Understanding & Controlling Aggression | Huberman Lab Podcast #71

00:00:00.320 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.040 | and I'm a professor of neurobiology and ophthalmology

00:00:12.960 | at Stanford School of Medicine.

00:00:14.960 | Today, we are discussing aggression.

00:00:17.440 | I'm going to explain to you

00:00:18.520 | that there are several different types of aggression.

00:00:20.780 | For instance, reactive aggression

00:00:22.360 | versus proactive aggression,

00:00:23.720 | meaning sometimes people will be aggressive

00:00:26.440 | because they feel threatened or they are protecting those

00:00:29.840 | that they love who also feel threatened.

00:00:32.440 | There's also proactive aggression

00:00:33.960 | where people go out of their way

00:00:35.520 | to deliberately try and harm others.

00:00:37.920 | And there is indirect aggression,

00:00:40.240 | which is aggression not involving physical violence,

00:00:43.320 | for instance, shaming people and things of that sort.

00:00:46.760 | It turns out that there are different biological mechanisms

00:00:49.240 | underlying each of the different types of aggression.

00:00:51.860 | And today I will define those for you.

00:00:53.980 | I'll talk about the neural circuits in the brain and body

00:00:55.880 | that mediate each of the different kinds of aggression,

00:00:58.680 | talk about some of the hormones and peptides

00:01:00.760 | and neurotransmitters involved.

00:01:02.480 | I promise to make it all accessible to you,

00:01:04.540 | even if you do not have any biology or science background.

00:01:07.960 | I will also discuss tools,

00:01:09.920 | psychological tools and biological tools

00:01:12.920 | that one can use to better control aggression.

00:01:16.360 | Now, right here at the outset,

00:01:17.440 | I want to acknowledge that any discussion about aggression

00:01:20.640 | has to have an element of context within it.

00:01:23.600 | To be fair, human beings invest a lot of money,

00:01:28.120 | a lot of time and a lot of energy,

00:01:30.400 | and indeed can even derive pleasure from aggression.

00:01:33.880 | Later, I'll talk about neural circuits in the brain and body

00:01:36.860 | that reinforce, in other words,

00:01:38.440 | reward through the release of chemicals

00:01:41.760 | that make people feel good, acts of aggression.

00:01:45.000 | However, what I'm mainly referring to

00:01:47.080 | is the context in which human beings will pay money

00:01:50.740 | in order to derive what we call vicarious aggression.

00:01:55.040 | Put it simply, people spend an enormous amount of money

00:01:58.400 | and time and energy watching other people engage in,

00:02:01.240 | for instance, aggressive sports.

00:02:02.880 | And we know that observing your team winning

00:02:05.440 | over another team causes the release of neurochemicals

00:02:08.440 | in your brain and body that make you feel good,

00:02:10.200 | and yes, that can make you feel more aggressive.

00:02:13.940 | We also know, of course,

00:02:16.000 | that most governments invest many billions,

00:02:19.080 | if not trillions of dollars in infrastructure technologies

00:02:22.600 | and human beings in order to engage in aggression if needed,

00:02:26.320 | so-called military warfare, et cetera.

00:02:29.180 | So today's discussion will include a description of aggression

00:02:32.600 | in the pathological sense.

00:02:34.300 | We'll actually talk about an explosive aggressive disorder

00:02:38.220 | that most of you probably haven't heard of,

00:02:39.820 | but is actually far more common than perhaps you know.

00:02:43.280 | We'll talk about the role of things

00:02:45.000 | like attention deficit hyperactivity disorder

00:02:47.200 | and how that can relate to aggression

00:02:49.520 | through the relationship between impulsivity

00:02:52.000 | and aggression.

00:02:52.840 | And we'll talk about verbal aggression, physical aggression,

00:02:55.760 | proactive aggression as mentioned before,

00:02:57.960 | and reactive aggression.

00:02:59.500 | I'm certain that by the end of the episode,

00:03:00.960 | you will come away with a much more thorough understanding

00:03:03.760 | of what this thing that we call aggression really is.

00:03:06.720 | And when you see it in other people,

00:03:08.900 | I think it will make more sense to you.

00:03:10.760 | And when you observe it in yourself

00:03:13.080 | or the impulse to engage in aggression,

00:03:15.280 | verbal or physical or otherwise,

00:03:17.640 | I hope that you'll understand it better as well.

00:03:19.660 | And of course, the tools that I will describe

00:03:22.060 | should allow you to modulate and control

00:03:25.200 | aggressive tendencies or predispositions to aggressiveness,

00:03:28.220 | and just generally to be able to engage with people

00:03:31.920 | in a more adaptive way overall.

00:03:34.060 | Before we begin, I'd like to emphasize that this podcast

00:03:36.700 | is separate from my teaching and research roles at Stanford.

00:03:39.580 | It is however, part of my desire and effort

00:03:42.000 | to bring zero cost to consumer information

00:03:43.960 | about science and science-related tools

00:03:45.880 | to the general public.

00:03:47.440 | In keeping with that theme,

00:03:48.480 | I'd like to thank the sponsors of today's podcast.

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00:08:30.040 | Let's talk about aggression.

00:08:31.780 | I think that many people out there are put off by aggression,

00:08:35.860 | although others are drawn to aggression,

00:08:37.980 | both in themselves and when observing it in others.

00:08:42.260 | The reason to talk about aggression is that,

00:08:44.440 | as mentioned before,

00:08:46.020 | the context of aggression really matters.

00:08:48.140 | So there are instances where aggression is adaptive.

00:08:51.740 | For instance, a mother protecting her children,

00:08:55.300 | if she's being attacked

00:08:56.400 | or if her children are being threatened,

00:08:57.580 | I think most people would agree

00:08:59.280 | that so-called maternal aggression of that sort,

00:09:02.180 | provided the context is right, is a great thing.

00:09:05.620 | Protecting our young is, after all,

00:09:07.780 | one of the primary adaptive drives of our species,

00:09:10.500 | and thank goodness it is.

00:09:12.240 | Of course, other forms of aggression

00:09:13.860 | like unprovoked proactive aggression,

00:09:16.880 | somebody simply being violent to somebody else,

00:09:19.900 | even when unprovoked.

00:09:21.220 | Most of us cringe when we see that kind of behavior.

00:09:23.700 | It can even evoke aggression in people

00:09:26.100 | when they observe that kind of behavior.

00:09:28.700 | So again, context really matters,

00:09:31.140 | but a more general and perhaps an even more important reason

00:09:34.900 | to think about and understand aggression

00:09:37.760 | is that by understanding the biology

00:09:39.580 | and psychology of aggression,

00:09:41.520 | you will be in a much better position

00:09:43.820 | to understand how all emotional states come to be,

00:09:46.820 | both in yourself and in others.

00:09:49.100 | For instance, many of you have probably heard the statement

00:09:52.800 | that I believe arises from pop psychology,

00:09:55.420 | not from formal academic psychology,

00:09:57.820 | that aggression is just sadness.

00:10:01.220 | It's a form of sadness that's amplified

00:10:03.220 | and it shows up as aggression.

00:10:05.020 | But when we look at the underlying biology

00:10:07.460 | and the peer-reviewed literature on this,

00:10:09.780 | nothing could be further from the truth.

00:10:11.600 | We have distinct circuits in the brain

00:10:13.920 | for aggression versus grief and mourning.

00:10:17.880 | Those are non-overlapping.

00:10:19.280 | Now, that doesn't mean that you can't be sad and aggressive

00:10:21.940 | or in a state of mourning and aggressive at the same time,

00:10:24.980 | but the idea that sadness and aggression

00:10:26.740 | are one and the same thing is simply not true.

00:10:30.460 | And by understanding that or perhaps by understanding

00:10:33.760 | that irritability and aggression are not the same thing,

00:10:37.060 | you'll be in a much better position to apply

00:10:39.080 | some of the tools that we will talk about in this episode

00:10:41.260 | in order to be able to reduce or eliminate,

00:10:44.940 | or if it's adaptive to you, to modulate aggression.

00:10:47.860 | And yes, there are cases where modulating your aggression,

00:10:50.680 | in some cases, even amplifying aggression can be adaptive.

00:10:54.460 | Now, this of course is not the first discussion

00:10:56.700 | about the biology of aggression

00:10:58.840 | or the psychology of aggression.

00:11:00.340 | And we really can look to the beginning of the last century

00:11:03.380 | as the time in which the formal study

00:11:06.520 | of aggression really began.

00:11:08.700 | One of the names that's most associated

00:11:10.980 | with the formal study of aggression

00:11:12.860 | is none other than Conrad Lorenz.

00:11:15.660 | Some of you may be familiar with that name.

00:11:17.540 | Others of you may not be familiar with that name.

00:11:20.660 | Conrad Lorenz studied so-called imprinting behaviors

00:11:25.420 | and fixed action pattern behaviors.

00:11:27.940 | He's most famous, at least in scientific circles,

00:11:30.840 | for getting geese to believe that he was their parent.

00:11:34.340 | And if you were to put into Google Conrad with a K Lorenz,

00:11:37.540 | just as it sounds, Conrad Lorenz geese,

00:11:40.140 | you're going to see a lot of photos of Conrad

00:11:41.860 | walking down roads with a lot of geese following him

00:11:44.240 | or swimming in lakes with a lot of geese following him.

00:11:46.860 | He had a habit of geese adopting him

00:11:49.820 | because of the behaviors that he partook in.

00:11:51.740 | So he would swim out on a lake

00:11:53.220 | in front of a bunch of little geese,

00:11:54.300 | and then they would think that he was the parent

00:11:55.980 | and they would imprint on him.

00:11:56.900 | He even lived with these animals and they lived with him.

00:11:59.380 | Sort of a strange character from what I hear.

00:12:01.620 | But nonetheless, all this work was deserving

00:12:04.080 | of a Nobel prize because what he discovered

00:12:06.460 | were fixed action patterns, that is patterns of behavior

00:12:11.140 | that could be evoked by a single stimulus.

00:12:14.300 | This is really important.

00:12:15.940 | The idea that you can get a whole category of behaviors,

00:12:19.160 | like swimming behind a parent

00:12:22.580 | or looking to somebody for comfort and only them.

00:12:26.640 | The idea that you could get a huge category

00:12:28.640 | of different behaviors in a bunch of different contexts

00:12:31.020 | triggered by just the presence of that person is remarkable

00:12:34.580 | because what it suggested and what turns out to be true

00:12:37.180 | is that there are neural circuits,

00:12:39.420 | not just individual brain areas,

00:12:40.740 | but collections of brain areas that work together

00:12:43.060 | to engage a pattern of behaviors.

00:12:45.620 | And that's the first fundamental principle

00:12:48.580 | that we need to define today.

00:12:50.260 | That when we talk about aggression,

00:12:52.600 | we're talking about activation of neural circuits,

00:12:55.520 | not individual brain areas,

00:12:56.980 | but neural circuits that get played out in sequence,

00:12:59.900 | like keys on a piano.

00:13:01.980 | But that playing out in sequence means that aggression

00:13:05.140 | is a verb, it has a beginning, a middle and an end.

00:13:08.220 | And it's a process, it's not an event.

00:13:10.900 | And as you'll see, that turns out to be very important

00:13:13.060 | in terms of thinking about how one can halt aggression,

00:13:16.900 | prevent it from happening before it's initiated,

00:13:21.060 | or maybe even prolonging aggression if that's what's needed.

00:13:24.740 | Now, Conrad Lorenz had no real knowledge of neural circuits.

00:13:28.000 | I mean, obviously he knew there was this thing

00:13:29.860 | that we call a brain and a nervous system.

00:13:32.260 | And he knew that there were chemicals in the brain

00:13:34.960 | and hormones and things of that sort

00:13:36.720 | that were likely to play a role,

00:13:38.240 | but he really didn't take any measures

00:13:40.160 | to define what the neural circuits were.

00:13:42.860 | Frankly, he didn't need to.

00:13:43.700 | He had his Nobel prize and he did all this beautiful work.

00:13:46.020 | He's known for an abundance of work,

00:13:48.800 | but he did think about what sorts of underlying processes

00:13:53.260 | could drive something like aggression.

00:13:55.740 | And he talked about one particular feature

00:13:58.600 | that's especially important.

00:14:00.060 | And that's this notion of a pressure.

00:14:02.540 | The idea that, yes, certain hormones will bias somebody

00:14:07.540 | or an animal to be aggressive.

00:14:10.380 | Certain neurotransmitter states,

00:14:11.980 | and you'll learn what those are today,

00:14:13.400 | will bias somebody to be more or less aggressive,

00:14:16.740 | maybe even submissive and passive,

00:14:18.640 | maybe outright proactively aggressive

00:14:21.340 | towards anyone or anything in front of them.

00:14:23.900 | And yes, of course, there will be historical features

00:14:26.640 | based on their childhood, et cetera, et cetera.

00:14:29.300 | He understood that there will be a constellation of things

00:14:31.540 | that would drive people to be aggressive.

00:14:34.620 | And he described a so-called pressure,

00:14:36.260 | almost like a hydraulic pressure.

00:14:37.740 | Just think about fluid pressure in a small container

00:14:40.340 | being pushed, pushed, pushed until the can

00:14:42.260 | or the container is ready to explode.

00:14:44.620 | And how multiple features, multiple variables

00:14:48.080 | could impinge on that and create that pressure.

00:14:51.220 | It turns out that's exactly the way the system works.

00:14:53.980 | There is no single brain area

00:14:55.540 | that flips the switch for aggression.

00:14:57.820 | Although we'll soon talk about a brain structure

00:14:59.620 | that generally houses the propensity

00:15:02.940 | and the output of aggression.

00:15:04.400 | This notion of a hydraulic pressure

00:15:07.700 | that can drive us toward aggressive behavior,

00:15:10.480 | or conversely can be very low pressure

00:15:14.460 | and keep us in a state of non-reactivity,

00:15:16.640 | maybe even passivity or submissiveness

00:15:19.660 | is a very important feature

00:15:21.100 | because it really captures the essence

00:15:23.300 | of how neural circuits work

00:15:24.900 | when we're talking about primitive behaviors generally.

00:15:27.380 | And you can start to notice this in yourself and in others.

00:15:31.320 | You can start to notice

00:15:32.480 | when you are veering toward aggression

00:15:34.800 | or when someone is veering toward aggression,

00:15:36.980 | verbal or physical.

00:15:39.100 | Now that veering is the buildup of this hydraulic pressure

00:15:43.980 | that Lorenz was referring to.

00:15:45.420 | And it really does have an underlying biological basis.

00:15:49.300 | Now it was some years later

00:15:51.980 | that the first experiments came along,

00:15:54.480 | which really started to identify the brain areas

00:15:57.940 | and the biological so-called pressures

00:16:00.600 | that can induce aggressive behavior.

00:16:03.340 | And the person that really gets credit for this

00:16:05.140 | is a guy by the name of Walter Hess,

00:16:08.100 | who at that time was working on cats.

00:16:10.780 | And I know that when you say working on cats,

00:16:12.960 | a lot of people will cringe,

00:16:13.860 | a lot of people have cats as pets,

00:16:15.240 | and certainly cats can be delightful.

00:16:17.380 | Some people like them more, some people like them less.

00:16:19.500 | Most people cringe at the idea of doing experiments on cats.

00:16:23.220 | I should say that these days,

00:16:24.640 | very few laboratories work on cats.

00:16:26.480 | Most laboratories that work on animal models

00:16:28.700 | will work on flies, Drosophila fruit flies

00:16:31.220 | for their capacity to do genetics,

00:16:33.380 | on laboratory mice, sometimes rats, but usually mice.

00:16:37.220 | And occasionally you'll find a lab

00:16:39.420 | that still works on cats.

00:16:41.400 | Back in the time of Hess,

00:16:43.300 | very few laboratories worked on mice.

00:16:45.100 | Most laboratories worked on cats or rats.

00:16:48.380 | And the reason for that is nowadays

00:16:49.940 | most laboratories use mice if they use animal models

00:16:53.220 | because of the genetic tools that exist in mice

00:16:55.560 | to knock out this gene or knock in this gene, et cetera,

00:16:58.480 | which can't be done in humans or non-human primates,

00:17:01.100 | at least not very easily at this point in history.

00:17:04.660 | So when I say he was working on cats,

00:17:06.380 | I realized that probably evoked some negative emotions

00:17:08.560 | in some of you, maybe even aggression in some of you.

00:17:11.540 | What we can do, however, is look at the data

00:17:14.900 | and make use of the data in terms of our understanding.

00:17:17.980 | What Hess did was he had cats that were awake

00:17:22.880 | and he was able to lower stimulating electrode

00:17:25.120 | into their brain.

00:17:25.960 | Now, keep in mind that the brain

00:17:26.780 | does not have any pain sensors.

00:17:28.520 | So after a small hole is made in the skull,

00:17:30.860 | electrodes are lowered into the brain.

00:17:32.300 | This is what's done commonly in human neurosurgery.

00:17:35.380 | And he was able to stimulate different brain areas.

00:17:38.440 | And he was sort of poking around.

00:17:40.180 | And when I say sort of,

00:17:41.100 | he was doing this with some logical intent and purpose.

00:17:44.660 | He wasn't just poking around in there for fun.

00:17:46.160 | He was trying to identify brain regions

00:17:49.220 | that could generate entire categories of behavior,

00:17:53.760 | a la Lorenz, right?

00:17:55.300 | These fixed action pattern behaviors.

00:17:57.160 | Eventually, his electrode landed in a site

00:18:01.320 | and he provided electrical stimulation to the cat

00:18:03.980 | that caused this otherwise passive purring, relaxing cat

00:18:08.980 | to suddenly go into an absolute rage.

00:18:13.120 | So arched back, hissing, hair up,

00:18:16.300 | so-called pyloerection where the hairs go up.

00:18:19.320 | Animals try and make themselves as big as possible,

00:18:21.340 | often when they're aggressive.

00:18:22.840 | Drooling, maybe even spitting, believe it or not,

00:18:27.200 | cats and other animals can do this.

00:18:29.080 | And the cat tried to attack him and anyone else

00:18:32.040 | and anything else, even inanimate objects

00:18:36.240 | when he stimulated this particular brain area.

00:18:38.860 | So Hess obviously took notice

00:18:41.120 | of this incredible transformation in behavior.

00:18:44.120 | And the fact that when he turned off the stimulation

00:18:47.280 | of this particular brain area,

00:18:48.760 | the cat very quickly within seconds

00:18:50.980 | went back to being passive calm kitty.

00:18:54.080 | Now, of course, he repeated this experiment in other animals

00:18:57.580 | because he had to confirm that it wasn't just happenstance,

00:19:00.760 | that there wasn't something unique about this one cat

00:19:04.340 | that perhaps he had stimulated an area

00:19:07.500 | that had been built up during the kittenhood

00:19:10.400 | of this cat and had been reactivated.

00:19:13.560 | Maybe this kitten had been traumatized early in life

00:19:15.780 | or scared and reactivation of a particular circuit

00:19:18.820 | unique to that cat created this aggressive behavior.

00:19:23.020 | That wasn't the case.

00:19:23.860 | Every cat that he looked at

00:19:26.600 | and stimulated this particular brain area,

00:19:28.800 | the cat would immediately go into an aggressive,

00:19:31.280 | almost rage type behavior.

00:19:32.560 | Now, of course, we can't anthropomorphize.

00:19:34.320 | We don't know what the cat was feeling.

00:19:35.720 | For all we know, the cat could be happy,

00:19:37.080 | although that seems pretty unlikely.

00:19:39.960 | And later experiments done in mice, but also in humans,

00:19:43.820 | confirm that indeed stimulation of this brain area

00:19:47.480 | evoked not just behavioral aggression,

00:19:49.800 | but also subjective feelings of aggression and anger.

00:19:53.360 | So what was this incredible brain area?

00:19:56.520 | Or rather, I should say,

00:19:57.760 | what is the brain area that harbored

00:19:59.540 | this incredible capacity to generate aggressive behavior

00:20:04.120 | in Hess's experiments?

00:20:05.500 | Well, for those of you that are regular listeners

00:20:08.560 | to this podcast, you'll probably be relieved to know

00:20:11.600 | that today we're going to talk

00:20:12.580 | about some new neural circuits.

00:20:14.320 | Oftentimes we'll center back on the amygdala

00:20:17.560 | or the prefrontal cortex, and those names will come up.

00:20:20.040 | And for those of you that haven't heard them before,

00:20:21.840 | don't worry, I'll make it clear

00:20:23.040 | as to what those brain areas are and what they do.

00:20:26.000 | But today we're going to talk a lot

00:20:27.560 | about the so-called VMH or ventromedial hypothalamus.

00:20:32.560 | The ventromedial hypothalamus is a nucleus,

00:20:36.360 | meaning a small collection of neurons.

00:20:38.760 | What are neurons?

00:20:39.880 | Nerve cells.

00:20:41.280 | And that small collection of neurons

00:20:43.520 | that we call the ventromedial hypothalamus is truly small.

00:20:46.420 | It's only about 1,500 neurons on one side of your brain

00:20:50.940 | and a matching 1,500 neurons on the other side of your brain.

00:20:54.400 | And that combined 3,000 neurons or so,

00:20:57.680 | it's not exactly 3,000, but 3,000 neurons or so

00:21:00.720 | is sufficient to generate aggressive behavior

00:21:05.920 | of the sort that Hess observed in the cat.

00:21:10.520 | And believe it or not,

00:21:11.660 | when you see somebody who's in an act of rage

00:21:14.560 | or in an act of verbal aggression

00:21:17.080 | or in an act of defensive aggression,

00:21:19.240 | protecting their family or loved ones or country, et cetera,

00:21:22.920 | almost certainly those neurons are engaged in that behavior.

00:21:28.320 | Those neurons are perhaps even generating that behavior.

00:21:32.680 | And next I'll describe some experiments

00:21:34.360 | that were done just recently within the last 10 years or so,

00:21:37.760 | but leading right up until this year and even last month

00:21:41.060 | that keep confirming again and again and again

00:21:43.960 | that it is the activity of neurons

00:21:45.600 | in the ventromedial hypothalamus

00:21:46.960 | that are both necessary and sufficient

00:21:49.360 | to generate the full catalog of aggressive behaviors.

00:21:53.780 | Now, before I go further to describe

00:21:56.400 | the beautiful recent studies on the VMH,

00:21:59.600 | the ventromedial hypothalamus,

00:22:01.240 | and the important role of testosterone,

00:22:03.080 | and more importantly estrogen

00:22:05.480 | in the activation of aggressive behavior.

00:22:07.200 | That's right, that's soon to be clear to you

00:22:09.680 | why that's the case.

00:22:10.800 | I want to emphasize that the ventromedial hypothalamus

00:22:15.060 | is something that we should all care about, why?

00:22:17.840 | Well, it turns out that many categories

00:22:21.380 | of psychiatric disorders, developmental disorders,

00:22:24.880 | and psychological challenges, things like schizophrenia,

00:22:28.120 | PTSD, post-traumatic stress disorder, depression,

00:22:31.680 | borderline personality disorder,

00:22:33.880 | and even certain forms of autism

00:22:35.960 | can include elements of aggression and even violence.

00:22:39.000 | Now, it's certainly not the case

00:22:40.700 | that aggression and violence are present

00:22:42.980 | in all people who suffer from schizophrenia or PTSD

00:22:46.840 | or depression or autism or borderline personality disorder.

00:22:50.360 | I'm absolutely not saying that.

00:22:53.240 | However, it can be a feature of those,

00:22:56.040 | and it's a well-described feature

00:22:58.720 | in terms of trying to understand the constellation

00:23:01.680 | of challenges that people suffer from when they have those.

00:23:04.120 | So thinking about the VMH goes way beyond

00:23:06.040 | just understanding basic aggression

00:23:08.160 | in the context of adaptive aggression.

00:23:10.120 | So when earlier I used the example maternal aggression,

00:23:14.200 | that's one adaptive form of aggression.

00:23:17.640 | It also can be pathologic aggression,

00:23:20.440 | meaning it can harm ourselves or others.

00:23:22.480 | So keep this in mind as we go forward,

00:23:24.040 | because later we're going to talk about specific tools

00:23:26.600 | designed to modulate or prevent aggression in,

00:23:30.760 | for instance, people with

00:23:31.800 | attention deficit hyperactivity disorder,

00:23:33.720 | and especially kids with ADHD.

00:23:35.720 | In the meantime, let's return to the VMH,

00:23:40.080 | this relatively small collection of neurons.

00:23:42.320 | And the reason I say relatively small is,

00:23:43.840 | well, your brain has many hundreds of billions of neurons,

00:23:47.200 | maybe even trillions of neurons.

00:23:48.640 | The exact number of neurons isn't really clear,

00:23:50.640 | but it's a lot.

00:23:52.040 | And it certainly is a lot relative to the number of neurons,

00:23:56.080 | this 3000 or so neurons living in your hypothalamus

00:23:59.680 | that can evoke this aggressive response.

00:24:02.500 | Experiments done by David Anderson's lab at Caltech,

00:24:07.960 | were really the first to parse the fine circuitry

00:24:10.980 | and to really show that the ventromedial hypothalamus

00:24:13.960 | is both necessary and sufficient for aggressive behavior.

00:24:17.280 | These are important experiments

00:24:18.360 | and they're worth knowing about.

00:24:20.460 | What they did was they identified,

00:24:24.500 | first of all, where the ventromedial hypothalamus

00:24:26.220 | was in the mouse.

00:24:27.120 | That was pretty straightforward to do,

00:24:28.360 | sort of known before they started these experiments.

00:24:30.800 | And then they analyzed which genes,

00:24:34.900 | meaning which DNA, which of course,

00:24:37.840 | becomes RNA and RNA becomes protein,

00:24:40.480 | which DNA and therefore which proteins are expressed

00:24:44.200 | in particular cells of the ventromedial hypothalamus.

00:24:47.860 | And it turns out that there's a particular category

00:24:50.560 | of neurons in the ventromedial hypothalamus

00:24:54.040 | that make an estrogen receptor.

00:24:56.420 | And it is those neurons in particular

00:25:00.020 | that are responsible for generating aggressive behavior.

00:25:04.080 | How did they know this?

00:25:05.020 | Well, they used a tool that's actually been described

00:25:07.540 | by a previous guest of this podcast.

00:25:09.160 | We had an episode with the psychiatrist and bio engineer

00:25:11.720 | and my colleague at Stanford School of Medicine,

00:25:13.620 | Carl Deisseroth.

00:25:14.800 | He and others have developed tools

00:25:18.000 | that allow people to control the activity of neurons,

00:25:21.600 | essentially by remote control,

00:25:22.880 | by shining light on those neurons.

00:25:24.560 | So in the context of an experiment on a mouse,

00:25:26.840 | which is what David's lab did,

00:25:28.240 | and these were the beautiful experiments of Dai Yu Lin,

00:25:30.160 | who's now in her own laboratory at New York University,

00:25:32.920 | put a little fiber optic cable down into the brain

00:25:36.160 | of the hypo, into the hypothalamus that is of the mouse.

00:25:39.220 | The mouse is able to move around in its cage, freely moving.

00:25:43.520 | Even though it has a little tether, this little wire,

00:25:45.400 | it's a very thin wire.

00:25:46.600 | And that little thin wire is actually a little,

00:25:48.360 | what we call optrode.

00:25:49.440 | And the experimentalist, in this case, Dai Yu,

00:25:51.840 | was able to stimulate the turning on

00:25:55.640 | of a little bit of blue light.

00:25:57.700 | And that blue light activated

00:26:00.000 | only those estrogen receptor neurons

00:26:03.340 | in only the ventromedial hypothalamus.

00:26:06.280 | And the way she was able to do that

00:26:07.400 | is she had introduced a gene

00:26:09.680 | that had been developed by our friend, Carl Deisseroth,

00:26:13.120 | that allows light to trigger electrical activity

00:26:17.240 | in those neurons.

00:26:18.060 | So if any of that is confusing,

00:26:19.180 | or if all of that is confusing, here's the experiment.

00:26:21.120 | There's a mouse in a cage,

00:26:23.160 | has a little wire coming out of its head.

00:26:24.620 | It doesn't notice, believe it or not.

00:26:26.520 | We know this 'cause it's still eating and mating

00:26:28.340 | and doing all the things that mice like to do

00:26:30.760 | on a daily basis and sleeping, et cetera.

00:26:33.240 | And the mere pressing of a button

00:26:35.320 | will activate a little bit of light

00:26:37.120 | released at the end of that wire.

00:26:38.680 | That light activates particular neurons.

00:26:41.040 | In this case, it's the estrogen receptor-containing neurons

00:26:43.920 | in only the ventromedial hypothalamus.

00:26:45.840 | When that mouse is in a cage with another mouse,

00:26:50.280 | a couple of things happen,

00:26:51.280 | depending on what the other mouse is,

00:26:53.820 | or we could say who the other mouse is.

00:26:56.200 | If it's a male mouse,

00:26:58.040 | and you put it in there with a female mouse,

00:27:00.240 | the male mouse will attempt to mate with a female mouse.

00:27:03.280 | Provided that the male mouse has gone through puberty,

00:27:05.320 | he will try to mount and mate with a female mouse.

00:27:07.900 | Now, female mice are either in a receptive phase

00:27:11.220 | or a non-receptive phase of their so-called estrous cycle.

00:27:13.720 | They don't have a menstrual 28-day cycle,

00:27:15.560 | they have an estrous cycle.

00:27:17.480 | And on particular days of that estrous cycle,

00:27:20.000 | they are not happy to mate.

00:27:22.400 | They will basically keep their hindquarters

00:27:25.420 | away from the male mouse at all costs.

00:27:27.540 | They'll even attack the male mouse.

00:27:29.280 | On certain days of the estrous cycle, however,

00:27:32.600 | the female mouse will undergo what's called lordosis,

00:27:34.760 | which is an arching of her back,

00:27:36.280 | and she'll allow the male to mount and mate with her.

00:27:39.760 | So a large number of experiments were done,

00:27:42.560 | but the first experiment really was

00:27:44.440 | to put the male mouse in with a female mouse

00:27:47.320 | who's in the so-called receptive phase of estrous.

00:27:50.300 | That is, she will allow mating.

00:27:52.120 | And he starts mating with her.

00:27:54.300 | And they go through the standard repertoire

00:27:56.720 | of mating behaviors that you observe in mice,

00:27:59.420 | mounting, thrusting, intromission,

00:28:02.600 | as it's called in the mouse sex world.

00:28:05.280 | Well, I guess, I don't know what the mice call it,

00:28:06.560 | but that's what the experimenters call it.

00:28:08.360 | And then afterwards, he will dismount, okay?

00:28:11.960 | So they observe this kind of mounting and sex behavior.

00:28:15.440 | It's very typical.

00:28:16.840 | But about halfway through the behavior,

00:28:20.080 | Dayu turned on the light

00:28:22.600 | to stimulate these estrogen receptor-containing neurons

00:28:25.880 | only in the male mouse.

00:28:27.200 | And what she observed was incredibly dramatic.

00:28:30.120 | The male mouse ceases from trying to mate

00:28:32.360 | with the female mouse

00:28:33.200 | and immediately tries to kill the female mouse.

00:28:35.500 | He starts attacking her.

00:28:36.700 | Then she turns off the light, the male stops,

00:28:41.120 | and goes back to trying to mate with the female mouse.

00:28:43.200 | I'm sure all of this was very confusing

00:28:45.240 | and disturbing to the female mouse.

00:28:46.840 | Nonetheless, that was the repertoire.

00:28:49.320 | They would mate.

00:28:50.480 | She would stimulate these ventromedial hypothalamus neurons.

00:28:53.420 | The male mouse would immediately

00:28:54.840 | try and attack and kill the female mouse.

00:28:57.800 | And then she would stop the stimulation,

00:28:59.660 | and he would stop trying to attack and kill the female mouse,

00:29:02.280 | return to the attempt, at least,

00:29:04.880 | to mate with the female mouse.

00:29:06.460 | These are such dramatic shifts in behavior

00:29:10.060 | triggered only by the activation

00:29:11.880 | of only the small set of neurons

00:29:13.660 | within the ventromedial hypothalamus.

00:29:15.600 | And for those of you that think

00:29:17.260 | that you can watch this sort of thing

00:29:18.880 | without being disturbed,

00:29:20.300 | I encourage you to go to YouTube.

00:29:23.180 | We will provide a link where you can see a video

00:29:26.240 | of this type of behavior.

00:29:27.180 | It's incredibly dramatic.

00:29:28.980 | The shift in behavior is almost instantaneous,

00:29:32.300 | occurs within seconds, if not milliseconds,

00:29:35.060 | thousandths of a second.

00:29:36.320 | The next experiment that she did was to put a male mouse

00:29:41.020 | with this stimulation with light capability

00:29:44.760 | in its ventromedial hypothalamus into a cage alone,

00:29:47.740 | but with a rubber glove filled with air or water.

00:29:50.340 | Mouse was walking around sniffing, peeing,

00:29:52.740 | which is what male mice seem to do.

00:29:54.000 | They seem to urinate everywhere.

00:29:55.520 | Essentially an interesting, perhaps interesting feature

00:29:58.000 | of male mice and actually many male animals,

00:30:00.920 | perhaps even humans, we don't know, or maybe we do know.

00:30:03.820 | Basically, this has been observed time and time again

00:30:06.580 | in experiments, mainly by Lisa Stowers' lab

00:30:09.380 | at the Scripps Institute has characterized this.

00:30:11.540 | If you put female mice into an arena or a cage,

00:30:14.240 | they always urinate in a very small corner of that cage.

00:30:17.900 | Whereas if you put male mice into an arena or a cage,

00:30:21.180 | they urinate everywhere.

00:30:22.340 | They have this kind of obsession

00:30:23.540 | with spraying their urine everywhere.

00:30:25.400 | You can sort of transpose that to human behavior

00:30:28.540 | if you like.

00:30:29.380 | In any event, Dayu put the mouse in the cage alone,

00:30:34.720 | but with this rubber glove,

00:30:36.300 | the mouse is walking around, urinating, et cetera,

00:30:38.720 | doing whatever it is that mice do.

00:30:40.220 | Then she stimulates the activation

00:30:42.460 | of these ventromedial hypothalamus neurons,

00:30:44.940 | and the mouse immediately tries to kill the glove.

00:30:48.380 | It goes into a rage attacking the glove

00:30:50.420 | as if it were another mouse or some other animate object,

00:30:55.040 | but of course it's an inanimate object.

00:30:56.780 | It's just a rubber glove.

00:30:58.340 | She stops the stimulation and the mouse immediately goes back

00:31:00.780 | to being completely calm or at least not attacking.

00:31:03.820 | Again, we don't know what the mouse was feeling.

00:31:06.680 | So these are very dramatic videos.

00:31:08.460 | Again, you can see them by following the link

00:31:10.080 | that we'll provide in the caption.

00:31:11.860 | If that sort of thing is going to disturb you

00:31:14.180 | to see, for instance, the attack,

00:31:16.200 | one mouse attacking another, please just don't watch them.

00:31:18.760 | I'm not interested in traumatizing anybody.

00:31:21.580 | Are you traumatizing yourself, that is?

00:31:23.480 | A number of different variations

00:31:26.020 | were done on this experiment.

00:31:27.080 | For instance, stimulating the VMH in female mice

00:31:32.080 | as opposed to male mice,

00:31:33.740 | putting the female mice in with other female mice

00:31:36.700 | or with other male mice.

00:31:38.420 | No matter what variation one carries out,

00:31:41.980 | so it doesn't matter if it's male with female,

00:31:43.680 | male with male, female with female, et cetera,

00:31:47.380 | stimulation of the ventromedial hypothalamus

00:31:50.060 | in a male mouse or a female mouse

00:31:51.660 | evokes this very dramatic,

00:31:53.580 | almost instantaneous aggressive behavior,

00:31:56.140 | physically aggressive behavior.

00:31:57.700 | Subsequent experiments done by Dai-Yu Lin

00:32:01.100 | in her own laboratory and other laboratories

00:32:03.540 | have shown that the ventromedial hypothalamus

00:32:05.840 | is connected with a bunch of other brain areas

00:32:07.720 | that are interesting,

00:32:08.560 | and I'll talk about some of those in a little bit,

00:32:10.520 | but one of them that I want to call out now

00:32:13.940 | is the so-called PAG, the periaqueductal gray nucleus.

00:32:17.240 | This is a large structure in the back of the brain

00:32:20.220 | that houses things like neurons that can create opioids.

00:32:23.820 | We all know of the opioid crisis,

00:32:25.040 | but these are neurons that can produce endogenous means

00:32:28.920 | made by the body, chemicals that can cause pain relief.

00:32:33.720 | You could understand why that might occur

00:32:35.800 | in a circuit for aggression, right?

00:32:37.260 | Even if one is the aggressor,

00:32:39.720 | it's likely that they may incur some physical damage

00:32:42.820 | and they'd want some pain relief.

00:32:44.480 | The PAG also is connected to a number of neural circuits

00:32:49.340 | that eventually through several processing stations,

00:32:53.380 | excuse me, arrive at things like the jaws.

00:32:56.220 | And in fact, stimulation of the ventromedial hypothalamus

00:32:58.620 | can evoke biting and aggressive biting behavior.

00:33:01.820 | Now, aggressive biting behavior is particularly interesting

00:33:05.240 | because in humans, and especially in human children,

00:33:08.440 | biting is something that while young children might do

00:33:12.300 | as a form of aggression,

00:33:13.440 | tends to disappear pretty early in childhood.

00:33:17.040 | And if it doesn't, it's often seen as a mark of pathology.

00:33:21.540 | I have a story about this.

00:33:22.400 | Actually, when I was a kid, I went to a summer sports camp

00:33:27.140 | and I'll never forget this.

00:33:29.080 | We were playing soccer and in a rare stroke of luck

00:33:33.260 | or accident, I happened to score a goal.

00:33:35.080 | I wasn't a particularly good soccer player,

00:33:36.580 | especially not at that stage of my life.

00:33:37.940 | They later figured out that it was just better

00:33:39.740 | to make me a fullback 'cause I could just wait there

00:33:42.020 | and do what fullbacks do.

00:33:43.420 | I was better at taking the ball or the person out

00:33:45.720 | than I was putting the ball in the goal.

00:33:49.460 | Nonetheless, I, again, by chance, I scored a goal

00:33:53.340 | and I was trotting back to my side of the field.

00:33:55.900 | And all of a sudden I felt this sting in my back.

00:33:59.600 | A kid, not to be named, although I do remember your name,

00:34:03.260 | I'm not going to tell you what his name was,

00:34:05.180 | a kid jumped on my back and bit me on the top of my back.

00:34:09.420 | And this, of course, resulted in a discussion

00:34:12.440 | and a timeout and all the usual things.

00:34:14.800 | And parents, I think, got involved.

00:34:16.540 | I don't recall.

00:34:17.700 | I didn't think much else of it.

00:34:19.180 | But I recall that this was considered

00:34:21.420 | especially troubling behavior because he bit me

00:34:24.740 | as opposed to hit me or shoved me down

00:34:26.880 | or something of that sort.

00:34:27.920 | And it does seem as if the tendency to use biting

00:34:31.520 | as an aggressive behavior is associated

00:34:34.500 | with a more primitive circuitry.

00:34:35.920 | Now here, I'm truly anthropomorphizing.

00:34:37.800 | I don't know what this other kid happened to be thinking

00:34:39.720 | or feeling at the time.

00:34:40.900 | How could I?

00:34:41.740 | And I certainly am not going to say that biting

00:34:44.460 | in every case reflects a pathology.

00:34:48.060 | Although I think there is general agreement

00:34:50.360 | in the psychology community and the psychiatric community

00:34:52.660 | that past a certain age, the using of one's teeth

00:34:55.480 | to impart aggression and damage on others

00:34:58.500 | is a particularly primitive and troubling,

00:35:01.660 | or at least for the observer or the person

00:35:03.560 | that experiences a pretty disturbing event.

00:35:06.320 | Daew's lab has shown that activation

00:35:08.980 | of the ventromedial hypothalamus triggers

00:35:10.540 | a downstream circuit in the periaqueductal gray,

00:35:13.240 | which then triggers a whole other set of circuits

00:35:15.780 | of fixed action patterns.

00:35:17.020 | Here we are back to Lorenz again with fixed action patterns,

00:35:20.760 | including swinging of the limbs, right, punching.

00:35:24.320 | This wouldn't necessarily be controlled punching,

00:35:26.700 | but also biting behavior.

00:35:28.600 | So it's remarkable to me at least that we have circuits

00:35:31.680 | in our brain that can evoke violent use of things

00:35:35.560 | like our mouth or violent use of things like our limbs

00:35:38.640 | that of course could be used for things like singing

00:35:41.340 | or kissing or eating or gesticulating

00:35:45.600 | in any kind of polite or impolite way.

00:35:48.120 | The point here is that neural circuits,

00:35:51.440 | not individual brain areas, evoke the constellation

00:35:54.180 | of behaviors that we call aggression.

00:35:56.400 | Now, many of you are probably puzzled

00:35:57.800 | or at least should be because I've been talking

00:36:01.020 | about this highly specialized brain area,

00:36:02.800 | the ventromedial hypothalamus,

00:36:04.000 | and this highly specialized subcategory of neurons

00:36:07.960 | in the ventromedial hypothalamus,

00:36:09.240 | these neurons that make estrogen receptor.

00:36:11.900 | And yet the activation of those cells

00:36:14.840 | triggers dramatic and immediate aggression,

00:36:17.580 | both in males and in females,

00:36:19.600 | and both against males and against females.

00:36:22.280 | So what's going on here?

00:36:24.600 | Most of us think about estrogen

00:36:26.600 | and we don't immediately think of aggression.

00:36:29.500 | Most of us hear testosterone

00:36:31.240 | and we might think about aggression,

00:36:32.600 | although other things as well.

00:36:34.100 | In order to understand this,

00:36:36.020 | I just want to briefly refer back to a conversation

00:36:39.560 | that I had on a previous episode

00:36:41.040 | of the Huberman Lab Podcast.

00:36:42.240 | And that was with my colleague, the great Robert Sapolsky,

00:36:45.920 | of course, is a professor at Stanford

00:36:47.200 | who studied testosterone and its impacts on behavior,

00:36:50.360 | as well as estrogen and other hormones

00:36:51.860 | and their impacts on behavior.

00:36:54.240 | To make a long story short

00:36:56.240 | and to dispel a still unfortunately very common myth,

00:37:01.240 | testosterone does not increase aggressiveness.

00:37:05.000 | Testosterone increases proactivity

00:37:07.840 | and the willingness to lean into effort

00:37:10.440 | in competitive scenarios.

00:37:12.420 | Sometimes this is referred to as the challenge hypothesis,

00:37:15.840 | but to make a long story short,

00:37:19.660 | if people are given testosterone,

00:37:22.480 | or if you look at people who have different levels,

00:37:26.560 | excuse me, of testosterone endogenously

00:37:28.600 | that they naturally make,

00:37:30.080 | what you'll find is that testosterone

00:37:32.600 | tends to increase competitiveness,

00:37:34.840 | but not just in aggressive scenarios.

00:37:37.320 | So if somebody is already aggressive,

00:37:40.360 | giving them testosterone will have the tendency

00:37:43.740 | to make them more aggressive.

00:37:45.140 | If somebody, however, is very benevolent and altruistic,

00:37:49.420 | giving them testosterone

00:37:50.400 | will make them more benevolent and altruistic,

00:37:52.480 | at least up to a point.

00:37:53.680 | Now, of course, there are certain forms

00:37:55.240 | of synthetic testosterone that are known

00:37:58.520 | in sports circles and in other circles

00:38:03.040 | to increase aggressiveness

00:38:04.720 | because of the way those particular forms

00:38:06.340 | of synthetic testosterone work.

00:38:08.080 | But in general, most of the experiments

00:38:09.560 | that I'm referring to have not been done using those.

00:38:11.140 | They've been done using the,

00:38:13.200 | let's call them the more traditional

00:38:15.640 | biological forms of testosterone

00:38:17.280 | or that resemble the biological forms of testosterone.

00:38:19.740 | In fact, Robert Sapolsky described

00:38:21.660 | a really interesting experiment

00:38:23.040 | in which if you look at testosterone levels

00:38:26.360 | or you administer additional testosterone

00:38:28.460 | to people who are doing philanthropy,

00:38:30.640 | giving money to organizations,

00:38:33.520 | and so they're essentially doing good

00:38:34.960 | because these are organizations doing good,

00:38:37.200 | what you find is that increased testosterone

00:38:40.180 | or further increasing testosterone

00:38:42.220 | makes people more willing to compete

00:38:43.740 | to give more money than the other person in the room

00:38:45.600 | in order to put it in air quotes,

00:38:48.140 | to alpha out the other person by giving more money.

00:38:51.000 | So this is an act of altruistic or benevolent philanthropy.

00:38:54.680 | It is not an act of aggression.

00:38:56.520 | Of course, we don't know what the people

00:38:58.040 | are feeling underneath all that.

00:38:59.720 | Again, we can't anthropomorphize

00:39:01.240 | or project onto other people what they're feeling.

00:39:04.100 | But the point is that testosterone itself

00:39:06.820 | does not make people more aggressive.

00:39:08.800 | And in the experiments that we've been talking about

00:39:11.960 | up until now, it's actually the activation

00:39:14.480 | of estrogen receptor containing neurons

00:39:17.040 | that makes these animals more aggressive.

00:39:19.220 | And it turns out there's evidence that in certain contexts,

00:39:22.600 | estrogen can make people more aggressive.

00:39:24.580 | So what's going on here?

00:39:25.780 | Well, what's going on is that

00:39:29.140 | testosterone can be converted into estrogen

00:39:32.500 | through a process called aromatization.

00:39:34.680 | There's an enzyme called aromatase.

00:39:36.640 | Anytime you have a word that ends in A-S-E,

00:39:39.680 | at least if it's in the context of biology,

00:39:41.400 | it's almost always, not always, but almost always an enzyme.

00:39:45.340 | So the aromatase enzyme converts testosterone into estrogen.

00:39:49.360 | And it is actually testosterone aromatized,

00:39:54.200 | converted into estrogen,

00:39:55.980 | and then binding to these estrogen-containing neurons

00:40:00.300 | in the ventromedial hypothalamus that triggers aggression.

00:40:04.460 | I want to repeat that.

00:40:05.300 | It is not testosterone itself that triggers aggression.

00:40:08.360 | It is testosterone aromatized into estrogen

00:40:11.100 | within the brain and binding to these estrogen receptor

00:40:14.680 | containing neurons in the ventromedial hypothalamus

00:40:17.140 | that evokes aggression and dramatic aggression at that.

00:40:21.100 | Now, this effect of estrogen causing aggression in the brain

00:40:24.680 | is very robust, so much so that if you take a mouse

00:40:28.900 | that lacks the aromatase enzyme

00:40:30.740 | or a human that lacks the aromatase enzyme,

00:40:33.120 | and they do exist,

00:40:34.380 | then there is a reduction in overall aggression

00:40:39.900 | despite high levels of testosterone.

00:40:42.940 | And if people who, or mice who have the aromatase enzyme

00:40:47.940 | have that enzyme blocked,

00:40:50.380 | well, then it doesn't matter

00:40:51.640 | how much you increase testosterone

00:40:53.480 | or any of its other derivatives.

00:40:55.440 | You do not observe this aggression.

00:40:58.660 | So this runs counter to everything that we know

00:41:01.020 | and think about the role of testosterone.

00:41:03.280 | Again, testosterone increases competitiveness.

00:41:06.340 | It can increase the desire to work under challenge.

00:41:09.800 | I've said it before, and I ran this or pressure tested this

00:41:14.280 | against Robert Sapolsky, who's been working on testosterone

00:41:16.900 | and its role in the brain and behavior for many decades now.

00:41:20.580 | It is fair to say that testosterone has the net effect

00:41:25.040 | of making effort feel good,

00:41:26.680 | or at least increasing the threshold

00:41:29.660 | at which effort feels bad or unsustainable.

00:41:32.860 | And it does that by way of changing the activity

00:41:36.480 | or the threshold for activation of brain structures

00:41:38.980 | like the amygdala and other brain structures

00:41:40.760 | associated with anxiety.

00:41:42.780 | So the next time somebody says

00:41:44.480 | testosterone makes people aggressive,

00:41:46.120 | you can say, ah, no, actually it's estrogen

00:41:49.460 | that makes people aggressive

00:41:51.280 | and animals aggressive for that matter.

00:41:53.860 | Now, of course, it is the case

00:41:55.660 | that because males have relatively less estrogen

00:42:00.220 | circulating in their brain and body than females, right?

00:42:03.220 | Because they have testes, not ovaries,

00:42:06.100 | that testosterone is required in the first place

00:42:09.440 | in order to be converted into estrogen

00:42:11.320 | to activate this aggressive circuit

00:42:13.620 | involving these estrogen receptor-containing neurons

00:42:16.140 | and the ventromedial hypothalamus.

00:42:17.880 | But nonetheless, it is estrogen that is the final step.

00:42:22.880 | It is the hormone on which aggression hinges.

00:42:27.440 | And I think for most people,

00:42:28.700 | that's a quite surprising finding.

00:42:30.600 | And yet this is perhaps one of the more robust findings

00:42:33.360 | in both the animal and human literature

00:42:36.280 | as it relates to hormones

00:42:38.420 | and psychological states and behavior.

00:42:40.560 | Now, of course, it is the case that if testosterone is low,

00:42:44.600 | that a person or an animal

00:42:46.680 | will exhibit less aggressive behavior,

00:42:50.000 | but that's not because of reduced testosterone per se,

00:42:52.400 | it's because of the subsequent reduction in testosterone,

00:42:55.880 | meaning if there's no testosterone

00:42:57.400 | to aromatize into estrogen, estrogen will also be lower.

00:43:00.400 | So we've established that it's not testosterone,

00:43:03.360 | but testosterone converted into estrogen

00:43:05.920 | that activates these circuits for aggression.

00:43:08.660 | But nonetheless, it's still surprising, right?

00:43:12.080 | I mean, most of us don't think about estrogen

00:43:14.600 | as the hormone that stimulates aggression,

00:43:17.440 | but turns out it's all contextual.

00:43:19.280 | There are beautiful data

00:43:21.760 | showing that whether or not estrogen stimulates aggression

00:43:26.120 | can be powerfully modulated

00:43:28.620 | by whether or not days are short or days are long.

00:43:31.760 | In other words, whether or not

00:43:33.000 | there's a lot of sunshine or not.

00:43:35.280 | Now, obviously brain is encased in skull,

00:43:39.800 | so it doesn't really know

00:43:41.320 | if there's a lot of sunshine out there,

00:43:42.640 | even though you can see the sun with your eyes,

00:43:44.160 | you can feel it on your skin.

00:43:46.360 | Day length is converted into hormonal signals

00:43:49.880 | and chemical signals,

00:43:50.800 | and the primary hormonal and chemical signals

00:43:53.000 | involve melatonin and dopamine and also the stress hormones.

00:43:57.740 | So to make a very long story short,

00:43:59.720 | in the long days where we get a lot of sunlight,

00:44:01.880 | both in our eyes and on our skin,

00:44:04.320 | melatonin levels are reduced.

00:44:06.000 | Melatonin is a hormone

00:44:06.920 | that tends to produce states of sleepiness and quiescence.

00:44:10.580 | It also tends to activate pathways

00:44:12.120 | that tend to reduce things like breeding

00:44:14.680 | and sexual behavior.

00:44:16.560 | In long days, dopamine is increased.

00:44:19.080 | Dopamine is a molecule associated

00:44:20.600 | with feelings of wellbeing and motivation,

00:44:23.860 | and the desire to seek out all sorts of things,

00:44:27.320 | all sorts of motivated behaviors.

00:44:29.180 | And in long days,

00:44:31.020 | provided we're getting enough sunlight on our skin

00:44:33.760 | and to our eyes, the stress hormones,

00:44:36.940 | especially cortisol and some of the other stress hormones

00:44:39.740 | are reduced in levels.

00:44:40.920 | If estrogen levels are increased experimentally

00:44:45.760 | under long day conditions, it does not evoke aggression.

00:44:49.980 | However, in short days, if estrogen is increased,

00:44:53.280 | there's a heightened predisposition for aggression.

00:44:57.100 | And that makes perfect sense

00:44:59.420 | if you think about what short days do

00:45:01.380 | to the biology of your brain and body.

00:45:03.500 | In short days, the melatonin signal goes up.

00:45:06.300 | There's more melatonin circulating

00:45:07.740 | for more of each 24 hour cycle.

00:45:09.700 | Stress hormones are circulating more.

00:45:13.440 | Why?

00:45:14.280 | Short days tend to be associated with winter.

00:45:16.240 | In winter, we are bombarded with more bacteria and viruses

00:45:19.500 | because bacteria and viruses actually survive better in cold

00:45:24.500 | than they do in heat.

00:45:25.600 | In fact, in my laboratory, we work with a lot of viruses

00:45:27.760 | and bacteria, and when we want to keep them alive,

00:45:29.380 | we put them in the freezer.

00:45:30.600 | If we want to kill them, if we want to inoculate them,

00:45:32.600 | we put them under UV light,

00:45:34.120 | like you would see from the sunlight.

00:45:35.720 | So shorter days are conducive to aggression,

00:45:38.680 | not because days are short per se,

00:45:41.620 | but because stress hormone levels are higher

00:45:43.800 | and because dopamine levels are lower.

00:45:47.520 | Now here's where all of this starts to converge

00:45:48.900 | on a very clear biological picture,

00:45:51.320 | a very clear psychological picture,

00:45:53.200 | and indeed a very clear set of tools

00:45:55.800 | that we can think about and use.

00:45:57.580 | Under conditions where cortisol is high,

00:46:01.380 | where the stress hormone is elevated,

00:46:04.360 | and under conditions where the neuromodulator serotonin

00:46:07.840 | is reduced, there is a greater propensity

00:46:11.680 | for estrogen to trigger aggression.

00:46:14.020 | Now, again, I know I've said it before,

00:46:17.480 | but for males who make a lot of testosterone

00:46:20.660 | relative to estrogen, you have to swap in your mind

00:46:23.880 | this idea that if testosterone is high,

00:46:26.380 | that means that estrogen is low,

00:46:27.800 | because while that can be true in the periphery in the body,

00:46:31.360 | if testosterone is high,

00:46:33.240 | there is going to be some aromatization,

00:46:35.320 | that conversion of testosterone to estrogen.

00:46:37.240 | So anytime you hear that testosterone is high,

00:46:39.520 | you should think testosterone is high in the body

00:46:42.160 | and perhaps estrogen is low in the body,

00:46:43.740 | but that means that there's going to be heightened levels

00:46:45.640 | of estrogen in the brain,

00:46:47.400 | and therefore increased propensity for aggression.

00:46:50.520 | In females who generally make less testosterone

00:46:54.540 | relative to estrogen,

00:46:55.960 | there is sufficient estrogen already present

00:46:59.800 | to trigger aggression.

00:47:01.660 | So both males and females are primed for aggression,

00:47:06.280 | but that's riding on a context,

00:47:09.220 | and that context of whether or not you get a tendency

00:47:12.040 | for aggression or not,

00:47:13.880 | depends on whether or not cortisol is high or low,

00:47:16.320 | and I'm telling you that if cortisol is relatively higher

00:47:19.760 | in any individual, there's going to be a tilt,

00:47:22.820 | an increase in that hydraulic pressure

00:47:25.240 | that Lorenz talked about toward aggression.

00:47:28.440 | And if serotonin, the neuromodulator

00:47:33.520 | that is associated with feelings of wellbeing,

00:47:35.880 | and sometimes even of slight passivity,

00:47:38.160 | but certainly of wellbeing,

00:47:40.160 | if serotonin is low,

00:47:41.480 | there's also going to be a further shift

00:47:43.620 | towards an aggressive tendency.

00:47:46.300 | So if we return to Lorenz's hydraulic pressure model

00:47:50.060 | of aggression and other internal states,

00:47:52.860 | we realize that external stimuli,

00:47:55.620 | things that we hear, things that we see,

00:47:57.900 | for instance, someone saying something upsetting

00:47:59.860 | or us seeing somebody do something

00:48:03.020 | that we don't like to others or to us,

00:48:06.660 | as well as our internal state,

00:48:08.920 | our subjective feelings of wellbeing,

00:48:11.020 | but also our stress level,

00:48:12.400 | our feelings of whether or not we have enough resources

00:48:15.280 | and are content with what we have,

00:48:17.100 | all of that is converging on this thing

00:48:18.840 | that we call internal state and creating this pressure

00:48:21.280 | of either to be more aggressive or less aggressive.

00:48:23.660 | And now we have some major players

00:48:26.020 | feeding into that final pathway,

00:48:29.100 | that question of whether or not,

00:48:30.360 | will we hit the other person?

00:48:31.680 | Will we say the thing that is considered aggressive?

00:48:35.160 | Will we not say it?

00:48:36.640 | If somebody says something or does something aggressive

00:48:39.620 | to us, will we respond or will we be submissive

00:48:41.880 | or even passive?

00:48:43.500 | Again, there are many things funneling into that question

00:48:46.620 | and dictating whether or not the answer is,

00:48:48.160 | absolutely, I'll fight back,

00:48:49.540 | or I'm going to attack them even unprovoked,

00:48:51.900 | or if they say this, I'm going to do that,

00:48:54.020 | or no matter what they do, I'm not going to respond.

00:48:57.100 | These kinds of things are very complex

00:48:59.020 | and yet we really can boil them down

00:49:00.980 | to just a few common elements.

00:49:02.540 | And I'm telling you that those elements

00:49:04.100 | are whether or not cortisol levels

00:49:06.020 | are relatively lower or relatively higher.

00:49:09.420 | Again, relatively higher is going to tend

00:49:11.280 | to make people more reactive, why?

00:49:13.680 | Because reactivity is really a function

00:49:17.100 | of the autonomic nervous system,

00:49:18.940 | which is sort of like a seesaw that oscillates

00:49:21.060 | between the so-called sympathetic arm

00:49:24.100 | of the autonomic nervous system,

00:49:25.140 | which tends to put us into a state of readiness

00:49:27.160 | through the release of adrenaline.

00:49:28.680 | Cortisol and adrenaline,

00:49:29.940 | when they're circulating in the brain and body,

00:49:31.580 | make us more likely to move and to react and to speak.

00:49:34.740 | It's actually what will induce a kind of low level tremor,

00:49:37.300 | which is an anticipatory tremor

00:49:38.840 | to be able to move more quickly, right?

00:49:40.860 | The body in motion is more easily set into further motion,

00:49:44.020 | that is.

00:49:44.860 | And the neuromodulator serotonin is a neuromodulator

00:49:50.020 | that in general is associated with feelings of wellbeing

00:49:54.860 | in response to what we already have.

00:49:56.400 | So when we are well-fed,

00:49:58.260 | serotonin tends to be released in our brain and body,

00:50:00.500 | in particular, well-fed with carbohydrates.

00:50:02.560 | The precursor to serotonin is tryptophan.

00:50:06.360 | And indeed, there are nice studies exploring

00:50:09.240 | the types of diets, nutritional programs,

00:50:12.400 | that can reduce aggressive behavior,

00:50:15.280 | both in children and in adults.

00:50:17.140 | And tryptophan-rich diets or supplementation with tryptophan.

00:50:20.780 | So for tryptophan-rich diets, things like white turkey meat,

00:50:24.240 | but then there are also a number of carbohydrates.

00:50:25.900 | You can look up, it's very easy to find,

00:50:28.340 | foods that contain lots of tryptophan.

00:50:30.380 | Those foods contain the precursor to serotonin.

00:50:34.940 | Now, it isn't simply the case that eating more foods

00:50:37.140 | with tryptophan will tend to reduce your aggression.

00:50:39.980 | I suppose it could do that if you ate it in abundance,

00:50:42.780 | it could make you tired,

00:50:43.780 | and then you're less likely to be aggressive.

00:50:45.660 | I don't recommend that strategy.

00:50:47.700 | But the idea here is that when it's been explored,

00:50:51.700 | increasing levels of tryptophan,

00:50:53.540 | either by supplementation or by food,

00:50:55.540 | or drugs, prescription drugs that increase serotonin,

00:50:59.100 | so for instance, fluoxetine, sometimes called Prozac

00:51:01.560 | or Zoloft or any number of the other SSRIs,

00:51:03.880 | tend to reduce aggressive behavior.

00:51:05.780 | Now, not always, but in general, that's the case.

00:51:08.900 | Similarly, because elevated cortisol

00:51:11.260 | tends to shift the whole system, again,

00:51:13.380 | create more of a hydraulic pressure

00:51:15.080 | towards aggressive states.

00:51:16.560 | If cortisol levels are reduced,

00:51:18.700 | well, then the tendency for aggressive behavior is reduced.

00:51:21.820 | This is supported by a number of peer-reviewed studies.

00:51:24.060 | We'll provide links to some of those

00:51:25.380 | in the caption show notes.

00:51:26.540 | And we're going to return to these a bit later

00:51:28.900 | in the context of specific studies

00:51:30.660 | that have looked at genetic variants in different individuals

00:51:35.340 | that cause them to make more or less serotonin,

00:51:38.100 | or at least to metabolize serotonin differently.

00:51:40.620 | This is also the case

00:51:41.460 | for so-called intermittent explosive disorder

00:51:44.940 | that can often be associated with gene variants

00:51:49.060 | that control how much serotonin is made

00:51:52.380 | or how it's metabolized or how much cortisol is made

00:51:54.560 | and how much it's metabolized.

00:51:56.460 | In thinking about tools,

00:51:57.460 | there are a number of things that one could consider.

00:51:59.160 | First of all, there are a number of decent studies

00:52:03.020 | exploring how supplementation with the omega-3 fatty acids,

00:52:06.620 | which are precursors of some of the transmitter systems,

00:52:11.620 | including serotonin, that can modulate,

00:52:14.540 | not directly mediate, but modulate mood and emotional tone.

00:52:18.860 | Supplementation with the omega-3s has been shown

00:52:20.920 | to reduce impulsivity and aggressiveness in certain contexts

00:52:24.660 | in things like ADHD or in individuals

00:52:27.420 | who have a predisposition for aggressive type behavior

00:52:30.780 | or aggressive thinking.

00:52:32.380 | Now, that doesn't necessarily mean

00:52:34.220 | that the omega-3 fatty acids are going directly

00:52:37.180 | to the ventromedial hypothalamus

00:52:38.560 | and changing the activity of neurons there.

00:52:40.480 | More likely, they are causing or modulating

00:52:43.300 | an overall shift in mood through the immune system,

00:52:47.580 | through hormone systems that are changing the overall tone

00:52:51.880 | or the propensity for neurons

00:52:53.620 | in the ventromedial hypothalamus to be activated.

00:52:56.880 | How much omega-3 fatty acid, what source?

00:52:59.020 | Well, we've talked about this on the podcast before.

00:53:01.440 | You can, of course, get omega-3 fatty acids

00:53:03.300 | from a number of different foods.

00:53:04.440 | Getting them from whole foods

00:53:05.740 | is probably the best way to do it.

00:53:07.480 | But many people, including people with depression,

00:53:10.060 | will often supplement with one gram or more

00:53:12.600 | of omega-3 fatty acids per day.

00:53:14.540 | Some people, including myself, will take them every day

00:53:17.980 | as just a general mood enhancer.

00:53:20.060 | I don't suffer from depression,

00:53:21.220 | but I've found it to be beneficial for my health.

00:53:24.420 | And so some people will do that.

00:53:25.760 | And I've talked about before

00:53:26.740 | how in double-blind placebo-controlled studies,

00:53:28.860 | people taking one to three grams of omega-3 fatty acids

00:53:31.760 | per day, typically in the form of a high-quality fish oil,

00:53:34.000 | although there are other sources as well,

00:53:35.800 | algae and so forth,

00:53:36.840 | can experience improvements in mood

00:53:40.460 | that are on par with some of the SSRIs,

00:53:43.000 | the selective serotonin reuptake inhibitors.

00:53:44.920 | And of course, if you are prescribed an SSRI

00:53:46.740 | by your psychiatrist or other doctor,

00:53:48.240 | please do take that and don't cease to take it,

00:53:50.620 | just simply to take omega-3s.

00:53:52.320 | However, you might mention to them,

00:53:54.860 | and you can find links to the studies

00:53:56.400 | in our previous episodes on depression,

00:53:58.400 | that supplementation with omega-3 fatty acids

00:54:02.060 | at this one gram or more of EPA specifically,

00:54:05.080 | so getting above that one gram threshold

00:54:06.820 | as high as three grams per day of the EPA

00:54:10.920 | has allowed people to take lower doses of SSRIs

00:54:14.520 | and still keep their mood in a place

00:54:16.480 | that's beneficial for them.

00:54:18.160 | And in terms of keeping cortisol in a range

00:54:20.600 | that's healthy and doesn't bias someone

00:54:22.540 | toward high levels of aggression and irritability,

00:54:27.000 | that's again going to be set

00:54:28.780 | by a number of larger modulators or contextual cues.

00:54:32.160 | And I've talked about some of those on the podcast,

00:54:33.780 | but I'll just briefly recap them now.

00:54:35.940 | Obviously getting sunlight in your eyes early in the day

00:54:39.000 | and as much sunlight as you safely can in your eyes

00:54:42.080 | throughout the day is going to be important.

00:54:44.120 | Again, because of this effect of estrogen in long days,

00:54:48.460 | not increasing aggression.

00:54:50.560 | However, in shorter days, estrogen increases aggression

00:54:53.520 | because of the increase in cortisol

00:54:55.860 | observed in short days.

00:54:57.780 | Another way to reduce cortisol was discussed

00:55:00.680 | in our episode on heat and the use of sauna and heat,

00:55:03.780 | but also hot baths.

00:55:04.820 | It turns out that hot baths and sauna

00:55:07.400 | can be very beneficial for reducing cortisol.

00:55:09.600 | All the details on that are included

00:55:10.960 | in the episode on heat and its timestamp,

00:55:12.600 | so you can go directly to that

00:55:14.120 | if you want to learn about the temperatures

00:55:15.540 | and the various durations,

00:55:16.660 | but to just give a synopsis of that,

00:55:20.320 | a 20 minute sauna at anywhere

00:55:23.400 | from 80 to 100 degrees Celsius

00:55:25.760 | is going to be beneficial for reducing cortisol.

00:55:29.900 | If you don't have access to a sauna,

00:55:31.280 | you could do a hot bath,

00:55:33.080 | adjust the temperature so you don't burn yourself.

00:55:34.840 | I think, you know, 80 to 100 degrees Celsius

00:55:36.720 | is going to be too hot for many people if it's a hot bath,

00:55:39.140 | whereas many people who can't tolerate that hot bath

00:55:42.160 | can tolerate the sauna.

00:55:43.180 | So safety first, always, and of course,

00:55:46.000 | but hot baths reduce cortisol.

00:55:49.400 | Hot saunas reduce cortisol of a duration

00:55:52.240 | about 20 or 30 minutes is going to be beneficial.

00:55:54.420 | And of course, some of you may be interested

00:55:56.040 | in exploring the supplementation route

00:55:57.520 | and for reductions in cortisol,

00:55:59.700 | really the chief player there is ashwagandha,

00:56:03.160 | which is known to decrease cortisol fairly potently.

00:56:06.800 | I should just warn you that if you're going to use ashwagandha

00:56:09.200 | in order to reduce cortisol,

00:56:11.320 | first of all, check with your doctor or healthcare provider

00:56:13.800 | before adding or subtracting anything

00:56:15.520 | from your supplementation or health regimen.

00:56:17.360 | Of course, I don't just say that to protect us.

00:56:18.980 | I say that to protect you.

00:56:20.120 | You are responsible for your health.

00:56:22.100 | What you take and what you don't take.

00:56:24.040 | Chronic supplementation with ashwagandha

00:56:27.080 | can have some not so great effects of disruption

00:56:30.300 | of other hormone pathways and neurotransmitter pathways.

00:56:33.060 | So the limit seems to be about two weeks of regular use

00:56:36.540 | before you'd want to take a break of about two weeks.

00:56:39.300 | So ashwagandha, again, a very potent inhibitor of cortisol,

00:56:42.920 | but with some other effects as well,

00:56:45.340 | don't use it chronically for longer than two weeks.

00:56:47.400 | But if your goal is to reduce cortisol,

00:56:49.480 | let's say you're going through a period

00:56:50.580 | of increased irritability and aggressive tendency,

00:56:53.720 | maybe you're also not getting

00:56:54.680 | as much light as you would like.

00:56:56.280 | And perhaps also if there are other circumstantial things

00:57:00.040 | leading you towards more aggressiveness

00:57:01.400 | and your goal is to reduce aggressiveness,

00:57:03.340 | that can be potentially helpful.

00:57:05.160 | And in light of all this stuff about cortisol

00:57:07.920 | and estrogen and day length,

00:57:10.920 | I should mention that there are in fact,

00:57:13.200 | some people who have a genetic predisposition

00:57:16.200 | to be more irritable and aggressive.

00:57:19.880 | And there are a couple of different gene pathways

00:57:21.900 | associated with this.

00:57:23.100 | We never like to think about just one gene

00:57:25.340 | causing a specific behavior.

00:57:27.540 | The way to think about genes is that genes generally code

00:57:30.620 | for things within our biology

00:57:33.620 | in the context of today's discussion,

00:57:35.040 | things like neural circuits

00:57:36.860 | or the amounts of neurotransmitters that are made

00:57:39.260 | or the amounts of hormones that are made

00:57:40.720 | or the amount of neurotransmitter hormone receptors

00:57:43.320 | or enzymes, et cetera,

00:57:45.280 | that shift the activity of our biology

00:57:48.540 | in a particular direction.

00:57:49.440 | They bias our biology.

00:57:51.600 | And in fact, there is a genetic variant

00:57:55.320 | present in certain people

00:57:58.160 | that adjusts their estrogen receptor sensitivity.

00:58:02.200 | And that estrogen receptor sensitivity

00:58:05.120 | can result in increased levels of aggression,

00:58:08.340 | sometimes dramatic increases.

00:58:10.320 | However, and also very interestingly,

00:58:13.180 | photoperiod, meaning day length,

00:58:15.840 | is a strong modulator of whether or not

00:58:18.820 | that aggressiveness turns up or not.

00:58:20.920 | Whether or not that person with the particular gene variant

00:58:25.080 | is more aggressive or not depends on how long the day is

00:58:28.720 | and how long the night is.

00:58:30.300 | One particular study that I like that references this

00:58:33.080 | is Treynor et al.

00:58:34.300 | The title of the study is photoperiod

00:58:36.480 | reverses the effects of estrogens on male aggression

00:58:39.420 | via genomic and non-genomic pathways.

00:58:41.660 | This was a paper published in the Proceedings

00:58:43.520 | of the National Academy of Sciences.

00:58:45.340 | We'll put a reference to this in the show notes

00:58:47.520 | if you'd like to explore it further.

00:58:49.240 | But it really points to the fact that rarely,

00:58:51.860 | sometimes, but rarely is it the case

00:58:55.300 | that just one gene will cause somebody

00:58:57.860 | to be hyper-aggressive.

00:58:59.180 | Almost always, there's going to be an interplay

00:59:02.240 | between genetics and environment.

00:59:04.080 | And as environment changes, such as day length changes

00:59:07.080 | and the length of night changes,

00:59:08.520 | so too will the tendency for people

00:59:10.640 | with a given genetic variant to be more aggressive or not.

00:59:14.620 | Now, of course, in the absence of detailed genetic testing

00:59:17.340 | for this particular estrogen receptor variant,

00:59:19.460 | most people, I'm guessing you,

00:59:21.140 | are probably not walking around knowing

00:59:22.540 | that you have this gene or not.

00:59:24.900 | Regardless, I think it's important to pay attention

00:59:28.820 | to how you feel at different times of year,

00:59:31.140 | depending on whether or not it's summer,

00:59:33.040 | whether or not it's winter,

00:59:33.880 | whether or not you're getting sufficient sunlight,

00:59:36.180 | meaning viewing sufficient sunlight or not,

00:59:38.140 | whether or not you're getting sufficient sunlight exposure

00:59:40.160 | to your skin or not,

00:59:41.280 | whether or not you're indoors all the time.

00:59:42.900 | Generally, those things correlate with season,

00:59:46.300 | but not always.

00:59:47.540 | You can go through long bouts of hard work

00:59:50.240 | in the summer months when days are long,

00:59:51.900 | but you're indoors a lot

00:59:52.920 | and getting a lot of fluorescent light exposure

00:59:54.700 | late in the evening,

00:59:55.540 | and perhaps that's when you're feeling more aggressive.

00:59:57.660 | So we have to be careful about drawing

00:59:58.900 | a one-to-one relationship between any biological feature

01:00:02.460 | and certainly psychological or behavioral feature

01:00:04.900 | like aggressiveness.

01:00:06.000 | But it's, I believe, helpful to know

01:00:08.020 | that these genetic biases exist, how they play out.

01:00:11.980 | Again, they shift our biology

01:00:13.380 | in a general thematic direction.

01:00:16.660 | They don't change one thing.

01:00:17.740 | They change a variety of things that bias us toward or away

01:00:20.360 | from certain psychological and behavioral outcomes

01:00:23.100 | and the various things that we can do

01:00:25.700 | in order to offset them.

01:00:27.300 | We described those earlier in terms of trying

01:00:28.900 | to keep cortisol low by getting sufficient sunlight

01:00:31.100 | regardless of time of year

01:00:32.700 | and regardless of whether or not you happen

01:00:34.740 | to have this particular genetic variant.

01:00:36.680 | So earlier I talked about how it is testosterone converted

01:00:39.740 | into estrogen that's activating aggression

01:00:42.180 | in the ventromedial hypothalamus, not testosterone itself.

01:00:45.520 | However, there are some studies carried out in humans

01:00:48.520 | that have evaluated the effects of testosterone

01:00:51.340 | and how levels of testosterone correlate

01:00:53.660 | with aggressiveness in the short term.

01:00:56.180 | I'm just going to detail a few of those studies

01:00:57.960 | because I think they are interesting and important.

01:01:00.980 | First of all, there is a study that has explored levels

01:01:05.660 | of testosterone in men of different professions.

01:01:09.020 | Now, before I tell you the data,

01:01:10.460 | I want to be very clear here.

01:01:12.160 | With a study such as this,

01:01:14.700 | one never knows whether or not these men went

01:01:17.600 | into a particular profession

01:01:19.180 | because they had a testosterone level of a given value

01:01:23.980 | or whether or not the work itself altered

01:01:27.420 | their testosterone levels or both.

01:01:30.300 | And I think it's fair to assume that it's probably both.

01:01:34.320 | So be very careful in assuming

01:01:36.020 | that a given testosterone level is causal

01:01:39.980 | for choosing a particular career

01:01:41.380 | or that a particular career is causal

01:01:43.420 | for creating a particular testosterone level.

01:01:46.260 | This study used salivary testosterone levels

01:01:49.460 | as the measure, which to be fair,

01:01:52.100 | is not the best way to measure testosterone.

01:01:55.260 | Typically, blood draw would be the best way

01:01:57.180 | to measure testosterone, but nonetheless,

01:01:59.460 | provided the appropriate methods are used,

01:02:01.760 | salivary testosterone can be a reasonable measure

01:02:04.060 | of testosterone.

01:02:05.800 | The different occupations that were looked at

01:02:09.100 | were, and here they just looked at men

01:02:11.100 | in this particular study, were ministers,

01:02:13.820 | salesmen, they didn't say what particular types of salesmen,

01:02:16.300 | firemen, professors of all things,

01:02:19.420 | physicians and NFL players.

01:02:21.740 | And what they discovered was that the testosterone levels

01:02:26.300 | were essentially in that order from low to highest.

01:02:29.380 | So minister, salesman, fireman, professor,

01:02:31.700 | physician, NFL player.

01:02:34.000 | Now we could micro dissect all the different stereotypes

01:02:38.500 | and all the different features of each of these jobs.

01:02:41.300 | For instance, we don't know whether or not the fact

01:02:44.280 | that the firemen happened, at least in this study,

01:02:47.140 | to have lower testosterone levels on average

01:02:49.640 | than the professors or the physicians

01:02:51.600 | was because firemen have lower testosterone levels

01:02:54.020 | or because they have a much more stressful job

01:02:55.960 | and their cortisol levels are higher

01:02:58.260 | than the professor or the physician.

01:03:01.120 | And cortisol and testosterone, not always,

01:03:03.480 | but generally are in somewhat antagonistic push-pull mode

01:03:07.680 | because they derive from the same precursor, et cetera.

01:03:09.740 | Typically when cortisol is high,

01:03:12.180 | testosterone tends to be lower and vice versa.

01:03:14.460 | So we don't know what's causing these effects.

01:03:17.180 | And again, this is just one study and just six occupations,

01:03:21.200 | but I think it's relatively interesting given the fact

01:03:23.180 | that each of these professions involves different levels

01:03:25.180 | of competitiveness, right?

01:03:27.380 | So we don't necessarily just want to think about the level

01:03:29.620 | of physical exertion that's required,

01:03:32.500 | but also the level of competitiveness

01:03:34.280 | because it's known that competitive interactions

01:03:36.740 | can cause increases in testosterone in particular

01:03:40.900 | in the winners of competitive interactions,

01:03:42.900 | a topic for a future podcast.

01:03:45.260 | Meanwhile, studies that have analyzed also, again,

01:03:48.980 | salivary testosterone in prisoners,

01:03:53.100 | in this case, female prisoners,

01:03:55.360 | so these are incarcerated individuals,

01:03:57.400 | have looked at levels of testosterone

01:03:59.740 | according to whether or not the person committed

01:04:02.620 | a nonviolent or a violent crime in order to arrive in prison

01:04:06.280 | and higher levels of salivary testosterone

01:04:08.940 | were related to those that had arrived in prison

01:04:13.780 | because of conviction of a violent crime

01:04:16.740 | as opposed to a nonviolent crime.

01:04:18.580 | Likewise, when they analyze prison rule violations,

01:04:21.780 | so an indirect measure of aggressiveness,

01:04:24.260 | but in this case, it was strongly associated

01:04:26.660 | with aggressiveness because they knew

01:04:27.700 | what the violations were.

01:04:29.260 | They found where for prisoners that had none,

01:04:32.060 | no prison violations, prison rule violations,

01:04:35.460 | I should say their testosterone levels tended to be lower

01:04:39.520 | than the testosterone levels of women that had some,

01:04:42.860 | even one or more aggressive violations of prison rules.

01:04:47.860 | We'll provide links to these studies in the show notes

01:04:51.440 | if you'd like to go into them further.

01:04:53.480 | Obviously, studies like this need to be taken

01:04:55.340 | with a grain of salt

01:04:56.220 | because there are so many different factors,

01:04:58.460 | different prisons have different degrees of violence

01:05:02.860 | to begin with and competitiveness to begin with.

01:05:05.460 | But just as a final pass at examining the role

01:05:07.980 | between testosterone and aggressiveness,

01:05:10.380 | there was a very interesting study from Gotz et al.

01:05:13.580 | G-O-E-T-Z published in 2014 that looked at serum,

01:05:18.580 | so in this case, blood levels of testosterone,

01:05:22.340 | 30 minutes after application of a gel-based testosterone

01:05:26.620 | that goes transdermal so that the testosterone

01:05:28.780 | can go very quickly into the bloodstream

01:05:30.540 | and then did brain imaging to evaluate the activity

01:05:34.820 | of neurons in the so-called corticomedial amygdala.

01:05:38.860 | The medial amygdala is one of the areas

01:05:41.540 | of the amygdala complex, as we call it,

01:05:43.420 | because it's complex, it's got a lot of different nuclei.

01:05:46.220 | You now know what nuclei are, little clusters of neurons.

01:05:48.260 | It's got a lot of different ones,

01:05:49.240 | but that medial and that corticomedial amygdala

01:05:52.980 | in particular is known to be associated

01:05:55.300 | with aggressive type behaviors.

01:05:57.260 | It's linked up with, it's part of the larger circuit

01:05:59.980 | that includes the ventromedial hypothalamus

01:06:02.780 | and other brain areas that we referred to earlier,

01:06:04.540 | such as the PAG.

01:06:05.900 | What is remarkable about this study is that it showed

01:06:10.260 | that just 30 minutes after application

01:06:13.120 | of this so-called androgel,

01:06:14.380 | this testosterone that seeps into the bloodstream,

01:06:16.980 | there was a significant increase in, of course, testosterone

01:06:21.120 | and corticomedial amygdala activation.

01:06:25.380 | So testosterone can have acute effects, immediate effects,

01:06:29.320 | on the pathways related to aggression.

01:06:31.240 | And I think this is something that's not often discussed

01:06:33.620 | because many of the effects of steroid hormones,

01:06:36.280 | like testosterone and estrogen, are very slow acting.

01:06:38.640 | In fact, steroid hormones,

01:06:40.320 | because they have a certain biochemical composition,

01:06:43.920 | can actually pass through the membranes of cells,

01:06:46.260 | so the outside of a cell and into the nucleus of the cell

01:06:48.660 | and change gene expression in the cell.

01:06:50.700 | You think about puberty,

01:06:51.520 | the kid that goes home for the summer

01:06:53.020 | and then comes back looking completely different.

01:06:55.120 | Well, that's because a lot of genes got turned on

01:06:57.240 | by steroid hormones like testosterone and estrogen,

01:07:00.700 | but the steroid hormones can also

01:07:02.480 | have very fast acting effects.

01:07:05.020 | And with testosterone in particular,

01:07:06.780 | those can be remarkably fast acting.

01:07:08.880 | And one of the most apparent

01:07:10.700 | and well-documented fast acting effects is this effect,

01:07:13.180 | the ability to activate cells within the amygdala.

01:07:16.200 | So you might say, well,

01:07:17.040 | I thought the amygdala was associated with fear.

01:07:18.740 | Wouldn't testosterone then cause fear?

01:07:20.340 | No, turns out that the amygdala harbors both cortisol,

01:07:25.020 | corticosterone receptors, and testosterone receptors,

01:07:27.840 | and they each adjust the activity

01:07:29.840 | in the amygdala differently,

01:07:31.640 | such that testosterone tends to activate amygdala circuitry

01:07:36.120 | for inducing states of mind and body

01:07:40.080 | that are more action-based.

01:07:41.940 | And indeed, in animals and in humans,

01:07:43.920 | testosterone application and activation

01:07:45.840 | of this corticomedial amygdala pathway

01:07:47.760 | will make animals and humans lean into effort.

01:07:50.080 | This is why I say testosterone makes effort feel good,

01:07:52.520 | or at least biases the organism toward leaning

01:07:55.380 | into challenge.

01:07:56.340 | So if you recall, there's not just one type of aggression.

01:07:59.660 | There's reactive aggression,

01:08:01.660 | which is triggered when one is confronted with something

01:08:04.500 | that sometimes is inevitable, right?

01:08:06.580 | One needs to fight for their life

01:08:07.940 | or for somebody else's life,

01:08:09.540 | but also proactive aggression.

01:08:12.340 | And proactive aggression involves activation

01:08:14.780 | of those go pathways in the basal ganglia

01:08:17.100 | and a leaning into effort to overcome

01:08:19.100 | whatever state one happens to be in to begin with.

01:08:22.020 | And so this is very important because it points to the fact

01:08:24.560 | that yes, estrogen is activating aggression pathways

01:08:27.560 | that are in the ventromedial hypothalamus,

01:08:30.580 | but it's very likely the case

01:08:32.300 | that testosterone is acting to accelerate

01:08:35.180 | or to bias states of mind and body

01:08:38.100 | toward those that will lead to aggression.

01:08:40.540 | Again, aggression is not like a switch on and off.

01:08:43.140 | It's a process.

01:08:44.060 | It has a beginning, a middle, and an end.

01:08:46.620 | Remember that hydraulic pressure

01:08:48.300 | that Konrad Lorenz hypothesized?

01:08:50.960 | Well, think of testosterone as increasing the pressure

01:08:55.460 | toward an aggressive episode

01:08:57.400 | and then estrogen actually triggering

01:08:59.580 | that aggressive episode in the ventromedial hypothalamus.

01:09:02.400 | So if somebody tells you that testosterone,

01:09:04.980 | endogenous or exogenous, makes people aggressive,

01:09:07.760 | tell them no.

01:09:08.980 | Testosterone tends to make people lean into effort.

01:09:13.120 | And if that effort involves being aggressive,

01:09:16.360 | either reactively aggressive or proactively aggressive,

01:09:20.280 | well, then it will indeed lead to aggression,

01:09:22.660 | but the actual aggression itself

01:09:25.180 | is triggered by estrogen, not testosterone.

01:09:28.380 | Now, thus far, we really haven't talked too much

01:09:30.580 | about the social context in which aggression occurs.

01:09:34.660 | And that's because there is a near infinite,

01:09:36.500 | if not infinite number of variables that will determine that.

01:09:40.340 | So for instance, violent aggression is entirely appropriate

01:09:44.220 | at a professional boxing match

01:09:46.100 | provided it's occurring inside the ring

01:09:48.300 | and only between the competitors

01:09:50.220 | and within the bounds of the rules of the sport, et cetera.

01:09:55.220 | However, there are some things

01:09:58.140 | that tend to bias certain social contexts

01:10:01.020 | toward being more aggressive or less aggressive

01:10:03.200 | and not always physical aggression.

01:10:05.460 | And those generally come in two forms

01:10:08.260 | that many of you are familiar with,

01:10:09.560 | which are alcohol and caffeine.

01:10:12.820 | Let's discuss caffeine first.

01:10:15.020 | Why would caffeine increase aggressive impulsivity?

01:10:18.300 | Well, the general effects of caffeine

01:10:20.380 | are to increase autonomic arousal,

01:10:22.200 | the activity of the so-called sympathetic arm

01:10:25.100 | of the autonomic nervous system,

01:10:26.840 | which is, to put it very much in plain language,

01:10:30.660 | it's the alertness arm of your nervous system.

01:10:34.360 | That is, it creates a sense of readiness

01:10:37.100 | in your brain and body.

01:10:38.420 | And it does so by activating

01:10:40.000 | the so-called sympathetic chain ganglia.

01:10:41.860 | Again, as I always remind people,

01:10:43.260 | simpa and sympathetic does not mean sympathy.

01:10:46.660 | Simpa means together or all at once.

01:10:49.660 | And caffeine tends to bias our brain and body

01:10:54.180 | to activate the sympathetic chain ganglia,

01:10:57.300 | which run from about the base of your neck

01:10:59.500 | until the top of your pelvis,

01:11:01.160 | and deploy a bunch of chemicals

01:11:03.280 | that jut out into the rest of your body,

01:11:04.860 | activate adrenaline release.

01:11:06.580 | There's a parallel increase of adrenaline in your brain,

01:11:10.140 | creating the state of alertness and readiness.

01:11:12.500 | That state of alertness and readiness

01:11:13.900 | can be for all sorts of things, not just aggression.

01:11:16.900 | However, when we are in a state

01:11:19.100 | of increased sympathetic tone, meaning more alert,

01:11:22.860 | such as after drinking caffeine,

01:11:25.180 | we will bias all those brain and body systems,

01:11:28.400 | the hormones, the chemicals, et cetera,

01:11:30.280 | that exist toward action as opposed to inaction.

01:11:34.360 | So put simply, caffeine can increase impulsivity.

01:11:37.840 | No surprise there.

01:11:39.020 | On the opposite end of things,

01:11:41.540 | alcohol tends to decrease activity

01:11:46.020 | in the sympathetic arm of the autonomic nervous system,

01:11:48.260 | tends to make us feel less alert.

01:11:50.020 | Now, initially it can create a state of alertness

01:11:52.580 | because of its effects in inhibiting the forebrain.

01:11:55.180 | Our forebrain prefrontal cortex in particular

01:11:58.040 | has what's called top-down inhibition.

01:11:59.920 | It exerts a inhibitory or a quieting effect

01:12:04.060 | on some of the circuits of the hypothalamus,

01:12:05.820 | such as the ventromedial hypothalamus.

01:12:08.020 | The way to conceptualize this is that your forebrain

01:12:10.100 | is able to rationalize and think clearly

01:12:12.460 | and to suppress behavior and to engage the no-go pathways

01:12:15.940 | telling you don't say that mean thing,

01:12:18.480 | don't do that violent thing, et cetera.

01:12:20.740 | Alcohol initially tends to increase

01:12:23.920 | our level of overall activity by reducing inhibition,

01:12:27.780 | not just in that forebrain circuit,

01:12:30.200 | but in other circuits, tends to make us more active.

01:12:32.200 | We tend to talk more than we normally would,

01:12:34.060 | move more than we normally would,

01:12:35.660 | but very shortly thereafter starts acting as a sedative

01:12:39.580 | by way of reducing activity in the forebrain,

01:12:43.380 | releasing some of the deeper brain circuits

01:12:45.980 | that are involved in impulsivity,

01:12:47.540 | but also causing a somewhat sedative effect.

01:12:51.120 | And then of course,

01:12:51.960 | as alcohol levels increase even further,

01:12:54.080 | people eventually will pass out, blackout, et cetera.

01:12:57.020 | So what we've got with alcohol and caffeine

01:12:59.900 | is we've got two opposite ends of the spectrum,

01:13:01.940 | caffeine increasing arousal and readiness

01:13:04.780 | and the tendency for impulsivity,

01:13:06.540 | and alcohol also increasing impulsivity,

01:13:10.820 | but through a different mechanism.

01:13:12.800 | A really interesting study,

01:13:16.180 | and I should just mention that the title of the study

01:13:18.140 | is Caffeinated and Non-Caffeinated Alcohol Use

01:13:20.900 | and Indirect Aggression, the Impact of Self-regulation.

01:13:23.820 | So the title is almost self-explanatory.

01:13:25.940 | This was a paper published in the Journal

01:13:27.700 | of Addictive Behavior in 2016,

01:13:30.260 | examining how ingestion of alcohol

01:13:34.180 | that's either caffeinated or non-caffeinated alcohol drinks

01:13:38.020 | impacted what they call indirect aggression.

01:13:40.860 | And just to remind you what indirect aggression is,

01:13:42.760 | these are not physical acts of aggression,

01:13:44.820 | these are verbal acts of aggression.

01:13:46.480 | So embarrassing others,

01:13:48.080 | or otherwise somehow trying to reduce

01:13:51.740 | the wellbeing of others by saying certain things,

01:13:54.380 | in particular, in groups.

01:13:56.060 | This study examined both males and females.

01:13:58.700 | This was done by way of a college campus study.

01:14:02.180 | Subjects were 18 to 47 years old.

01:14:04.720 | I guess there's some older students on that campus,

01:14:06.320 | or maybe they use some non-students,

01:14:07.580 | but these days you've also got some students

01:14:09.400 | that are in their 30s and 40s.

01:14:11.060 | So they have a fairly broad swath of subjects included,

01:14:15.200 | fairly broad racial background as well,

01:14:18.020 | included not at equal numbers,

01:14:19.520 | but at least they included a pretty broad spectrum

01:14:22.220 | of people with different backgrounds.

01:14:23.740 | They looked in particular at people

01:14:26.260 | that ingested non-caffeinated alcohol drinks

01:14:29.020 | at a frequency of 9.18 drinks per week.

01:14:32.620 | Okay, again, this is a college campus,

01:14:34.140 | not that I encourage that.

01:14:35.140 | I'm one of these people that I've never really liked,

01:14:38.340 | drugs or alcohol, and since we're fortunate in that way,

01:14:40.440 | I can drink or not drink and tend to not drink.

01:14:43.700 | But so to me, 9.18 drinks per week sounds like a lot,

01:14:47.580 | but I know for some people that might actually be typical.

01:14:50.300 | And then others who were drinking

01:14:52.620 | at least one caffeinated alcoholic beverage per week,

01:14:56.820 | and those individuals end as high, I should say,

01:14:59.940 | as 7.87 caffeinated alcohol beverages per week.

01:15:04.380 | So this would be energy drinks

01:15:05.480 | combined typically with hard alcohol

01:15:07.140 | that's fairly commonly available in bars and so forth.

01:15:10.840 | And some individuals drank as much as, goodness,

01:15:14.460 | 20.36 alcoholic drinks per week total,

01:15:18.680 | some that were caffeinated, some that were not caffeinated.

01:15:21.620 | The basic outcome of this study was that

01:15:24.500 | the more alcohol someone tended to consume,

01:15:26.740 | the more likely it was that they would engage

01:15:28.540 | in these indirect aggressive type behaviors.

01:15:31.820 | And in terms of the caffeinated alcoholic beverages,

01:15:34.520 | there the effect was especially interesting.

01:15:36.160 | Here I'm just going to paraphrase,

01:15:37.420 | or I'll actually read from the study.

01:15:39.780 | Quote, "With regard to caffeinated alcoholic beverage use,

01:15:43.200 | our findings indicated that heavier

01:15:45.100 | caffeinated alcohol beverage use

01:15:46.920 | was associated positively with indirect aggression

01:15:49.420 | even after considering one's typical alcohol use

01:15:51.880 | and dispositional aggression."

01:15:53.900 | What this means is that even though alcohol

01:15:57.460 | can bias certain individuals to be more aggressive,

01:15:59.460 | and even though certain individuals

01:16:00.660 | already have a disposition toward being more aggressive,

01:16:03.740 | there was an effect that was independent,

01:16:06.620 | meaning above and beyond both alcohol and a predisposition,

01:16:11.300 | meaning if someone was consuming

01:16:13.480 | caffeinated alcoholic beverages,

01:16:15.260 | they had a particularly high likelihood

01:16:18.100 | of engaging in indirect aggressive behavior.

01:16:21.380 | Now, this makes perfect sense in light of the model

01:16:23.860 | they propose, which is this self-regulation model

01:16:27.340 | that basically self-regulation involves several things.

01:16:29.580 | It involves engaging in certain behaviors

01:16:32.060 | and suppressing other behaviors.

01:16:33.420 | So as described before,

01:16:36.220 | because alcohol tends to have a sedative,

01:16:40.100 | suppressive effect on the autonomic nervous system,

01:16:42.660 | at least after the initial period,

01:16:45.340 | it's going to tend to reduce the likelihood

01:16:47.860 | that people will engage in any type of behavior,

01:16:50.540 | whereas caffeine will increase autonomic arousal

01:16:53.060 | and increase the likelihood that someone will engage

01:16:55.580 | in a particular type of behavior, aggressive or otherwise.

01:16:58.920 | So the combination of caffeine and alcohol

01:17:01.340 | is really acting as a two-prong system

01:17:03.740 | to bias people towards more impulsivity,

01:17:06.300 | that is less self-regulation.

01:17:07.820 | So it's really yanking your volitional control,

01:17:10.940 | your ability to engage in prefrontal top-down inhibition

01:17:14.280 | over your hypothalamus from two distinct

01:17:16.920 | and specific circuits.

01:17:18.020 | By now, you should be getting the impression

01:17:19.660 | that self-regulation is a key feature

01:17:22.300 | of whether or not somebody, maybe even you,

01:17:25.420 | is going to engage in aggressive speech

01:17:27.260 | or aggressive behavior.

01:17:28.500 | And we've talked about a number of tools

01:17:29.820 | that one can use to reduce the probability

01:17:32.780 | that that will happen.

01:17:34.320 | I suppose if the context were appropriate,

01:17:36.340 | you could even take those two recommendations

01:17:39.380 | and just invert them and increase the likelihood

01:17:41.900 | that aggressiveness would happen.

01:17:43.460 | But regardless, self-regulation is key.

01:17:46.980 | And in light of that, I want to share with you a study

01:17:49.780 | that's focused on kids, but that has important ramifications

01:17:54.780 | for adults as well.

01:17:56.220 | As you probably are already aware,

01:18:00.060 | there are many kids out there that suffer

01:18:01.980 | from so-called attention deficit hyperactivity disorder,

01:18:04.580 | ADHD.

01:18:05.600 | There are also many adults we are finding

01:18:07.340 | that are suffering from ADHD.

01:18:09.140 | And there's also an epidemic, I would say,

01:18:12.400 | of people that are concerned

01:18:13.720 | about whether or not they have ADHD.

01:18:15.500 | Now, whether or not they have true clinical ADHD or not

01:18:18.640 | is not clear.

01:18:19.500 | We did an episode all about ADHD and tools for ADHD.

01:18:22.840 | I would encourage you to check out that episode

01:18:24.500 | and some of the diagnostic criteria.

01:18:26.820 | If you have the opportunity,

01:18:28.020 | you can find that at hubermanlab.com.

01:18:30.340 | As this study I'm about to share with you aptly points out,

01:18:34.380 | there is no objective diagnostic marker of ADHD.

01:18:36.980 | There's no biomarker or blood draw or blood test for ADHD.

01:18:40.580 | Whether or not one has ADHD depends on their performance

01:18:44.880 | on a number of different cognitive tests

01:18:46.900 | and behavioral tests and self-report.

01:18:49.640 | In any event, the study I'm about to share with you

01:18:52.280 | explored how a particular pattern of supplementation

01:18:55.520 | in kids with ADHD was able to reduce aggressive episodes

01:19:00.240 | and impulsivity and increase self-regulation.

01:19:03.440 | And the title of the study is efficacy of carnitine

01:19:06.340 | in the treatment of children

01:19:07.440 | with attention deficit hyperactivity disorder.

01:19:10.120 | Even though they put carnitine in the title,

01:19:12.000 | that what they focused on was

01:19:13.620 | whether or not acetyl-L-carnitine supplementation

01:19:17.040 | could somehow adjust the behavioral tendency

01:19:19.660 | of these kids with ADHD.

01:19:21.280 | And to make a long story short, indeed, it did.

01:19:24.400 | There was a very significant effect

01:19:25.880 | of acetyl-carnitine supplementation

01:19:28.000 | on improving some of the symptomology of ADHD.

01:19:32.780 | A few details about the study that might be relevant to you.

01:19:36.660 | This was a randomized double blind placebo controlled

01:19:38.840 | double crossover study.

01:19:40.560 | This was done as an outpatient study.

01:19:42.620 | So the kids weren't in a hospital.

01:19:44.200 | They were living out in the world.

01:19:45.520 | This again was done on younger kids.

01:19:47.320 | So this was six to 13 year old kids

01:19:49.760 | that were diagnosed with ADHD.

01:19:53.460 | They received either acetyl-L-carnitine or placebo.

01:19:58.460 | And they did all the good practice stuff

01:20:02.640 | that good researchers do of making sure

01:20:04.280 | that the placebo and the acetyl-L-carnitine

01:20:06.720 | had similar look and taste.

01:20:08.840 | It was consumed twice daily after meals.

01:20:11.840 | Now she just mentioned that acetyl-L-carnitine

01:20:13.400 | typically is taken in capsule form

01:20:16.200 | or occasionally an injectable form here.

01:20:18.240 | They were using this as a drink,

01:20:19.680 | which essentially the same as capsule form,

01:20:21.480 | but the powder is just going directly into liquid.

01:20:23.920 | And the carnitine dosage was 100 milligrams per kilogram.

01:20:27.920 | So they're doing this according to the body weight

01:20:29.760 | of these kids with a maximum dosage of four grams per day.

01:20:34.280 | The quantity of the medication was supplied.

01:20:36.080 | Here I'm reading for a period of eight weeks.

01:20:37.860 | And every eight weeks,

01:20:38.700 | a new quantity of medication was supplied.

01:20:40.280 | So basically this is a fairly long-term study

01:20:43.360 | exploring behavioral outcomes and psychological outcomes

01:20:48.240 | in week eight, 16, and 24.

01:20:50.720 | They also looked at things

01:20:53.240 | that you could only get through a blood draw.

01:20:54.840 | So things like hemoglobin, hematocrit,

01:20:56.740 | red blood cell count, white blood cell count, et cetera.

01:20:58.840 | These are kids.

01:20:59.680 | And even if it were adults,

01:21:01.040 | they were quite appropriately examining

01:21:02.600 | a lot of the physiological measures

01:21:04.000 | that one would want to carry out to make sure, first of all,

01:21:08.280 | that blood levels of carnitine are increasing

01:21:10.840 | and indeed they confirm that,

01:21:11.900 | but also that no negative effects are showing up

01:21:15.180 | in the physiology as well as the psychology of these kids.

01:21:17.900 | So first I'll just tell you the basic outcome of the study,

01:21:20.000 | which was here I'm paraphrasing.

01:21:21.760 | Given twice daily, carnitine appeared to be effective

01:21:23.880 | in well-tolerated treatment

01:21:24.980 | for a group of children with ADHD.

01:21:26.960 | They showed significant abnormal behavior

01:21:29.460 | compared to these other boys.

01:21:31.680 | And now I'm moving to the table of results.

01:21:35.100 | They showed significant reductions

01:21:36.680 | in their so-called total problem score.

01:21:38.960 | The total problem score is a well-established measure

01:21:41.120 | of behavioral problems in kids with ADHD.

01:21:44.480 | And I should say adults with ADHD has to do with challenges

01:21:49.440 | in social and learning environments

01:21:51.920 | and how well or poorly an individual tends to perform.

01:21:56.080 | Reductions in attentional problems overall,

01:21:58.040 | reductions in delinquency,

01:21:59.320 | and most important for sake of today's discussion,

01:22:01.920 | significant reductions in aggressive behavior.

01:22:04.700 | Now, what's especially nice about this study I think

01:22:07.020 | is that even though it's a relatively small number

01:22:09.380 | of subjects and certainly needs to be repeated

01:22:13.060 | in other studies and other laboratories,

01:22:16.020 | that they were able to confirm the shifts in L-carnitine

01:22:21.020 | within the bloodstream of these kids.

01:22:22.400 | That is, they were able to correlate the physiology

01:22:24.760 | with the psychological changes.

01:22:27.000 | In studies like this,

01:22:28.360 | and frankly in all studies of human pharmacology,

01:22:31.840 | you have to worry about effects that show up

01:22:33.700 | not just because of placebo effects,

01:22:35.560 | but because of so-called off-target effects

01:22:37.620 | or related things totally independent of the drug

01:22:41.320 | or the particular supplement

01:22:42.360 | that you happen to be looking at.

01:22:43.840 | To put it in the words of a great neuroscientist,

01:22:46.460 | unfortunately he passed away some years ago,

01:22:48.680 | but he was a member of the National Academy,

01:22:50.120 | extremely accomplished neuroscientist,

01:22:53.400 | who once turned to me and said,

01:22:54.520 | "Never forget, a drug is a substance

01:22:57.120 | "that when injected into an animal or a human being

01:22:59.840 | "creates a paper."

01:23:02.520 | Meaning you can see effects of pretty much any drug

01:23:06.580 | or any supplement in most all conditions.

01:23:09.300 | However, it is in cases such as this study

01:23:12.080 | where you can quite convincingly see

01:23:15.480 | that the particular feature of physiology

01:23:18.080 | that you expected to change actually changed,

01:23:21.180 | and you see a psychological outcome

01:23:23.420 | that you can gain much greater confidence

01:23:26.040 | that the changes in delinquency,

01:23:28.820 | in this case reduced delinquency, improved attention,

01:23:31.160 | reduced aggressiveness, and so forth

01:23:33.160 | was at least somehow related to the shift in blood physiology

01:23:38.040 | and levels of L-carnitine or acetyl-L-carnitine and carnitine

01:23:41.680 | in the bloodstream of these children,

01:23:43.280 | as opposed to something else,

01:23:44.880 | like L-carnitine going and affecting some downstream target

01:23:48.460 | that you have no knowledge of.

01:23:49.560 | Now, of course, that's still entirely possible,

01:23:52.040 | but I think studies such as these increase our confidence

01:23:54.680 | that things like L-carnitine can be used

01:23:57.840 | perhaps in concert with things

01:23:59.320 | like omega-3 supplementation,

01:24:01.200 | diets that are biased towards increasing more tryptophan

01:24:04.480 | and therefore more serotonin,

01:24:06.880 | obviously avoiding things like alcohol,

01:24:08.720 | and as it appears from the study I just described,

01:24:10.960 | reducing one's intake

01:24:13.080 | or not consuming any caffeinated alcoholic beverages,

01:24:16.760 | seems like it would be a good idea

01:24:17.760 | if your goal is to reduce aggressiveness,

01:24:19.840 | to think about the hormone context

01:24:21.660 | and whether or not you tend to have higher testosterone

01:24:25.440 | and estrogen or lower testosterone and estrogen,

01:24:27.840 | maybe even thinking about the work environment,

01:24:29.360 | whether or not you are existing

01:24:30.920 | in a particularly competitive work environment

01:24:32.920 | and even day life, time of year,

01:24:35.960 | and whether or not you're getting sufficient sunlight,

01:24:37.860 | whether or not you're avoiding light

01:24:39.240 | in the evening and so on.

01:24:40.660 | So studies such as this I think are useful

01:24:42.920 | because they point to the fact that very seldom, if ever,

01:24:47.880 | will there be one supplement or one nutritional change

01:24:51.320 | or even one behavioral change

01:24:52.740 | that's going to completely shift an individual

01:24:55.140 | from being aggressive and impulsive,

01:24:57.240 | but rather that by combining different behavioral regimens,

01:25:01.660 | by paying attention to things like time of year

01:25:04.300 | and work conditions and school conditions

01:25:06.360 | and overall levels of stress

01:25:07.640 | and likely therefore levels of cortisol, et cetera,

01:25:11.540 | that you can use behaviors, diet, and supplementation

01:25:14.920 | as a way to shift that overall internal milieu

01:25:18.580 | from one of providing a lot of internal hydraulic pressure,

01:25:22.040 | as it's been called throughout the episode,

01:25:24.100 | toward aggressive impulsivity and relax some

01:25:27.540 | of that hydraulic pressure and reduce aggressive tendencies.

01:25:31.820 | So once again, and frankly, as always,

01:25:34.480 | we've done a deep dive into the neurobiology

01:25:38.340 | and the psychology of what I believe

01:25:40.300 | to be an important feature of our lives,

01:25:42.100 | in this case, aggression.

01:25:43.860 | I want to point out that in a episode

01:25:46.260 | in the not too distant future,

01:25:47.560 | I'm going to be hosting Dr. Professor David Anderson

01:25:50.820 | from Caltech University, who is the world expert

01:25:54.260 | on the neurobiology of aggression.

01:25:56.980 | In fact, he is the senior author on many of the studies

01:25:59.640 | related to the ventromedial hypothalamus

01:26:01.280 | that I discussed today.

01:26:02.880 | Our discussion will touch on aggression, of course.

01:26:05.880 | So hearing today's episode will help you digest

01:26:08.940 | that information, but we are also going to talk

01:26:10.660 | about other emotional states.

01:26:12.340 | He is an expert, not just in aggression,

01:26:14.220 | but in motivated states related to sex and mating behavior,

01:26:17.960 | social relationships of all kinds and how those relate,

01:26:21.800 | not just to biology and psychology,

01:26:23.460 | but also certain forms of pathology,

01:26:25.860 | things like PTSD and the relationship, for instance,

01:26:28.080 | between anger, fear, anxiety, and depression,

01:26:31.480 | and many other important topics that I know many of you,

01:26:34.520 | if not all of you, will be interested in.

01:26:36.360 | In the meantime, I want to point you

01:26:37.620 | to his recently released and wonderful book entitled

01:26:42.280 | "The Nature of the Beast, How Emotions Guide Us."

01:26:45.000 | And again, the author is David Anderson from Caltech.

01:26:48.760 | This is a wonderful book.

01:26:50.420 | It serves as a tremendous introduction

01:26:53.880 | to the history of the study of these areas,

01:26:56.360 | the current science and discoveries being made

01:26:58.900 | in these areas, all made accessible to the scientists

01:27:02.320 | and non-scientists alike.

01:27:03.600 | It's a very engaging read and so much so

01:27:07.520 | that even though he was gracious in sending me a copy,

01:27:10.040 | I also purchased myself a copy to give to somebody

01:27:12.680 | who is a therapist, and I've purchased another copy

01:27:15.660 | to give to a high school kid that I mentor

01:27:17.960 | because he's very interested in the neuroscience

01:27:19.840 | of emotions, and I think we are all interested in emotions,

01:27:23.000 | not just fear and some of these negative states,

01:27:25.780 | not just aggression, but also the positive emotions

01:27:27.960 | of our lives.

01:27:28.800 | And so "The Nature of the Beast, How Emotions Guide Us"

01:27:31.800 | by David Anderson is a wonderful read.

01:27:34.160 | I can't recommend it highly enough.

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01:28:20.620 | During today's episode and on many previous episodes

01:28:22.980 | of the Huberman Lab Podcast, we discussed supplements.

01:28:25.880 | While supplements aren't necessary for everybody,

01:28:28.220 | many people derive tremendous benefit from them

01:28:30.640 | for things like improving the transition time

01:28:33.120 | and the quality of your sleep,

01:28:35.160 | and improving alertness and focus, and so on.

01:28:38.520 | Anytime you're considering taking supplements,

01:28:40.640 | there are several key considerations.

01:28:42.080 | First of all, those supplements

01:28:43.300 | should be of the very highest quality,

01:28:45.240 | and you want to make sure that what's listed on the bottle

01:28:47.800 | is actually what's in the bottle,

01:28:49.080 | which is a problem for many supplement companies out there.

01:28:52.160 | The Huberman Lab Podcast is pleased to announce

01:28:54.640 | that we are now partnered with Momentous Supplements

01:28:57.720 | because we believe Momentous Supplements

01:28:59.500 | to be of the very highest quality

01:29:01.520 | of any supplements out there,

01:29:03.400 | and we've been working very closely with them

01:29:05.480 | in order to direct them to create supplements

01:29:07.620 | that are individual ingredient supplements

01:29:09.880 | of the particular quality and sources

01:29:12.180 | that we would like to see,

01:29:13.320 | and that relate to the science and studies covered

01:29:15.740 | on the Huberman Lab Podcast.

01:29:17.300 | If you'd like to see some of those supplements,

01:29:19.000 | you can go to livemomentous.com/huberman,

01:29:22.480 | and there you will see some of the supplements

01:29:24.940 | that we've talked about on this podcast before,

01:29:26.840 | such as magnesium threonate for augmenting sleep,

01:29:30.420 | things like L-tyrosine for augmenting dopamine,

01:29:32.640 | and things like L-carnitine,

01:29:34.480 | which we've discussed on today's podcast.

01:29:36.800 | Right now, the list of supplements

01:29:38.640 | and the products that are there is only partial

01:29:40.880 | to what will soon be included in the future,

01:29:42.580 | so that's an ever-expanding catalog of, again,

01:29:45.100 | what we believe to be

01:29:46.000 | the very highest quality supplements available to you.

01:29:48.620 | For those of you that are interested in behavioral,

01:29:50.980 | nutritional, and supplementation-based tools

01:29:53.880 | for neuroscience and other aspects of your biology

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01:30:33.880 | but much of which is distinct from the content

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01:30:38.200 | Once again, thank you for joining me for our discussion

01:30:40.440 | about the biology, psychology,

01:30:42.480 | and actionable tools around aggression.

01:30:45.320 | And as always, thank you for your interest in science.

01:30:48.220 | [upbeat music]

01:30:50.800 | (upbeat music)

Understanding & Controlling Aggression | Huberman Lab Podcast #71

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