Understanding & Controlling Aggression | Huberman Lab Podcast #71

- Welcome to the Huberman Lab Podcast,

where we discuss science and science based tools

for everyday life.

[cheerful music]

I'm Andrew Huberman,

and I'm a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, we are discussing aggression.

I'm going to explain to you that there are

several different types of aggression, for instance,

reactive aggression versus proactive aggression.

Meaning sometimes people will be aggressive

because they feel threatened or they are protecting

those that they love, who also feel threatened.

There's also proactive aggression where people

go out of their way to deliberately try and harm others.

And there is indirect aggression, which is aggression,

not involving physical violence, for instance,

shaming people and things of that sort.

It turns out that there are different biological mechanisms

underlying each of the different types of aggression.

And today I will define those for you.

I'll talk about the neural circuits in the brain and body

that mediate each of the different kinds of aggression.

Talk about some of the hormones and peptides

and neurotransmitters involved.

I promise to make it all accessible to you,

even if you do not have any biology or science background,

I will also discuss tools, psychological tools

and biological tools that one can use to

better control aggression.

Now, right here at the outset,

I want to acknowledge that any discussion about aggression

has to have an element of context within it.

To be fair, human beings invest a lot of money,

a lot of time, and a lot of energy,

and indeed can even derive pleasure from aggression.

Later I'll talk about neural circuits in the brain and body

that reinforce, in other words, reward through the release

of chemicals that make people feel good.

Acts of aggression.

However, what I'm mainly referring to

is the context in which human beings will pay money

in order to derive what we call vicarious aggression,

put it simply people spend an enormous amount of money

and time and energy watching other people engage in,

for instance, aggressive sports.

And we know that observing your team winning

over another team causes the release of neurochemicals

in your brain and body that make you feel good.

And yes, that can make you feel more aggressive.

We also know of course that most governments invest

many billions if not trillions of dollars

in infrastructure, technologies and human beings

in order to engage in aggression if needed,

so-called military warfare, et cetera.

So today's discussion will include a description of

aggression in the pathological sense.

We'll actually talk about an explosive aggressive disorder

that most of you probably haven't heard of,

but is actually far more common than perhaps, you know,

we'll talk about the role of things like attention deficit,

hyperactivity disorder,

and how that can relate to aggression through

the relationship between impulsivity and aggression.

And we'll talk about verbal aggression,

physical aggression, proactive aggression,

as mentioned before, and reactive aggression.

I'm certain that by the end of the episode,

you will come away with a much more thorough understanding

of what this thing that we call aggression really is.

And when you see it in other people,

I think it will make more sense to you.

And when you observe it in yourself or the impulse to engage

in aggression, verbal, or physical or otherwise,

I hope that you'll understand it better as well.

And of course, the tools that I will describe

should allow you to modulate and control

aggressive tendencies or predispositions to aggressiveness

and just generally to be able to engage with people

in a more adaptive way overall.

Before we begin, I'd like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

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.

In keeping with that theme,

I'd like to thank the sponsors of today's podcast.

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Let's talk about aggression.

I think that many people out there are put off

by aggression, although others are drawn to aggression

both in themselves and when observing it in others.

The reason to talk about aggression is,

that as mentioned before,

the context of aggression really matters.

So there are instances where aggression is adaptive.

For instance, a mother protecting her children

if she's being attacked,

or if her children are being threatened.

I think most people would agree that so-called

maternal aggression of that sort,

provided the context is right, is a great thing.

Protecting our young is after all one of the primary

adaptive drives of our species, and thank goodness it is.

Of course, other forms of aggression

like unprovoked, proactive aggression,

somebody simply being violent to somebody else,

even when unprovoked, most of us cringe

when we see that kind of behavior,

it can even evoke aggression in people

when they observe that kind of behavior.

So again, context really matters,

but a more general and perhaps an even more important reason

to think about and understand aggression

is that by understanding the biology

and psychology of aggression, you will be

in a much better position to understand

how all emotional states come to be,

both in yourself and in others.

For instance, many of you have probably heard the statement

that I believe arises from pop psychology,

not from formal academic psychology,

that aggression is just sadness.

It's a form of sadness that's amplified

and it shows up as aggression.

But when we look at the underlying biology

and the peer reviewed literature on this,

nothing could be further from the truth.

We have distinct circuits in the brain for aggression

versus grief and mourning, those are non-overlapping.

Now that doesn't mean that you can't be sad and aggressive

or in a state of mourning and aggressive at the same time,

but the idea that sadness and aggression

are one in the same thing is simply not true.

And by understanding that, or perhaps by understanding

that irritability and aggression are not the same thing,

you'll be in a much better position to apply

some of the tools that we will talk about in this episode

in order to be able to reduce or eliminate,

or if it's adaptive to you to modulate aggression.

And yes, there are cases where modulating your aggression

in some cases, even amplifying aggression can be adaptive.

Now this of course is not the first discussion

about the biology of aggression

or the psychology of aggression.

And we really can look to the beginning of the last century

as the time in which the formal study

of aggression really began.

One of the names that's most associated with the formal

study of aggression is none other than Konrad Lorenz.

Some of you may be familiar with that name,

others of you may not be familiar with that name.

Konrad Lorenz studied so-called imprinting behaviors

and fixed action pattern behaviors.

He's most famous, at least in scientific circles,

for getting geese to believe that he was their parent.

And if you were to put into Google Conrad with a K, Lorenz,

just as it sounds, Konrad Lorenz, geese,

you're going to see a lot of photos of Conrad

walking down roads with a lot of geese following him

or swimming in lakes with a lot of geese following him.

He had a habit of geese adopting him

because of the behaviors that he partook in.

So he would swim out on a lake

in front of a bunch of little geese and then

they would think that he was the parent

and they would imprint on him.

He even lived with these animals and they lived with him,

sort of a strange character from what I hear.

But nonetheless, all this work was deserving

of a Nobel prize because what he discovered

were fixed action patterns.

That is patterns of behavior

that could be evoked by a single stimulus.

Okay. This is really important.

The idea that you can get a whole category of behaviors,

like swimming behind a parent,

or looking to somebody for comfort, and only them,

the idea that you could get a huge category

of different behaviors in a bunch of different contexts

triggered by just the presence of that person is remarkable,

because what it suggested and what turns out to be true

is that there are neural circuits,

not just individual brain areas, but collections

of brain areas that work together

to engage a pattern of behaviors.

And that's the first fundamental principle

that we need to define today,

that when we talk about aggression,

we are talking about activation of neural circuits,

not individual brain areas, but neural circuits

that get played out in sequence like keys on a piano,

but that playing out in sequence means

that aggression is a verb.

It has a beginning, a middle and an end, and it's a process.

It's not an event.

And as you'll see, that turns out to be very important

in terms of thinking about how one can halt aggression,

prevent it from happening before it's initiated,

or maybe even prolonging aggression,

if that's what's needed.

Now, Konrad Lorenz had no real knowledge of neural circuits.

I mean, obviously he knew there was this thing

that we call a brain and a nervous system,

and he knew that there were chemicals in the brain

and hormones and things of that sort

that were likely to play a role,

but he really didn't take any measures to define

what the neural circuits were, frankly, he didn't need to.

He had his Nobel prize and he did all this beautiful work.

He's known for an abundance of work,

but he did think about what sorts of underlying processes

could drive something like aggression.

And he talked about one particular feature

that's especially important,

and that's this notion of a pressure.

The idea that yes, certain hormones will bias somebody

or an animal to be aggressive,

certain neural transmitter states, and you'll learn

what those are today will bias somebody

to be more or less aggressive,

maybe even submissive and passive,

maybe outright proactively aggressive towards anyone

or anything in front of them.

And yes, of course there will be historical features

based on their childhood, et cetera, et cetera.

He understood that there will be a constellation of things

that would drive people to be aggressive.

And he described a so-called pressure,

almost like a hydraulic pressure.

Just think about fluid pressure in a small container

being pushed, pushed, pushed until the can,

or the container is ready to explode

and how multiple features, multiple variables

could impinge on that and create that pressure.

It turns out that's exactly the way the system works.

There is no single brain area

that flips the switch for aggression.

Although we'll soon talk about a brain structure

that generally houses the propensity

and the output of aggression.

This notion of a hydraulic pressure that can drive us

toward aggressive behavior or conversely can be

very low pressure and keep us in a state of non-reactivity,

maybe even passivity or submissiveness

is a very important feature because it really captures

the essence of how neural circuits work

when we're talking about primitive behaviors generally.

And you can start to notice this in yourself and in others,

you can start to notice when you are veering

toward aggression or when someone is veering

toward aggression, verbal or physical.

Now that veering is the buildup of this hydraulic pressure

that Lorenz was referring to,

and it really does have an underlying biological basis.

Now it was some years later that the first experiments

came along, which really started to identify

the brain areas and the biological so-called pressures

that can induce aggressive behavior.

And the person that really gets credit for this

is a guy by the name of Walter Hess,

who at that time was working on cats.

And I know that when say working on cats,

a lot of people will cringe.

A lot of people have cats as pets,

and certainly cats can be delightful.

Some people like them more, some people like them less.

Most people cringe at the idea of doing experiments on cats.

I should say that these days,

very few laboratories work on cats.

Most laboratories that work on animal models

will work on flies, Drosophila fruit flies

for their capacity to do genetics,

on laboratory mice, sometimes rats, but usually mice.

And occasionally you'll find a lab that still works on cats.

Back in the time of Hess, very few laboratories

worked on mice, most laboratories worked on cats or rats.

And the reason for that is nowadays most laboratories

use mice if they use animal models

because of the genetic tools that exist in mice

to knock out this gene or knock in this gene, et cetera,

which can't be done in humans or non-human primates,

at least not very easily at this point in history.

So when I say he was working on cats,

I realized that probably evokes some negative emotions

in some of you, maybe even aggression in some of you,

what we can do, however, is look at the data

and make use of the data in terms of our understanding.

What Hess did was he had cats that were awake

and he was able to lower a stimulating electrode

into their brain.

Now keep in mind that the brain

does not have any pain sensors.

So after a small hole is made in the skull,

electrodes are lowered into the brain.

This is what's done commonly in human neurosurgery.

And he was able to stimulate different brain areas

and he was sort of poking around.

And when I say sort of, he was doing this with

some logical intent and purpose,

he wasn't just poking around in there for fun.

He was trying to identify brain regions that could generate

entire categories of behavior, ALA Lorenz, right?

These fixed action pattern behaviors.

Eventually his electrode landed in a site

and he provided electrical stimulation to the cat

that caused this otherwise passive purring relaxing cat

to suddenly go into an absolute rage.

So arched back, hissing hair up.

So called piloerection, where the hairs go up,

animals try to make themselves as big as possible

often when they're aggressive.

Drooling, maybe even spitting, believe it or not,

cats and other animals can do this.

And the cat tried to attack him or anyone else,

and anything else, even inanimate objects

when he stimulated this particula brain area.

So Hess obviously took notice

of this incredible transformation in behavior.

And the fact that when he turned off the stimulation

of this particular brain area,

the cat very quickly within seconds,

went back to being passive calm kitty.

Now, of course, he repeated this experiment in other animals

because he had to confirm that it wasn't just happenstance,

that there wasn't something unique about this one cat

that perhaps he had stimulated an area

that had been built up during the kittenhood of this cat

and had been reactivated.

Maybe this kitten had been traumatized early in life

or scared and reactivation of a particular circuit,

unique to that cat created this aggressive behavior.

That wasn't the case, every cat that he looked at

and stimulated this particular brain area,

the cat would immediately go into an aggressive,

almost rage type behavior.

Now, of course we can't anthropomorphize.

We don't know what the cat was feeling.

For all we know the cat could be happy,

although that seems pretty unlikely

and later experiments done in mice,

but also in humans confirm that indeed,

stimulation of this brain area evoked

not just behavioral aggression,

but also subjective feelings of aggression and anger.

So what was this incredible brain area,

or rather, I should say, what is the brain area

that harbored this incredible capacity

to generate aggressive behavior in Hess's experiments?

Well, for those of you that are regular listeners

of this podcast, you'll probably be relieved to know

that today we're going to talk about some new neural circuits,

oftentimes we'll center back on the amygdala

or the prefrontal cortex, and those names will come up.

And for those of you that haven't heard them before,

don't worry, I'll make it clear as to what

those brain areas are and what they do.

But today we're going to talk a lot about

the so-called VMH or ventromedial hypothalamus.

The ventromedial hypothalamus is a nucleus,

meaning a small collection of neurons...

What are neurons?

Nerve cells, and that small collection of neurons

that we call the ventromedial hypothalamus is truly small.

It's only about 1,500 neurons on one side of your brain

and a matching 1,500 neurons on the other side of your brain

and that combined 3000 neurons or so, it's not exactly 3000,

but 3000 neurons or so is sufficient to generate

aggressive behavior of the sort

that Hess observed in the cat, and believe it or not,

when you see somebody who's in an act of rage

or in an act of verbal aggression

or in an act of defensive aggression,

protecting their family or loved ones or country, et cetera,

almost certainly those neurons are engaged in that behavior.

Those neurons are perhaps even generating that behavior.

And next I'll describe some experiments that were done

just recently within the last 10 years or so,

but leading right up until this year

and even last month that keep confirming

again and again and again,

that it is the activity of neurons

in the ventromedial hypothalamus that are both necessary

and sufficient to generate the full catalog

of aggressive behaviors.

Now, before I go further to describe

the beautiful recent studies on the VMH,

the ventromedial hypothalamus,

and the important role of testosterone,

and more importantly, estrogen,

in the activation of aggressive behavior, that's right.

That's soon to be clear to you why that's the case.

I want to emphasize that the ventromedial hypothalamus

is something that we should all care about.

Why?

Well, it turns out that many categories

of psychiatric disorders, developmental disorders,

and psychological challenges, things like schizophrenia,

PTSD, post-traumatic stress disorder, depression,

borderline personality disorder,

and even certain forms of autism can include elements

of aggression and even violence.

Now it's certainly not the case that aggression and violence

are present in all people who suffer from schizophrenia

or PTSD or depression or autism

or borderline personality disorder.

I'm absolutely not saying that.

However, it can be a feature of those.

And it's a well described feature

in terms of trying to understand the constellation

of challenges that people suffer from when they have those.

So thinking about the VMH goes way beyond just understanding

basic aggression in the context of adaptive aggression.

So, you know, when earlier I use the example,

maternal aggression, that's one adaptive form of aggression.

It also can be pathologic aggression,

meaning it can harm ourselves or others.

So keep this in mind as we go forward,

because later we're going to talk about specific tools

designed to modulate or prevent aggression in, for instance,

people with attention deficit hyperactivity disorder,

and especially kids with ADHD.

In the meantime, let's return to the VMH,

this relatively small collection of neurons.

And the reason I say relatively small is, well,

your brain has many hundreds of billions of neurons,

maybe even trillions of neurons,

the exact number of neurons isn't really clear,

but it's a lot.

And it certainly is a lot relative to the number of neurons

this 3000 or so neurons living in your hypothalamus

that can evoke this aggressive response.

Experiments done by David Anderson's lab at Caltech

were really the first to parse the fine circuitry

and to really show that the ventromedial hypothalamus

is both necessary and sufficient for aggressive behavior.

These are important experiments

and they're worth knowing about.

What they did was they identified, first of all,

where the ventromedial hypothalamus was in the mouse,

that was pretty straightforward to do was sort of known

before they started these experiments.

And then they analyzed which genes, meaning which DNA,

which of course becomes RNA and RNA becomes protein,

which DNA and therefore which proteins are expressed

in particular cells of the ventromedial hypothalamus.

And it turns out that there's a particular category

of neurons in the ventromedial hypothalamus

that make an estrogen receptor.

And it is those neurons in particular that are responsible

for generating aggressive behavior.

How did they know this?

Well, they used a tool that's actually been described

by a previous guest of this podcast.

We had an episode with the psychiatrist and bioengineer

and my colleague at Stanford School of Medicine,

Karl Deisseroth, he and others have developed tools

that allow people to control the activity of neurons

essentially by remote control,

by shining light on those neurons.

So in the context of an experiment on a mouse,

which is what David's lab did, and these were

the beautiful experiments of Dayu Lin

who's now in her own laboratory at New York University,

put a little fiber optic cable down into the brain

into the hypothalamus that is of the mouse.

The mouse is able to move around in its cage freely moving,

even though it has a little tether, this little wire,

it's a very thin wire.

And that little thin wire is actually

a little what we call optrode.

And the experimentalist in this case, Dayu,

was able to stimulate the turning on

of a little bit of blue light and that blue light

activated only those estrogen receptor neurons

in only the ventromedial hypothalamus

and the way she was able to do that,

is she had introduced a gene that had been developed

by our friend, Karl Deisseroth that allows light

to trigger electrical activity in those neurons.

So if any of that is confusing,

or if all of that is confusing, here's the experiment.

There's a mouse in a cage.

It has a little wire coming out of its head.

It doesn't notice, believe it or not.

We know this 'cause it's still eating and mating

and doing all the things that mics like to do

on a daily basis and sleeping, et cetera.

And the mere pressing of a button will activate

a little bit of light released at the end of that wire,

that light activates particular neurons in this case,

it's the estrogen receptor containing neurons

in only the ventromedial hypothalamus.

When that mouse is in a cage with another mouse,

a couple of things happen depending on

what the other mouse is, or we could say

who the other mouse is.

If it's a male mouse and you put in there

with a female mouse, the male mouse will attempt to mate

with a female mouse provided that the male mouse

has gone through puberty.

He will try to mount and mate with the female mouse.

Now female mice are either in a receptive phase

or a non-receptive phase of their so-called estrous cycle.

They don't have a menstrual 28 day cycle

They have an estrous cycle.

And on particular days of the estrous cycle,

they are not happy to mate.

They will basically keep their hindquarters

away from the male mouse at all costs.

They'll even attack the male mouse.

On certain days of the estrous cycle, however,

the female mouse will undergo what's called lordosis,

which is an arching of her back and she'll allow the male

to mount and mate with her.

So a large number of experiments were done,

but the first experiment really was to put the male mouse

in with a female mouse who's in the so-called

receptive phase of estrus.

That is, she will allow mating and he starts mating with her

and they go through the standard repertoire

of mating behaviors that you observe in mice:

mounting, thrusting, intromission as it's called

in the mouse sex world.

Well, I guess I don't know what the mice call it,

but that's what the experimenters call it.

And then afterwards that he will dismount, okay.

So they observe this kind of mounting and sex behavior

is very typical, but about halfway through the behavior,

Dayu turned on the light to stimulate

these estrogen receptor containing neurons

only in the male mouse and what she observed

was incredibly dramatic.

The male mouse ceases from trying to mate

with the female mouse and immediately tries

to kill the female mouse.

He starts attacking her.

Then she turns off the light, the male stops

and goes back to trying to mate with the female mouse.

So I'm sure all of this was very confusing

and disturbing to the female mouse.

Nonetheless, that was the repertoire.

They would mate.

She would stimulate these ventromedial hypothalamus neurons.

The male mouse would immediately try and attack

and kill the female mouse.

And then she would stop the stimulation

and he would stop trying to attack and kill

the female mouse, return to the attempt, at least,

to mate with the female mouse.

These are such dramatic shifts in behavior

triggered only by the activation of only the small set

of neurons within the ventromedial hypothalamus.

And for those of you that think

that you can watch this sort of thing

without being disturbed, I encourage you to go to YouTube.

We will provide a link where you can see a video

of this type of behavior.

It's incredibly dramatic.

The shift in behavior is almost instantaneous,

occurs within seconds, if not milliseconds,

thousandths of a second.

The next experiment that she did was to put a male mouse

with this stimulation with light capability

in its ventromedial hypothalamus into a cage alone,

but with a rubber glove filled with air or water.

Mouse, walking around sniffing, peeing,

which is what male mice seem to do.

They seem to urinate everywhere, that's actually

an interesting, perhaps interesting feature of male mice

and actually many male animals, perhaps even humans.

We don't know, or maybe we do know,

basically this has been an observed time and time again

in experiments, mainly by Lisa Stowers's lab

at the Scripps Institute, that's characterized this.

If you put female mice into an arena or a cage,

they always urinate in a very small corner of that cage.

Whereas if you put mail mice into an arena or a cage,

the urinate everywhere, they have this obsession

with spraying their urine everywhere,

you can transpose that to human behavior if you like.

In any event, Dayu put the mouse in the cage alone,

but with this rubber glove,

the mouse is walking around urinating, et cetera,

doing whatever is that mice do,

then she stimulates the activation

of these ventromedial hypothalamus neurons,

and the mouse immediately tries to kill the glove.

It goes into a rage, attacking the glove

as if it were another mouse or some other animate object.

But of course it's an inanimate object.

It's just a rubber glove.

She stops the stimulation and the mouse

immediately goes back to being completely calm

or at least not attacking.

Again, we don't know what the mouse was feeling.

So these are very dramatic videos.

Again, you can see them by following the link

that we'll provide in the caption.

If that sort of thing is going to disturb you,

by to see, for instance, the attack,

one mouse attacking another,

please just don't watch them.

I'm not interested in traumatizing anybody

or you traumatizing yourself, that is.

A number of different variations

were done on this experiment.

For instance, stimulating the VMH in female mice,

as opposed to male mice,

putting the female mice in with other female mice

or with other male mice, no matter what variation

one carries out, so it doesn't matter

if it's male with female, male with male,

female with female, et cetera,

stimulation of the ventromedial hypothalamus

in a male mouse or a female mouse evokes this very dramatic,

almost instantaneous aggressive behavior,

physically aggressive behavior.

Subsequent experiments done by Dayu Lin

in her own laboratory and other laboratories

have shown that the ventromedial hypothalamus connected

with a bunch of other brain areas that are interesting,

And I'll talk about some of those in a little bit,

but one of them that I want to call out now

is the so-called PAG, the periaqueductal gray nucleus.

This is a large structure in the back of the brain

that houses things like neurons that can create opioids.

We all know of the opioid crisis, but these are neurons

that can produce endogenous, means made by the body,

chemicals that can cause pain relief.

You could understand why that might occur

in a circuit for aggression, right?

Even if one is the aggressor, it's likely

that they may incur some physical damage

and they'd want some pain relief.

The PAG also is connected to a number

of neural circuits that eventually,

through several processing stations, excuse me,

arrive at things like the jaws.

And in fact, stimulation of the ventromedial hypothalamus

can evoke biting and aggressive biting behavior.

Now aggressive biting behavior is particularly interesting

because in humans and especially in human children,

biting is something that, while young children might do

as a form of aggression, tends to disappear

pretty early in childhood.

And if it doesn't, it's often seen as a mark of pathology.

I have a story about this, actually, when I was a kid,

I went to a summer sports camp and I'll never forget this,

so we're playing soccer and in a rare stroke of luck

or accident, I happened to score a goal.

I wasn't a particularly good soccer player,

especially not at that stage of my life.

They later figured out that it was just better

to make me a fullback, 'cause I could just wait there

and do what fullbacks do.

I was better at taking the ball or the person out

than I was putting the ball in the goal.

Nonetheless, I, again, by chance, scored a goal

and I was trotting back to my side of the field,

and all of a sudden I felt this sting in my back,

a kid, not to be named, although I do remember your name,

I'm not going to tell you what his name was.

A kid jumped on my back and bit me on the top of my back.

And this of course resulted in a discussion and a timeout

and all the usual things and parents I think got involved.

I don't recall, I didn't think much else of it,

but I recall that this was considered especially troubling

behavior because he bit me as opposed to hit me

or shoved me down or something that sort,

and it does seem as if the tendency to use biting

as an aggressive behavior is associated

with a more primitive circuitry.

Now here I'm truly anthropomorphizing.

I don't know what this other kid happened to be thinking

or feeling at the time, how could I?

And I certainly am not going to say

that biting in every case reflects a pathology,

although I think there is general agreement

in the psychology community,

in the psychiatric community that past a certain age,

the using of one's teeth to impart aggression and damage

on others is a particularly primitive and troubling

or at least for the observer or the person experiencing

is a pretty disturbing event.

Dayu's lab has shown that activation

of the ventromedial hypothalamus triggers

a downstream circuit in the periaqueductal gray

which then triggers a whole other set of circuits of fixed

action patterns.

Here we are back to Lorenz with fixed action patterns,

including swinging of the limbs, right punching.

And this wouldn't necessarily be controlled punching,

but also biting behavior.

So it's remarkable to me,

at least that we have circuits in our brain that can evoke

violent use of things like our mouth or violent use of

things like our limbs.

That of course could be used for things like singing or

kissing or eating or, you know,

gesticulating in any kind of polite or impolite way.

The point here is that neural circuits,

not individual brain areas evoke the constellation

of behaviors that we call aggression.

Now, many of you are probably puzzled or at least should be

because I've been talking about

this highly specialized brain area,

the ventromedial hypothalamus and this highly specialized

subcategory of neurons in the ventromedial hypothalamus,

these neurons that make estrogen receptors.

And yet the activation of those cells

triggers dramatic and immediate aggression,

both in males and in females and both

against males and against females.

So what's going on here?

Most of us think about estrogen and we don't

immediately think of aggression.

Most of us hear testosterone and we might

think about aggression, although other things as well.

In order to understand this, I just want to briefly refer back

to a conversation that I had

on a previous episode of the Huberman Lab Podcast.

And that was with my colleague, the great Robert Sapolsky

of course, is a professor at Stanford

who studied testosterone and its impacts on behavior

as well as estrogen and other hormones

and their impacts on behavior.

To make a long story short and to dispel

a still unfortunately very common myth.

Testosterone does not increase aggressiveness,

testosterone increases proactivity and the willingness

to lean into effort in competitive scenarios.

Sometimes this is referred to as the challenge hypothesis,

but to make a long story short,

if people are given testosterone,

or if you look at people who have different levels,

excuse me, of testosterone,

endogenously that they naturally make.

What you'll find is that testosterone tends to increase

competitiveness, but not just in aggressive scenarios.

So if somebody is already aggressive,

giving them testosterone will have the tendency

to make them more aggressive.

If somebody however is very benevolent and altruistic,

giving them testosterone will make them more benevolent

and altruistic, at least up to a point.

Now, of course there are certain forms

of synthetic testosterones that are known in sports circles

and in other circles to increase aggressiveness

because of the way those particular forms

of synthetic testosterones work.

But in general, most of the experiments

that I'm referring to have not been done using those,

they've been done using the let's call them

the more traditional biological forms of testosterone

or that resemble the biological forms of testosterone.

In fact, Robert Sapolsky described

a really interesting experiment in which,

if you look at testosterone levels or you administer

additional testosterone to people

who are doing philanthropy, giving money to organizations

and so they're essentially doing good

because these are organizations doing good.

What you find is that increased testosterone

or further increasing testosterone makes people

more willing to compete, to give more money

than the other person in the room in order,

you know, to put it in air quotes,

"To Alpha out the other person," by giving more money.

So this is an act of altruistic or benevolent philanthropy.

It is not an act of aggression.

Of course, we don't know what the people

are feeling underneath all that.

Again, we can't anthropomorphize or project

onto other people what they're feeling.

But the point is that testosterone itself

does not make people more aggressive.

And in the experiments that we've been talking about

up until now, it's actually the activation

of estrogen receptor containing neurons

that makes these animals more aggressive.

And it turns out there's evidence that in certain context,

estrogen can make people more aggressive.

So what's going on here?

Well, what's going on is that testosterone can be converted

into estrogen through a process called aromatization.

There's an enzyme called aromatase.

Anytime you have word that ends in A-S-E,

at least if it's in the context of biology,

it's almost always not always, but almost always an enzyme.

So the aromatase enzyme converts testosterone into estrogen,

and it is actually testosterone, aromatized,

converted into estrogen and then binding

to these estrogen containing neurons

in the ventromedial hypothalamus that triggers aggression.

I want to repeat that, it is not testosterone itself,

that triggers aggression.

It is testosterone aromatized into estrogen within the brain

and binding to these estrogen receptor containing neurons

in the ventromedial hypothalamus that evokes aggression

and dramatic aggression at that.

Now this effect of estrogen causing aggression in the brain

is very robust, so much so that if you take a mouse

that lacks the aromatase enzyme or a human

that lacks the aromatase enzyme, and they do exist,

then there is a reduction in overall aggression,

despite high levels of testosterone.

And if people who or mice who have the aromatase enzyme have

that enzyme blocked, well, then it doesn't matter

how much you increase testosterone

or any of its other derivatives.

You do not observe this aggression.

So this runs counter to everything that we know and think

about the role of testosterone.

Again, testosterone increases competitiveness.

It can increase the desire to work under challenge.

I've said it before, and I ran this

or pressure tested this against Robert Sapolsky

who's been working on testosterone and it's role

in the brain and behavior for many decades now.

It is fair to say that testosterone has the net effect

of making effort feel good, or at least increasing

the threshold at which effort feels bad or unsustainable.

And it does that by way of changing the activity

or the threshold for activation of brain structures,

like the amygdala and other brain structures

associated with anxiety.

So the next time somebody says,

testosterone makes people aggressive.

You can say, "Ah, no, actually it's estrogen

that makes people aggressive, and animals aggressive

for that matter.

Now of course it is the case that because males

have relatively less estrogen circulating

in their brain and body than females, right?

Because they have testes, not ovaries,

that testosterone is required in the first place

in order to be converted into estrogen,

to activate this aggressive circuit involving

these estrogen receptor containing neurons

in the ventromedial hypothalamus.

But nonetheless, it is estrogen that is the final step.

It is the hormone on which aggression hinges.

And I think for most people,

that's a quite surprising finding.

And yet this is perhaps one of the more robust findings

in both the animal and human literature, as it relates

to hormones and psychological states and behavior.

Now, of course it is the case that if testosterone is low,

that a person or an animal will exhibit

less aggressive behavior, but that's not

because of reduced testosterone per se.

It's because of the subsequent reduction in testosterone,

meaning if there's no testosterone to aromatize

into estrogen, estrogen will also be lower.

So we've established that it's not testosterone,

but testosterone converted into estrogen

that activates these circuits for aggression.

But nonetheless, it's still surprising, right?

I mean, most of us don't think about estrogen

as the hormone that stimulates aggression,

but it turns out it's all contextual.

There are beautiful data showing that whether or not

estrogen stimulates aggression, can be powerfully modulated

by whether or not days are short or days are long.

In other words, whether or not

here's a lot of sunshine or not.

Now, obviously brain is encased in skull.

So it doesn't really know if there's a lot of sunshine

out there even though you can see the sun with your eyes,

you can feel it on your skin.

Day length is converted into hormonal signals

and chemical signals and the primary hormonal

and chemical signals involve melatonin and dopamine

and also the stress hormones.

So to make a very long story short,

in the long days where we get a lot of sunlight,

both in our eyes and on our skin,

melatonin levels are reduced.

Melatonin is a hormone that tends to produce

states of sleepiness and quiescence.

It also tends to activate pathways that tend to reduce

things like breeding and sexual behavior.

In long days, dopamine is increased.

Dopamine is a molecule associated with feelings of wellbeing

and motivation and the desire to seek out

all sorts of things, all sorts of motivated behaviors.

And in long days provided we're getting enough sunlight

on our skin and to our eyes, the stress hormones,

especially cortisol, and some of the other

stress hormones are reduced in levels.

If estrogen levels are increased experimentally

under long day conditions, it does not evoke aggression.

However, in short days, if estrogen is increased,

there's a heightened predisposition for aggression.

And that makes perfect sense.

If you think about what short days do

to the biology of your brain and body.

In short days, the melatonin signal goes up.

There's more melatonin circulating

for more of each 24 hour cycle.

Stress hormones are circulating more.

Why? Short days tend to be associated with winter.

In winter, we are bombarded with more bacterial viruses

because bacterial viruses actually survive

better in cold than they do in heat.

In fact, in my laboratory, we work with

a lot of viruses and bacteria and when we want

to keep them alive, we put them in the freezer.

If we want to kill them, if we want to inoculate them,

we put them under UV light.

Like you would see from the sunlight.

So shorter days are conducive to aggression.

Not because days are short per se,

but because stress hormone levels are higher

and because dopamine levels are lower.

Now, here's where all of this starts to converge

on a very clear biological picture,

a very clear psychological picture, and indeed

a very clear set of tools that we can think about and use.

Under conditions where cortisol is high,

where this stress hormone is elevated and under conditions

where the neuromodulator serotonin is reduced

there is a greater propensity for estrogen

to trigger aggression.

Now, again, I know I've said it before,

but for males who make a lot of testosterone

relative to estrogen, you have to swap in your mind

this idea that if testosterone is high,

that means that estrogen is low because

while that can be true in the periphery in the body,

if testosterone is high, there is going to be

some aromatization, that conversion of

testosterone to estrogen.

So anytime you hear that testosterone is high,

you should think testosterone is high in the body

and perhaps estrogen is low in the body.

But that means that there's going to be heightened levels

of estrogen in the brain and therefore

increased propensity for aggression.

In females who generally make less testosterone

relative to estrogen, there is sufficient estrogen

already present to trigger aggression.

So both males and females are primed for aggression,

but that's riding on a context and that context

of whether or not you get a tendency for aggression or not.

depends on whether or not cortisol is high or low,

and I'm telling you that if cortisol is relatively higher

in any individual, there's going to be a tilt,

an increase in that hydraulic pressure that Lorenz talked

about toward aggression.

And if serotonin, the neuromodulator that is associated

with feelings of wellbeing and sometimes

even of slight passivity, but certainly of wellbeing,

if serotonin is low, there's also going to be a further shift

towards an aggressive tendency.

So if we return to Lorenz's hydraulic pressure model

of aggression in other internal states,

we realize that external stimuli, things that we hear,

things that we see, for instance,

someone saying something upsetting or us,

seeing somebody do something that we don't like to others

or to us, as well as our internal state,

our subjective feelings of wellbeing,

but also our stress level,

our feelings of whether or not we have enough resources

and are content with what we have.

All of that is converging on this thing

that we call internal state and creating

this pressure of either to be

more aggressive or less aggressive.

And now we have some major players feeding

into that final pathway.

That question of whether or not

will we hit the other, person, will we say the thing

that is considered aggressive?

Will we not say it?

If somebody says something or does something

aggressive to us, will we respond or will we be

submissive or even passive?

Again, there are many things funneling into that question

and dictating whether or not the answer is,

"Absolutely I'll fight back,"

or, "I'm going to attack them even unprovoked."

Or if they say this, I'm going to do that,

or no matter what they do, I'm not going to respond.

These kinds of things are very complex.

And yet we really can boil them down

to just a few common elements.

And I'm telling you that those elements are whether or not

cortisol levels are relatively lower or relatively higher.

Again, relatively higher is going to tend

to make people more reactive.

Why?

Because reactivity is really a function

of the autonomic nervous system,

which is sort of like a seesaw that oscillates

between the so-called sympathetic arm

of the autonomic nervous system,

which tends to put us into a state of readiness

through the release of adrenaline.

Cortisol and adrenaline when they're circulating

the brain and body, make us more likely to move

and to react and to speak.

It's actually what will induce a kind of low level tremor,

which is an anticipatory tremor to be able

to move more quickly, right?

A body in motion is more easily set into further motion,

that is, and the neuromodulator serotonin

is a neuromodulator that in general is associated

with feelings of wellbeing in response

to what we already have.

So when we are well fed,

serotonin tends to be released in our brain and body,

in particular, well fed with carbohydrates,

the precursor to serotonin is tryptophan.

And indeed there are nice studies

exploring the types of diets, nutritional programs

that can reduce aggressive behavior, both in children

and in adults and tryptophan-rich diets

or supplementation with tryptophan.

So for tryptophan rich diets,

things like white turkey meat,

but then there are also a number of carbohydrates

you can look up.

It's very easy to find foods

that contain lots of tryptophan.

Those foods contain the precursor to serotonin.

Now it isn't simply the case that eating more foods

with tryptophan will tend to reduce your aggression.

I suppose it could do that, if you ate it in abundance,

it could make you tired and then you're less likely

to be aggressive, I don't recommend that strategy,

but the idea here is that when it's been explored,

increasing levels of tryptophan either by supplementation

or by food or drugs, prescription drugs

that increase serotonin.

So for instance, fluoxetine sometimes called Prozac

or Zoloft or any number of the other SSRIs

tend to reduce aggressive behavior.

Now, not always, but in general, that's the case.

Similarly, because elevated cortisol tends

to shift the whole system, again, create more

of a hydraulic pressure towards aggressive states.

If cortisol levels are reduced, well then the tendency

for aggressive behavior is reduced.

This is supported by a number of peer reviewed studies.

We'll provide links to some of those

in the caption show notes.

And we're going to return to these a bit later in the context

of specific studies that have looked at genetic variants

in different individuals that cause them

to make more or less serotonin,

or at least to metabolize serotonin differently.

This is also the case for so-called

intermittent explosive disorder that can often be associated

with gene variants that control how much serotonin is made

or how it's metabolized or how much cortisol is made

and how much it's metabolized.

In thinking about tools that are a number of things

that one could consider.

First of all, there are a number of decent studies

exploring how supplementation with the Omega-3 fatty acids,

which are precursors of some of the transmitter systems,

including serotonin that can modulate not directly mediate,

but modulate mood and emotional tone supplementation with

the omega 3 S has been shown to reduce impulsivity and

aggressiveness in certain contexts in things like ADHD

or in individuals who have a predisposition

for aggressive type behavior or aggressive thinking.

Now that doesn't necessarily mean that the omega 3

fatty acids are going directly

to the ventromedial hypothalamus and changing the activity

of neurons there more likely they are

causing or modulating an overall shift in mood

through the immune system, through hormone systems that are

changing the overall tone or the propensity for neurons

in the ventromedial hypothalamus to be activated.

How much omega 3 fatty acid, what source?

Well, we've talked about this on the podcast before.

You can, of course get omega 3 fatty acids

from a number of different foods.

Getting them from whole foods is probably the best way

to do it, but many people, including people with depression

will often supplement with one gram or more

of omega 3 fatty acid per day.

Some people including myself will take them every day

as just a general mood enhancer.

I don't suffer from depression,

but I've found it be beneficial for my health.

And so some people do that, and I've talked about before,

how in double blind placebo controlled studies,

people taking one to three grams of omega 3 fatty acids

per day, typically in the form of a high quality fish oil,

although there are other sources as well,

algae and so forth, can experience improvements in mood

that are on par with some of the SSRIs,

the selective serotonin reuptake inhibitors.

And of course, if you're prescribed an SSRI

by your psychiatrist or other doctor, please do take that

and don't cease to take it just simply to take omega 3s.

However you might mention to them, and you can find links

to the studies in our previous episodes on depression

that supplementation with omega 3 fatty acids

of at this one gram or more of EPA specifically,

so getting above that one gram threshold,

as high as three grams per day of the EPA has allowed people

to take lower doses of SSRIs and still keep their mood

in a place that's beneficial for them.

And in terms of keeping cortisol in a range that's healthy

and doesn't bias someone toward high levels of aggression

and irritability, that's again, going to be set

by a number of larger modulators or contextual cues.

And I've talked about some of those on the podcast,

but I'll just briefly recap them now,

obviously getting sunlight in your eyes early in the day,

and as much sunlight as you safely can in your eyes

throughout the day is going to be important.

Again, because of this effect of estrogen in long days,

not increasing aggression, however, in shorter days,

estrogen increases aggression because of the increase

in cortisol observed in short days.

Another way to reduce cortisol was discussed in our episode

on heat and the use of sauna and heat, but also hot baths.

It turns out that hot baths and sauna

can be very beneficial for reducing cortisol.

All the details on that are included in the episode on heat

and it's timestamped, so you can go directly to that

if you want to learn about the temperatures

and the various durations, but to just give

a synopsis of that, a 20 minute sauna at anywhere

from 80 to a hundred degrees Celsius is going to be

beneficial for reducing cortisol.

If you don't have access to a sauna,

you could do a hot bath, adjust the temperature

so you don't burn yourself.

I think 80 to a hundred degrees Celsius

is going to be too hot for many people

if it's a hot bath, whereas many people who can't tolerate

that hot bath can tolerate the sauna.

So safety first always, and of course,

but hot baths reduce cortisol, hot saunas, reduce cortisol

of a duration about 20 or 30 minutes is going to be beneficial.

And of course, some of you may be interested in exploring

the supplementation route and for reductions in cortisol,

really the chief player there is ashwagandha,

which is known to decrease cortisol, fairly potently.

I should just warn you that if you're going to use

ashwagandha in order to reduce cortisol, first of all,

check with your doctor or healthcare provider

before adding or subtracting anything

from your supplementation or health regimen.

Of course, I don't just say that to protect us.

I say that to protect you,

you are responsible for your health,

what you take and what you don't take.

Chronic supplementation with ashwagandha can have some

not so great effects of disruption of other hormone pathways

and neurotransmitter pathways.

So the limit seems to be about two weeks of regular use

before you'd want to take a break of about two weeks.

So ashwagandha again, a very potent inhibitor of cortisol,

but with some other effects as well,

don't use it chronically for longer than two weeks.

But if your goal is to reduce cortisol,

let's say you're going through a period of increased

irritability and aggressive tendency,

maybe you're also not getting as much light

as you would like, and perhaps also, if there are

other circumstantial things leading you towards

more aggressiveness and your goal is to reduce

aggressiveness, that can be potentially helpful.

And in light of all this stuff about cortisol and estrogen

and day length, I should mention that there are in fact,

some people who have a genetic predisposition

to be more irritable and aggressive,

and there are a couple of different gene pathways

associated with this.

We never like to think about just one gene

causing a specific behavior.

The way to think about genes is that genes generally code

for things within our biology.

In the context of today's discussion, things like

neural circuits or the amounts of neurotransmitters

that are made, or the amounts of hormones that are made,

or the amount of neurotransmitter hormone receptors

or enzymes, et cetera, that shift the activity

of our biology in a particular direction.

They bias our biology.

And in fact, there is a genetic variant present

in certain people that adjusts

their estrogen receptor sensitivity,

and that estrogen receptor sensitivity can result

in increased levels of aggression,

sometimes dramatic increases, however,

and also very interestingly, photo period,

meaning day length, is a strong modulator of whether or not

that aggressiveness turns up or not.

Whether or not that person with the particular gene variant

is more aggressive or not, depends on how long the day is

and how long the night is.

One particular study that I like that references this

is Trainer, et al, the title of the study is

"Photo period reverses the effects of estrogens

on male aggression, via genomic and non-genomic pathways."

This was a paper published in the proceedings

of the National Academy of Sciences.

We'll put a reference to this in the show notes,

if you'd like to explore it further,

but it really points to the fact that rarely, sometimes,

but rarely, is it the case that just one gene

will cause somebody to be hyper aggressive.

Almost always there's going to be an interplay

between genetics and environment and as environment changes

such as day length changes and the length of night changes,

so too, will the tendency for people

with a given genetic variant to be more aggressive or not.

Now, of course, in the absence of detailed genetic testing

for this particular estrogen receptor variant,

most people, I'm guessing you, are probably

not walking around knowing that you have this gene or not.

Regardless, I think it's important to pay attention

to how you feel at different times of year,

depending on whether or not summer,

whether or not it's winter,

whether or not you're getting sufficient sunlight,

meaning viewing sufficient sunlight or not,

whether or not you're getting sufficient sunlight exposure

to your skin or not, whether or not

you're indoors all the time.

Generally those things correlate with season,

but not always.

You can go through long bouts of hard work

in the summer months when days are long,

but you're indoors a lot and getting a lot of fluorescent

light exposure late in the evening.

And perhaps that's when you're feeling more aggressive.

So we have to be careful about drawing a one-to-one

relationship between any biological feature

and certainly psychological or behavioral feature

like aggressiveness, but it's, I believe, helpful

to know that these genetic biases exist,

how they play out again, they shift our biology

in a general thematic direction.

They don't change one thing.

They change a variety of things that bias us toward or away

from certain psychological and behavioral outcomes

and the various things that we can do

in order to offset them.

And we described those earlier in terms of trying

to keep cortisol low by getting sufficient sunlight

regardless of time of year, and regardless of whether or not

you happen to have this particular genetic variant.

So earlier I talked about how it is testosterone

converted into estrogen that's activating aggression

in the ventromedial hypothalamus, not testosterone itself.

However, there are some studies carried out in humans

that have evaluated the effects of testosterone

and how levels of testosterone correlate with aggressiveness

in the short term.

I'm just going to detail a few of those studies

because I think they are interesting and important.

First of all, there is a study that has explored

levels of testosterone in men of different professions.

Now, before I tell you the data,

I want to be very clear here, with a study such as this,

one never knows whether or not these men

went into a particular profession because

they had a testosterone level of a given value

or whether or not the work itself

altered their testosterone levels or both.

And I think it's fair to assume that it's probably both.

So be very careful in assuming that a given testosterone

level is causal for choosing a particular career

or that a particular career is causal

for creating a particular testosterone level.

This study used salivary testosterone levels

as the measure, which to be fair is not the best way

to measure testosterone.

Typically blood draw would be the best way

to measure testosterone, but nonetheless, provided

the appropriate methods are used, salivary testosterone

can be a reasonable measure of testosterone.

The different occupations that were looked at were,

and here they just looked at men in this particular study

were ministers, salesmen, they didn't say

what particular types of salesmen, firemen,

professors, of all things, physicians and NFL players.

And what they discovered was that the testosterone levels

were essentially in that order from low to highest.

So minister, salesman, fireman,

professor, physician, NFL player.

Now we could micro dissect all the different stereotypes

and all the different features of each of these jobs.

For instance, we don't know whether or not the fact

that the firemen happened, at least in this study

to have lower testosterone levels on average

than the professors or the physicians

was because firemen have lower testosterone levels

or because they have a much more stressful job

and their cortisol levels are higher than the professor

or the physician and cortisol and testosterone, not always,

but generally are in somewhat antagonistic push-pull mode

because they derive from the same precursor, et cetera.

Typically, when cortisol is high,

testosterone tends to be lower and vice versa.

So we don't know what's causing these effects.

And again, this is just one study and just six occupations,

but I think it's relatively interesting given the fact

that each of these professions involves different levels

of competitiveness, right?

So we don't necessarily just want to think about

the level of physical exertion that's required,

but also the level of competitiveness because it's known

that competitive interactions can cause increases

in testosterone, in particular, in the winners

of competitive interactions, a topic for a future podcast.

Meanwhile, studies that have analyzed also again,

salivary testosterone in prisoners, in this case,

female prisoners, so these are incarcerated individuals,

have looked at levels of testosterone

according to whether or not the person committed

a non-violent or a violent crime in order

to arrive in prison.

And higher levels of salivary testosterone were related

to those that had arrived in prison

because of conviction of a violent crime,

as opposed to a nonviolent crime.

Likewise, when they analyzed prison rule violations,

so an indirect measure of aggressiveness, but in this case,

it was strongly associated with aggressiveness

because they knew what the violations were,

they found were for prisoners that had none,

no prison violations, prison rule violations I should say,

their testosterone levels tended to be lower

than the testosterone levels of women that had some,

even one, or more aggressive violations of prison rules.

We'll provide links to these studies in the show notes

if you'd like to go into them further,

obviously studies like this need to be taken

with a grain of salt because there are so many

different factors, different prisons have different degrees

of violence to begin with and competitiveness to begin with.

But just as a final pass at examining the role

between testosterone and aggressiveness,

there was a very interesting study from Goetz, et al,

G-O-E-T-Z published in 2014, that looked at serum,

so in this case, blood levels of testosterone.

30 minutes after application of a gel-based testosterone

that goes transdermal so that the testosterone

can go very quickly into the bloodstream,

and then did brain imaging to evaluate the activity

of neurons in the so-called corticomedial amygdala,

the cortico, the medial amygdala is one of the areas

of the amygdala complex as we call it because it's complex,

it's got a lot of different nuclei,

you know, know what nuclei are, low clusters of neurons.

It's got a lot of different ones, but that medial

and that cortico medial amygdala in particular,

is known to be associated with aggressive type behaviors.

It's linked up with as part of the larger circuit that

includes the ventromedial hypothalamus and other brain areas

that we referred to earlier, such as the PAG.

What is remarkable about this study is that it showed that

just 30 minutes after application of this so-called

AndroGel, this testosterone that seeps

into the bloodstream, there was a significant

increase in of course, testosterone

and corticomedial amygdala activation.

So testosterone can have acute effects,

immediate effects on the pathways related to aggression.

And I think this is something that's not often discussed

because many of the effects of steroid hormones

like testosterone, and estrogen are very slow acting.

In fact, steroid hormones, because they have a certain

biochemical composition can actually pass

through the membranes of cells, so the outside of a cell

and into the nucleus of the cell

and change gene expression in the cell,

you think about puberty, the kid that goes home

for the summer and then comes back

looking completely different.

Well that's because of a lot of genes got turned on

by steroid hormones like testosterone and estrogen,

but the steroid hormones can also

have very fast acting effects and with testosterone

in particular, those can be remarkably fast acting

and one of the most apparent and well documented fast acting

effects is this effect: the ability to activate cells within

the amygdala, so you might say,

"Well, I thought the amygdala was associated with fear?"

Wouldn't testosterone then cause fear? No.

Turns out that the amygdala harbors, both cortisol,

corticosteroid receptors and testosterone receptors,

and they each adjust the activity

in the amygdala differently,

such that testosterone tends to activate amygdala circuitry

for inducing states of mind and body

that are more action based and indeed in animals

and in humans, testosterone application and activation

of this corticomedial amygdala pathway

will make animals and humans lean into effort.

This is why I say testosterone makes effort feel good,

or at least biases the organism

toward leaning into challenge.

So if you recall, there's not just one type of aggression,

there's reactive aggression,

which is triggered when one is confronted with something

that sometimes is inevitable, right?

One needs to fight for their life

or for somebody else's life, but also proactive aggression

and proactive aggression involves activation

of those go-pathways in the basal ganglia

and a leaning into effort to overcome

whatever state one happens to be in to begin with.

And so this is very important because it points to the fact

that yes, estrogen is activating aggression pathways

that are in the ventromedial hypothalamus,

but it's very likely the case that testosterone is acting

to accelerate or to bias states of mind and body

toward those that will lead to aggression.

Again, aggression is not like a switch, on and off.

It's a process.

It has a beginning, a middle and an end.

Remember that hydraulic pressure

that Conrad Lorenz hypothesized?

Well, think of testosterone as increasing the pressure

toward an aggressive episode and then estrogen

actually triggering that aggressive episode

in the ventromedial hypothalamus.

So if somebody tells you that testosterone,

endogenous or exogenous makes people aggressive,

tell them no, testosterone tends to make

people lean into effort.

And if that effort involves being aggressive,

either reactively aggressive or proactively aggressive,

well then it will indeed lead to aggression.

But the actual aggression itself is triggered by estrogen,

not testosterone.

Now, thus far, we really haven't talked too much

about the social context in which aggression occurs.

And that's because there is a near infinite,

if not infinite number of variables

that will determine that.

So for instance, violent aggression is entirely appropriate

at a professional boxing match provided

it's occurring inside the ring and only

between the competitors and within the bounds

of the rules of the sport, et cetera.

However, there are some things that tend to bias

certain social context toward being more aggressive

or less aggressive and not always physical aggression.

And those generally come in two forms

that many of you are familiar with,

which are alcohol and caffeine.

Let's discuss caffeine first.

Why would caffeine increase aggressive impulsivity?

Well, the general effects of caffeine

are to increase autonomic arousal.

The activity of the so-called sympathetic arm

of the autonomic nervous system,

which is to put it very much in plain language

it's the alertness arm of your nervous system.

That is, it creates a sense of readiness

in your brain and body and it does so by activating

the so-called sympathetic chain ganglia.

Again, as I always remind people,

simpa and sympathetic does not mean sympathy.

Simpa means together, we're all at ones.

And caffeine tends to bias our brain and body

to activate the sympathetic chain ganglia,

which run from about the base of your neck

until the top of your pelvis and deploy a bunch of chemicals

that jut out into the rest of your body,

activate adrenaline release.

There's a parallel increase in of adrenaline in your brain,

creating the state of alertness and readiness.

That state of alertness and readiness can be

for all sorts of things, not just aggression.

However when we are in a state of increased

sympathetic tone, meaning more alert,

such as after drinking caffeine,

we will bias all those brain and body systems, the hormones,

the chemicals, et cetera that exist,

toward action as opposed to inaction.

So put simply, caffeine can increase impulsivity,

no surprise there.

On the opposite end of things, alcohol tends to decrease

activity in the sympathetic arm of the autonomic

nervous system, tends to make us feel less alert.

Now, initially it can create a state of alertness

because of its effects in inhibiting the forebrain,

our forebrain prefrontal cortex in particular

has what's called top-down inhibition.

It exerts a inhibitory or a quieting effect

on some of the circuits of the hypothalamus,

such as the ventromedial hypothalamus.

The way to conceptualize this is that your forebrain

is able to rationalize and think clearly

and to suppress behavior and to engage the no-go pathways

telling you, "Don't say that mean thing."

"Don't do that violent thing," et cetera.

Alcohol initially tends to increase our level

of overall activity by reducing inhibition,

not just in that forebrain circuit, but in other circuits.

Tends to make us more active.

We tend to talk more than we normally would,

move more than we normally would,

but very shortly thereafter starts acting as a sedative

by way of reducing activity in the forebrain,

releasing some of the deeper brain circuits

that are involved in impulsivity,

but also causing a somewhat sedative effect.

And then of course, as alcohol levels increase even further,

people eventually will pass out, blackout, et cetera.

So what we've got with alcohol and caffeine

is we've got two opposite ends of the spectrum,

caffeine increasing arousal and readiness,

and the tendency for impulsivity and alcohol also increasing

impulsivity, but through a different mechanism.

A really interesting study, and I should just mention

that the title of the study is,

"Caffeinated and non-caffeinated alcohol use

and indirect aggression at the impact of self-regulation."

So the title is almost self-explanatory.

This was a paper published in the Journal of Addictive

Behavior in 2016, examining how ingestion of alcohol

that's either caffeinated or non-decaffeinated

alcohol drinks impacted what they call indirect aggression.

And just to remind you what indirect aggression is,

these are not physical acts of aggression.

These are verbal acts of aggression,

so embarrassing others or otherwise,

somehow trying to reduce the wellbeing of others

by saying certain things in particular in groups,

this study examined both males and females.

This was done on by way of a college campus study,

subjects were 18 to 47 years old.

I guess there's some older students on that campus,

or maybe they use some non-students, but you know,

these days you've also got some students

that are in their thirties and forties.

So they have a fairly broad swath of subjects included,

fairly broad racial background as well, included,

not at equal numbers, but at least they included

a pretty broad spectrum of people

with different backgrounds.

They looked in particular people that ingested

non-caffeinated alcohol drinks at a frequency

of 9.18 drinks per week, okay.

Again, there's a college campus, not that I encourage that.

I'm one of these people that I don't,

I've never really liked drugs or alcohol

and sort fortunate in that way I can drink or not drink

and tend to not drink.

But so to me, 9.18, drinks per week sounds like a lot,

but I know for some people that might actually be typical.

And then others who are drinking at least

one caffeinated alcoholic beverage per week.

And those individuals end as high,

I should say as 7.87 caffeinated alcohol beverages per week.

So this would be energy drinks combined,

typically with hard alcohol,

that's fairly commonly available in bars and so forth.

And some individuals drank as much as goodness,

20.36 alcoholic drinks per week, total,

some that were caffeinated, some that were not caffeinated.

The basic outcome of this study was that

the more alcohol someone tended to consume,

the more likely it was that they would engage

in these indirect aggressive type behaviors.

And in terms of the caffeinated alcoholic beverages,

there, the effect was especially interesting.

Here I'm just going to paraphrase or I'll actually

read from the study, quote, "With regard to caffeinated

alcoholic beverage use, our findings indicated

that heavier caffeinated alcohol beverage use

was associated positively with indirect aggression,

even after considering one's typical alcohol use

and dispositional aggression."

What this means is that even though alcohol

can bias certain individuals to be more aggressive,

and even though certain individuals already have

a disposition toward being more aggressive,

there was an effect that was independent,

meaning above and beyond both alcohol and a predisposition,

meaning if someone was consuming

caffeinated alcoholic beverages, they had

a particularly high likelihood of engaging

in indirect aggressive behavior.

Now this makes perfect sense in light of the model

they propose, which is this self-regulation model,

that basically self-regulation involves several things.

It involves engaging in certain behaviors

and suppressing other behaviors.

So as described before, because alcohol tends to have

a sedative suppressive effect on the autonomic

nervous system, at least after the initial period,

it's going to tend to reduce the likelihood

that people will engage in any type of behavior.

Whereas caffeine will increase autonomic arousal

and increase the likelihood that someone will engage

in a particular type of behavior, aggressive or otherwise.

So the combination of caffeine and alcohol is really acting

as a two prong system to bias people towards

more impulsivity that is less self-regulation.

So it's really yanking your volitional control,

your ability to engage in prefrontal top down inhibition

over your hypothalamus from two distinct

and specific circuits.

By now, you should be getting the impression

that self-regulation is a key feature

of whether or not somebody, maybe even you,

is going to engage in aggressive speech

or aggressive behavior.

And we've talked about a number of tools that one can use

to reduce the probability that that will happen.

I suppose, if the context were appropriate,

you could even take those tool recommendations

and just invert them and increase the likelihood

that aggressiveness would happen.

But regardless, self-regulation is key.

And in light of that, I want to share with you a study

that's focused on kids, but that has important ramifications

for adults as well.

As you probably are already aware there are many kids

out there that suffer from so-called

attention deficit hyperactivity, disorder, ADHD.

There are also many adults we are finding

that are suffering from ADHD.

And there's also an epidemic I would say of people

that are concerned about whether or not they have ADHD.

Now whether or not they have true,

clinical ADHD or not, is not clear.

We did an episode all about ADHD and tools for ADHD.

I would encourage you to check out that episode

and some of the diagnostic criteria.

If you have the opportunity you can find at hubermanlab.com,

as this study I'm about to share with you aptly points out,

there is no objective diagnostic marker of ADHD.

There's no biomarker or blood draw or blood test for ADHD,

whether or not one has ADHD depends on their performance

on a number of different cognitive tests

and behavioral tests and self report.

In any event, the study I'm about to share with you

explored how a particular pattern of supplementation

in kids with ADHD was able to reduce aggressive episodes

and impulsivity and increased self-regulation.

And the title of the study is,

"Efficacy of carnitine in the treatment of children

with attention deficit, hyperactivity disorder."

Even though they put carnitine in the title,

that what they focused on was whether or not

acetyl-L-carnitine supplementation could somehow

adjust the behavioral tendency of these kids with ADHD

and to make a long story short, indeed it did.

There was a very significant effect of acetyl L-carnitine

supplementation on improving some of the symptomology,

excuse me, of ADHD.

A few details about this study

that might be relevant to you.

This was a randomized double blind placebo controlled double

crossover study, this was done as an outpatient study.

So the kids weren't in a hospital,

they were living out in the world.

This again was done on younger kids.

So this was six to six to 13 year old kids

that were diagnosed with ADHD.

They received either acetyl L-carnitine or placebo,

and they did all the good practice stuff

that good researchers do of making sure

that the placebo and the acetyl L-carnitine

had similar look and taste.

It was consumed twice daily after meals.

I should just mentioned that acetyl L-carnitine

typically is taken in capsule form or occasionally

an injectable form.

Here, they they were using this as a drink,

which essentially the same as capsule form,

but the powders just going directly into liquid

and the carnitine dosage was 100 milligrams per kilogram.

So they're doing this according to the body weight

of these kids with a maximum dosage of four grams per day,

the quantity of the medication was supplied here.

I'm reading for a period of eight weeks and every eight

weeks a new quantity of medication was supplied.

So basically this is a fairly long term study,

exploring behavioral outcomes and psychological outcomes

in week eight, 16 and 24.

They also looked at blood things that you could only get

through a blood draw, so things like hemoglobin, hematocrit,

red blood cell count, white blood cell count, et cetera,

they, these are kids and even if it were adults,

they were quite appropriately examining

a lot of the physiological measures

that one would want to carry out to make sure,

first of all, that blood levels of carnitine are increasing.

And indeed they confirmed that, but also that

no negative effects are showing up in the physiology

as well as the psychology of these kids.

So, first I'll just tell you the basic outcome of the study,

which was, here I'm paraphrasing,

"Here, given twice daily, carnitine appeared

to be effective and well tolerated

treatment for a group of children with ADHD."

"They showed significant, the abnormal behavior

compared to these other boys."

And now I'm moving to the table of results.

They showed significant reductions

in their so-called "Total Problem Score."

The total problem score is a well-established measure

of behavioral problems in kids with ADHD.

And I should say adults with ADHD,

has to do with challenges in social and learning

environments and how well or poorly

an individual tends to perform.

Reductions in intentional problems, overall reductions

in delinquency, and most important

for sake of today's discussion,

significant reductions in aggressive behavior.

Now what's especially nice about this study, I think,

is that even though it's a relatively small number

of subjects and certainly needs to be repeated

in other studies and other laboratories,

that they were able to confirm the shifts in L-carnitine

within the bloodstream of these kids,

that is they were able to correlate the physiology

with the psychological changes, in studies like this.

And frankly in all studies of human pharmacology,

you have to worry about effects that show up,

not just because of placebo effects,

but because of so-called off target effects

or related things, totally independent of the drug

or the particular supplement that you happen

to be looking at,

to put in the words of a great neuroscientist.

Unfortunately, he passed away some years ago,

but he was a member of the national academy,

extremely accomplished neuroscientist once turned to me

and said, "Never forget a drug is a substance

that when injected into an animal or a human being

creates a paper," meaning you can see effects of pretty much

any drug or any supplement in most all conditions.

However, it is in cases such as this study,

where you can quite convincingly see that the particular

feature of physiology that you expected to change,

actually changed.

And you see a psychological outcome

that you can gain much greater confidence that the changes

in delinquency, in this case reduced delinquency,

improved attention, reduced aggressiveness and so forth

was at least somehow related to the shift

in blood physiology and levels of L-carnitine

or acetyl L-carnitine and carnitine in the bloodstream

of these children, as opposed to something else

like L-carnitine going and affecting some downstream target

that you have no knowledge of.

Now, of course that's still entirely possible,

but I think studies such as these increase our confidence

that things like L-carnitine can be used

perhaps in concert with things like omega 3 supplementation,

diets that are biased towards increasing more tryptophan

and therefore more serotonin,

obviously avoiding things like alcohol

and as it appears from the study I just described,

reducing one's intake or not consuming

any caffeinated alcoholic beverages seems like

it would be a good idea if your goal is

to reduce aggressiveness, to think about the hormone context

and whether or not you tend to have higher testosterone,

an estrogen or lower testosterone, an estrogen,

maybe even think about the work environment,

whether or not you are existing in a particularly

competitive work environment and even day life,

time of year and whether or not

you're getting sufficient sunlight, whether or not

you're avoiding light in the evening and so on.

So studies such as this I think are useful

because they point to the fact that very seldom, if ever,

will there be one supplement or one nutritional change

or even one behavioral change,

that's going to completely shift in individual

from being aggressive and impulsive,

but rather that by combining different behavioral regimens,

by paying attention to things like time of year

and work conditions and school conditions

and overall levels of stress and likely therefore

levels of cortisol, et cetera,

that you can use behaviors, diet, and supplementation

as a way to shift that overall internal milieu from one

of providing a lot of internal hydraulic pressure

as it's been called throughout the episode

toward aggressive impulsivity and relax

some of that hydraulic pressure

and reduce aggressive tendencies.

So once again, and frankly, as always,

we've done a deep dive into the neurobiology

and the psychology of what I believe to be

an important feature of our lives, in this case aggression.

I want to point out that in a episode

in the not too distant future, I'm going to be hosting

Dr. Professor David Anderson from Caltech University,

who is the world expert on the neurobiology of aggression.

In fact, he is the senior author on many of the studies

related to the ventromedial hypothalamus

that I discussed today.

Our discussion will touch on aggression, of course.

So hearing today's episode will help you

digest that information, but we are also going to talk

about other emotional states.

He is an expert, not just in aggression,

but in motivated states related to sex and mating behavior,

social relationships of all kinds and how those relate,

not just to biology and psychology,

but also certain forms of pathology,

things like PTSD and the relationship for instance,

between anger, fear, anxiety, and depression,

and many other important topics that I know many of you,

if not all of you will be interested in.

In the meantime, I want to point you

to his recently released and wonderful book entitled,

"The Nature of the Beast, How Emotions Guide Us."

And again, the author is David Anderson from Caltech.

This is a wonderful book.

It serves as a tremendous introduction

to the history of the study of these areas,

the current science and discoveries being made

in these areas, all made accessible to the scientist

and non-scientist alike.

It's a very engaging read and so much so

that even though he was gracious in sending me a copy,

I also purchased myself a copy to give to somebody

who is a therapist, and I've purchased another copy

to give to a high school kid that I mentor

because he's very interested

in the neuroscience of emotions.

And I think we are all interested in emotions,

not just fear and some of these negative states,

not just aggression, but also the positive emotions

of our lives.

And so, "The Nature of the Beast, How Emotions Guide Us,"

by David Anderson is a wonderful read.

I can't recommend it highly enough.

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[inspirational music]