癫痫发作？

Well, the way it reduces seizures is by increasing what's called GABA transmission.

嗯，它减少癫痫发作的方法是增加所谓的 GABA 传输。

GABA is a substance that is naturally released in our brain.

GABA 是一种在我们大脑中自然释放的物质。

It's an inhibitory neurotransmitter, meaning that when it's released into the synapse, it has the tendency to reduce the firing, reduce the electrical activity, of the next neuron or sets of neurons.

它是一种抑制性神经递质，这意味着当它被释放到突触时，它倾向于减少下一个神经元或神经元组的放电，减少电活动。

There are various compounds that increase GABA, in particular GABA in the forebrain.

有多种化合物可以增加 GABA，特别是前脑中的 GABA。

One common example would be something like alcohol; drinking an alcoholic drink or two will increase GABA transmission, ironically will lower your social inhibitions by increasing your neurochemical inhibition.

一个常见的例子是酒精之类的东西。喝一两杯酒精饮料会增加 GABA 的传输，讽刺的是，它会通过增加神经化学抑制来降低你的社交抑制。

It basically suppresses the self-monitoring pathways.

它基本上抑制了自我监控途径。

And if people drink enough, it will suppress all pathways, and people will urinate themselves and fall over.

而人喝多了，就会抑制一切通路，人就会小便、摔倒。

It will eventually inhibit all sorts of pathways.

它最终会抑制各种途径。

Andrew Huberman:

安德鲁·休伯曼：

So the GABA system has a rich array of effects all over the brain and body, but alcohol tends to activate the release of GABA.

因此，GABA 系统对整个大脑和身体都有丰富的影响，但酒精往往会激活 GABA 的释放。

You might say, "Well then why not just take alcohol to suppress seizures?" Well, that would be a terrible idea because there tends to be a rebound excitability after alcohol stops having its effects on the GABA receptors.

你可能会说，“那为什么不直接喝酒来抑制癫痫发作呢？”嗯，这将是一个糟糕的主意，因为酒精对 GABA 受体的影响停止后，兴奋性往往会反弹。

And so then there's an excitability, for which in epilepsy would be terrible.

因此就会产生兴奋性，这对于癫痫来说是可怕的。

The reason why the epileptic diet is useful for epilepsy is that it increases what we call the tonic level, the sort of the tide, the level of GABA in the brain, and that suppresses some of the hyperexcitability that is the characteristic feature of epilepsy.

癫痫饮食之所以对癫痫有用，是因为它可以增加我们所说的强直水平，即大脑中 GABA 的水平，并抑制某些癫痫的特征性过度兴奋。

Andrew Huberman:

安德鲁·休伯曼：

And there are other drugs, for instance the benzodiazepines and things of the Xanax variety, Valium and so forth, those increase GABA transmission.

还有其他药物，例如苯二氮卓类药物和 Xanax 品种、安定等，它们会增加 GABA 的传输。

Those drugs also have a lot of potential for abuse and addiction, et cetera, and they're problematic for other reasons.

这些药物也很可能被滥用和成瘾等，并且由于其他原因它们也存在问题。

But the ketogenic diet, by way of increasing ketone metabolism, or shifting brain's metabolism over to ketones, tends to modulate GABA such that GABA is more active and adjusts the so-called GABA-glutamate balance.

但生酮饮食通过增加酮代谢，或将大脑的代谢转移到酮，往往会调节 GABA，使 GABA 更加活跃，并调整所谓的 GABA-谷氨酸平衡。

This is getting technical, but glutamate is an excitatory neurotransmitter, GABA's an inhibitory neurotransmitter.

这有点技术性了，但谷氨酸是一种兴奋性神经递质，GABA 是一种抑制性神经递质。

And their balance is vital for neuroplasticity, for maintaining healthy levels of activity in the brain, et cetera.

它们的平衡对于神经可塑性、维持大脑活动的健康水平等至关重要。

Andrew Huberman:

安德鲁·休伯曼：

And so there is decent evidence that people with major depressive disorders, in particular the people with major depressive disorders that are refractory, meaning they don't respond to classical antidepressants, can benefit, it seems, from the ketogenic diet.

因此，有充分的证据表明，患有重度抑郁症的人，特别是患有难治性重度抑郁症的人，这意味着他们对经典抗抑郁药没有反应，似乎可以从生酮饮食中受益。

Now, this is not always the case, but for those of you out there who are struggling with major depression and for drugs have not worked, please talk to your psychiatrist.

现在，情况并非总是如此，但对于那些正在与重度抑郁症作斗争且药物无效的人来说，请咨询您的精神科医生。

I don't know how many of them are up on the literature about the ketogenic diet or the EPAs and the rest.

我不知道他们中有多少人阅读过有关生酮饮食或 EPA 等的文献。

Psychiatrists vary in terms of how involved in the current literature they tend to be, but there are many excellent psychiatrists out there.

精神病学家对当前文献的参与程度各不相同，但有很多优秀的精神病学家。

Most of them, in my experience, are actually quite avid learners about what's happening and what's new in this realm that they call psychiatry.

根据我的经验，他们中的大多数人实际上都是非常热衷于了解他们称之为精神病学的领域正在发生的事情和新事物。

Andrew Huberman:

安德鲁·休伯曼：

So it's really interesting that eating in a particular way, lowering carbohydrates to the point where you rely on ketogenic metabolism in the brain, increases GABA and can provide some relief for depressive symptoms.

因此，以特定的方式饮食，将碳水化合物降低到依赖大脑生酮代谢的程度，增加 GABA 水平，并可以缓解抑郁症状，这真的很有趣。

And that in particular, that seems to have positive effects in people that are refractory or don't respond to classic antidepressants.

尤其是，这似乎对那些难治或对经典抗抑郁药没有反应的人有积极的影响。

And that would include things like fluoxetine, et cetera.

其中包括氟西汀等。

I'll make one final point about ketogenic diets and GABA and depression, which is that it's also been shown that for people that respond well to these drugs that impact the serotonin system, dopamine system or norepinephrine, the ketogenic diet there may improve the ability for those drugs to work at lower dosages, which is reminiscent of what we saw with the EPA supplementation.

关于生酮饮食、GABA 和抑郁症，我要提出最后一点，那就是，对于那些对影响血清素系统、多巴胺系统或去甲肾上腺素的药物反应良好的人来说，生酮饮食可能会提高这些药物在较低剂量下发挥作用的能力，这让人想起我们在补充 EPA 时看到的情况。

Andrew Huberman:

安德鲁·休伯曼：

So today we've covered what, at least, feels to me like a tremendous amount of material.

所以今天我们讨论的内容至少在我看来是大量的内容。

This topic of depression is indeed an enormous topic to try and get our arms around.

抑郁症这个话题确实是一个值得我们尝试解决的巨大话题。

We talked about the symptomology, we talked about some of the underlying neurochemistry and biology, and then we talked about approaches to deal with it that are really grounded in the neurochemistry and biology.

我们讨论了症状学，讨论了一些潜在的神经化学和生物学，然后我们讨论了真正基于神经化学和生物学的处理方法。

I just want to recap a few of those tools and what those things are.

我只想回顾一下其中的一些工具以及它们是什么。

First of all, we talked about making the effort to not overwhelm the pleasure system.

首先，我们谈到要努力不压倒快乐系统。

That might seem counterintuitive, to not overly seek out pleasure, or else one can find themselves in a place of depression.

不要过度寻求快乐，这似乎违反直觉，否则一个人可能会发现自己陷入沮丧的境地。

Andrew Huberman:

安德鲁·休伯曼：

I mentioned, way back at the beginning of the episode, a young man who I know to be really struggling with depression, and it is thought, and we don't know for sure, but it's thought that some of that depression was probably triggered by an overindulgence in video games and other highly dopaminergic activities, to the point where those activities eventually were countered by the pain balance that Dr. Anna Lembke described.

我在本集一开始就提到过，我知道一个年轻人确实在与抑郁症作斗争，据认为，我们不确定，但人们认为，部分抑郁症可能是由过度沉迷于电子游戏和其他高多巴胺能活动引发的，以至于这些活动最终被安娜·伦布克博士描述的疼痛平衡所抵消。

And he now has to do those activities repeatedly and for many, many hours each day just to feel okay, not even to derive pleasure from them, and worse, many other activities, practically all other activities have lost their zest, they've lost their excitement and his sense of pleasure for them.

现在他每天必须重复做这些活动很多很多小时只是为了感觉良好，甚至不能从中获得快乐，更糟糕的是，许多其他活动，几乎所有其他活动都失去了热情，失去了兴奋感和他对这些活动的快乐感。

And so there's a really active campaign now to reset that system.

因此，现在有一场非常活跃的活动来重置该系统。

Andrew Huberman:

安德鲁·休伯曼：

So number one, don't overwhelm your pleasure centers, either through activities or compounds.

所以第一，不要通过活动或化合物压垮你的快乐中心。

It might seem counterintuitive, but you're setting yourself up for anhedonia and depression if you do that.

这可能看起来违反直觉，但如果你这样做，你就会让自己陷入快感缺失和抑郁症。

It's not just about addiction, that too, but it's also about setting yourself for anhedonia and depression.

这不仅与成瘾有关，而且还与让自己陷入快感缺失和抑郁有关。

How often can you engage in these activities?

您多久可以参与一次这些活动？

Well, that's going to differ from person to person.

嗯，这因人而异。

Everyone's slightly different, but you should really mind your extreme highs and your extreme lows and be cautious about those.

每个人都略有不同，但你应该真正介意你的极端高点和极端低点，并对它们保持谨慎。

We'll probably have Dr. Lembke on again at a future time to try and get some more specifics about that.

我们可能会在未来某个时间再次邀请 Lembke 博士来尝试了解更多相关细节。

But if you do feel like you need to reset that system, it really does seem like a 30-day complete detox from whatever activity or substance that is, and ideally, it doesn't continue after that 30 days, especially in conditions of drugs of abuse.

但是，如果您确实觉得需要重置该系统，那么这确实看起来像是 30 天的完全戒毒，无论是什么活动或物质，理想情况下，这 30 天之后就不会再继续了，尤其是在滥用药物的情况下。

Andrew Huberman:

安德鲁·休伯曼：

Second of all, talked about the norepinephrine system and how the norepinephrine system is really deficient in many forms of major depression.

其次，谈到了去甲肾上腺素系统以及去甲肾上腺素系统在多种形式的重度抑郁症中确实缺乏。

And in depression there is now more deliberate pursuit of norepinephrine-inducing activities that are healthy, that aren't adrenaline-seeking per se.

在抑郁症中，人们现在更加刻意地追求健康的去甲肾上腺素诱导活动，而这些活动本身并不是寻求肾上腺素。

Things like cold showers, things like particular patterns of breathing that engage and tend to make us more alert.

像冷水淋浴、特定的呼吸模式这样的事情会让我们更加警觉。

Things like exercise that will increase our levels of noradrenaline.

像运动这样的事情会增加我们的去甲肾上腺素水平。

I'd be remiss if I said that these activities could completely eliminate depressive symptoms in people with major depressive disorder.

如果我说这些活动可以完全消除重度抑郁症患者的抑郁症状，那我就失职了。

I don't think that's the case.

我认为情况并非如此。

And again, I want to acknowledge that people with major depressive symptoms often don't have the energy, the willingness or the capacity to engage in some of these activities.

再次，我想承认，患有严重抑郁症状的人通常没有精力、意愿或能力参与其中一些活动。

But things like cold showers, deliberate cold showers, things like regular exercise, they aren't just feel-good activities.

但像洗冷水澡、刻意洗冷水澡、定期锻炼这样的事情，它们不仅仅是让人感觉良好的活动。

They actually engage the norepinephrine system and keep that system tuned up and allow us to increase our norepinephrine levels at will on a regular basis.

它们实际上参与去甲肾上腺素系统并保持该系统的调节，使我们能够定期随意增加去甲肾上腺素水平。

And their mood-enhancing effects are real effects at the level of neurochemistry.

它们的情绪增强作用是神经化学水平上的真实作用。

Andrew Huberman:

安德鲁·休伯曼：

Then we talked about EPAs, these essential fatty acids, and it's clear that for most people, getting above 1000 milligrams, and probably even closer to 2000 milligrams per day of EPAs can be beneficial for mood, especially in attempts to treat or offset major depressive disorder.

然后我们讨论了 EPA，这些必需脂肪酸，很明显，对于大多数人来说，每天摄入 1000 毫克以上，甚至可能接近 2000 毫克的 EPA 对情绪有益，尤其是在尝试治疗或抵消重度抑郁症时。

Are there side effects?

有副作用吗？

Well, you need to explore those for yourself and with your doctor.

那么，您需要自己并与​​您的医生一起探索这些内容。

Everyone has a different health background.

每个人都有不同的健康背景。

The margins of safety, for most people, will probably be quite large, but for some people, that might not be the case.

对于大多数人来说，安全边际可能会很大，但对于某些人来说，情况可能并非如此。

So definitely, definitely check with your physician.

所以一定要咨询你的医生。

Andrew Huberman:

安德鲁·休伯曼：

We also talked about exercise and how EPA and exercise on a regular basis can offset these inflammatory pathways.

我们还讨论了锻炼以及 EPA 和定期锻炼如何抵消这些炎症途径。

I want to mention something I've mentioned on a previous podcast, but in terms of keeping the inflammatome, all these molecules that create inflammation, and then the inflammation can limit the amount of serotonin through the pathways we described, in order to do that, it's also very, very useful to ingest two to four servings of fermented foods on a daily basis or near daily basis.

我想提一下我在之前的播客中提到过的事情，但就保持炎症而言，所有这些产生炎症的分子，然后炎症可以通过我们描述的途径限制血清素的量，为了做到这一点，每天或几乎每天摄入两到四份发酵食品也非常非常有用。

These are data that were published by the Sonnenburg Lab at Stanford recently in the journal Cell — Cell Press journal, excellent journal.

这些是斯坦福大学Sonnenburg实验室最近在Cell杂志上发表的数据——Cell Press杂志，优秀杂志。

That ingestion of these fermented foods really keeps the gut microbiome tuned up, so to speak, well in order to offset these inflammatory cytokines, keeping inflammation at bay.

可以这么说，摄入这些发酵食物确实可以保持肠道微生物组的调节，从而抵消这些炎症细胞因子，从而防止炎症。

It just turns out to be a really good thing in order to keep our mood in a good place.

事实证明，这确实是一件好事，可以让我们保持良好的心情。

Andrew Huberman:

安德鲁·休伯曼：

So EPA, exercise, fermented foods, creatine as a potential source of relief from depression or offsetting or keeping us away from major depression or relapse into depression.

因此，EPA、锻炼、发酵食品、肌酸是缓解抑郁症或抵消或让我们远离重度抑郁症或抑郁症复发的潜在来源。

And then we talked about the prescription compounds and the compounds that are being used mainly in the course of studies and of psychiatry and depression, things like ketamine, PCP, psilocybin and related compounds.

然后我们讨论了处方化合物以及主要在研究过程中以及精神病学和抑郁症中使用的化合物，例如氯胺酮、PCP、裸盖菇素和相关化合物。

And then lastly, we talked about ketosis, which may not be right for everybody, but might be right for certain individuals out there who are grappling with this.

最后，我们讨论了酮症，它可能并不适合所有人，但可能适合某些正在努力解决这个问题的人。

Andrew Huberman:

安德鲁·休伯曼：

If you're learning from this podcast and hopefully enjoying it and applying some of the tools that we describe, please subscribe to the podcast on YouTube, that really helps us.

如果您正在学习此播客，并希望喜欢它并应用我们描述的一些工具，请订阅 YouTube 上的播客，这对我们确实有帮助。

As well, please leave us a comment and some feedback for future episodes and topics that you'd like to see us cover.

另外，请给我们留下评论和一些反馈，以了解您希望我们讨论的未来剧集和主题。

You can do that on YouTube in the comment section.

您可以在 YouTube 上的评论部分执行此操作。

As well, please follow us on Instagram.

另外，请在 Instagram 上关注我们。

It's Huberman Lab on Instagram.

这是 Instagram 上的 Huberman Lab。

There I provide some recaps of some of this material.

在那里我对其中一些材料进行了一些回顾。

I also provide some original material that doesn't show up in the podcast.

我还提供了一些播客中未出现的原始材料。

Please also subscribe on Apple and Spotify, if you haven't already.

如果您还没有订阅，也请在 Apple 和 Spotify 上订阅。

And on Apple, you have the opportunity to leave us up to a five-star rating as well as a comment and some feedback.

在 Apple 上，您有机会给我们五星级的评级以及评论和一些反馈。

Please also check out the sponsors that we mention at the beginning of the podcast, that's a terrific way to support what we're doing.

另请查看我们在播客开头提到的赞助商，这是支持我们正在做的事情的绝佳方式。

And last but not least, I want to thank you for embarking on this journey of trying to understand what is depression, how does it work and how to treat it.

最后但并非最不重要的一点是，我要感谢您踏上这段旅程，试图了解什么是抑郁症、它是如何运作的以及如何治疗它。

And thank you for your interest in science.

感谢您对科学的兴趣。

PART 3 OF 3 ENDS

第 3 部分（共 3 部分）结束