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Understanding & Controlling Aggression | Huberman Lab Podcast #71



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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, we are discussing aggression.
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I'm going to explain to you
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that there are several different types of aggression.
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For instance, reactive aggression
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versus proactive aggression,
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meaning sometimes people will be aggressive
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because they feel threatened or they are protecting those
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that they love who also feel threatened.
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There's also proactive aggression
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where people go out of their way
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to deliberately try and harm others.
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And there is indirect aggression,
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which is aggression not involving physical violence,
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for instance, shaming people and things of that sort.
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It turns out that there are different biological mechanisms
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underlying each of the different types of aggression.
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And today I will define those for you.
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I'll talk about the neural circuits in the brain and body
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that mediate each of the different kinds of aggression,
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talk about some of the hormones and peptides
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and neurotransmitters involved.
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I promise to make it all accessible to you,
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even if you do not have any biology or science background.
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I will also discuss tools,
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psychological tools and biological tools
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that one can use to better control aggression.
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Now, right here at the outset,
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I want to acknowledge that any discussion about aggression
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has to have an element of context within it.
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To be fair, human beings invest a lot of money,
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a lot of time and a lot of energy,
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and indeed can even derive pleasure from aggression.
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Later, I'll talk about neural circuits in the brain and body
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that reinforce, in other words,
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reward through the release of chemicals
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that make people feel good, acts of aggression.
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However, what I'm mainly referring to
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is the context in which human beings will pay money
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in order to derive what we call vicarious aggression.
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To put it simply, people spend an enormous amount of money
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and time and energy watching other people engage in,
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for instance, aggressive sports.
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And we know that observing your team winning
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over another team causes the release of neurochemicals
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in your brain and body that make you feel good,
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and yes, that can make you feel more aggressive.
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We also know, of course,
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that most governments invest many billions,
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if not trillions of dollars in infrastructure technologies
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and human beings in order to engage in aggression if needed,
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so-called military warfare, et cetera.
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So today's discussion will include a description of aggression
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in the pathological sense.
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We'll actually talk about an explosive aggressive disorder
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that most of you probably haven't heard of,
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but is actually far more common than perhaps you know.
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We'll talk about the role of things
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like attention deficit hyperactivity disorder
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and how that can relate to aggression
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through the relationship between impulsivity
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and aggression.
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And we'll talk about verbal aggression,
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physical aggression, proactive aggression
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as mentioned before, and reactive aggression.
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I'm certain that by the end of the episode,
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you will come away with a much more thorough understanding
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of what this thing that we call aggression really is.
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And when you see it in other people,
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I think it will make more sense to you.
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And when you observe it in yourself
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or the impulse to engage in aggression,
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verbal or physical or otherwise,
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I hope that you'll understand it better as well.
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And of course, the tools that I will describe
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should allow you to modulate and control
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aggressive tendencies or predispositions to aggressiveness,
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and just generally to be able to engage with people
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in a more adaptive way overall.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is however, part of my desire and effort
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to bring zero cost to consumer information
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about science and science-related tools
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to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Let's talk about aggression.
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I think that many people out there are put off by aggression
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although others are drawn to aggression,
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both in themselves and when observing it in others.
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The reason to talk about aggression is that,
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as mentioned before,
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the context of aggression really matters.
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So there are instances where aggression is adaptive.
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For instance, a mother protecting her children,
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if she's being attacked
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or if her children are being threatened,
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I think most people would agree
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that so-called maternal aggression of that sort,
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provided the context is right, is a great thing.
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Protecting our young is, after all,
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one of the primary adaptive drives of our species,
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and thank goodness it is.
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Of course, other forms of aggression
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like unprovoked proactive aggression,
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somebody simply being violent to somebody else,
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even when unprovoked.
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Most of us cringe when we see that kind of behavior.
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It can even evoke aggression in people
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when they observe that kind of behavior.
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So again, context really matters,
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but a more general and perhaps an even more important reason
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to think about and understand aggression
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is that by understanding the biology
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and psychology of aggression,
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you will be in a much better position
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to understand how all emotional states come to be,
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both in yourself and in others.
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For instance, many of you have probably heard the statement
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that I believe arises from pop psychology,
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not from formal academic psychology,
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that aggression is just sadness.
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It's a form of sadness that's amplified,
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and it shows up as aggression.
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But when we look at the underlying biology
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and the peer-reviewed literature on this,
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nothing could be further from the truth.
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We have distinct circuits in the brain
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for aggression versus grief and mourning.
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Those are non-overlapping.
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Now, that doesn't mean that you can't be sad and aggressive
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or in a state of mourning and aggressive at the same time.
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But the idea that sadness and aggression
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are one and the same thing is simply not true.
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And by understanding that,
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or perhaps by understanding that irritability and aggression
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are not the same thing,
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you'll be in a much better position to apply
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some of the tools that we will talk about in this episode
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in order to be able to reduce or eliminate,
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or if it's adaptive to you, to modulate aggression.
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And yes, there are cases where modulating your aggression,
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in some cases even amplifying aggression, can be adaptive.
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Now, this of course is not the first discussion
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about the biology of aggression
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or the psychology of aggression.
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And we really can look to the beginning of the last century
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as the time in which the formal study of aggression
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really began.
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One of the names that's most associated
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with the formal study of aggression
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is none other than Konrad Lorenz.
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Some of you may be familiar with that name.
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Others of you may not be familiar with that name.
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Konrad Lorenz studied so-called imprinting behaviors
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and fixed action pattern behaviors.
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He's most famous, at least in scientific circles,
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for getting geese to believe that he was their parent.
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And if you were to put into Google Konrad with a K Lorenz,
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just as it sounds, Konrad Lorenz geese,
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you're going to see a lot of photos of Konrad
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walking down roads with a lot of geese following him
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or swimming in lakes with a lot of geese following him.
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He had a habit of geese adopting him
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because of the behaviors that he partook in.
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So he would swim out on a lake
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in front of a bunch of little geese,
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and then they would think that he was the parent
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and they would imprint on him.
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He even lived with these animals and they lived with him.
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Sort of a strange character from what I hear.
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But nonetheless, all this work was deserving
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of a Nobel prize because what he discovered
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were fixed action patterns.
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That is patterns of behavior that could be evoked
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by a single stimulus, okay?
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This is really important.
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The idea that you can get a whole category of behaviors,
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like swimming behind a parent
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or looking to somebody for comfort and only them.
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The idea that you could get a huge category
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of different behaviors in a bunch of different contexts
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triggered by just the presence of that person is remarkable
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because what it suggested and what turns out to be true
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is that there are neural circuits,
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not just individual brain areas,
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but collections of brain areas that work together
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to engage a pattern of behaviors.
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And that's the first fundamental principle
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that we need to define today.
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That when we talk about aggression,
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we're talking about activation of neural circuits,
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not individual brain areas,
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but neural circuits that get played out in sequence,
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like keys on a piano.
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But that playing out in sequence means that aggression
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is a verb, it has a beginning, a middle, and an end,
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and it's a process, it's not an event.
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And as you'll see, that turns out to be very important
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in terms of thinking about how one can halt aggression,
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prevent it from happening before it's initiated,
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or maybe even prolonging aggression if that's what's needed.
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Now, Konrad Lorenz had no real knowledge of neural circuits.
link |
00:13:28.000
I mean, obviously he knew there was this thing
link |
00:13:29.880
that we call a brain and a nervous system,
link |
00:13:32.280
and he knew that there were chemicals in the brain
link |
00:13:34.960
and hormones and things of that sort
link |
00:13:36.720
that were likely to play a role,
link |
00:13:38.240
but he really didn't take any measures
link |
00:13:40.160
to define what the neural circuits were.
link |
00:13:42.860
Frankly, he didn't need to.
link |
00:13:43.700
He had his Nobel Prize and he did all this beautiful work.
link |
00:13:46.040
He's known for an abundance of work,
link |
00:13:48.800
but he did think about what sorts of underlying processes
link |
00:13:53.260
could drive something like aggression.
link |
00:13:55.760
And he talked about one particular feature
link |
00:13:58.600
that's especially important,
link |
00:14:00.080
and that's this notion of a pressure.
link |
00:14:02.560
The idea that, yes, certain hormones will bias somebody
link |
00:14:08.760
or an animal to be aggressive.
link |
00:14:10.400
Certain neurotransmitter states,
link |
00:14:11.960
and you'll learn what those are today,
link |
00:14:13.400
will bias somebody to be more or less aggressive,
link |
00:14:16.720
maybe even submissive and passive,
link |
00:14:18.640
maybe outright proactively aggressive
link |
00:14:21.340
towards anyone or anything in front of them.
link |
00:14:23.720
And yes, of course, there will be historical features
link |
00:14:26.640
based on their childhood, et cetera, et cetera.
link |
00:14:29.320
He understood that there will be a constellation of things
link |
00:14:31.540
that would drive people to be aggressive.
link |
00:14:34.600
And he described a so-called pressure,
link |
00:14:36.240
almost like a hydraulic pressure.
link |
00:14:37.740
Just think about fluid pressure in a small container
link |
00:14:40.320
being pushed, pushed, pushed until the can
link |
00:14:42.280
or the container is ready to explode,
link |
00:14:44.480
and how multiple features, multiple variables
link |
00:14:48.080
could impinge on that and create that pressure.
link |
00:14:51.220
It turns out that's exactly the way the system works.
link |
00:14:53.980
There is no single brain area
link |
00:14:55.540
that flips the switch for aggression,
link |
00:14:57.840
although we'll soon talk about a brain structure
link |
00:14:59.620
that generally houses the propensity
link |
00:15:02.960
and the output of aggression.
link |
00:15:05.720
This notion of a hydraulic pressure
link |
00:15:07.720
that can drive us toward aggressive behavior,
link |
00:15:10.480
or conversely can be very low pressure
link |
00:15:14.480
and keep us in a state of non-reactivity,
link |
00:15:16.640
maybe even passivity or submissiveness,
link |
00:15:19.660
is a very important feature because it really captures
link |
00:15:22.380
the essence of how neural circuits work
link |
00:15:24.920
when we're talking about primitive behaviors generally.
link |
00:15:27.360
And you can start to notice this in yourself and in others.
link |
00:15:31.320
You can start to notice
link |
00:15:32.480
when you are veering toward aggression
link |
00:15:34.800
or when someone is veering toward aggression,
link |
00:15:36.960
verbal or physical.
link |
00:15:39.100
Now, that veering is the buildup of this hydraulic pressure
link |
00:15:44.000
that Lorenz was referring to,
link |
00:15:45.420
and it really does have an underlying biological basis.
link |
00:15:48.220
Now, it was some years later
link |
00:15:51.980
that the first experiments came along,
link |
00:15:54.500
which really started to identify the brain areas
link |
00:15:57.940
and the biological so-called pressures
link |
00:16:00.600
that can induce aggressive behavior.
link |
00:16:03.340
And the person that really gets credit for this
link |
00:16:05.140
is a guy by the name of Walter Hess,
link |
00:16:08.100
who at that time was working on cats.
link |
00:16:10.780
And I know that when you say working on cats,
link |
00:16:12.960
a lot of people will cringe,
link |
00:16:13.860
a lot of people have cats as pets,
link |
00:16:15.240
and certainly cats can be delightful.
link |
00:16:17.380
Some people like them more, some people like them less.
link |
00:16:19.500
Most people cringe at the idea of doing experiments on cats.
link |
00:16:23.220
I should say that these days,
link |
00:16:24.640
very few laboratories work on cats.
link |
00:16:26.480
Most laboratories that work on animal models
link |
00:16:28.700
will work on flies, Drosophila fruit flies
link |
00:16:31.220
for their capacity to do genetics,
link |
00:16:33.380
on laboratory mice, sometimes rats, but usually mice.
link |
00:16:37.220
And occasionally you'll find a lab
link |
00:16:39.420
that still works on cats.
link |
00:16:41.400
Back in the time of Hess,
link |
00:16:43.300
very few laboratories worked on mice.
link |
00:16:45.100
Most laboratories worked on cats or rats.
link |
00:16:48.380
And the reason for that is nowadays,
link |
00:16:49.940
most laboratories use mice if they use animal models
link |
00:16:53.220
because of the genetic tools that exist in mice
link |
00:16:55.560
to knock out this gene or knock in this gene, et cetera,
link |
00:16:58.480
which can't be done in humans or non-human primates,
link |
00:17:01.100
at least not very easily at this point in history.
link |
00:17:04.660
So when I say he was working on cats,
link |
00:17:06.380
I realized that probably evoked some negative emotions
link |
00:17:08.560
in some of you, maybe even aggression in some of you.
link |
00:17:11.540
What we can do, however, is look at the data
link |
00:17:14.900
and make use of the data in terms of our understanding.
link |
00:17:19.080
What Hess did was he had cats that were awake
link |
00:17:22.880
and he was able to lower stimulating electrode
link |
00:17:25.120
into their brain.
link |
00:17:25.960
Now, keep in mind that the brain
link |
00:17:26.780
does not have any pain sensors.
link |
00:17:28.520
So after a small hole is made in the skull,
link |
00:17:30.860
electrodes are lowered into the brain.
link |
00:17:32.300
This is what's done commonly in human neurosurgery.
link |
00:17:35.380
And he was able to stimulate different brain areas.
link |
00:17:38.440
And he was sort of poking around.
link |
00:17:40.180
And when I say sort of,
link |
00:17:41.100
he was doing this with some logical intent and purpose.
link |
00:17:44.660
He wasn't just poking around in there for fun.
link |
00:17:46.160
He was trying to identify brain regions
link |
00:17:49.220
that could generate entire categories of behavior,
link |
00:17:53.780
a la Lorenz, right?
link |
00:17:55.300
These fixed action pattern behaviors.
link |
00:17:58.640
Eventually, his electrode landed in a site
link |
00:18:01.320
and he provided electrical stimulation to the cat
link |
00:18:03.980
that caused this otherwise passive purring, relaxing cat
link |
00:18:10.420
to suddenly go into an absolute rage.
link |
00:18:13.120
So arched back, hissing, hair up,
link |
00:18:16.300
so-called pyloerection where the hairs go up.
link |
00:18:19.340
Animals try and make themselves as big as possible,
link |
00:18:21.340
often when they're aggressive.
link |
00:18:24.440
Drooling, maybe even spitting, believe it or not,
link |
00:18:27.180
cats and other animals can do this.
link |
00:18:29.080
And the cat tried to attack him and anyone else
link |
00:18:32.020
and anything else, even inanimate objects
link |
00:18:36.260
when he stimulated this particular brain area.
link |
00:18:38.860
So Hess obviously took notice
link |
00:18:41.140
of this incredible transformation in behavior.
link |
00:18:44.100
And the fact that when he turned off the stimulation
link |
00:18:47.280
of this particular brain area,
link |
00:18:48.780
the cat very quickly within seconds
link |
00:18:50.980
went back to being passive calm kitty.
link |
00:18:54.100
Now, of course, he repeated this experiment in other animals
link |
00:18:57.580
because he had to confirm that it wasn't just happenstance,
link |
00:19:00.780
that there wasn't something unique about this one cat
link |
00:19:04.340
that perhaps he had stimulated an area
link |
00:19:07.500
that had been built up during the kittenhood
link |
00:19:10.400
of this cat and had been reactivated.
link |
00:19:13.560
Maybe this kitten had been traumatized early in life
link |
00:19:15.780
or scared and reactivation of a particular circuit
link |
00:19:18.820
unique to that cat created this aggressive behavior.
link |
00:19:23.020
That wasn't the case.
link |
00:19:23.860
Every cat that he looked at
link |
00:19:26.580
and stimulated this particular brain area,
link |
00:19:28.800
the cat would immediately go into an aggressive,
link |
00:19:31.300
almost rage-type behavior.
link |
00:19:32.540
Now, of course, we can't anthropomorphize.
link |
00:19:34.300
We don't know what the cat was feeling.
link |
00:19:35.740
For all we know, the cat could be happy,
link |
00:19:37.100
although that seems pretty unlikely.
link |
00:19:39.060
And later experiments done in mice, but also in humans,
link |
00:19:43.820
confirm that indeed stimulation of this brain area
link |
00:19:47.480
evoked not just behavioral aggression,
link |
00:19:49.820
but also subjective feelings of aggression and anger.
link |
00:19:53.340
So what was this incredible brain area?
link |
00:19:56.520
Or rather, I should say, what is the brain area
link |
00:19:58.780
that harbored this incredible capacity
link |
00:20:01.540
to generate aggressive behavior in Hess's experiments?
link |
00:20:06.460
Well, for those of you that are regular listeners
link |
00:20:08.580
to this podcast, you'll probably be relieved to know
link |
00:20:11.620
that today we're going to talk about
link |
00:20:12.780
some new neural circuits.
link |
00:20:14.380
Oftentimes we'll center back on the amygdala
link |
00:20:17.580
or the prefrontal cortex, and those names will come up.
link |
00:20:20.060
And for those of you that haven't heard them before,
link |
00:20:21.860
don't worry, I'll make it clear
link |
00:20:23.100
as to what those brain areas are and what they do.
link |
00:20:26.040
But today we're going to talk a lot about
link |
00:20:28.300
the so-called VMH or ventromedial hypothalamus.
link |
00:20:33.020
The ventromedial hypothalamus is a nucleus,
link |
00:20:36.380
meaning a small collection of neurons.
link |
00:20:38.780
What are neurons?
link |
00:20:39.900
Nerve cells.
link |
00:20:41.300
And that small collection of neurons
link |
00:20:43.500
that we call the ventromedial hypothalamus is truly small.
link |
00:20:46.420
It's only about 1,500 neurons on one side of your brain
link |
00:20:50.940
and a matching 1,500 neurons
link |
00:20:52.900
on the other side of your brain.
link |
00:20:54.420
And that combined 3,000 neurons or so,
link |
00:20:57.700
it's not exactly 3,000, but 3,000 neurons or so
link |
00:21:01.620
is sufficient to generate aggressive behavior
link |
00:21:05.900
of the sort that Hess observed in the cat.
link |
00:21:10.540
And believe it or not,
link |
00:21:11.660
when you see somebody who's in an act of rage
link |
00:21:14.560
or in an act of verbal aggression
link |
00:21:17.080
or in an act of defensive aggression,
link |
00:21:19.240
protecting their family or loved ones or country, et cetera,
link |
00:21:23.860
almost certainly those neurons are engaged in that behavior.
link |
00:21:28.300
Those neurons are perhaps even generating that behavior.
link |
00:21:32.660
And next I'll describe some experiments
link |
00:21:34.340
that were done just recently within the last 10 years or so,
link |
00:21:37.740
but leading right up until this year and even last month
link |
00:21:41.060
that keep confirming again and again and again
link |
00:21:43.980
that it is the activity of neurons
link |
00:21:45.580
in the ventromedial hypothalamus
link |
00:21:46.940
that are both necessary and sufficient
link |
00:21:49.340
to generate the full catalog of aggressive behaviors.
link |
00:21:53.780
Now, before I go further to describe
link |
00:21:56.400
the beautiful recent studies on the VMH,
link |
00:21:59.580
the ventromedial hypothalamus
link |
00:22:01.220
and the important role of testosterone
link |
00:22:03.100
and more importantly estrogen
link |
00:22:05.480
in the activation of aggressive behavior.
link |
00:22:07.200
That's right.
link |
00:22:08.040
That's soon to be clear to you why that's the case.
link |
00:22:11.700
I want to emphasize that the ventromedial hypothalamus
link |
00:22:15.060
is something that we should all care about.
link |
00:22:16.540
Why?
link |
00:22:17.820
Well, it turns out that many categories
link |
00:22:21.380
of psychiatric disorders, developmental disorders
link |
00:22:24.860
and psychological challenges,
link |
00:22:26.360
things like schizophrenia, PTSD,
link |
00:22:28.700
post-traumatic stress disorder, depression,
link |
00:22:31.680
borderline personality disorder,
link |
00:22:33.880
and even certain forms of autism
link |
00:22:35.960
can include elements of aggression and even violence.
link |
00:22:39.000
Now, it's certainly not the case
link |
00:22:40.700
that aggression and violence are present
link |
00:22:42.980
in all people who suffer from schizophrenia or PTSD
link |
00:22:46.820
or depression or autism or borderline personality disorder.
link |
00:22:50.340
I'm absolutely not saying that.
link |
00:22:53.220
However, it can be a feature of those
link |
00:22:56.060
and it's a well-described feature
link |
00:22:58.740
in terms of trying to understand the constellation
link |
00:23:01.660
of challenges that people suffer from when they have those.
link |
00:23:04.140
So thinking about the VMH goes way beyond
link |
00:23:06.060
just understanding basic aggression
link |
00:23:08.160
in the context of adaptive aggression.
link |
00:23:10.120
So, you know, when earlier I use the example
link |
00:23:13.160
of maternal aggression,
link |
00:23:14.200
that's one adaptive form of aggression.
link |
00:23:17.660
It also can be pathologic aggression,
link |
00:23:20.440
meaning it can harm ourselves or others.
link |
00:23:22.500
So keep this in mind as we go forward
link |
00:23:24.060
because later we're going to talk about specific tools
link |
00:23:26.580
designed to modulate or prevent aggression
link |
00:23:30.220
in, for instance,
link |
00:23:31.240
people with attention deficit hyperactivity disorder
link |
00:23:33.720
and especially kids with ADHD.
link |
00:23:37.600
In the meantime, let's return to the VMH,
link |
00:23:40.100
this relatively small collection of neurons.
link |
00:23:42.320
And the reason I say relatively small is,
link |
00:23:43.820
well, your brain has many hundreds of billions of neurons,
link |
00:23:47.200
maybe even trillions of neurons.
link |
00:23:48.640
The exact number of neurons isn't really clear,
link |
00:23:50.640
but it's a lot.
link |
00:23:52.020
And it certainly is a lot relative to the number of neurons,
link |
00:23:56.080
this 3000 or so neurons living in your hypothalamus
link |
00:23:59.680
that can evoke this aggressive response.
link |
00:24:04.220
Experiments done by David Anderson's lab at Caltech
link |
00:24:07.940
were really the first to parse the fine circuitry
link |
00:24:10.980
and to really show that the ventromedial hypothalamus
link |
00:24:13.980
is both necessary and sufficient for aggressive behavior.
link |
00:24:17.280
These are important experiments
link |
00:24:18.340
and they're worth knowing about.
link |
00:24:20.460
What they did was they identified,
link |
00:24:24.500
first of all, where the ventromedial hypothalamus
link |
00:24:26.220
was in the mouse.
link |
00:24:27.140
That was pretty straightforward to do,
link |
00:24:28.340
sort of known before they started these experiments.
link |
00:24:30.780
And then they analyzed which genes,
link |
00:24:34.900
meaning which DNA, which of course becomes RNA
link |
00:24:38.500
and RNA becomes protein,
link |
00:24:40.500
which DNA and therefore which proteins are expressed
link |
00:24:44.200
in particular cells of the ventromedial hypothalamus.
link |
00:24:47.860
And it turns out that there's a particular category
link |
00:24:50.540
of neurons in the ventromedial hypothalamus
link |
00:24:54.040
that make an estrogen receptor.
link |
00:24:57.300
And it is those neurons in particular
link |
00:25:00.020
that are responsible for generating aggressive behavior.
link |
00:25:04.080
How did they know this?
link |
00:25:05.020
Well, they used a tool that's actually been described
link |
00:25:07.540
by a previous guest of this podcast.
link |
00:25:09.160
We had an episode with the psychiatrist and bio engineer
link |
00:25:11.720
and my colleague at Stanford School of Medicine,
link |
00:25:13.620
Carl Deisseroth.
link |
00:25:14.820
He and others have developed tools
link |
00:25:18.020
that allow people to control the activity of neurons
link |
00:25:21.620
essentially by remote control,
link |
00:25:22.860
by shining light on those neurons.
link |
00:25:24.540
So in the context of an experiment on a mouse,
link |
00:25:26.860
which is what David's lab did,
link |
00:25:28.240
and these were the beautiful experiments of Dai Yu Lin,
link |
00:25:30.180
who's now in her own laboratory at New York University,
link |
00:25:33.900
put a little fiber optic cable down into the brain
link |
00:25:36.180
of the hypo, into the hypothalamus that is of the mouse.
link |
00:25:39.220
The mouse is able to move around in its cage, freely moving.
link |
00:25:43.500
Even though it has a little tether, this little wire,
link |
00:25:45.380
it's a very thin wire.
link |
00:25:46.580
And that little thin wire is actually a little,
link |
00:25:48.360
what we call optrode.
link |
00:25:49.460
And the experimentalist, in this case, Dai Yu,
link |
00:25:51.820
was able to stimulate the turning on
link |
00:25:55.620
of a little bit of blue light.
link |
00:25:57.700
And that blue light activated
link |
00:26:00.020
only those estrogen receptor neurons
link |
00:26:03.340
in only the ventromedial hypothalamus.
link |
00:26:06.260
And the way she was able to do that
link |
00:26:07.400
is she had introduced a gene
link |
00:26:09.700
that had been developed by our friend, Carl Deisseroth,
link |
00:26:13.140
that allows light to trigger electrical activity
link |
00:26:17.220
in those neurons.
link |
00:26:18.060
So if any of that is confusing
link |
00:26:19.180
or if all of that is confusing, here's the experiment.
link |
00:26:21.120
There's a mouse in a cage,
link |
00:26:23.160
has a little wire coming out of its head.
link |
00:26:24.620
It doesn't notice, believe it or not.
link |
00:26:26.520
We know this because it's still eating and mating
link |
00:26:28.340
and doing all the things that mice like to do
link |
00:26:30.760
on a daily basis and sleeping, et cetera.
link |
00:26:33.220
And the mere pressing of a button
link |
00:26:35.340
will activate a little bit of light released
link |
00:26:37.720
at the end of that wire.
link |
00:26:38.680
That light activates particular neurons.
link |
00:26:41.020
In this case, it's the estrogen receptor-containing neurons
link |
00:26:43.940
in only the ventromedial hypothalamus.
link |
00:26:47.860
When that mouse is in a cage with another mouse,
link |
00:26:50.300
a couple of things happen,
link |
00:26:51.300
depending on what the other mouse is,
link |
00:26:53.820
or we could say who the other mouse is.
link |
00:26:56.200
If it's a male mouse
link |
00:26:58.020
and you put it in there with a female mouse,
link |
00:27:00.240
the male mouse will attempt to mate with a female mouse.
link |
00:27:03.280
Provided that the male mouse has gone through puberty,
link |
00:27:05.300
he will try to mount and mate with a female mouse.
link |
00:27:07.900
Now, female mice are either in a receptive phase
link |
00:27:11.220
or a non-receptive phase of their so-called estrous cycle.
link |
00:27:13.740
They don't have a menstrual 28-day cycle.
link |
00:27:15.540
They have an estrous cycle.
link |
00:27:17.500
And on particular days of that estrous cycle,
link |
00:27:20.000
they are not happy to mate.
link |
00:27:22.400
They will basically keep their hindquarters
link |
00:27:25.420
away from the male mouse at all costs.
link |
00:27:27.540
They'll even attack the male mouse.
link |
00:27:30.860
On certain days of the estrous cycle, however,
link |
00:27:32.600
the female mouse will undergo what's called lordosis,
link |
00:27:34.780
which is an arching of her back,
link |
00:27:36.300
and she'll allow the male to mount and mate with her.
link |
00:27:39.760
So a large number of experiments were done,
link |
00:27:42.560
but the first experiment really was to put the male mouse in
link |
00:27:46.420
with a female mouse who's in the so-called
link |
00:27:48.080
receptive phase of estrous.
link |
00:27:50.300
That is, she will allow mating.
link |
00:27:52.140
And he starts mating with her.
link |
00:27:54.300
And they go through the standard repertoire
link |
00:27:56.720
of mating behaviors that you observe in mice,
link |
00:28:00.380
mounting, thrusting, intromission,
link |
00:28:02.600
as it's called in the mouse sex world.
link |
00:28:05.300
Well, I guess, I don't know what the mice call it,
link |
00:28:06.540
but that's what the experimenters call it.
link |
00:28:08.360
And then afterwards that he will dismount, okay?
link |
00:28:11.960
So they observe this kind of mounting and sex behavior.
link |
00:28:15.420
It's very typical.
link |
00:28:16.840
But about halfway through the behavior,
link |
00:28:20.080
Dayu turned on the light to stimulate
link |
00:28:23.560
these estrogen receptor-containing neurons
link |
00:28:25.880
only in the male mouse.
link |
00:28:27.200
And what she observed was incredibly dramatic.
link |
00:28:30.120
The male mouse ceases from trying to mate
link |
00:28:32.360
with the female mouse and immediately tries
link |
00:28:34.000
to kill the female mouse.
link |
00:28:35.500
He starts attacking her.
link |
00:28:38.180
Then she turns off the light, the male stops,
link |
00:28:41.120
and goes back to trying to mate with the female mouse.
link |
00:28:43.200
I'm sure all of this was very confusing
link |
00:28:45.240
and disturbing to the female mouse.
link |
00:28:46.840
Nonetheless, that was the repertoire.
link |
00:28:49.340
They would mate.
link |
00:28:50.480
She would stimulate these ventromedial hypothalamus neurons.
link |
00:28:53.420
The male mouse would immediately try and attack
link |
00:28:55.680
and kill the female mouse.
link |
00:28:57.800
And then she would stop the stimulation
link |
00:28:59.660
and he would stop trying to attack and kill the female mouse
link |
00:29:02.280
returned to the attempt at least
link |
00:29:04.880
to mate with the female mouse.
link |
00:29:07.680
These are such dramatic shifts in behavior
link |
00:29:10.060
triggered only by the activation
link |
00:29:11.880
of only the small set of neurons
link |
00:29:13.660
within the ventromedial hypothalamus.
link |
00:29:15.600
And for those of you that think that you can watch
link |
00:29:18.340
this sort of thing without being disturbed,
link |
00:29:20.280
I encourage you to go to YouTube.
link |
00:29:23.180
We will provide a link where you can see a video
link |
00:29:26.240
of this type of behavior.
link |
00:29:27.180
It's incredibly dramatic.
link |
00:29:28.960
The shift in behavior is almost instantaneous.
link |
00:29:32.280
It occurs within seconds, if not milliseconds,
link |
00:29:35.060
thousandths of a second.
link |
00:29:37.240
The next experiment that she did was to put a male mouse
link |
00:29:41.040
with this stimulation with light capability
link |
00:29:44.760
in its ventromedial hypothalamus into a cage alone,
link |
00:29:47.740
but with a rubber glove filled with air or water.
link |
00:29:50.360
Mouse is walking around sniffing, peeing,
link |
00:29:52.740
which is what male mice seem to do.
link |
00:29:54.000
They seem to urinate everywhere.
link |
00:29:55.520
Essentially an interesting, perhaps interesting feature
link |
00:29:58.000
of male mice and actually many male animals,
link |
00:30:00.920
perhaps even humans, we don't know, or maybe we do know.
link |
00:30:03.820
Basically, this has been observed time and time again
link |
00:30:06.580
in experiments, mainly by Lisa Stowers' lab
link |
00:30:09.360
at the Scripps Institute has characterized this.
link |
00:30:11.520
If you put female mice into an arena or a cage,
link |
00:30:14.240
they always urinate in a very small corner of that cage.
link |
00:30:17.880
Whereas if you put male mice into an arena or a cage,
link |
00:30:21.180
they urinate everywhere.
link |
00:30:22.340
They have this kind of obsession
link |
00:30:23.560
with spraying their urine everywhere.
link |
00:30:25.400
You can sort of transpose that
link |
00:30:27.600
to human behavior if you like.
link |
00:30:30.360
In any event, Dayu put the mouse in the cage alone,
link |
00:30:34.720
but with this rubber glove,
link |
00:30:36.280
the mouse is walking around urinating, et cetera,
link |
00:30:38.720
doing whatever it is that mice do.
link |
00:30:40.200
Then she stimulates the activation
link |
00:30:42.460
of these ventromedial hypothalamus neurons,
link |
00:30:44.920
and the mouse immediately tries to kill the glove.
link |
00:30:48.400
It goes into a rage attacking the glove
link |
00:30:50.440
as if it were another mouse or some other animate object,
link |
00:30:55.040
but of course it's an inanimate object.
link |
00:30:56.780
It's just a rubber glove.
link |
00:30:58.360
She stops the stimulation,
link |
00:30:59.480
and the mouse immediately goes back to being completely calm
link |
00:31:02.000
or at least not attacking.
link |
00:31:03.840
Again, we don't know what the mouse was feeling.
link |
00:31:06.680
So these are very dramatic videos.
link |
00:31:08.480
Again, you can see them by following the link
link |
00:31:10.080
that we'll provide in the caption.
link |
00:31:11.880
If that sort of thing is going to disturb you
link |
00:31:14.160
to see, for instance, one mouse attacking another,
link |
00:31:17.360
please just don't watch them.
link |
00:31:18.760
I'm not interested in traumatizing anybody,
link |
00:31:21.580
or you traumatizing yourself, that is.
link |
00:31:24.540
A number of different variations
link |
00:31:26.000
were done on this experiment.
link |
00:31:27.080
For instance, stimulating the VMH in female mice
link |
00:31:32.680
as opposed to male mice,
link |
00:31:33.760
putting the female mice in with other female mice
link |
00:31:36.680
or with other male mice,
link |
00:31:38.400
no matter what variation one carries out,
link |
00:31:41.980
so it doesn't matter if it's male with female,
link |
00:31:43.680
male with male, female with female, et cetera,
link |
00:31:47.400
stimulation of the ventromedial hypothalamus
link |
00:31:50.080
in a male mouse or a female mouse evokes
link |
00:31:52.320
this very dramatic, almost instantaneous,
link |
00:31:55.080
aggressive behavior, physically aggressive behavior.
link |
00:31:58.840
Subsequent experiments done by Dai-Yu Lin
link |
00:32:01.120
in her own laboratory and other laboratories
link |
00:32:03.540
have shown that the ventromedial hypothalamus
link |
00:32:05.840
is connected with a bunch of other brain areas
link |
00:32:07.720
that are interesting,
link |
00:32:08.560
and I'll talk about some of those in a little bit,
link |
00:32:10.520
but one of them that I want to call out now
link |
00:32:13.960
is the so-called PAG, the periaqueductal gray nucleus.
link |
00:32:17.240
This is a large structure in the back of the brain
link |
00:32:20.220
that houses things like neurons that can create opioids.
link |
00:32:23.800
We all know of the opioid crisis,
link |
00:32:25.040
but these are neurons that can produce endogenous means
link |
00:32:28.920
made by the body, chemicals that can cause pain relief.
link |
00:32:33.720
You could understand why that might occur
link |
00:32:35.800
in a circuit for aggression, right?
link |
00:32:37.260
Even if one is the aggressor,
link |
00:32:39.720
it's likely that they may incur some physical damage
link |
00:32:42.800
and they'd want some pain relief.
link |
00:32:45.680
The PAG also is connected to a number of neural circuits
link |
00:32:49.340
that eventually, through several processing stations,
link |
00:32:53.440
excuse me, arrive at things like the jaws,
link |
00:32:56.200
and in fact, stimulation of the ventromedial hypothalamus
link |
00:32:58.640
can evoke biting and aggressive biting behavior.
link |
00:33:01.820
Now, aggressive biting behavior is particularly interesting
link |
00:33:05.240
because in humans, and especially in human children,
link |
00:33:08.440
biting is something that,
link |
00:33:10.540
while young children might do as a form of aggression,
link |
00:33:13.440
tends to disappear pretty early in childhood,
link |
00:33:17.040
and if it doesn't, it's often seen as a mark of pathology.
link |
00:33:21.540
I have a story about this, actually.
link |
00:33:22.680
When I was a kid, I went to a summer sports camp,
link |
00:33:27.140
and I'll never forget this.
link |
00:33:29.080
We were playing soccer,
link |
00:33:30.400
and in a rare stroke of luck or accident,
link |
00:33:34.040
I happened to score a goal.
link |
00:33:35.080
I wasn't a particularly good soccer player,
link |
00:33:36.560
especially not at that stage in my life.
link |
00:33:37.920
They later figured out that it was just better
link |
00:33:39.720
to make me a fullback,
link |
00:33:40.740
because I could just wait there and do what fullbacks do.
link |
00:33:43.440
I was better at taking the ball or the person out
link |
00:33:45.720
than I was putting the ball in the goal.
link |
00:33:49.460
Nonetheless, I, again, by chance, I scored a goal,
link |
00:33:53.320
and I was trotting back to my side of the field,
link |
00:33:55.880
and all of a sudden, I felt this sting in my back.
link |
00:33:59.600
A kid, not to be named, although I do remember your name,
link |
00:34:03.280
I'm not going to tell you what his name was,
link |
00:34:05.160
a kid jumped on my back and bit me on the top of my back,
link |
00:34:09.420
and this, of course, resulted in a discussion
link |
00:34:12.440
and a timeout and all the usual things,
link |
00:34:14.800
and parents, I think, got involved.
link |
00:34:16.520
I don't recall.
link |
00:34:17.720
I didn't think much else of it,
link |
00:34:19.180
but I recall that this was considered
link |
00:34:21.440
especially troubling behavior,
link |
00:34:23.760
because he bit me as opposed to hit me
link |
00:34:25.960
or shoved me down or something of that sort,
link |
00:34:27.920
and it does seem as if the tendency to use biting
link |
00:34:31.520
as an aggressive behavior is associated
link |
00:34:34.520
with a more primitive circuitry.
link |
00:34:35.920
Now, here, I'm truly anthropomorphizing.
link |
00:34:37.800
I don't know what this other kid happened to be thinking
link |
00:34:39.720
or feeling at the time.
link |
00:34:40.900
How could I?
link |
00:34:41.740
And I certainly am not going to say that biting
link |
00:34:44.460
in every case reflects a pathology,
link |
00:34:48.060
although I think there is general agreement
link |
00:34:50.360
in the psychology community and the psychiatric community
link |
00:34:52.680
that past a certain age, the using of one's teeth
link |
00:34:55.480
to impart aggression and damage on others
link |
00:34:58.500
is a particularly primitive and troubling,
link |
00:35:01.660
or at least for the observer,
link |
00:35:02.800
the person that experiences a pretty disturbing event.
link |
00:35:06.320
Daew's lab has shown that activation
link |
00:35:08.980
of the ventromedial hypothalamus
link |
00:35:10.220
triggers a downstream circuit in the periaqueductal gray,
link |
00:35:13.240
which then triggers a whole other set of circuits
link |
00:35:15.780
of fixed action patterns.
link |
00:35:17.020
Here we are back to Lorenz again with fixed action patterns,
link |
00:35:20.760
including swinging of the limbs, right, punching.
link |
00:35:24.320
This wouldn't necessarily be controlled punching,
link |
00:35:26.700
but also biting behavior.
link |
00:35:28.600
So it's remarkable to me at least
link |
00:35:30.400
that we have circuits in our brain
link |
00:35:32.360
that can evoke violent use of things like our mouth
link |
00:35:36.160
or violent use of things like our limbs
link |
00:35:38.640
that of course could be used for things like singing
link |
00:35:41.340
or kissing or eating or gesticulating
link |
00:35:45.600
in any kind of polite or impolite way.
link |
00:35:49.000
The point here is that neural circuits,
link |
00:35:51.440
not individual brain areas,
link |
00:35:53.000
evoke the constellation of behaviors
link |
00:35:54.780
that we call aggression.
link |
00:35:56.400
Now, many of you are probably puzzled
link |
00:35:57.800
or at least should be
link |
00:35:59.560
because I've been talking about
link |
00:36:01.240
this highly specialized brain area,
link |
00:36:02.800
the ventromedial hypothalamus,
link |
00:36:04.000
and this highly specialized subcategory of neurons
link |
00:36:07.960
in the ventromedial hypothalamus,
link |
00:36:09.240
these neurons that make estrogen receptor.
link |
00:36:11.920
And yet the activation of those cells
link |
00:36:14.840
triggers dramatic and immediate aggression,
link |
00:36:17.580
both in males and in females
link |
00:36:19.600
and both against males and against females.
link |
00:36:23.640
So what's going on here?
link |
00:36:24.600
Most of us think about estrogen
link |
00:36:26.600
and we don't immediately think of aggression.
link |
00:36:29.500
Most of us hear testosterone
link |
00:36:31.240
and we might think about aggression,
link |
00:36:32.600
although other things as well.
link |
00:36:34.960
In order to understand this,
link |
00:36:36.020
I just want to briefly refer back to a conversation
link |
00:36:39.580
that I had on a previous episode
link |
00:36:41.040
of the Huberman Lab podcast
link |
00:36:42.240
and that was with my colleague,
link |
00:36:44.280
the great Robert Sapolsky,
link |
00:36:45.920
of course, as a professor at Stanford
link |
00:36:47.200
who studied testosterone and its impacts on behavior
link |
00:36:50.360
as well as estrogen and other hormones
link |
00:36:51.860
and their impacts on behavior.
link |
00:36:53.400
To make a long story short
link |
00:36:56.240
and to dispel a still unfortunately very common myth,
link |
00:37:01.260
testosterone does not increase aggressiveness.
link |
00:37:05.000
Testosterone increases proactivity
link |
00:37:07.840
and the willingness to lean into effort
link |
00:37:10.440
in competitive scenarios.
link |
00:37:13.400
Sometimes this is referred to as the challenge hypothesis,
link |
00:37:15.840
but to make a long story short,
link |
00:37:20.480
if people are given testosterone
link |
00:37:22.480
or if you look at people who have different levels,
link |
00:37:26.560
excuse me, of testosterone endogenously
link |
00:37:28.600
that they naturally make,
link |
00:37:30.080
what you'll find is that testosterone
link |
00:37:32.600
tends to increase competitiveness,
link |
00:37:34.840
but not just in aggressive scenarios.
link |
00:37:37.320
So if somebody is already aggressive,
link |
00:37:40.360
giving them testosterone will have the tendency
link |
00:37:43.740
to make them more aggressive.
link |
00:37:46.320
If somebody, however, is very benevolent and altruistic,
link |
00:37:49.420
giving them testosterone
link |
00:37:50.400
will make them more benevolent and altruistic,
link |
00:37:52.500
at least up to a point.
link |
00:37:53.680
Now, of course, there are certain forms
link |
00:37:55.240
of synthetic testosterone that are known
link |
00:37:58.520
in sports circles and in other circles
link |
00:38:03.040
to increase aggressiveness
link |
00:38:04.720
because of the way those particular forms
link |
00:38:06.340
of synthetic testosterone work.
link |
00:38:08.080
But in general, most of the experiments
link |
00:38:09.560
that I'm referring to have not been done using those.
link |
00:38:11.160
They've been done using the,
link |
00:38:13.200
let's call them the more traditional
link |
00:38:15.640
biological forms of testosterone
link |
00:38:17.280
or that resemble the biological forms of testosterone.
link |
00:38:19.740
In fact, Robert Sapolsky described
link |
00:38:21.660
a really interesting experiment
link |
00:38:23.040
in which if you look at testosterone levels
link |
00:38:26.360
or you administer additional testosterone
link |
00:38:28.460
to people who are doing philanthropy,
link |
00:38:30.640
giving money to organizations,
link |
00:38:33.520
and so they're essentially doing good
link |
00:38:34.960
because these are organizations doing good,
link |
00:38:37.200
what you find is that increased testosterone
link |
00:38:40.160
or further increasing testosterone
link |
00:38:42.220
makes people more willing to compete
link |
00:38:43.760
to give more money than the other person in the room
link |
00:38:45.600
in order to put it in air quotes,
link |
00:38:48.140
to alpha out the other person by giving more money.
link |
00:38:51.000
So this is an act of altruistic or benevolent philanthropy.
link |
00:38:54.680
It is not an act of aggression.
link |
00:38:56.520
Of course, we don't know what the people
link |
00:38:58.040
are feeling underneath all that.
link |
00:38:59.720
Again, we can't anthropomorphize
link |
00:39:01.240
or project onto other people what they're feeling.
link |
00:39:04.100
But the point is that testosterone itself
link |
00:39:06.820
does not make people more aggressive.
link |
00:39:10.140
And in the experiments that we've been talking about
link |
00:39:11.960
up until now, it's actually the activation
link |
00:39:14.480
of estrogen receptor containing neurons
link |
00:39:17.040
that makes these animals more aggressive.
link |
00:39:19.240
And it turns out there's evidence
link |
00:39:20.760
that in certain contexts,
link |
00:39:22.600
estrogen can make people more aggressive.
link |
00:39:24.580
So what's going on here?
link |
00:39:26.660
Well, what's going on is that
link |
00:39:29.140
testosterone can be converted into estrogen
link |
00:39:32.500
through a process called aromatization.
link |
00:39:34.680
There's an enzyme called aromatase.
link |
00:39:36.640
Anytime you have a word that ends in A-S-E,
link |
00:39:39.680
at least if it's in the context of biology,
link |
00:39:41.400
it's almost always, not always,
link |
00:39:43.240
but almost always an enzyme.
link |
00:39:45.340
So the aromatase enzyme converts testosterone into estrogen.
link |
00:39:50.480
And it is actually testosterone aromatized,
link |
00:39:54.200
converted into estrogen,
link |
00:39:56.160
and then binding to these estrogen-containing neurons
link |
00:40:00.300
in the ventromedial hypothalamus that triggers aggression.
link |
00:40:04.460
I want to repeat that.
link |
00:40:05.300
It is not testosterone itself that triggers aggression.
link |
00:40:08.360
It is testosterone aromatized into estrogen
link |
00:40:11.120
within the brain and binding to these estrogen receptor
link |
00:40:14.680
containing neurons in the ventromedial hypothalamus
link |
00:40:17.160
that evokes aggression and dramatic aggression at that.
link |
00:40:21.100
Now, this effect of estrogen causing aggression in the brain
link |
00:40:24.680
is very robust, so much so that if you take a mouse
link |
00:40:28.880
that lacks the aromatase enzyme
link |
00:40:30.720
or a human that lacks the aromatase enzyme,
link |
00:40:33.120
and they do exist,
link |
00:40:35.800
then there is a reduction in overall aggression
link |
00:40:39.880
despite high levels of testosterone.
link |
00:40:42.960
And if people who, or mice who have the aromatase enzyme
link |
00:40:48.200
have that enzyme blocked,
link |
00:40:50.400
well, then it doesn't matter
link |
00:40:51.640
how much you increase testosterone
link |
00:40:53.480
or any of its other derivatives.
link |
00:40:55.440
You do not observe this aggression.
link |
00:40:58.660
So this runs counter to everything that we know
link |
00:41:01.040
and think about the role of testosterone.
link |
00:41:03.280
Again, testosterone increases competitiveness.
link |
00:41:06.360
It can increase the desire to work under challenge.
link |
00:41:09.800
I've said it before, and I ran this or pressure tested this
link |
00:41:14.280
against Robert Sapolsky, who's been working on testosterone
link |
00:41:16.880
and its role in the brain and behavior for many decades now.
link |
00:41:20.580
It is fair to say that testosterone has the net effect
link |
00:41:25.040
of making effort feel good,
link |
00:41:26.680
or at least increasing the threshold
link |
00:41:29.660
at which effort feels bad or unsustainable.
link |
00:41:32.840
And it does that by way of changing the activity
link |
00:41:36.480
or the threshold for activation of brain structures
link |
00:41:38.960
like the amygdala and other brain structures
link |
00:41:40.760
associated with anxiety.
link |
00:41:42.800
So the next time somebody says
link |
00:41:44.480
testosterone makes people aggressive,
link |
00:41:46.120
you can say, ah, no, actually it's estrogen
link |
00:41:49.460
that makes people aggressive
link |
00:41:51.280
and animals aggressive for that matter.
link |
00:41:53.860
Now, of course, it is the case
link |
00:41:55.660
that because males have relatively less estrogen
link |
00:42:00.240
circulating in their brain and body than females, right?
link |
00:42:03.220
Because they have testes, not ovaries,
link |
00:42:05.120
that testosterone is required in the first place
link |
00:42:09.440
in order to be converted into estrogen
link |
00:42:11.320
to activate this aggressive circuit
link |
00:42:13.620
involving these estrogen receptor containing neurons
link |
00:42:16.160
in the ventromedial hypothalamus.
link |
00:42:17.880
But nonetheless, it is estrogen that is the final step.
link |
00:42:23.080
It is the hormone on which aggression hinges.
link |
00:42:27.440
And I think for most people,
link |
00:42:28.720
that's a quite surprising finding.
link |
00:42:30.600
And yet this is perhaps one of the more robust findings
link |
00:42:33.360
in both the animal and human literature
link |
00:42:36.280
as it relates to hormones
link |
00:42:38.400
and psychological states and behavior.
link |
00:42:40.560
Now, of course, it is the case that if testosterone is low,
link |
00:42:44.600
that a person or an animal
link |
00:42:46.680
will exhibit less aggressive behavior,
link |
00:42:50.000
but that's not because of reduced testosterone per se,
link |
00:42:52.400
it's because of the subsequent reduction in testosterone,
link |
00:42:55.880
meaning if there's no testosterone
link |
00:42:57.400
to aromatize into estrogen, estrogen will also be lower.
link |
00:43:00.400
So we've established that it's not testosterone,
link |
00:43:03.360
but testosterone converted into estrogen
link |
00:43:05.920
that activates these circuits for aggression.
link |
00:43:08.660
But nonetheless, it's still surprising, right?
link |
00:43:12.080
I mean, most of us don't think about estrogen
link |
00:43:14.600
as the hormone that stimulates aggression,
link |
00:43:17.440
but turns out it's all contextual.
link |
00:43:20.440
There are beautiful data
link |
00:43:21.760
showing that whether or not estrogen stimulates aggression
link |
00:43:26.120
can be powerfully modulated
link |
00:43:28.620
by whether or not days are short or days are long.
link |
00:43:31.760
In other words, whether or not
link |
00:43:33.000
there's a lot of sunshine or not.
link |
00:43:35.280
Now, obviously brain is encased in skull,
link |
00:43:39.800
so it doesn't really know
link |
00:43:41.320
if there's a lot of sunshine out there,
link |
00:43:42.640
even though you can see the sun with your eyes,
link |
00:43:44.160
you can feel it on your skin.
link |
00:43:46.360
Day length is converted into hormonal signals
link |
00:43:49.880
and chemical signals,
link |
00:43:50.800
and the primary hormonal and chemical signals
link |
00:43:53.000
involve melatonin and dopamine and also the stress hormones.
link |
00:43:57.720
So to make a very long story short,
link |
00:43:59.700
in the long days where we get a lot of sunlight,
link |
00:44:01.860
both in our eyes and on our skin,
link |
00:44:04.320
melatonin levels are reduced.
link |
00:44:06.000
Melatonin is a hormone
link |
00:44:06.920
that tends to produce states of sleepiness and quiescence.
link |
00:44:10.580
It also tends to activate pathways
link |
00:44:12.120
that tend to reduce things like breeding
link |
00:44:14.680
and sexual behavior.
link |
00:44:16.560
In long days, dopamine is increased.
link |
00:44:19.080
Dopamine is a molecule associated
link |
00:44:20.600
with feelings of wellbeing and motivation,
link |
00:44:23.860
and the desire to seek out all sorts of things,
link |
00:44:27.320
all sorts of motivated behaviors.
link |
00:44:29.200
And in long days,
link |
00:44:31.020
provided we're getting enough sunlight on our skin
link |
00:44:33.760
and to our eyes,
link |
00:44:36.080
the stress hormones, especially cortisol
link |
00:44:38.420
and some of the other stress hormones
link |
00:44:39.720
are reduced in levels.
link |
00:44:42.420
If estrogen levels are increased experimentally
link |
00:44:45.760
under long day conditions,
link |
00:44:48.120
it does not evoke aggression.
link |
00:44:49.960
However, in short days, if estrogen is increased,
link |
00:44:53.280
there's a heightened predisposition for aggression.
link |
00:44:56.240
And that makes perfect sense
link |
00:44:59.420
if you think about what short days do
link |
00:45:01.360
to the biology of your brain and body.
link |
00:45:03.520
In short days, the melatonin signal goes up.
link |
00:45:06.320
There's more melatonin circulating
link |
00:45:07.740
for more of each 24 hour cycle.
link |
00:45:10.780
Stress hormones are circulating more.
link |
00:45:13.440
Why?
link |
00:45:14.280
Short days tend to be associated with winter.
link |
00:45:16.240
In winter, we are bombarded with more bacteria and viruses
link |
00:45:19.480
because bacteria and viruses actually survive better
link |
00:45:24.020
in cold than they do in heat.
link |
00:45:25.600
In fact, in my laboratory,
link |
00:45:26.520
we work with a lot of viruses and bacteria
link |
00:45:28.280
and when we want to keep them alive,
link |
00:45:29.380
we put them in the freezer.
link |
00:45:30.600
If we want to kill them, if we want to inoculate them,
link |
00:45:32.600
we put them under UV light
link |
00:45:34.120
like you would see from the sunlight.
link |
00:45:35.720
So shorter days are conducive to aggression,
link |
00:45:38.680
not because days are short per se,
link |
00:45:41.600
but because stress hormone levels are higher
link |
00:45:43.800
and because dopamine levels are lower.
link |
00:45:47.520
Now here's where all of this starts to converge
link |
00:45:48.900
on a very clear biological picture,
link |
00:45:51.320
a very clear psychological picture,
link |
00:45:53.200
and indeed a very clear set of tools
link |
00:45:55.800
that we can think about and use.
link |
00:45:59.360
Under conditions where cortisol is high,
link |
00:46:01.380
where the stress hormone is elevated,
link |
00:46:04.360
and under conditions where the neuromodulator serotonin
link |
00:46:07.840
is reduced, there is a greater propensity
link |
00:46:11.680
for estrogen to trigger aggression.
link |
00:46:14.880
Now, again, I know I've said it before,
link |
00:46:17.480
but for males who make a lot of testosterone
link |
00:46:20.660
relative to estrogen, you have to swap in your mind
link |
00:46:23.880
this idea that if testosterone is high,
link |
00:46:26.380
that means that estrogen is low
link |
00:46:27.800
because while that can be true in the periphery in the body,
link |
00:46:31.360
if testosterone is high,
link |
00:46:33.240
there is going to be some aromatization,
link |
00:46:35.320
that conversion of testosterone to estrogen.
link |
00:46:37.240
So anytime you hear that testosterone is high,
link |
00:46:39.520
you should think testosterone is high in the body
link |
00:46:42.160
and perhaps estrogen is low in the body,
link |
00:46:43.760
but that means that there's going to be heightened levels
link |
00:46:45.640
of estrogen in the brain
link |
00:46:47.400
and therefore increased propensity for aggression.
link |
00:46:51.480
In females who generally make less testosterone
link |
00:46:54.520
relative to estrogen,
link |
00:46:57.520
there is sufficient estrogen already present
link |
00:46:59.800
to trigger aggression.
link |
00:47:01.660
So both males and females are primed for aggression,
link |
00:47:06.280
but that's riding on a context
link |
00:47:09.240
and that context of whether or not you get a tendency
link |
00:47:12.040
for aggression or not
link |
00:47:13.880
depends on whether or not cortisol is high or low
link |
00:47:16.320
and I'm telling you that if cortisol is relatively higher
link |
00:47:19.760
in any individual, there's going to be a tilt,
link |
00:47:22.820
an increase in that hydraulic pressure
link |
00:47:25.240
that Lorenz talked about toward aggression.
link |
00:47:29.400
And if serotonin, the neuromodulator
link |
00:47:33.520
that is associated with feelings of wellbeing
link |
00:47:35.880
and sometimes even of slight passivity,
link |
00:47:38.160
but certainly of wellbeing, if serotonin is low,
link |
00:47:41.480
there's also going to be a further shift
link |
00:47:43.620
towards an aggressive tendency.
link |
00:47:46.280
So if we return to Lorenz's hydraulic pressure model
link |
00:47:50.080
of aggression and other internal states,
link |
00:47:52.840
we realize that external stimuli,
link |
00:47:55.620
things that we hear, things that we see,
link |
00:47:57.900
for instance, someone saying something upsetting
link |
00:47:59.860
or us seeing somebody do something
link |
00:48:03.000
that we don't like to others or to us,
link |
00:48:06.680
as well as our internal state,
link |
00:48:08.920
our subjective feelings of wellbeing,
link |
00:48:11.040
but also our stress level,
link |
00:48:12.400
our feelings of whether or not we have enough resources
link |
00:48:15.280
and are content with what we have,
link |
00:48:17.120
all of that is converging on this thing
link |
00:48:18.840
that we call internal state and creating this pressure
link |
00:48:21.280
of either to be more aggressive or less aggressive.
link |
00:48:23.660
And now we have some major players
link |
00:48:26.020
feeding into that final pathway,
link |
00:48:29.100
that question of whether or not
link |
00:48:30.360
will we hit the other person?
link |
00:48:31.680
Will we say the thing that is considered aggressive?
link |
00:48:35.160
Will we not say it?
link |
00:48:36.640
If somebody says something or does something aggressive
link |
00:48:39.620
to us, will we respond or will we be submissive
link |
00:48:41.880
or even passive?
link |
00:48:43.520
Again, there are many things funneling into that question
link |
00:48:46.640
and dictating whether or not the answer is,
link |
00:48:48.160
absolutely, I'll fight back,
link |
00:48:49.540
or I'm going to attack them even unprovoked,
link |
00:48:51.920
or if they say this, I'm going to do that,
link |
00:48:54.020
or no matter what they do, I'm not going to respond.
link |
00:48:57.120
These kinds of things are very complex
link |
00:48:59.040
and yet we really can boil them down
link |
00:49:00.980
to just a few common elements.
link |
00:49:02.560
And I'm telling you that those elements
link |
00:49:04.080
are whether or not cortisol levels are relatively lower
link |
00:49:08.240
or relatively higher.
link |
00:49:09.420
Again, relatively higher is going to tend
link |
00:49:11.280
to make people more reactive, why?
link |
00:49:13.680
Because reactivity is really a function
link |
00:49:17.080
of the autonomic nervous system,
link |
00:49:18.940
which is sort of like a seesaw that oscillates
link |
00:49:21.040
between the so-called sympathetic arm
link |
00:49:24.080
of the autonomic nervous system,
link |
00:49:25.160
which tends to put us into a state of readiness
link |
00:49:27.160
through the release of adrenaline.
link |
00:49:28.680
Cortisol and adrenaline,
link |
00:49:29.940
when they're circulating in the brain and body,
link |
00:49:31.560
make us more likely to move and to react and to speak.
link |
00:49:34.760
It's actually what will induce a kind of low-level tremor,
link |
00:49:37.280
which is an anticipatory tremor
link |
00:49:38.840
to be able to move more quickly, right?
link |
00:49:40.840
A body in motion is more easily set into further motion,
link |
00:49:44.020
that is.
link |
00:49:45.900
And the neuromodulator serotonin is a neuromodulator
link |
00:49:50.040
that in general is associated with feelings of wellbeing
link |
00:49:54.880
in response to what we already have.
link |
00:49:56.400
So when we are well-fed,
link |
00:49:58.280
serotonin tends to be released in our brain and body,
link |
00:50:00.480
in particular, well-fed with carbohydrates.
link |
00:50:02.560
The precursor to serotonin is tryptophan.
link |
00:50:06.360
And indeed, there are nice studies exploring
link |
00:50:09.240
the types of diets, nutritional programs,
link |
00:50:12.400
that can reduce aggressive behavior,
link |
00:50:15.280
both in children and in adults.
link |
00:50:16.960
And tryptophan-rich diets or supplementation with tryptophan.
link |
00:50:20.760
So for tryptophan-rich diets, things like white turkey meat,
link |
00:50:24.240
but then there are also a number of carbohydrates.
link |
00:50:25.880
You can look up, it's very easy to find,
link |
00:50:28.360
foods that contain lots of tryptophan.
link |
00:50:30.400
Those foods contain the precursor to serotonin.
link |
00:50:34.960
Now, it isn't simply the case that eating more foods
link |
00:50:37.140
with tryptophan will tend to reduce your aggression.
link |
00:50:39.960
I suppose it could do that if you ate it in abundance,
link |
00:50:42.760
it could make you tired,
link |
00:50:43.800
and then you're less likely to be aggressive.
link |
00:50:45.680
I don't recommend that strategy.
link |
00:50:47.720
But the idea here is that when it's been explored,
link |
00:50:51.680
increasing levels of tryptophan,
link |
00:50:53.520
either by supplementation or by food,
link |
00:50:55.520
or drugs, prescription drugs that increase serotonin,
link |
00:50:59.100
so for instance, fluoxetine, sometimes called Prozac
link |
00:51:01.560
or Zoloft or any number of the other SSRIs,
link |
00:51:03.880
tend to reduce aggressive behavior.
link |
00:51:05.760
Now, not always, but in general, that's the case.
link |
00:51:08.900
Similarly, because elevated cortisol
link |
00:51:11.240
tends to shift the whole system,
link |
00:51:13.120
again, create more of a hydraulic pressure
link |
00:51:15.080
towards aggressive states.
link |
00:51:16.560
If cortisol levels are reduced,
link |
00:51:18.700
well, then the tendency for aggressive behavior is reduced.
link |
00:51:21.800
This is supported by a number of peer-reviewed studies.
link |
00:51:24.080
We'll provide links to some of those
link |
00:51:25.360
in the caption show notes.
link |
00:51:26.680
And we're going to return to these a bit later
link |
00:51:28.880
in the context of specific studies
link |
00:51:30.680
that have looked at genetic variants
link |
00:51:34.000
in different individuals that cause them
link |
00:51:36.040
to make more or less serotonin,
link |
00:51:38.120
or at least to metabolize serotonin differently.
link |
00:51:40.620
This is also the case for so-called
link |
00:51:42.720
intermittent explosive disorder
link |
00:51:44.960
that can often be associated with gene variants
link |
00:51:49.080
that control how much serotonin is made
link |
00:51:52.360
or how it's metabolized or how much cortisol is made
link |
00:51:54.560
and how much it's metabolized.
link |
00:51:56.440
In thinking about tools,
link |
00:51:57.460
there are a number of things that one could consider.
link |
00:51:59.160
First of all, there are a number of decent studies
link |
00:52:03.000
exploring how supplementation with the omega-3 fatty acids,
link |
00:52:06.600
which are precursors of some of the transmitter systems,
link |
00:52:11.640
including serotonin, that can modulate,
link |
00:52:14.520
not directly mediate, but modulate mood and emotional tone.
link |
00:52:18.840
Supplementation with the omega-3s
link |
00:52:20.320
has been shown to reduce impulsivity and aggressiveness
link |
00:52:23.260
in certain contexts, in things like ADHD
link |
00:52:26.520
or in individuals who have a predisposition
link |
00:52:29.160
for aggressive type behavior or aggressive thinking.
link |
00:52:32.380
Now, that doesn't necessarily mean
link |
00:52:34.240
that the omega-3 fatty acids are going directly
link |
00:52:37.160
to the ventromedial hypothalamus
link |
00:52:38.560
and changing the activity of neurons there.
link |
00:52:40.480
More likely, they are causing or modulating
link |
00:52:43.320
an overall shift in mood through the immune system,
link |
00:52:47.600
through hormone systems that are changing the overall tone
link |
00:52:51.880
or the propensity for neurons
link |
00:52:53.600
in the ventromedial hypothalamus to be activated.
link |
00:52:56.880
How much omega-3 fatty acid, what source?
link |
00:52:59.040
Well, we've talked about this on the podcast before.
link |
00:53:01.440
You can, of course, get omega-3 fatty acids
link |
00:53:03.300
from a number of different foods.
link |
00:53:04.440
Getting them from whole foods
link |
00:53:05.720
is probably the best way to do it.
link |
00:53:07.480
But many people, including people with depression,
link |
00:53:10.060
will often supplement with one gram or more
link |
00:53:12.600
of omega-3 fatty acids per day.
link |
00:53:14.520
Some people, including myself, will take them every day
link |
00:53:17.960
as just a general mood enhancer.
link |
00:53:20.060
I don't suffer from depression,
link |
00:53:21.240
but I've found it to be beneficial for my health.
link |
00:53:24.400
And so some people will do that.
link |
00:53:25.760
And I've talked about before
link |
00:53:26.740
how in double-blind placebo-controlled studies,
link |
00:53:28.860
people taking one to three grams of omega-3 fatty acids
link |
00:53:31.760
per day, typically in the form of a high-quality fish oil,
link |
00:53:34.000
although there are other sources as well,
link |
00:53:35.800
algae and so forth,
link |
00:53:38.120
can experience improvements in mood
link |
00:53:40.460
that are on par with some of the SSRIs,
link |
00:53:43.000
the selective serotonin reuptake inhibitors.
link |
00:53:44.920
And of course, if you are prescribed an SSRI
link |
00:53:46.740
by your psychiatrist or other doctor,
link |
00:53:48.240
please do take that and don't cease to take it,
link |
00:53:50.620
just simply to take omega-3s.
link |
00:53:52.320
However, you might mention to them,
link |
00:53:54.860
and you can find links to the studies
link |
00:53:56.400
in our previous episodes on depression,
link |
00:53:58.400
that supplementation with omega-3 fatty acids
link |
00:54:02.080
at this one gram or more of EPA specifically,
link |
00:54:05.080
so getting above that one gram threshold
link |
00:54:06.820
as high as three grams per day of the EPA
link |
00:54:10.920
has allowed people to take lower doses of SSRIs
link |
00:54:14.520
and still keep their mood in a place
link |
00:54:16.480
that's beneficial for them.
link |
00:54:18.160
And in terms of keeping cortisol in a range
link |
00:54:20.600
that's healthy and doesn't bias someone
link |
00:54:22.560
toward high levels of aggression and irritability,
link |
00:54:25.940
that's again going to be set
link |
00:54:28.780
by a number of larger modulators or contextual cues.
link |
00:54:32.140
And I've talked about some of those on the podcast,
link |
00:54:33.780
but I'll just briefly recap them now.
link |
00:54:35.940
Obviously getting sunlight in your eyes early in the day
link |
00:54:39.000
and as much sunlight as you safely can in your eyes
link |
00:54:42.080
throughout the day is going to be important.
link |
00:54:44.100
Again, because of this effect of estrogen in long days,
link |
00:54:48.460
not increasing aggression.
link |
00:54:50.540
However, in shorter days, estrogen increases aggression
link |
00:54:53.500
because of the increase in cortisol observed in short days.
link |
00:54:57.780
Another way to reduce cortisol was discussed
link |
00:55:00.660
in our episode on heat and the use of sauna and heat,
link |
00:55:03.780
but also hot baths.
link |
00:55:04.820
It turns out that hot baths and sauna
link |
00:55:07.380
can be very beneficial for reducing cortisol.
link |
00:55:09.580
All the details on that are included
link |
00:55:10.980
in the episode on heat and its timestamp,
link |
00:55:12.620
so you can go directly to that
link |
00:55:14.100
if you want to learn about the temperatures
link |
00:55:15.540
and the various durations,
link |
00:55:16.660
but to just give a synopsis of that,
link |
00:55:20.340
a 20 minute sauna at anywhere from 80 to 100 degrees Celsius
link |
00:55:26.900
is going to be beneficial for reducing cortisol.
link |
00:55:29.900
If you don't have access to a sauna,
link |
00:55:31.300
you could do a hot bath,
link |
00:55:33.100
adjust the temperature so you don't burn yourself.
link |
00:55:34.820
I think 80 to 100 degrees Celsius is going to be too hot
link |
00:55:37.460
for many people if it's a hot bath,
link |
00:55:39.140
whereas many people who can't tolerate that hot bath
link |
00:55:42.180
can tolerate the sauna.
link |
00:55:43.180
So safety first, always, and of course,
link |
00:55:46.020
but hot baths reduce cortisol.
link |
00:55:49.420
Hot saunas reduce cortisol of a duration
link |
00:55:52.260
about 20 or 30 minutes is going to be beneficial.
link |
00:55:54.420
And of course, some of you may be interested
link |
00:55:56.060
in exploring the supplementation route
link |
00:55:57.500
and for reductions in cortisol,
link |
00:55:59.700
really the chief player there is ashwagandha,
link |
00:56:03.180
which is known to decrease cortisol fairly potently.
link |
00:56:06.820
I should just warn you that if you're going to use
link |
00:56:08.540
ashwagandha in order to reduce cortisol,
link |
00:56:11.300
first of all, check with your doctor or healthcare provider
link |
00:56:13.820
before adding or subtracting anything
link |
00:56:15.540
from your supplementation or health regimen.
link |
00:56:17.380
Of course, I don't just say that to protect us.
link |
00:56:18.980
I say that to protect you.
link |
00:56:20.140
You are responsible for your health,
link |
00:56:22.100
what you take and what you don't take.
link |
00:56:25.280
Chronic supplementation with ashwagandha
link |
00:56:27.100
can have some not so great effects of disruption
link |
00:56:30.300
of other hormone pathways and neurotransmitter pathways.
link |
00:56:33.060
So the limit seems to be about two weeks of regular use
link |
00:56:36.540
before you'd want to take a break of about two weeks.
link |
00:56:39.300
So ashwagandha, again, a very potent inhibitor of cortisol,
link |
00:56:42.940
but with some other effects as well,
link |
00:56:45.340
don't use it chronically for longer than two weeks.
link |
00:56:47.380
But if your goal is to reduce cortisol,
link |
00:56:49.460
let's say you're going through a period
link |
00:56:50.580
of increased irritability and aggressive tendency,
link |
00:56:53.700
maybe you're also not getting as much light
link |
00:56:55.420
as you would like, and perhaps also
link |
00:56:57.340
if there are other circumstantial things
link |
00:57:00.020
leading you towards more aggressiveness
link |
00:57:01.400
and your goal is to reduce aggressiveness,
link |
00:57:03.340
that can be potentially helpful.
link |
00:57:05.180
And in light of all this stuff about cortisol
link |
00:57:07.900
and estrogen and day length,
link |
00:57:10.900
I should mention that there are in fact some people
link |
00:57:13.700
who have a genetic predisposition
link |
00:57:16.220
to be more irritable and aggressive.
link |
00:57:19.860
There are a couple of different gene pathways
link |
00:57:21.900
associated with this.
link |
00:57:23.100
We never like to think about just one gene
link |
00:57:25.340
causing a specific behavior.
link |
00:57:27.540
The way to think about genes is that genes generally code
link |
00:57:30.620
for things within our biology,
link |
00:57:33.620
in the context of today's discussion,
link |
00:57:35.060
things like neural circuits
link |
00:57:36.860
or the amounts of neurotransmitters that are made
link |
00:57:39.260
or the amounts of hormones that are made
link |
00:57:40.740
or the amount of neurotransmitter hormone receptors
link |
00:57:43.320
or enzymes, et cetera,
link |
00:57:45.280
that shift the activity of our biology
link |
00:57:48.540
in a particular direction, they bias our biology.
link |
00:57:51.620
And in fact, there is a genetic variant
link |
00:57:55.320
present in certain people
link |
00:57:58.140
that adjusts their estrogen receptor sensitivity
link |
00:58:02.180
and that estrogen receptor sensitivity
link |
00:58:05.100
can result in increased levels of aggression,
link |
00:58:08.340
sometimes dramatic increases.
link |
00:58:10.300
However, and also very interestingly,
link |
00:58:13.180
photoperiod, meaning day length,
link |
00:58:15.860
is a strong modulator of whether or not
link |
00:58:18.820
that aggressiveness turns up or not.
link |
00:58:20.920
Whether or not that person with the particular gene variant
link |
00:58:25.080
is more aggressive or not depends on how long the day is
link |
00:58:28.700
and how long the night is.
link |
00:58:30.300
One particular study that I like that references this
link |
00:58:33.060
is Trainor et al, the title of the study is
link |
00:58:35.680
photoperiod reverses the effects of estrogens
link |
00:58:38.180
on male aggression via genomic and non-genomic pathways.
link |
00:58:41.660
This was a paper published in the Proceedings
link |
00:58:43.500
of the National Academy of Sciences.
link |
00:58:45.340
We'll put a reference to this in the show notes
link |
00:58:47.520
if you'd like to explore it further.
link |
00:58:49.220
But it really points to the fact that rarely,
link |
00:58:52.720
sometimes, but rarely is it the case
link |
00:58:55.300
that just one gene will cause somebody
link |
00:58:57.860
to be hyper aggressive.
link |
00:59:00.300
Almost always, there's going to be an interplay
link |
00:59:02.260
between genetics and environment
link |
00:59:04.080
and as environment changes, such as day length changes
link |
00:59:07.080
and the length of night changes,
link |
00:59:08.520
so too will the tendency for people with a given
link |
00:59:11.660
genetic variant to be more aggressive or not.
link |
00:59:14.620
Now, of course, in the absence of detailed genetic testing
link |
00:59:17.340
for this particular estrogen receptor variant,
link |
00:59:19.460
most people, I'm guessing you,
link |
00:59:21.140
are probably not walking around knowing
link |
00:59:22.540
that you have this gene or not.
link |
00:59:26.100
Regardless, I think it's important to pay attention
link |
00:59:28.820
to how you feel at different times of year,
link |
00:59:31.140
depending on whether or not it's summer,
link |
00:59:33.040
whether or not it's winter,
link |
00:59:33.880
whether or not you're getting sufficient sunlight,
link |
00:59:36.200
meaning viewing sufficient sunlight or not,
link |
00:59:38.140
whether or not you're getting sufficient sunlight exposure
link |
00:59:40.180
to your skin or not,
link |
00:59:41.320
whether or not you're indoors all the time.
link |
00:59:42.940
Generally, those things correlate with season,
link |
00:59:46.320
but not always.
link |
00:59:47.580
You can go through long bouts of hard work
link |
00:59:50.280
in the summer months when days are long,
link |
00:59:51.940
but you're indoors a lot and getting a lot
link |
00:59:53.640
of fluorescent light exposure late in the evening,
link |
00:59:55.460
and perhaps that's when you're feeling more aggressive.
link |
00:59:57.700
So we have to be careful about drawing
link |
00:59:58.940
a one-to-one relationship between any biological feature
link |
01:00:02.500
and certainly psychological or behavioral feature
link |
01:00:04.940
like aggressiveness, but it's, I believe,
link |
01:00:07.420
helpful to know that these genetic biases exist,
link |
01:00:11.020
how they play out.
link |
01:00:11.980
Again, they shift our biology
link |
01:00:13.380
in a general thematic direction.
link |
01:00:16.660
They don't change one thing.
link |
01:00:17.740
They change a variety of things that bias us toward
link |
01:00:20.020
or away from certain psychological and behavioral outcomes
link |
01:00:23.100
and the various things that we can do
link |
01:00:25.700
in order to offset them.
link |
01:00:27.300
We described those earlier in terms of trying
link |
01:00:28.900
to keep cortisol low by getting sufficient sunlight
link |
01:00:31.100
regardless of time of year and regardless of whether
link |
01:00:34.180
or not you happen to have this particular genetic variant.
link |
01:00:36.680
So earlier I talked about how it is testosterone converted
link |
01:00:39.740
into estrogen that's activating aggression
link |
01:00:42.180
in the ventromedial hypothalamus, not testosterone itself.
link |
01:00:45.520
However, there are some studies carried out in humans
link |
01:00:48.520
that have evaluated the effects of testosterone
link |
01:00:51.340
and how levels of testosterone correlate
link |
01:00:53.660
with aggressiveness in the short term.
link |
01:00:56.180
I'm just going to detail a few of those studies
link |
01:00:57.960
because I think they are interesting and important.
link |
01:01:02.460
First of all, there is a study that has explored levels
link |
01:01:05.660
of testosterone in men of different professions.
link |
01:01:09.020
Now, before I tell you the data,
link |
01:01:10.460
I want to be very clear here.
link |
01:01:13.500
With a study such as this, one never knows whether
link |
01:01:15.940
or not these men went into a particular profession
link |
01:01:19.180
because they had a testosterone level of a given value
link |
01:01:23.980
or whether or not the work itself altered
link |
01:01:27.420
their testosterone levels or both.
link |
01:01:30.300
And I think it's fair to assume that it's probably both.
link |
01:01:34.320
So be very careful in assuming
link |
01:01:36.020
that a given testosterone level is causal
link |
01:01:39.980
for choosing a particular career
link |
01:01:41.380
or that a particular career is causal
link |
01:01:43.420
for creating a particular testosterone level.
link |
01:01:46.260
This study used salivary testosterone levels
link |
01:01:49.460
as the measure, which to be fair,
link |
01:01:52.100
is not the best way to measure testosterone.
link |
01:01:55.260
Typically blood draw would be the best way
link |
01:01:57.180
to measure testosterone, but nonetheless,
link |
01:01:59.460
provided the appropriate methods are used,
link |
01:02:01.760
salivary testosterone can be a reasonable measure
link |
01:02:04.060
of testosterone.
link |
01:02:05.820
The different occupations that were looked at were,
link |
01:02:09.700
and here they just looked at men in this particular study,
link |
01:02:12.440
were ministers, salesmen,
link |
01:02:14.540
they didn't say what particular types of salesmen,
link |
01:02:16.300
firemen, professors of all things,
link |
01:02:19.420
physicians and NFL players.
link |
01:02:21.740
And what they discovered was that the testosterone levels
link |
01:02:26.300
were essentially in that order from low to highest.
link |
01:02:29.380
So minister, salesman, fireman, professor,
link |
01:02:31.700
physician, NFL player.
link |
01:02:34.000
Now we could micro dissect all the different stereotypes
link |
01:02:38.500
and all the different features of each of these jobs.
link |
01:02:41.300
For instance, we don't know whether or not the fact
link |
01:02:44.280
that the fireman happened, at least in this study,
link |
01:02:47.140
to have lower testosterone levels on average
link |
01:02:49.660
than the professors or the physicians
link |
01:02:51.600
was because firemen have lower testosterone levels
link |
01:02:54.020
or because they have a much more stressful job
link |
01:02:55.960
and their cortisol levels are higher
link |
01:02:58.260
than the professor or the physician
link |
01:03:01.120
and cortisol and testosterone, not always,
link |
01:03:03.480
but generally are in somewhat antagonistic push-pull mode
link |
01:03:07.680
because they derive from the same precursor, et cetera.
link |
01:03:09.740
Typically when cortisol is high,
link |
01:03:12.180
testosterone tends to be lower and vice versa.
link |
01:03:14.460
So we don't know what's causing these effects.
link |
01:03:17.180
And again, this is just one study and just six occupations,
link |
01:03:21.200
but I think it's relatively interesting
link |
01:03:22.600
given the fact that each of these professions
link |
01:03:24.200
involves different levels of competitiveness, right?
link |
01:03:27.380
So we don't necessarily just want to think about the level
link |
01:03:29.620
of physical exertion that's required,
link |
01:03:32.500
but also the level of competitiveness
link |
01:03:34.280
because it's known that competitive interactions
link |
01:03:36.740
can cause increases in testosterone,
link |
01:03:40.220
in particular in the winners of competitive interactions,
link |
01:03:42.900
a topic for a future podcast.
link |
01:03:45.260
Meanwhile, studies that have analyzed
link |
01:03:48.380
also again salivary testosterone in prisoners,
link |
01:03:53.100
in this case, female prisoners,
link |
01:03:55.340
so these are incarcerated individuals,
link |
01:03:57.400
have looked at levels of testosterone
link |
01:03:59.740
according to whether or not the person committed
link |
01:04:02.620
a nonviolent or a violent crime
link |
01:04:04.720
in order to arrive in prison,
link |
01:04:06.300
and higher levels of salivary testosterone
link |
01:04:08.940
were related to those that had arrived in prison
link |
01:04:13.780
because of conviction of a violent crime
link |
01:04:16.740
as opposed to a nonviolent crime.
link |
01:04:18.580
Likewise, when they analyze prison rule violations,
link |
01:04:21.780
so an indirect measure of aggressiveness,
link |
01:04:24.260
but in this case, it was strongly associated
link |
01:04:26.660
with aggressiveness because they knew
link |
01:04:27.700
what the violations were,
link |
01:04:29.260
they found were for prisoners that had none,
link |
01:04:32.060
no prison violations, prison rule violations,
link |
01:04:35.460
I should say their testosterone levels tended to be lower
link |
01:04:39.520
than the testosterone levels of women that had some,
link |
01:04:42.860
even one or more aggressive violations of prison rules.
link |
01:04:48.020
We'll provide links to these studies in the show notes
link |
01:04:51.440
if you'd like to go into them further.
link |
01:04:53.480
Obviously studies like this need to be taken
link |
01:04:55.340
with a grain of salt because there are so many
link |
01:04:57.700
different factors, different prisons have different degrees
link |
01:05:00.940
of violence to begin with and competitiveness to begin with.
link |
01:05:05.460
But just as a final pass at examining the role
link |
01:05:07.980
between testosterone and aggressiveness,
link |
01:05:10.380
there was a very interesting study from Gotz et al.
link |
01:05:13.580
G-O-E-T-Z published in 2014 that looked at serum,
link |
01:05:19.620
so in this case, blood levels of testosterone,
link |
01:05:22.380
30 minutes after application of a gel-based testosterone
link |
01:05:26.620
that goes transdermal so that the testosterone
link |
01:05:28.780
can go very quickly into the bloodstream
link |
01:05:30.500
and then did brain imaging to evaluate the activity
link |
01:05:34.820
of neurons in the so-called corticomedial amygdala.
link |
01:05:38.860
The medial amygdala is one of the areas
link |
01:05:41.540
of the amygdala complex as we call it because it's complex,
link |
01:05:44.460
it's got a lot of different nuclei,
link |
01:05:46.220
you now know what nuclei are, little clusters of neurons,
link |
01:05:48.260
it's got a lot of different ones,
link |
01:05:49.240
but that medial and that corticomedial amygdala
link |
01:05:52.980
in particular is known to be associated
link |
01:05:55.300
with aggressive type behaviors.
link |
01:05:57.260
It's linked up with, it's part of the larger circuit
link |
01:05:59.980
that includes the ventromedial hypothalamus
link |
01:06:02.760
and other brain areas that we referred to earlier,
link |
01:06:04.540
such as the PAG.
link |
01:06:07.340
What is remarkable about this study is that it showed
link |
01:06:10.260
that just 30 minutes after application
link |
01:06:13.120
of this so-called androgel,
link |
01:06:14.380
this testosterone that seeps into the bloodstream,
link |
01:06:16.980
there was a significant increase in, of course,
link |
01:06:20.080
testosterone and corticomedial amygdala activation.
link |
01:06:25.360
So testosterone can have acute effects,
link |
01:06:27.900
immediate effects on the pathways related to aggression.
link |
01:06:31.220
And I think this is something that's not often discussed
link |
01:06:33.620
because many of the effects of steroid hormones
link |
01:06:36.280
like testosterone and estrogen are very slow acting.
link |
01:06:38.640
In fact, steroid hormones,
link |
01:06:40.300
because they have a certain biochemical composition,
link |
01:06:43.900
can actually pass through the membranes of cells,
link |
01:06:46.260
so the outside of a cell and into the nucleus of the cell
link |
01:06:48.660
and change gene expression in the cell.
link |
01:06:50.700
Think about puberty, the kid that goes home for the summer
link |
01:06:53.020
and then comes back looking completely different.
link |
01:06:55.120
Well, that's because a lot of genes got turned on
link |
01:06:57.240
by steroid hormones like testosterone and estrogen,
link |
01:07:00.700
but the steroid hormones can also have
link |
01:07:02.580
very fast acting effects.
link |
01:07:05.020
And with testosterone in particular,
link |
01:07:06.780
those can be remarkably fast acting.
link |
01:07:08.880
And one of the most apparent
link |
01:07:10.700
and well-documented fast acting effects is this effect,
link |
01:07:13.180
the ability to activate cells within the amygdala.
link |
01:07:16.200
So you might say, well,
link |
01:07:17.040
I thought the amygdala was associated with fear,
link |
01:07:18.760
wouldn't testosterone then cause fear?
link |
01:07:20.340
No, turns out that the amygdala harbors both cortisol,
link |
01:07:25.020
corticosterone receptors, and testosterone receptors,
link |
01:07:27.840
and they each adjust the activity
link |
01:07:29.840
in the amygdala differently,
link |
01:07:31.640
such that testosterone tends to activate amygdala circuitry
link |
01:07:36.140
for inducing states of mind and body
link |
01:07:40.080
that are more action-based.
link |
01:07:41.940
And indeed in animals and in humans,
link |
01:07:43.900
testosterone application and activation
link |
01:07:45.840
of this corticomedial amygdala pathway
link |
01:07:47.780
will make animals and humans lean into effort.
link |
01:07:50.100
This is why I say testosterone makes effort feel good,
link |
01:07:52.500
or at least biases the organism
link |
01:07:54.640
toward leaning into challenge.
link |
01:07:56.340
So if you recall, there's not just one type of aggression,
link |
01:07:59.660
there's reactive aggression,
link |
01:08:01.660
which is triggered when one is confronted with something
link |
01:08:04.500
that sometimes is inevitable, right?
link |
01:08:06.580
One needs to fight for their life
link |
01:08:07.940
or for somebody else's life,
link |
01:08:09.540
but also proactive aggression.
link |
01:08:12.340
And proactive aggression involves activation
link |
01:08:14.780
of those go pathways in the basal ganglia
link |
01:08:17.100
and a leaning into effort to overcome
link |
01:08:19.100
whatever state one happens to be in to begin with.
link |
01:08:22.020
And so this is very important because it points to the fact
link |
01:08:24.560
that yes, estrogen is activating aggression pathways
link |
01:08:28.500
that are in the ventromedial hypothalamus,
link |
01:08:30.580
but it's very likely the case
link |
01:08:32.300
that testosterone is acting to accelerate
link |
01:08:35.180
or to bias states of mind and body
link |
01:08:38.100
toward those that will lead to aggression.
link |
01:08:40.540
Again, aggression is not like a switch on and off,
link |
01:08:43.140
it's a process, it has a beginning, a middle, and an end.
link |
01:08:46.620
Remember that hydraulic pressure
link |
01:08:48.300
that Konrad Lorenz hypothesized?
link |
01:08:50.940
Well, think of testosterone as increasing the pressure
link |
01:08:55.460
toward an aggressive episode
link |
01:08:57.420
and then estrogen actually triggering
link |
01:08:59.580
that aggressive episode in the ventromedial hypothalamus.
link |
01:09:02.400
So if somebody tells you that testosterone,
link |
01:09:04.980
endogenous or exogenous, makes people aggressive,
link |
01:09:07.780
tell them no.
link |
01:09:08.980
Testosterone tends to make people lean into effort
link |
01:09:13.100
and if that effort involves being aggressive,
link |
01:09:16.340
either reactively aggressive or proactively aggressive,
link |
01:09:20.280
well, then it will indeed lead to aggression,
link |
01:09:22.660
but the actual aggression itself
link |
01:09:25.180
is triggered by estrogen, not testosterone.
link |
01:09:28.380
Now, thus far, we really haven't talked too much
link |
01:09:30.580
about the social context in which aggression occurs
link |
01:09:34.660
and that's because there is a near infinite,
link |
01:09:36.500
if not infinite number of variables that will determine that.
link |
01:09:40.340
So for instance, violent aggression is entirely appropriate
link |
01:09:44.220
at a professional boxing match
link |
01:09:46.100
provided it's occurring inside the ring
link |
01:09:48.300
and only between the competitors
link |
01:09:50.220
and within the bounds of the rules of the sport, et cetera.
link |
01:09:55.740
However, there are some things
link |
01:09:58.140
that tend to bias certain social contexts
link |
01:10:01.020
toward being more aggressive or less aggressive
link |
01:10:03.200
and not always physical aggression
link |
01:10:05.460
and those generally come in two forms
link |
01:10:08.260
that many of you are familiar with,
link |
01:10:09.560
which are alcohol and caffeine.
link |
01:10:12.820
Let's discuss caffeine first.
link |
01:10:15.020
Why would caffeine increase aggressive impulsivity?
link |
01:10:18.300
Well, the general effects of caffeine
link |
01:10:20.380
are to increase autonomic arousal,
link |
01:10:22.180
the activity of the so-called sympathetic arm
link |
01:10:25.100
of the autonomic nervous system,
link |
01:10:26.840
which is, to put it very much in plain language,
link |
01:10:30.660
it's the alertness arm of your nervous system.
link |
01:10:34.380
That is, it creates a sense of readiness
link |
01:10:37.100
in your brain and body
link |
01:10:38.420
and it does so by activating
link |
01:10:40.000
the so-called sympathetic chain ganglia.
link |
01:10:41.860
Again, as I always remind people,
link |
01:10:43.260
simpa and sympathetic does not mean sympathy.
link |
01:10:46.660
Simpa means together or all at once
link |
01:10:49.660
and caffeine tends to bias our brain and body
link |
01:10:54.180
to activate the sympathetic chain ganglia,
link |
01:10:57.320
which run from about the base of your neck
link |
01:10:59.500
until the top of your pelvis
link |
01:11:01.160
and deploy a bunch of chemicals
link |
01:11:03.280
that jut out into the rest of your body,
link |
01:11:04.860
activate adrenaline release.
link |
01:11:06.580
There's a parallel increase of adrenaline in your brain,
link |
01:11:10.140
creating the state of alertness and readiness.
link |
01:11:12.500
That state of alertness and readiness
link |
01:11:13.900
can be for all sorts of things, not just aggression.
link |
01:11:16.900
However, when we are in a state
link |
01:11:19.100
of increased sympathetic tone, meaning more alert,
link |
01:11:22.860
such as after drinking caffeine,
link |
01:11:25.200
we will bias all those brain and body systems,
link |
01:11:28.400
the hormones, the chemicals, et cetera,
link |
01:11:30.280
that exist toward action as opposed to inaction.
link |
01:11:34.360
So put simply, caffeine can increase impulsivity.
link |
01:11:37.840
No surprise there.
link |
01:11:39.860
On the opposite end of things,
link |
01:11:41.540
alcohol tends to decrease activity
link |
01:11:46.020
in the sympathetic arm of the autonomic nervous system,
link |
01:11:48.260
tends to make us feel less alert.
link |
01:11:50.020
Now, initially it can create a state of alertness
link |
01:11:52.580
because of its effects in inhibiting the forebrain.
link |
01:11:55.180
Our forebrain prefrontal cortex in particular
link |
01:11:58.040
has what's called top-down inhibition.
link |
01:11:59.940
It exerts a inhibitory or a quieting effect
link |
01:12:04.060
on some of the circuits of the hypothalamus,
link |
01:12:05.820
such as the ventromedial hypothalamus.
link |
01:12:08.020
The way to conceptualize this is that your forebrain
link |
01:12:10.100
is able to rationalize and think clearly
link |
01:12:12.440
and to suppress behavior and to engage the no-go pathways,
link |
01:12:15.940
telling you don't say that mean thing,
link |
01:12:18.480
don't do that violent thing, et cetera.
link |
01:12:20.740
Alcohol initially tends to increase
link |
01:12:23.920
our level of overall activity by reducing inhibition,
link |
01:12:27.760
not just in that forebrain circuit,
link |
01:12:30.200
but in other circuits, tends to make us more active.
link |
01:12:32.200
We tend to talk more than we normally would,
link |
01:12:34.020
move more than we normally would,
link |
01:12:35.660
but very shortly thereafter starts acting as a sedative
link |
01:12:39.580
by way of reducing activity in the forebrain,
link |
01:12:43.380
releasing some of the deeper brain circuits
link |
01:12:45.980
that are involved in impulsivity,
link |
01:12:47.540
but also causing a somewhat sedative effect.
link |
01:12:51.120
And then of course, as alcohol levels increase even further,
link |
01:12:54.100
people eventually will pass out, blackout, et cetera.
link |
01:12:57.940
So what we've got with alcohol and caffeine
link |
01:12:59.900
is we've got two opposite ends of the spectrum,
link |
01:13:01.940
caffeine increasing arousal and readiness
link |
01:13:04.780
and the tendency for impulsivity,
link |
01:13:06.540
and alcohol also increasing impulsivity,
link |
01:13:10.820
but through a different mechanism.
link |
01:13:14.660
A really interesting study,
link |
01:13:16.180
and I should just mention that the title of the study
link |
01:13:18.140
is caffeinated and non-caffeinated alcohol use
link |
01:13:20.900
and indirect aggression, the impact of self-regulation.
link |
01:13:23.820
So the title is almost self-explanatory.
link |
01:13:25.940
This was a paper published in the Journal
link |
01:13:27.700
of Addictive Behavior in 2016,
link |
01:13:30.260
examining how ingestion of alcohol
link |
01:13:34.180
that's either caffeinated or non-caffeinated alcohol drinks
link |
01:13:38.020
impacted what they call indirect aggression.
link |
01:13:40.860
And just to remind you what indirect aggression is,
link |
01:13:42.760
these are not physical acts of aggression,
link |
01:13:44.820
these are verbal acts of aggression.
link |
01:13:46.460
So embarrassing others or otherwise somehow
link |
01:13:50.660
trying to reduce the wellbeing of others
link |
01:13:52.920
by saying certain things in particular in groups.
link |
01:13:56.060
This study examined both males and females.
link |
01:13:58.700
This was done by way of a college campus study.
link |
01:14:02.180
Subjects were 18 to 47 years old.
link |
01:14:04.740
I guess there's some older students on that campus,
link |
01:14:06.340
or maybe they use some non-students,
link |
01:14:07.580
but these days you've also got some students
link |
01:14:09.400
that are in their 30s and 40s.
link |
01:14:11.020
So they have a fairly broad swath of subjects included,
link |
01:14:15.200
fairly broad racial background as well,
link |
01:14:18.020
included not at equal numbers,
link |
01:14:19.520
but at least they included a pretty broad spectrum
link |
01:14:22.220
of people with different backgrounds.
link |
01:14:23.740
They looked in particular at people
link |
01:14:26.260
that ingested non-caffeinated alcohol drinks
link |
01:14:29.020
at a frequency of 9.18 drinks per week.
link |
01:14:32.620
Okay, again, this is a college campus,
link |
01:14:34.140
not that I encourage that.
link |
01:14:35.140
I'm one of these people that I've never really liked,
link |
01:14:38.340
drugs or alcohol, and it's sort of fortunate in that way,
link |
01:14:40.440
I can drink or not drink and tend to not drink.
link |
01:14:43.700
But so to me, 9.18 drinks per week sounds like a lot,
link |
01:14:47.580
but I know for some people that might actually be typical.
link |
01:14:50.300
And then others who were drinking
link |
01:14:52.620
at least one caffeinated alcoholic beverage per week,
link |
01:14:56.820
and those individuals end as high, I should say,
link |
01:14:59.960
as 7.87 caffeinated alcohol beverages per week.
link |
01:15:04.380
So this would be energy drinks
link |
01:15:05.480
combined typically with hard alcohol.
link |
01:15:07.140
That's fairly commonly available in bars and so forth.
link |
01:15:10.840
And some individuals drank as much as, goodness,
link |
01:15:14.460
20.36 alcoholic drinks per week total,
link |
01:15:18.680
some that were caffeinated, some that were not caffeinated.
link |
01:15:21.640
The basic outcome of this study
link |
01:15:23.540
was that the more alcohol someone tended to consume,
link |
01:15:26.740
the more likely it was that they would engage
link |
01:15:28.540
in these indirect aggressive type behaviors.
link |
01:15:31.820
And in terms of the caffeinated alcoholic beverages,
link |
01:15:34.520
there the effect was especially interesting.
link |
01:15:36.160
Here I'm just going to paraphrase,
link |
01:15:37.420
or I'll actually read from the study.
link |
01:15:39.780
Quote, with regard to caffeinated alcoholic beverage use,
link |
01:15:43.200
our findings indicated
link |
01:15:44.300
that heavier caffeinated alcohol beverage use
link |
01:15:46.900
was associated positively with indirect aggression
link |
01:15:49.420
even after considering one's typical alcohol use
link |
01:15:51.880
and dispositional aggression.
link |
01:15:53.900
What this means is that even though alcohol
link |
01:15:57.460
can bias certain individuals to be more aggressive,
link |
01:15:59.460
and even though certain individuals
link |
01:16:00.660
already have a disposition toward being more aggressive,
link |
01:16:03.740
there was an effect that was independent,
link |
01:16:06.600
meaning above and beyond both alcohol and a predisposition,
link |
01:16:11.300
meaning if someone was consuming
link |
01:16:13.480
caffeinated alcoholic beverages,
link |
01:16:15.260
they had a particularly high likelihood
link |
01:16:18.100
of engaging in indirect aggressive behavior.
link |
01:16:21.380
Now, this makes perfect sense
link |
01:16:22.740
in light of the model they propose,
link |
01:16:24.580
which is this self-regulation model
link |
01:16:26.980
that basically self-regulation involves several things.
link |
01:16:29.580
It involves engaging in certain behaviors
link |
01:16:32.060
and suppressing other behaviors.
link |
01:16:33.420
So as described before,
link |
01:16:36.200
because alcohol tends to have a sedative,
link |
01:16:40.100
suppressive effect on the autonomic nervous system,
link |
01:16:43.620
at least after the initial period,
link |
01:16:45.340
it's going to tend to reduce the likelihood
link |
01:16:47.860
that people will engage in any type of behavior,
link |
01:16:50.540
whereas caffeine will increase autonomic arousal
link |
01:16:53.060
and increase the likelihood that someone will engage
link |
01:16:55.580
in a particular type of behavior, aggressive or otherwise.
link |
01:16:58.940
So the combination of caffeine and alcohol
link |
01:17:01.340
is really acting as a two-prong system
link |
01:17:03.740
to bias people towards more impulsivity,
link |
01:17:06.300
that is less self-regulation.
link |
01:17:07.820
So it's really yanking your volitional control,
link |
01:17:10.940
your ability to engage in prefrontal top-down inhibition
link |
01:17:14.280
over your hypothalamus
link |
01:17:15.460
from two distinct and specific circuits.
link |
01:17:18.020
By now, you should be getting the impression
link |
01:17:19.660
that self-regulation is a key feature
link |
01:17:22.300
of whether or not somebody, maybe even you,
link |
01:17:25.420
is going to engage in aggressive speech
link |
01:17:27.260
or aggressive behavior.
link |
01:17:28.500
And we've talked about a number of tools
link |
01:17:29.820
that one can use to reduce the probability
link |
01:17:32.780
that that will happen.
link |
01:17:34.320
I suppose if the context were appropriate,
link |
01:17:36.340
you could even take those two recommendations
link |
01:17:39.380
and just invert them and increase the likelihood
link |
01:17:41.900
that aggressiveness would have happened.
link |
01:17:43.460
But regardless, self-regulation is key.
link |
01:17:46.980
And in light of that, I want to share with you a study
link |
01:17:49.780
that's focused on kids,
link |
01:17:51.740
but that has important ramifications for adults as well.
link |
01:17:57.660
As you probably are already aware,
link |
01:18:00.060
there are many kids out there that suffer
link |
01:18:01.980
from so-called attention deficit hyperactivity disorder,
link |
01:18:04.580
ADHD.
link |
01:18:05.620
There are also many adults we are finding
link |
01:18:07.340
that are suffering from ADHD.
link |
01:18:09.140
And there's also an epidemic, I would say,
link |
01:18:12.400
of people that are concerned about
link |
01:18:13.940
whether or not they have ADHD.
link |
01:18:15.500
Now, whether or not they have true clinical ADHD or not
link |
01:18:18.620
is not clear.
link |
01:18:19.500
We did an episode all about ADHD and tools for ADHD.
link |
01:18:22.840
I would encourage you to check out that episode
link |
01:18:24.500
and some of the diagnostic criteria.
link |
01:18:26.820
If you have the opportunity,
link |
01:18:28.020
you can find that at hubermanlab.com.
link |
01:18:30.340
As this study I'm about to share with you aptly points out,
link |
01:18:34.380
there is no objective diagnostic marker of ADHD.
link |
01:18:36.960
There's no biomarker or blood draw or blood test for ADHD.
link |
01:18:40.580
Whether or not one has ADHD depends on their performance
link |
01:18:44.880
on a number of different cognitive tests
link |
01:18:46.900
and behavioral tests and self-report.
link |
01:18:49.620
In any event, the study I'm about to share with you
link |
01:18:52.260
explored how a particular pattern of supplementation
link |
01:18:55.540
in kids with ADHD was able to reduce aggressive episodes
link |
01:19:00.220
and impulsivity and increase self-regulation.
link |
01:19:03.460
And the title of the study is efficacy of carnitine
link |
01:19:06.340
in the treatment of children
link |
01:19:07.420
with attention deficit hyperactivity disorder,
link |
01:19:10.120
even though they put carnitine in the title,
link |
01:19:12.020
that what they focused on was
link |
01:19:13.620
whether or not acetyl-L-carnitine supplementation
link |
01:19:17.040
could somehow adjust the behavioral tendency
link |
01:19:19.660
of these kids with ADHD.
link |
01:19:21.280
And to make a long story short, indeed it did.
link |
01:19:24.380
There was a very significant effect
link |
01:19:25.880
of acetyl-carnitine supplementation
link |
01:19:28.000
on improving some of the symptomology of ADHD.
link |
01:19:33.700
A few details about this study
link |
01:19:35.020
that might be relevant to you.
link |
01:19:36.660
This was a randomized double blind placebo controlled
link |
01:19:38.820
double crossover study.
link |
01:19:40.560
This was done as an outpatient study
link |
01:19:42.620
so the kids weren't in a hospital.
link |
01:19:44.200
They were living out in the world.
link |
01:19:45.500
This again was done on younger kids.
link |
01:19:47.340
So this was six to 13-year-old kids
link |
01:19:50.940
that were diagnosed with ADHD.
link |
01:19:53.460
They received either acetyl-L-carnitine or placebo,
link |
01:19:58.820
and they did all the good practice stuff
link |
01:20:02.640
that good researchers do of making sure that the placebo
link |
01:20:05.660
and the acetyl-L-carnitine had similar look and taste.
link |
01:20:08.820
It was consumed twice daily after meals.
link |
01:20:11.820
Now she just mentioned that acetyl-L-carnitine
link |
01:20:13.380
typically is taken in capsule form
link |
01:20:16.200
or occasionally an injectable form here.
link |
01:20:18.220
They were using this as a drink,
link |
01:20:19.700
which is essentially the same as capsule form,
link |
01:20:21.460
but the powder is just going directly into liquid.
link |
01:20:23.920
And the carnitine dosage was 100 milligrams per kilogram.
link |
01:20:27.900
So they're doing this according to the body weight
link |
01:20:29.740
of these kids with a maximum dosage of four grams per day.
link |
01:20:34.300
The quantity of the medication was supplied.
link |
01:20:36.080
Here I'm reading for a period of eight weeks,
link |
01:20:37.860
and every eight weeks,
link |
01:20:38.700
a new quantity of medication was supplied.
link |
01:20:40.280
So basically this is a fairly long-term study
link |
01:20:44.520
exploring behavioral outcomes and psychological outcomes
link |
01:20:48.220
in week eight, 16, and 24.
link |
01:20:50.740
They also looked at things
link |
01:20:53.240
that you could only get through a blood draw.
link |
01:20:54.820
So things like hemoglobin, hematocrit,
link |
01:20:56.740
red blood cell count, white blood cell count, et cetera.
link |
01:20:58.840
These are kids, and even if it were adults,
link |
01:21:01.060
they were quite appropriately examining
link |
01:21:02.600
a lot of the physiological measures
link |
01:21:03.980
that one would want to carry out to make sure,
link |
01:21:07.620
first of all, that blood levels of carnitine are increasing,
link |
01:21:10.840
and indeed they confirm that,
link |
01:21:11.900
but also that no negative effects
link |
01:21:14.580
are showing up in the physiology
link |
01:21:16.220
as well as the psychology of these kids.
link |
01:21:17.900
So first I'll just tell you the basic outcome of the study,
link |
01:21:20.000
which was, here I'm paraphrasing,
link |
01:21:21.760
given twice daily, carnitine appeared to be effective
link |
01:21:23.860
in well-tolerated treatment
link |
01:21:24.980
for a group of children with ADHD.
link |
01:21:26.980
They showed significant abnormal behavior
link |
01:21:29.460
compared to these other boys.
link |
01:21:31.700
And now I'm moving to the table of results.
link |
01:21:35.100
They showed significant reductions
link |
01:21:36.680
in their so-called total problem score.
link |
01:21:38.960
The total problem score is a well-established measure
link |
01:21:41.120
of behavioral problems in kids with ADHD.
link |
01:21:44.460
And I should say adults with ADHD
link |
01:21:47.300
has to do with challenges in social and learning environments
link |
01:21:51.940
and how well or poorly an individual tends to perform.
link |
01:21:56.060
Reductions in attentional problems overall,
link |
01:21:58.060
reductions in delinquency,
link |
01:21:59.300
and most important for sake of today's discussion,
link |
01:22:01.940
significant reductions in aggressive behavior.
link |
01:22:04.700
Now, what's especially nice about this study, I think,
link |
01:22:07.020
is that even though it's a relatively small number
link |
01:22:09.380
of subjects and certainly it needs to be repeated
link |
01:22:13.060
in other studies and other laboratories,
link |
01:22:16.020
that they were able to confirm the shifts
link |
01:22:18.820
in L-carnitine within the bloodstream of these kids.
link |
01:22:22.380
That is, they were able to correlate the physiology
link |
01:22:24.760
with the psychological changes.
link |
01:22:27.020
In studies like this, and frankly, in all studies
link |
01:22:29.900
of human pharmacology, you have to worry about effects
link |
01:22:33.140
that show up, not just because of placebo effects,
link |
01:22:35.560
but because of so-called off-target effects
link |
01:22:37.620
or related things totally independent of the drug
link |
01:22:41.340
or the particular supplement
link |
01:22:42.340
that you happen to be looking at.
link |
01:22:43.840
To put it in the words of a great neuroscientist,
link |
01:22:46.460
unfortunately, he passed away some years ago,
link |
01:22:48.680
but he was a member of the National Academy,
link |
01:22:50.100
extremely accomplished neuroscientist,
link |
01:22:53.140
who once turned to me and said,
link |
01:22:54.540
never forget, a drug is a substance
link |
01:22:57.180
that when injected into an animal or a human being
link |
01:23:00.780
creates a paper.
link |
01:23:02.520
Meaning you can see effects of pretty much any drug
link |
01:23:06.580
or any supplement in most all conditions.
link |
01:23:09.300
However, it is in cases such as this study
link |
01:23:12.100
where you can quite convincingly see
link |
01:23:15.480
that the particular feature of physiology
link |
01:23:18.100
that you expected to change actually changed,
link |
01:23:21.180
and you see a psychological outcome
link |
01:23:23.420
that you can gain much greater confidence
link |
01:23:26.060
that the changes in delinquency,
link |
01:23:28.820
in this case, reduced delinquency,
link |
01:23:30.140
improved attention, reduced aggressiveness, and so forth,
link |
01:23:33.140
was at least somehow related to the shift
link |
01:23:36.660
in blood physiology and levels of L-carnitine
link |
01:23:39.980
or acetyl-L-carnitine and carnitine
link |
01:23:41.700
in the bloodstream of these children,
link |
01:23:43.300
as opposed to something else,
link |
01:23:44.860
like L-carnitine going and affecting some downstream target
link |
01:23:48.460
that you have no knowledge of.
link |
01:23:49.580
Now, of course, that's still entirely possible,
link |
01:23:52.060
but I think studies such as these increase our confidence
link |
01:23:54.700
that things like L-carnitine can be used
link |
01:23:57.820
perhaps in concert with things
link |
01:23:59.320
like omega-3 supplementation,
link |
01:24:01.180
diets that are biased towards increasing more tryptophan
link |
01:24:04.460
and therefore more serotonin,
link |
01:24:06.880
obviously avoiding things like alcohol,
link |
01:24:08.700
and as it appears from the study I just described,
link |
01:24:10.960
reducing one's intake
link |
01:24:13.080
or not consuming any caffeinated alcoholic beverages.
link |
01:24:16.780
Seems like it would be a good idea
link |
01:24:17.740
if your goal is to reduce aggressiveness
link |
01:24:19.860
to think about the hormone context
link |
01:24:21.660
and whether or not you tend to have higher testosterone
link |
01:24:25.420
and estrogen or lower testosterone and estrogen.
link |
01:24:27.860
Maybe even thinking about the work environment,
link |
01:24:29.360
whether or not you are existing
link |
01:24:30.900
in a particularly competitive work environment
link |
01:24:32.940
and even day life, time of year,
link |
01:24:35.940
and whether or not you're getting sufficient sunlight,
link |
01:24:37.860
whether or not you're avoiding light
link |
01:24:39.220
in the evening and so on.
link |
01:24:40.660
So studies such as this I think are useful
link |
01:24:42.920
because they point to the fact that very seldom, if ever,
link |
01:24:47.860
will there be one supplement or one nutritional change
link |
01:24:51.300
or even one behavioral change
link |
01:24:52.740
that's going to completely shift an individual
link |
01:24:55.140
from being aggressive and impulsive,
link |
01:24:57.240
but rather that by combining different behavioral regimens,
link |
01:25:01.660
by paying attention to things like time of year
link |
01:25:04.300
and work conditions and school conditions
link |
01:25:06.380
and overall levels of stress
link |
01:25:07.620
and likely therefore levels of cortisol, et cetera,
link |
01:25:11.540
that you can use behaviors, diet, and supplementation
link |
01:25:14.940
as a way to shift that overall internal milieu
link |
01:25:18.580
from one of providing a lot of internal hydraulic pressure,
link |
01:25:22.020
as it's been called throughout the episode,
link |
01:25:24.100
toward aggressive impulsivity
link |
01:25:26.400
and relax some of that hydraulic pressure
link |
01:25:29.400
and reduce aggressive tendencies.
link |
01:25:31.820
So once again, and frankly, as always,
link |
01:25:34.480
we've done a deep dive into the neurobiology
link |
01:25:38.340
and the psychology of what I believe
link |
01:25:40.300
to be an important feature of our lives,
link |
01:25:42.100
in this case, aggression.
link |
01:25:43.880
I want to point out that in a episode
link |
01:25:46.260
in the not too distant future,
link |
01:25:47.580
I'm going to be hosting Dr. Professor David Anderson
link |
01:25:50.820
from Caltech University,
link |
01:25:52.300
who is the world expert on the neurobiology of aggression.
link |
01:25:56.980
In fact, he is the senior author
link |
01:25:58.260
on many of the studies related
link |
01:25:59.980
to the ventromedial hypothalamus that I discussed today.
link |
01:26:02.880
Our discussion will touch on aggression, of course.
link |
01:26:05.880
So hearing today's episode
link |
01:26:07.920
will help you digest that information,
link |
01:26:09.580
but we are also going to talk about other emotional states.
link |
01:26:12.340
He is an expert, not just in aggression,
link |
01:26:14.220
but in motivated states related to sex
link |
01:26:16.100
and mating behavior, social relationships of all kinds,
link |
01:26:20.540
and how those relate not just to biology and psychology,
link |
01:26:23.460
but also certain forms of pathology,
link |
01:26:25.860
things like PTSD and the relationship, for instance,
link |
01:26:28.080
between anger, fear, anxiety, and depression,
link |
01:26:31.480
and many other important topics that I know many of you,
link |
01:26:34.520
if not all of you, will be interested in.
link |
01:26:36.360
In the meantime, I want to point you
link |
01:26:37.620
to his recently released and wonderful book entitled
link |
01:26:42.380
The Nature of the Beast, How Emotions Guide Us.
link |
01:26:44.980
And again, the author is David Anderson from Caltech.
link |
01:26:48.740
This is a wonderful book.
link |
01:26:50.420
It serves as a tremendous introduction
link |
01:26:53.860
to the history of the study of these areas,
link |
01:26:56.360
the current science and discoveries being made
link |
01:26:58.900
in these areas, all made accessible
link |
01:27:01.300
to the scientist and non-scientist alike.
link |
01:27:03.600
It's a very engaging read.
link |
01:27:05.860
And so much so that even though he was gracious
link |
01:27:09.180
in sending me a copy, I also purchased myself a copy
link |
01:27:11.900
to give to somebody who is a therapist,
link |
01:27:14.060
and I've purchased another copy to give to a high school kid
link |
01:27:16.740
that I mentor because he's very interested
link |
01:27:18.980
in the neuroscience of emotions.
link |
01:27:20.420
And I think we are all interested in emotions,
link |
01:27:23.020
not just fear and some of these negative states,
link |
01:27:25.780
not just aggression,
link |
01:27:26.620
but also the positive emotions of our lives.
link |
01:27:28.780
And so The Nature of the Beast, How Emotions Guide Us
link |
01:27:31.800
by David Anderson is a wonderful read.
link |
01:27:34.140
I can't recommend it highly enough.
link |
01:27:36.120
If you're learning from and or enjoying this podcast,
link |
01:27:38.500
please subscribe to our YouTube channel.
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01:27:40.460
That's a terrific zero cost way to support us.
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01:27:43.140
In addition, please subscribe to our podcast
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01:27:45.420
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01:27:47.020
And on Apple, you have the opportunity
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01:27:49.180
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Also, if there are any episodes of the podcast
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01:27:53.580
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01:27:59.200
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link |
01:28:01.860
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link |
01:28:04.280
We do read all those comments.
link |
01:28:06.740
Please also check out the sponsors mentioned
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01:28:08.620
at the beginning of today's episode.
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01:28:10.140
That is the best way to support this podcast.
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01:28:12.940
We also have a Patreon, it's patreon.com
link |
01:28:15.460
slash Andrew Huberman, and there you can support
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01:28:18.300
the podcast at any level that you like.
link |
01:28:20.620
During today's episode and on many previous episodes
link |
01:28:22.980
of the Huberman Lab Podcast, we discussed supplements.
link |
01:28:25.880
While supplements aren't necessary for everybody,
link |
01:28:28.220
many people derive tremendous benefit from them
link |
01:28:30.620
for things like improving the transition time
link |
01:28:33.120
and the quality of your sleep
link |
01:28:35.140
and improving alertness and focus and so on.
link |
01:28:38.540
Anytime you're considering taking supplements,
link |
01:28:40.620
there are several key considerations.
link |
01:28:42.080
First of all, those supplements
link |
01:28:43.300
should be of the very highest quality.
link |
01:28:45.240
And you want to make sure that what's listed on the bottle
link |
01:28:47.800
is actually what's in the bottle,
link |
01:28:49.080
which is a problem for many supplement companies out there.
link |
01:28:52.180
The Huberman Lab Podcast is pleased to announce
link |
01:28:54.640
that we are now partnered with Momentous Supplements
link |
01:28:57.720
because we believe Momentous Supplements
link |
01:28:59.500
to be of the very highest quality
link |
01:29:01.520
of any supplements out there.
link |
01:29:03.380
And we've been working very closely with them
link |
01:29:05.500
in order to direct them to create supplements
link |
01:29:07.620
that are individual ingredient supplements
link |
01:29:09.900
of the particular quality and sources
link |
01:29:12.200
that we would like to see
link |
01:29:13.360
and that relate to the science and studies covered
link |
01:29:15.780
on the Huberman Lab Podcast.
link |
01:29:17.340
If you'd like to see some of those supplements,
link |
01:29:19.020
you can go to livemomentous.com slash Huberman,
link |
01:29:22.540
and there you will see some of the supplements
link |
01:29:24.980
that we've talked about on this podcast before,
link |
01:29:26.860
such as magnesium threonate for augmenting sleep,
link |
01:29:30.460
things like L-tyrosine for augmenting dopamine,
link |
01:29:32.700
and things like L-carnitine,
link |
01:29:34.540
which we've discussed on today's podcast.
link |
01:29:36.840
Right now, the list of supplements
link |
01:29:38.660
and the products that are there is only partial
link |
01:29:40.900
to what will soon be included in the future,
link |
01:29:42.580
so that's an ever-expanding catalog of, again,
link |
01:29:45.100
what we believe to be the very highest quality supplements
link |
01:29:47.520
available to you.
link |
01:29:48.620
For those of you that are interested in behavioral,
link |
01:29:50.980
nutritional, and supplementation-based tools
link |
01:29:53.880
for neuroscience and other aspects of your biology
link |
01:29:57.060
that impact your health and performance,
link |
01:29:58.900
we have a newsletter.
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It is a zero-cost newsletter.
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01:30:02.180
It's called the Neural Network Newsletter.
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01:30:03.900
You can go to HubermanLab.com, and there in the menu,
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01:30:07.320
you'll find the Neural Network Newsletter signup.
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01:30:09.700
You can just put your email.
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You will also find examples of the newsletter
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And if you're not already following us
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we are HubermanLab on both Instagram and Twitter,
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01:30:27.080
and at both places,
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01:30:28.820
I describe science and science-based tools,
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01:30:30.760
some of which overlaps
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01:30:31.780
with the content of the HubermanLab podcast,
link |
01:30:33.880
but much of which is distinct
link |
01:30:35.620
from the content of the HubermanLab podcast.
link |
01:30:38.200
Once again, thank you for joining me
link |
01:30:39.660
for our discussion about the biology, psychology,
link |
01:30:42.460
and actionable tools around aggression,
link |
01:30:45.300
and as always, thank you for your interest in science.
link |
01:30:48.200
And as always, thank you for your interest in science.