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The Science & Treatment of Bipolar Disorder | Huberman Lab Podcast #82



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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 going to be discussing bipolar disorder,
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often called bipolar depression.
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Bipolar depression is a condition
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in which people undergo massive shifts in their energy,
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their perception, and their mood.
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However, it is very important to note
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that the shifts in mood, energy, and perception
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are all maladaptive.
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They can often cause tremendous damage
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to the person suffering from bipolar disorder
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and tremendous damage to the people in their lives.
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Today, we're going to parse the biology
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that leads to the shifts in mood, energy, and perception,
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and we are going to talk about
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the various treatments that exist.
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Some of those treatments have been around
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for a very long time, and indeed, one of those treatments,
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lithium, has an incredible backstory about its discovery,
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and in understanding how lithium works
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and some of the ways in which it does not work well,
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it reveals a tremendous amount
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about how the brain works normally in all individuals.
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So that's a miraculous story
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that I look forward to sharing with you.
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As we go forward in this discussion about bipolar disorder,
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I want everyone to keep in mind
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that it is a very severe condition.
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In fact, people suffering from bipolar disorder
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are at 20 to 30 times greater risk of suicide.
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So today is a serious discussion,
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and it's certainly one in which people
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who are suffering from manic bipolar disorder
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or who know people that are suffering
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from manic bipolar disorder can benefit from.
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However, for those of you that might know people
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or who themselves suffer from major depression,
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we will also be talking about important treatment
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developments for major depression.
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Major depression is a very common thing for many people.
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In fact, most people will suffer from depression
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of some sort at some point in their life,
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although not necessarily a major depressive episode,
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and yet major depression is very common.
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So you'll soon learn up to 20% of people
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will suffer from major depression.
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So today's discussion will encompass all of that,
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and it will also encompass basic brain mechanisms
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of neuroplasticity, the brain's ability to change
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in response to experience both for good and for worse,
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and you'll learn a lot about the basic biology
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of how the brain regulates mood, energy, and perception.
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I'm pleased to announce that the Huberman Lab Podcast
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is now partnered with Momentous Supplements.
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We often talk about supplements on the Huberman Lab Podcast,
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and while supplements aren't necessary for everybody,
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many people derive tremendous benefit from them
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for things like enhancing the quality and speed
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with which you get into sleep,
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or for enhancing focus, or for hormone support.
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The reason we partnered with Momentous Supplements
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is several fold.
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First of all, their supplements
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Second of all, they ship internationally,
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which is important because many of our podcast listeners
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reside outside the US.
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Third, many of the supplements that Momentous makes,
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and most all of the supplements
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that we partnered with them directly on
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are single ingredient formulations.
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This is important for a number of reasons.
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First of all, if you're going to create
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a supplement protocol that's customized for your needs,
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you want to be able to figure out
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and only use those,
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and supplements that combine lots of ingredients
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simply won't allow you to do that.
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If you'd like to see the supplements
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that we partnered with Momentous on,
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you can go to livemomentous.com slash Huberman,
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and there you'll see many of the supplements
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that we've talked repeatedly about
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on the Huberman Lab podcast episodes.
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I should mention that the catalog of supplements
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that are available at livemomentous.com slash Huberman
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is constantly being expanded,
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so you can check back there livemomentous.com slash Huberman
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to see what's currently available,
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and from time to time,
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you'll notice new supplements being added to the inventory.
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Before we dive into the discussion
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about manic bipolar disorder,
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I want to highlight some recent findings
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in an area totally separate from mental health
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that I think are really important for everyone to know about.
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This is a paper published in the journal Cell,
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which is a Cell Press journal, an excellent journal,
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in fact, one of the three apex journals,
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so for those of you that are curious,
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papers published in the journal Nature, Science, and Cell
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are considered the sort of Super Bowl, Stanley Cup,
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and NBA championships of publishing,
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and this paper entitled
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An Interorgan Neural Circuit for Appetite Suppression
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illustrates a very important principle
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that I think everyone should know about,
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and that's the principle of so-called parallel pathways.
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Parallel pathways, as the name suggests, are pathways.
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They could be neural pathways or hormonal pathways
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or otherwise that operate independently of one another
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to accomplish a common goal,
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and what this paper really shows
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is that there's a set of peptides in the body,
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and the peptide that I'm referring to today
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is called GLP-1, glucagon-like peptide one,
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and some related peptides.
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I've talked about these on the podcast before
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for two reasons.
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First of all, I'm a big proponent and consumer
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of Yerba Mate, Yerba Mate is a tea
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that can promote the release of glucagon-like peptide one,
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and there are also new prescription drugs
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that are now hitting the market
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and for which there are really impressive clinical trials
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for diabetes and obesity
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that are essentially glucagon-like peptide one stimulators,
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so they stimulate the release of that,
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or they are in fact a synthetic version
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of glucagon-like peptide one.
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What is glucagon-like peptide one?
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It is a peptide, which is a small little protein
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that can dramatically suppress appetite,
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so that's why these drugs are being explored
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and are showing quite impressive results
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for things like treatment of type 2 diabetes
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and other forms of diabetes as well as obesity,
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so they lead to weight loss.
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Now, in terms of the Yerba Mate stimulation
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of glucagon-like peptide one,
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that's going to be a much lower amount of glucagon-like
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peptide one that's released from drinking Yerba Mate
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as opposed to, say, taking a drug that stimulates GLP-1
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or taking a drug that is GLP-1.
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Nonetheless, I should also point out
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that Yerba Mate comes in a bunch of different forms.
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There is some concern about certain smoky-flavored forms
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of Yerba Mate being carcinogenic,
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so that's why I avoid those forms of Yerba Mate,
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but for me, Yerba Mate is one of the preferred sources
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of caffeine for me.
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I like the way it tastes.
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It does provide that sort of caffeine kick
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that I like to have early in the day
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for focus and for work and for exercise,
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and yet I actively avoid the smoked varieties
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of Yerba Mate because of the potential carcinogenic effects
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of the smoked varieties.
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Glucagon-like peptide one, as I mentioned earlier,
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can suppress appetite, but what this paper shows
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is it does that by at least two mechanisms
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through parallel pathways.
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What this paper shows is that glucagon-like peptide one
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acts on receptors in the body
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in a portion of the nervous system
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called the enteric nervous system, E-N-T-E-R-I-C,
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enteric nervous system.
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This is a component of your nervous system
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that you don't really have control over.
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It's autonomic or automatic.
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GLP-1 binds to what are called
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intestinal fugal enteric neurons.
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You don't need to know the name,
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but those neurons do two things.
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First of all, they cause some gut distension,
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so they actually make you feel full.
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This is incredible, right?
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A peptide, not actual physical food,
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but a peptide that stimulates neurons
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that cause changes in the so-called mechanoreceptors
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of the gut of the enteric nervous system
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and make people feel full.
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So it can lead to actually mild,
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or I suppose if levels of GLP-1 are very high,
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to major gut distension, okay?
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I think that the levels of GLP-1
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that would come from drinking Yerba Mate
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and hopefully from appropriate dosaging
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of the synthetic forms of GLP-1
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or drugs that stimulate GLP-1 would cause mild,
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not major gut distension
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because major gut distension would be uncomfortable.
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So GLP-1 is acting at the level of gut
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to increase gut distension
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and by way of a pathway that goes from the gut
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up to the hypothalamus, this little cluster of neurons
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about the size of a marble
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that sits above the roof of your mouth
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is also suppressing appetite through brain mechanisms.
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So this is really beautiful, right?
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You have a peptide, a small little protein
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that's released in the gut
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and that release within the gut causes gut distension
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which makes you feel full
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and by way of neural stimulation of the hypothalamus
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also activates neural pathways within the brain
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that trigger satiety,
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the feeling of having had enough food.
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So to me, GLP-1 is both impressive and important, why?
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Because this recent category of drugs
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that's now hitting the market seems to adjust obesity
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or can help people with weight loss
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in order to help their health
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and it's doing so by at least two mechanisms.
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One is within the brain
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and the other is within the gut and communication
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through the so-called gut brain access
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because again, these enteric neurons
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are communicating to the brain, the hypothalamus
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by way of this what's called
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the sympathogastrospinal reticular hypothalamic pathway.
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You absolutely do not need to know all of that.
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That's a mouthful.
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That's enough to make your mouth feel distended
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but at the same time, things like yerba mate
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and I'm sure there are other compounds out there as well
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but certainly yerba mate can stimulate the release of GLP-1.
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So for those of you that are looking
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for some mild appetite suppression
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and want to accomplish that while also ingesting caffeine,
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yerba mate might be a good option for that
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and just know that it's operating through two mechanisms
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on the body through mild gut distension
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to make you feel full and on the brain
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to increase satiety or make you feel less hungry.
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And then for everybody,
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not just those that are interested in appetite suppression,
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I think it's important to understand
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that these parallel pathways are fundamental
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to how we are organized.
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Another good example of this would be
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when we are excited by something, positive or negative,
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so it could be stressful or we're positively aroused,
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there is a parallel activation of epinephrine, adrenaline,
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both from your adrenals and from an area in the brain
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called the locus coeruleus.
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So again and again, we see this in biology
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and in neuroscience,
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that your brain and your body are acting in concert.
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They're acting together through mechanisms
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that either are independent, so separately in the brain
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and separately in the body,
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but directed towards a common goal
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or through communication between brain and body
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and almost always,
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that communication is going to be bi-directional,
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body to brain and brain to body.
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So I think these results are really interesting
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and really important for sake of weight loss,
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for sake of appetite suppression
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and just generally for the way that they illustrate
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this very important theme of the way that we are constructed
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at a biological level, which is parallel pathways.
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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 about science
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and science related tools 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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Our first sponsor is InsideTracker.
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I've long been a believer in getting regular blood work done
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for the simple reason that many of the factors
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One major problem with most blood tests
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and enter the code Huberman at checkout.
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Let's talk about bipolar disorder.
link |
00:14:25.100
And today I'm going to refer to bipolar disorder
link |
00:14:27.200
interchangeably with bipolar depression.
link |
00:14:30.320
Although, as you will soon learn,
link |
00:14:32.320
not everyone with bipolar disorder
link |
00:14:34.320
necessarily goes through highs and lows.
link |
00:14:37.520
There is a subset of people who suffer from bipolar disorder
link |
00:14:40.880
who experienced the manic phases,
link |
00:14:42.840
the highly elevated mood and energy,
link |
00:14:45.920
and then dropped down to so-called baseline.
link |
00:14:48.600
So they don't necessarily go down into a depressive state.
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00:14:51.760
They often will return to a somewhat normal state.
link |
00:14:54.420
In fact, we will talk about the percentage of time
link |
00:14:57.640
that people with bipolar disorder
link |
00:14:59.340
tend to be symptom-free, manic, or depressed
link |
00:15:02.840
in the context of the different categories
link |
00:15:04.440
of bipolar disorder.
link |
00:15:05.680
But as we wade into this topic that is bipolar disorder,
link |
00:15:09.120
I just want to give you a little bit
link |
00:15:10.040
of the background statistics to anchor us
link |
00:15:12.680
in just how serious and prevalent bipolar disorder is.
link |
00:15:16.840
So bipolar disorder impacts about 1% of people.
link |
00:15:20.260
That might seem like a small percentage,
link |
00:15:22.560
but if you think about a room of 100 people,
link |
00:15:25.240
that means that at least one of them
link |
00:15:27.080
is very likely to have bipolar disorder.
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00:15:30.680
And as I mentioned earlier in the introduction,
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00:15:32.880
bipolar disorder is very serious.
link |
00:15:35.260
It has a 20 to 30% greater incidence of suicide
link |
00:15:39.720
than the general population,
link |
00:15:41.400
which is, first of all,
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00:15:42.660
extremely tragic and extremely concerning.
link |
00:15:45.540
So anyone that thinks they might have bipolar disorder
link |
00:15:48.560
or who knows someone with bipolar disorder
link |
00:15:50.240
should be especially vigilant about this.
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00:15:52.120
And we'll talk about some of the signs and risk factors,
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00:15:55.840
age of onset, et cetera, as we move forward.
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00:15:58.720
So 1% of people have bipolar disorder.
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00:16:01.100
The typical age of onset is anywhere from 20 to 25 years old
link |
00:16:05.180
although it can be much earlier.
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00:16:07.580
And the earlier the onset of a bipolar episode,
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00:16:11.420
which we will define in a few minutes,
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00:16:13.160
the earlier the onset of that episode,
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00:16:15.640
the higher likelihood that the bipolar disorder
link |
00:16:18.480
is going to be a stable feature
link |
00:16:20.260
of that person's psychology going forward.
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00:16:22.960
And yet, I also want to point out
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00:16:24.740
that there are some very good treatments
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00:16:27.120
for bipolar disorder
link |
00:16:28.040
that those people could still benefit from.
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00:16:30.660
There are basically two kinds of bipolar disorder
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00:16:33.940
referred to as bipolar I and bipolar II.
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00:16:36.980
So let's just talk about bipolar I first.
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00:16:39.760
Bipolar I is characterized
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00:16:41.840
by a fairly extended period of mania.
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00:16:45.080
What is mania?
link |
00:16:46.200
Mania is a period of very elevated mood, energy,
link |
00:16:50.200
distractibility, impulsivity, and some other symptomology
link |
00:16:53.520
that we'll talk about going forward.
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00:16:55.600
But this manic episode is extreme.
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00:16:59.640
This is a condition in which the energy lift,
link |
00:17:03.520
the mood lift, and the sort of impulsivity
link |
00:17:06.580
and actions and words of the person
link |
00:17:08.760
suffering from manic bipolar disorder
link |
00:17:10.640
are very noticeable and very extreme.
link |
00:17:13.800
Now, a key thing, however,
link |
00:17:15.160
is that it's not always noticeable
link |
00:17:16.960
to the person suffering from it
link |
00:17:18.920
that they are in this mode.
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00:17:20.440
Sometimes they recognize that, sometimes they don't,
link |
00:17:22.740
but it's always highly recognizable to other people
link |
00:17:25.920
that the person suffering from manic bipolar disorder
link |
00:17:29.200
is not like other people.
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00:17:30.960
So let's talk about bipolar I in a little bit more depth.
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00:17:34.480
One of the key clinical criteria
link |
00:17:36.680
or diagnostic criteria for bipolar I
link |
00:17:39.100
is that a person suffer from these manic episodes
link |
00:17:42.640
or display these manic episodes for seven days or more.
link |
00:17:46.600
That turns out to be very key.
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00:17:47.720
The stability of that manic episode for seven days or more
link |
00:17:51.760
turns out to be very important.
link |
00:17:53.880
And for those seven days,
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00:17:55.880
the person is in an elevated mood, expansive thought
link |
00:17:59.260
all day, every day for those seven days.
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00:18:02.400
Now, there are a lot of reasons
link |
00:18:03.520
why somebody could be in a manic mode.
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00:18:06.240
It doesn't necessarily mean
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00:18:07.660
that somebody has bipolar disorder.
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00:18:09.720
In fact, someone could be in a manic mode
link |
00:18:11.840
for seven days or more
link |
00:18:13.620
and still not be diagnosed with bipolar disorder.
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00:18:15.880
Why?
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00:18:16.720
Well, there are other things
link |
00:18:18.720
that can create manic episodes,
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00:18:20.640
things like traumatic brain injury,
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00:18:22.520
things like seizure,
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00:18:23.820
things like various prescription drugs or illicit drugs,
link |
00:18:26.400
things like amphetamine and cocaine.
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00:18:28.560
That is not the same as bipolar disorder,
link |
00:18:30.800
even though from a symptomology perspective,
link |
00:18:34.040
they might look even identical.
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00:18:36.040
So let's think about these symptoms
link |
00:18:37.340
and the diagnostic criteria that a psychiatrist would use
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00:18:41.000
in order to ask whether or not someone is manic
link |
00:18:44.020
because they have manic bipolar disorder
link |
00:18:46.480
or whether or not that person is manic
link |
00:18:48.400
for some other reason,
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00:18:50.040
such as traumatic brain injury, illicit drugs, et cetera.
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00:18:53.500
So typically a person will be brought into a clinic
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00:18:57.800
or a person would bring themselves to a clinic
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00:19:00.680
or meet with a psychiatrist.
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00:19:02.480
It seems more likely that they would be directed
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00:19:04.520
toward a psychiatrist
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00:19:05.520
because oftentimes people who are in a manic episode
link |
00:19:08.140
just simply won't have the perspective
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00:19:10.320
or the foresight to bring themselves into the clinic.
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00:19:13.480
And the psychiatrist is going to start to evaluate
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00:19:16.200
for a couple of different things.
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00:19:17.800
But first of all, what they're going to try and figure out
link |
00:19:20.240
is whether or not the person has at least three
link |
00:19:22.680
of the following symptoms.
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00:19:25.840
The first symptom is distractibility.
link |
00:19:28.280
Is the person distractible?
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00:19:29.400
Are they going from one thing to the next?
link |
00:19:30.920
People who are in a manic episode
link |
00:19:32.260
will be talking about a pen
link |
00:19:33.240
and then they'll be talking about, you know,
link |
00:19:34.580
something they saw the other day
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00:19:35.580
and then something they want to purchase
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00:19:36.680
and then a place they're going to travel to, et cetera.
link |
00:19:38.680
But they are also very prone to any stimulus
link |
00:19:41.780
within the room, meaning, you know, a bell could go off
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00:19:44.300
or there could be a sound out in the hallway
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00:19:45.480
and they'll orient to that.
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00:19:46.460
And then they'll orient to the clinician
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00:19:47.800
and then they'll orient to something in their pocket.
link |
00:19:49.480
So they're all over the place.
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00:19:50.780
You could think of this a little bit like ADHD
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00:19:53.280
or attention deficit disorder, but it's very extreme.
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00:19:56.340
So highly distractible, highly impulsive.
link |
00:19:59.060
Impulsivity relates to actions.
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00:20:01.680
So the person might be fidgeting with something
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00:20:03.640
and then they might try and leave the room
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00:20:05.220
or the person might, if they were out in the real world,
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00:20:08.640
somebody might notice that the person is going
link |
00:20:11.720
and purchasing, you know, multiples of something
link |
00:20:14.360
that would be unusual for someone to purchase.
link |
00:20:16.760
So for instance, I happen to know someone
link |
00:20:18.560
whose ex-spouse had bipolar disorder
link |
00:20:21.060
and their ex-spouse went out
link |
00:20:22.800
and bought 10 plus air fryers, right?
link |
00:20:25.960
I mean, I think unless you're a restaurant
link |
00:20:27.640
that's using a lot of air fryers,
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00:20:28.840
the idea that you would need more than one
link |
00:20:30.480
or two air fryers might just seem
link |
00:20:33.280
a little bit out of the norm.
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00:20:34.880
And so that impulsivity can be purchasing.
link |
00:20:38.000
It can be other things as well.
link |
00:20:39.960
It could be booking, you know, 12 international trips
link |
00:20:42.420
in one afternoon or going and buying three cars, et cetera.
link |
00:20:45.480
So impulsivity.
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00:20:46.640
The other is grandiosity.
link |
00:20:48.640
People who have manic bipolar disorder
link |
00:20:51.240
who are in a manic episode will often display words of
link |
00:20:55.440
or actions of grandiosity.
link |
00:20:57.160
And keep in mind, these are not lies
link |
00:20:59.700
in the sense that the person isn't lying
link |
00:21:01.520
in order to try and pull one over on anybody.
link |
00:21:04.120
These are actual beliefs that the person comes to have
link |
00:21:06.960
about their grandiose position in the world
link |
00:21:09.820
or grandiose opportunities or potential in the world.
link |
00:21:13.200
Typical forms of grandiosity in manic episodes would be
link |
00:21:16.600
that the person suddenly decides
link |
00:21:18.100
that they are going to win a Pulitzer Prize.
link |
00:21:20.080
They are the person selected to win a Pulitzer Prize.
link |
00:21:22.200
They're going to write a novel that afternoon
link |
00:21:24.200
and they're going to win a Pulitzer Prize that year,
link |
00:21:26.320
which is more or less a delusion of grandeur, right?
link |
00:21:29.480
The idea that someone could do that in one afternoon,
link |
00:21:31.340
I suppose it is possible in the realm of all possibilities,
link |
00:21:35.220
but it's extremely unlikely.
link |
00:21:37.720
Other forms of grandiosity that often present themselves
link |
00:21:41.080
in people suffering from a manic episode
link |
00:21:43.440
will be that they're going to run for president
link |
00:21:45.440
or that they are the person that they believe is selected
link |
00:21:50.560
by the citizens of a given country
link |
00:21:53.480
or by the universe to be the president of that country
link |
00:21:56.980
or to be president of the universe, right?
link |
00:21:58.780
It sounds ridiculous, but those sorts of delusions
link |
00:22:01.360
of grandiosity are one condition that often presents itself
link |
00:22:04.720
or one set of symptoms that presents itself.
link |
00:22:07.740
Flight of ideas are also typical of manic episodes.
link |
00:22:11.160
So this is a little bit like distractibility,
link |
00:22:13.000
but this would be people talking extensively about one thing
link |
00:22:16.040
and then switching and talking extensively
link |
00:22:17.960
about something else.
link |
00:22:18.800
It would be as if I was doing this podcast,
link |
00:22:20.480
talking about manic bipolar disorder,
link |
00:22:21.800
and then suddenly switching to OCD
link |
00:22:23.600
and then to deliberate cold exposure
link |
00:22:25.200
and then to the role of sugar
link |
00:22:27.040
and its impact on the brain, et cetera.
link |
00:22:28.480
So essentially a random selection
link |
00:22:31.560
of the different topics that exist in science,
link |
00:22:34.800
all of which I happen to be very interested in
link |
00:22:36.520
and curious about, but just as we have episodes
link |
00:22:39.980
of the podcast that are about one or two topics
link |
00:22:42.560
and we focus on those in a fairly narrow trench
link |
00:22:45.120
of discussion, somebody who has a flight of ideas
link |
00:22:48.460
would be jumping between categories and topics
link |
00:22:51.960
in a kind of pseudo random way.
link |
00:22:53.600
So they might take off down a path of one thing
link |
00:22:55.700
and then switch to another without any transition
link |
00:22:58.320
or with transitions that don't have
link |
00:22:59.960
any logical structure to them.
link |
00:23:02.000
The other aspect of manic bipolar disorder
link |
00:23:05.060
that often presents itself in the manic episodes
link |
00:23:07.160
are agitation, people feeling extremely physically agitated,
link |
00:23:10.060
so a lot of shaking and moving about.
link |
00:23:12.240
This can venture into the realm of paranoia,
link |
00:23:14.560
but a lot of agitation, a difficulty sitting down
link |
00:23:17.880
and being still, a difficulty in just looking,
link |
00:23:22.100
feeling and acting calm.
link |
00:23:24.920
And then another condition is no sleep.
link |
00:23:28.000
And when I say no sleep, I mean no sleep
link |
00:23:30.820
or very minimal sleep.
link |
00:23:32.980
As incredible as it sounds, people who are in a manic episode
link |
00:23:36.920
can often go seven days or more with zero sleep.
link |
00:23:40.920
And a key feature of this zero sleep
link |
00:23:43.000
is that they're not troubled by it.
link |
00:23:44.240
They're not thinking, oh, I'm suffering from insomnia
link |
00:23:46.520
and I really, really want to sleep.
link |
00:23:47.720
Sometimes that's the case, but more often than not,
link |
00:23:50.340
they are simply not sleeping.
link |
00:23:51.940
They're staying up 24 hours, then another 24 hours,
link |
00:23:54.760
it just continues for an entire week.
link |
00:23:56.940
Again, inconceivable to those of us
link |
00:23:59.020
that don't suffer from manic episodes,
link |
00:24:01.520
can only imagine how pulled apart most of us would feel
link |
00:24:04.960
under those conditions and yet they are just going
link |
00:24:07.680
and going and going with no sleep up all hours,
link |
00:24:11.480
shopping, talking, running,
link |
00:24:14.680
doing all sorts of different things
link |
00:24:16.140
in the categories of other symptoms
link |
00:24:17.560
that we talked about before.
link |
00:24:19.160
And it doesn't bother them that they're not sleeping.
link |
00:24:22.360
And then the last sort of category of symptoms
link |
00:24:25.620
that the psychiatrist is evaluating for
link |
00:24:27.780
and seeing if they present is rapid pressured speech.
link |
00:24:31.560
The rapid pressured speech is something
link |
00:24:33.440
that when you hear it, you recognize it.
link |
00:24:35.200
This is somebody that almost seems to be hitting you
link |
00:24:37.120
a speech like machine gun fire.
link |
00:24:39.640
It's coming at you, coming at you, coming at you,
link |
00:24:41.640
and there's really no room for conversation.
link |
00:24:43.840
They're not offering any opportunity for a back and forth,
link |
00:24:46.860
or if there is a back and forth,
link |
00:24:47.840
they might ask you how you feel about something
link |
00:24:49.160
and then you started, well, then they're going to hit you
link |
00:24:51.520
with another barrage or a paragraph of information
link |
00:24:55.680
or of just speech that's pseudo random.
link |
00:24:58.080
So we've got distractibility, impulsivity, grandiosity,
link |
00:25:01.100
flight of ideas, agitation, no sleep,
link |
00:25:04.120
and rapid pressured speech.
link |
00:25:06.240
For someone to be diagnosed as in a manic episode,
link |
00:25:09.120
they do not have to be engaging in
link |
00:25:11.960
or displaying all of those symptoms.
link |
00:25:15.300
They do, however, need to present
link |
00:25:17.640
at least three of those symptoms.
link |
00:25:19.560
And then in order to meet the condition of bipolar I,
link |
00:25:23.080
they have to be presenting those three symptoms
link |
00:25:25.240
for at least seven days.
link |
00:25:27.780
It could be longer, but at least seven days.
link |
00:25:30.880
Now, this seems pretty straightforward, right?
link |
00:25:34.140
At one level, the way that I describe this
link |
00:25:36.620
and the way that it exists in the clinical literature,
link |
00:25:38.440
you could think, well, this should be pretty easy
link |
00:25:40.380
to diagnose, and yet there's a complication there
link |
00:25:43.080
or a challenge there because the psychiatrist, again,
link |
00:25:45.640
has to determine that these manic episodes
link |
00:25:48.220
are not due to something other than bipolar disorder.
link |
00:25:53.460
For instance, again, it could be TBI, traumatic brain injury,
link |
00:25:56.400
it could be seizures or meds or other sorts of drugs.
link |
00:25:58.920
Corticosteroids, which are often prescribed
link |
00:26:00.880
for a number of immune conditions or for wound healing,
link |
00:26:03.620
can also cause manic episodes.
link |
00:26:05.760
So they have to determine that everything that's happening
link |
00:26:09.320
meets the criteria I described before,
link |
00:26:10.960
three out of seven of these symptom categories
link |
00:26:13.020
for seven days or more,
link |
00:26:14.400
and that it can't be better explained
link |
00:26:16.560
by something else going on in that person's life
link |
00:26:19.200
or immediate medical history.
link |
00:26:21.320
That's very important.
link |
00:26:22.520
Now, the other challenge,
link |
00:26:23.580
and this is something that's going to come up
link |
00:26:24.880
again and again today,
link |
00:26:26.200
not just in the description of the biology
link |
00:26:28.220
of bipolar disorder, but also in the description
link |
00:26:31.300
of different treatments and treatment approaches,
link |
00:26:33.580
is that typically when somebody is sitting
link |
00:26:36.980
in front of a psychiatrist,
link |
00:26:39.200
in particular for the first time,
link |
00:26:41.780
those two people are interacting,
link |
00:26:44.020
the psychiatrist is just getting one snapshot
link |
00:26:46.880
of the person at that moment, right?
link |
00:26:49.000
So the person could be on day one of a manic episode,
link |
00:26:52.160
the person might be on day six of a manic episode,
link |
00:26:54.680
the person could be transitioning out of a manic episode,
link |
00:26:57.680
or the person could be suffering
link |
00:26:59.640
from a combination of manic episode
link |
00:27:01.600
where because of the impulsivity of bipolar disorder,
link |
00:27:04.620
they went out and used illicit drugs,
link |
00:27:06.040
they also used cocaine.
link |
00:27:07.680
So the psychiatrist has a serious challenge.
link |
00:27:10.860
The psychiatrist has to determine
link |
00:27:12.500
based on a conversation, right?
link |
00:27:14.080
This isn't a blood test,
link |
00:27:15.880
this isn't a measurement that you can take on a scale
link |
00:27:18.240
or with a biomarker,
link |
00:27:19.480
they have to use language,
link |
00:27:21.140
a conversation with somebody who by all accounts
link |
00:27:23.720
is pretty impaired at conversation
link |
00:27:25.720
to determine whether or not
link |
00:27:27.320
they're suffering from a manic episode
link |
00:27:29.840
that is the consequence of bipolar disorder.
link |
00:27:33.360
You can imagine this in the real world as somebody says,
link |
00:27:35.480
well, how long has it been since you slept?
link |
00:27:37.280
And the person starts to answer,
link |
00:27:39.360
oh, well, the other day I went down to the basement,
link |
00:27:41.840
I was going to get something out of the refrigerator
link |
00:27:44.040
and I thought I might take a nap
link |
00:27:44.880
and then all of a sudden
link |
00:27:45.720
they're talking about something completely different.
link |
00:27:46.720
So they might not even have an answer.
link |
00:27:48.880
So the psychiatrist has to be a really good detective,
link |
00:27:53.000
a benevolent detective, but a detective nonetheless
link |
00:27:56.040
in determining whether or not
link |
00:27:57.160
these symptoms have existed for seven days or more
link |
00:27:59.200
and whether or not they meet at least three,
link |
00:28:01.520
it could be more, but at least three of the criteria
link |
00:28:03.680
of symptom categories I talked about before.
link |
00:28:06.280
Now, assuming that they do,
link |
00:28:08.240
assuming that the patient meets those criteria,
link |
00:28:10.760
they are likely to be diagnosed with bipolar I.
link |
00:28:14.100
Now bipolar I disorder
link |
00:28:16.880
means they're having these extended manic episodes,
link |
00:28:18.660
seven days or more,
link |
00:28:19.840
but it does not necessarily mean that they are dropping
link |
00:28:23.080
into a depressive episode as well.
link |
00:28:25.820
This is a common misconception about bipolar disorder
link |
00:28:28.760
because as it's often called,
link |
00:28:30.720
bipolar disorder is referred to as bipolar depression
link |
00:28:34.240
and yet many people with bipolar disorder
link |
00:28:36.840
don't necessarily experience the deep depressive episodes.
link |
00:28:40.000
Many of them do, but many of them do not.
link |
00:28:42.460
So somebody can truly be diagnosed accurately
link |
00:28:46.240
with bipolar I,
link |
00:28:48.260
even though they're only experiencing manic episodes
link |
00:28:50.600
and then dropping down to baseline.
link |
00:28:52.200
Manic episode, then dropping down to baseline.
link |
00:28:54.320
That's very important to understand.
link |
00:28:56.880
Now, the second category of bipolar disorder is bipolar II.
link |
00:29:00.640
So BP2 or bipolar disorder II
link |
00:29:03.200
is somewhat different than bipolar disorder I.
link |
00:29:05.520
First of all, it's characterized most often
link |
00:29:08.560
by the presence of both manic episodes,
link |
00:29:11.000
mania and depressive episodes,
link |
00:29:13.320
or what's referred to as hypomania.
link |
00:29:15.880
Now, anytime in biology or in medicine you hear hypo,
link |
00:29:19.960
it's the opposite of hyper, okay?
link |
00:29:22.040
So we've got normal, hyper and hypo.
link |
00:29:24.180
Hypomania is a somewhat suppressed level of mania.
link |
00:29:27.760
So this is not going to be as extreme as the mania
link |
00:29:30.600
that we typically think of.
link |
00:29:32.020
And yet the hypo can be due to the duration,
link |
00:29:36.120
not the intensity of mania.
link |
00:29:38.400
That's right.
link |
00:29:39.240
Hypomania can mean a lessened intensity of mania,
link |
00:29:43.000
but it can also be used
link |
00:29:44.680
to refer to a shorter duration of mania.
link |
00:29:47.120
In fact, that's one of the key criteria for bipolar II.
link |
00:29:50.440
Bipolar II is often diagnosed
link |
00:29:52.200
on the basis of the presence of manic episodes
link |
00:29:54.900
that are lasting four days or even less.
link |
00:29:58.700
So someone with BP2 might have four days
link |
00:30:01.080
of this increased energy, goal-directed activity.
link |
00:30:03.600
They're irritable, they're euphoric,
link |
00:30:05.080
they're not sleeping, et cetera,
link |
00:30:06.620
but it's only lasting for about four days.
link |
00:30:09.100
Or they could be having longer extended periods of mania,
link |
00:30:12.520
but they are hypomanic episodes.
link |
00:30:15.240
They're not quite as intense.
link |
00:30:16.560
So the pressured speech isn't quite as pressured.
link |
00:30:19.480
The impulsivity isn't quite as severe, et cetera, et cetera.
link |
00:30:22.760
The other aspect of bipolar II
link |
00:30:24.040
is one that I had mentioned briefly a moment ago,
link |
00:30:26.480
which is that it's often associated
link |
00:30:28.980
with the drops into the depressive episodes.
link |
00:30:31.440
So people are going from manic episodes
link |
00:30:33.560
for four days or less,
link |
00:30:34.860
then they're dropping into a depression,
link |
00:30:36.960
going back to normal, manic again.
link |
00:30:40.780
I do want to point out, however,
link |
00:30:41.840
that people who have bipolar I
link |
00:30:43.540
can indeed go from manic episodes
link |
00:30:45.620
to severe what we call major depression.
link |
00:30:47.740
So they can oscillate like a sine wave,
link |
00:30:50.040
really high highs, really low lows.
link |
00:30:53.080
And very important to understand
link |
00:30:55.840
in terms of understanding both bipolar I and bipolar II
link |
00:30:59.680
is that it's not always a sine wave.
link |
00:31:01.720
This is really important.
link |
00:31:02.640
And it's something that frankly I did not know
link |
00:31:05.200
until I started researching this episode
link |
00:31:06.800
and talking to some psychiatrists.
link |
00:31:08.400
I should mention I've talked
link |
00:31:09.240
to several board-certified psychiatrists
link |
00:31:11.000
in preparation for this episode.
link |
00:31:12.800
I'll give some references to them.
link |
00:31:14.280
And in fact, some of them are going to be coming
link |
00:31:15.640
on the podcast as guests in the future
link |
00:31:17.520
for a more in-depth discussion about bipolar
link |
00:31:19.400
and other psychiatric disorders.
link |
00:31:21.620
But all of the psychiatrists I spoke to
link |
00:31:23.240
confirmed what the other was saying,
link |
00:31:25.680
which was that the way that bipolar disorder can present
link |
00:31:29.320
can vary tremendously between individuals.
link |
00:31:32.040
One person might go from very high highs
link |
00:31:34.120
that last seven days or more to very low lows,
link |
00:31:36.160
bouts of depression, major depression
link |
00:31:38.600
that could last two weeks or more.
link |
00:31:40.600
Other people are rapid cycling by way of three days manic,
link |
00:31:44.200
three days normal, three days manic,
link |
00:31:45.920
and then dropping into three days depression.
link |
00:31:48.000
So you want to erase that picture in your mind
link |
00:31:50.480
that manic bipolar disorder is this sine wave,
link |
00:31:53.480
this cycling up and down between mania and depression.
link |
00:31:56.480
It can take a lot of different forms.
link |
00:31:58.920
And again, this is a serious challenge
link |
00:32:02.160
for the psychiatrist to diagnose people
link |
00:32:04.400
because of that fact
link |
00:32:06.360
that they're only getting a snapshot of the person
link |
00:32:08.360
unless they've known them for some time
link |
00:32:09.820
and are working with them for some time.
link |
00:32:11.680
But this is also especially important for those of you
link |
00:32:14.560
that either have bipolar depression
link |
00:32:17.720
or suspect that you might,
link |
00:32:18.960
or that know someone with bipolar depression
link |
00:32:22.640
or suspect somebody might have bipolar depression,
link |
00:32:26.160
AKA bipolar disorder.
link |
00:32:27.880
Because if you're noticing that somebody
link |
00:32:29.960
is very manic and then normal,
link |
00:32:32.380
well, that's a very different picture
link |
00:32:34.240
than somebody who's going from very manic
link |
00:32:36.040
to very deep bouts of depression.
link |
00:32:38.560
The very manic to deep bouts of depression
link |
00:32:40.800
is easier to recognize
link |
00:32:42.480
because of the extremes of those highs and lows.
link |
00:32:44.760
Now, this might seem somewhat obvious to all of you
link |
00:32:46.960
as I describe it.
link |
00:32:47.880
And yet it's very important as a, frankly,
link |
00:32:51.120
a citizen of the planet who knows other human beings
link |
00:32:54.280
to keep an eye out for these manic episodes
link |
00:32:56.360
because again, whether or not it's four days or less
link |
00:32:59.000
or whether or not it's seven days or more,
link |
00:33:01.440
these manic episodes really are the defining criteria
link |
00:33:05.040
of bipolar disorder, AKA bipolar depression.
link |
00:33:08.000
There are a couple other key features
link |
00:33:10.600
about bipolar I and bipolar II
link |
00:33:12.760
that can allow us to get better insight
link |
00:33:14.560
into whether or not somebody has bipolar I or bipolar II.
link |
00:33:17.240
And that's the percentage of time
link |
00:33:19.440
that people with bipolar I versus bipolar II
link |
00:33:22.240
spend in a manic state, a depressed state,
link |
00:33:24.980
or a symptom-free state.
link |
00:33:26.660
And this is also important to discuss
link |
00:33:28.080
because it turns out that people with genuine,
link |
00:33:31.720
diagnosed bipolar I or bipolar II are often symptom-free,
link |
00:33:36.460
which again can make it difficult
link |
00:33:38.620
for us as people that know them
link |
00:33:40.780
or for people that are treating people
link |
00:33:43.420
with bipolar disorder to identify
link |
00:33:46.280
whether or not somebody is in a manic episode
link |
00:33:48.700
or a depressive episode,
link |
00:33:49.680
or whether or not they are headed
link |
00:33:50.720
into a manic or depressive episode.
link |
00:33:52.960
So the numbers on this have been studied.
link |
00:33:55.680
It's from a paper, actually two papers,
link |
00:33:57.680
first author Judd, J-U-D-D et al,
link |
00:34:00.120
published some years ago, 20 years ago,
link |
00:34:02.100
but the data hold up really nicely over time.
link |
00:34:04.360
These were both published
link |
00:34:05.280
in Journal of American Medical Association Psychiatry.
link |
00:34:07.880
So JAMA Psychiatry is a superb journal.
link |
00:34:10.360
And basically people who have bipolar I on average
link |
00:34:13.920
spend about 50%, it's actually 53%
link |
00:34:17.040
was the number that was eventually converged upon,
link |
00:34:20.420
but about 50% of their time symptom-free.
link |
00:34:22.840
That's interesting, right?
link |
00:34:23.760
Somebody who has genuine bipolar I disorder
link |
00:34:27.160
can spend as much as half of their life symptom-free,
link |
00:34:29.920
sleeping normally, speaking normally, et cetera,
link |
00:34:32.400
about 32% of the time depressed.
link |
00:34:36.480
And when we say depressed, we mean major depression.
link |
00:34:38.520
So severe challenges with waking up
link |
00:34:41.440
at two or three in the morning
link |
00:34:43.020
and having trouble falling back asleep,
link |
00:34:44.520
that's one of the defining characteristics of depression
link |
00:34:46.520
or sleeping far too much,
link |
00:34:47.760
having a hard time getting out of bed in the morning,
link |
00:34:49.280
suppressed appetite, suppressed libido,
link |
00:34:51.000
suppressed motivation, all the general symptoms
link |
00:34:53.640
of major depression,
link |
00:34:54.480
which we'll talk about a little bit more later
link |
00:34:56.240
and in an upcoming episode
link |
00:34:57.800
about major depression in particular.
link |
00:34:59.680
And then about 15% of their time
link |
00:35:01.940
in this kind of manic state or mixed manic state
link |
00:35:04.840
where they are showing long,
link |
00:35:07.640
again, seven days or more bouts of sleeplessness,
link |
00:35:09.960
irritability, pressured speech, grandiosity, et cetera.
link |
00:35:14.000
Contrast that with people who have bipolar II disorder
link |
00:35:16.760
who are spending about half of their time
link |
00:35:20.000
in a depressed state.
link |
00:35:21.780
So that's interesting.
link |
00:35:22.860
People with bipolar II disorder,
link |
00:35:24.440
while not always displaying depressed states
link |
00:35:27.280
or oscillations between mania or hypomania
link |
00:35:29.960
and depressed states,
link |
00:35:31.120
they tend to be in a depressed state more often.
link |
00:35:33.640
And again, this is major depression.
link |
00:35:34.960
This isn't just a little bit of a low.
link |
00:35:36.460
This is a serious depression of their nervous system,
link |
00:35:39.300
their mood, and as we say, their affect,
link |
00:35:41.720
their outlook on life.
link |
00:35:42.840
And that's one of the key distinguishing features
link |
00:35:45.200
of major depression is that people's outlook on life
link |
00:35:48.560
becomes very diminished in the sense
link |
00:35:50.920
that they don't see a future.
link |
00:35:52.120
You ask them about, you know, how's work going?
link |
00:35:54.540
How are relationships?
link |
00:35:55.380
And it's not just that they feel that that's going poorly.
link |
00:35:58.280
They really feel as if there's no opportunity
link |
00:36:00.240
for those things to improve.
link |
00:36:02.660
Those people with bipolar II tend to be symptom-free
link |
00:36:05.960
about 45% of the time.
link |
00:36:07.520
Again, these are averages.
link |
00:36:09.360
So about 45% of the time.
link |
00:36:11.360
That's a considerable amount of the time.
link |
00:36:13.340
And they tend to be in these hypomanic states
link |
00:36:15.820
only about four or 5% of the time.
link |
00:36:18.240
Again, the criteria for BP2, bipolar II,
link |
00:36:20.740
is these four days or less of mania or hypomania.
link |
00:36:24.320
But only 4% of the time or 5% of the time
link |
00:36:27.420
is a small enough sliver of the pie
link |
00:36:30.760
that is these people's existence
link |
00:36:32.800
that you can imagine why it would be easy
link |
00:36:36.200
for them or other people to overlook the fact
link |
00:36:38.800
that they have bipolar disorder and not major depression.
link |
00:36:41.600
Think about it.
link |
00:36:42.440
This is a person who, or I should say a collection of people
link |
00:36:45.440
who are spending about half of their time depressed,
link |
00:36:48.240
close to half, 45% of their time symptom-free,
link |
00:36:52.480
and then about 5% of their time in a hypomanic state.
link |
00:36:56.120
So either shortened bouts of high intensity mania
link |
00:37:00.680
or hypomania that is of reduced intensity.
link |
00:37:04.480
One of the reasons that I mentioned these percentages
link |
00:37:07.020
of time spent in a symptom-free depressed manic
link |
00:37:09.280
or hypomanic state is because one of my major goals
link |
00:37:11.320
for today's episode is that it will increase awareness
link |
00:37:14.840
of whether or not you or somebody you know,
link |
00:37:17.840
could be a coworker, could be a family member, et cetera,
link |
00:37:19.960
might be suffering from bipolar I or bipolar II.
link |
00:37:22.680
I think it's fair to say that if somebody is suffering
link |
00:37:24.560
from bipolar I, that is likely to be revealed
link |
00:37:29.160
or to reveal itself before too long
link |
00:37:32.340
because of the fact that people have these extended periods
link |
00:37:35.100
of mania and mania is such an extreme state,
link |
00:37:37.360
not just for the person who's experiencing it,
link |
00:37:39.480
but the way that it presents is just so extreme
link |
00:37:41.680
and out of the ordinary.
link |
00:37:43.540
But bipolar II, you can imagine,
link |
00:37:45.560
could really duck under the radar of our awareness.
link |
00:37:48.880
And you could imagine that we might just think
link |
00:37:50.800
somebody is low or depressed,
link |
00:37:52.220
especially if that person tends to self-medicate
link |
00:37:54.520
with alcohol or other substances.
link |
00:37:56.440
We might think, oh, well, they're drinking more than often,
link |
00:37:58.520
more than usual, excuse me,
link |
00:37:59.760
or they're spending more time alone and isolating.
link |
00:38:02.560
But then when they're in their hypomanic state,
link |
00:38:04.200
that might actually present as normal to us
link |
00:38:06.680
because they were in such a depressed state before.
link |
00:38:09.400
So it's very important that we dial up our awareness,
link |
00:38:11.960
that we can tune our antennae to the possibility
link |
00:38:14.260
that people out there who might appear depressed
link |
00:38:16.360
or that we haven't heard from in a while
link |
00:38:17.880
might actually be suffering from bipolar II disorder.
link |
00:38:20.600
Before we move into a in-depth discussion
link |
00:38:22.960
about the different kinds of treatments
link |
00:38:24.340
for bipolar disorder,
link |
00:38:25.940
I'd like to touch on just a few additional aspects
link |
00:38:28.600
of what bipolar disorder can do
link |
00:38:31.060
in terms of its negative consequences
link |
00:38:32.720
and also talk about some of the inherited risk,
link |
00:38:35.320
that is the genetic factors and the environmental factors
link |
00:38:38.480
that can contribute to bipolar disorder.
link |
00:38:40.620
In terms of the burden,
link |
00:38:43.280
the very real emotional and occupational
link |
00:38:46.480
and educational burden
link |
00:38:47.880
that can occur for somebody with bipolar disorder,
link |
00:38:50.680
that's actually been studied.
link |
00:38:51.680
There's a measure of this, it's called global burden,
link |
00:38:53.960
which is defined as the years lost
link |
00:38:56.840
in engaging in normal life due to some disability.
link |
00:39:00.340
So that disability could be cancer,
link |
00:39:02.280
that disability in this case is bipolar disorder.
link |
00:39:05.080
And basically the way this sort of study is done
link |
00:39:07.900
is that through questionnaires,
link |
00:39:09.200
I should say quite in-depth questionnaires,
link |
00:39:11.600
there's a probing for whether or not somebody
link |
00:39:13.980
has lost two consecutive weeks or more
link |
00:39:17.600
of interest in normal activities.
link |
00:39:19.480
Now, for people who have depression,
link |
00:39:21.040
that's a kind of straightforward thing to address, right?
link |
00:39:23.560
You ask somebody, when was the last time you ate?
link |
00:39:25.900
Or when was the last time that you went a few days
link |
00:39:27.760
without food or lost interest in relationships
link |
00:39:31.200
or work or sex or things of that sort?
link |
00:39:32.880
And they answer and you can figure out
link |
00:39:34.880
the amount of time that you've essentially been withdrawn
link |
00:39:37.720
from normal levels of activity for them.
link |
00:39:41.740
With bipolar disorder, what it turns out
link |
00:39:44.240
is that the global burden of having bipolar I
link |
00:39:47.760
and even bipolar II is massive.
link |
00:39:50.160
In fact, having bipolar disorder sits
link |
00:39:53.340
as one of the highest risk factors
link |
00:39:56.080
for being in the top 10 of all categories of disabilities
link |
00:40:00.920
leading to global burden.
link |
00:40:02.120
Put in plain English, what that means is having bipolar I
link |
00:40:05.360
or bipolar II disorder is extremely debilitating.
link |
00:40:08.520
It really slows down one's life trajectory
link |
00:40:12.220
unless it's treated properly.
link |
00:40:14.160
Now, the other aspect of bipolar disorder
link |
00:40:16.360
is its heritability.
link |
00:40:17.640
And this gets into a little bit of some tricky science
link |
00:40:20.720
related to heritability versus the genetic contribution
link |
00:40:26.160
of a given disease.
link |
00:40:28.040
So that might sound like the same thing.
link |
00:40:30.020
You think, okay, genes relate to heritability,
link |
00:40:32.320
heritability relates to genes,
link |
00:40:33.720
but of course everything about the way
link |
00:40:36.560
that our nervous system works and functions
link |
00:40:38.660
and expresses itself, healthy or otherwise,
link |
00:40:41.360
is an interaction between our genes and our environment.
link |
00:40:45.080
And so typically the way these studies are done
link |
00:40:47.080
is you address what is the risk of somebody
link |
00:40:50.460
having a given condition in the general population?
link |
00:40:52.740
We talked about that before.
link |
00:40:53.700
Bipolar disorder is a 1% of the world's population.
link |
00:40:57.160
Compare that to people who have only major depression.
link |
00:41:00.040
So this would be repeated bouts of two weeks or more
link |
00:41:03.520
of serious depression, not just low mood
link |
00:41:06.160
or something due to a life loss, but major depression,
link |
00:41:09.860
which is 10 to 17% of people have major depression.
link |
00:41:13.660
Okay, they suffer from major depressive disorder
link |
00:41:17.120
compared to bipolar disorder, which again is 1%.
link |
00:41:19.780
Now you can address how much of the 1% of bipolar disorder
link |
00:41:24.940
that exists is due to genes versus environment
link |
00:41:28.460
in a somewhat exact way.
link |
00:41:30.220
This is never an exact science.
link |
00:41:31.760
And the way that this is typically done
link |
00:41:33.340
is to look at concordance, that is the likelihood
link |
00:41:37.740
that two identical twins will both have a given condition
link |
00:41:42.380
as opposed to two fraternal twins,
link |
00:41:44.200
which have more different genes
link |
00:41:46.880
than identical twins, of course.
link |
00:41:48.220
And then two siblings who have similar genes, of course,
link |
00:41:51.220
but less similar than identical or fraternal twins
link |
00:41:54.420
and so on and so forth.
link |
00:41:55.480
So what you basically do is you evaluate the probability
link |
00:41:57.900
that two people in the general population
link |
00:41:59.540
who are completely unrelated will have the same condition
link |
00:42:02.780
versus two people in the general population
link |
00:42:05.540
who are very related identical twins.
link |
00:42:07.340
And what you find is that in identical twins,
link |
00:42:10.900
if one identical twin has true major depression
link |
00:42:14.800
or major depressive disorder,
link |
00:42:16.640
there's a 20 to 45% chance that their identical twin
link |
00:42:21.300
will also have major depressive disorder.
link |
00:42:23.660
Now that tells you right there that it can't all be genes.
link |
00:42:27.360
That is not a gene for major depression per se,
link |
00:42:29.660
or if it is a gene or a collection of genes,
link |
00:42:33.340
that those genes are also subject to environmental
link |
00:42:35.860
influences, either prenatal within the womb
link |
00:42:37.900
or after children are born.
link |
00:42:40.140
Now, the large range there of 20 to 45%
link |
00:42:42.500
could be due to any number of things.
link |
00:42:44.420
It could be experimental,
link |
00:42:46.140
meaning the techniques that were used in experiments.
link |
00:42:48.020
It could be due to regional differences, right?
link |
00:42:51.540
One part of the world versus another.
link |
00:42:52.780
There are a lot of different factors.
link |
00:42:54.480
Right now, we probably shouldn't delve into all that.
link |
00:42:56.760
At some point, we'll probably do an episode
link |
00:42:58.180
all about the genetics of nervous system heritability
link |
00:43:01.740
and heritability of features and mental health, et cetera.
link |
00:43:04.580
But we can compare major depression and the heritability
link |
00:43:07.980
or the genetic concordance between identical twins
link |
00:43:10.780
in major depression and bipolar disorder and ask,
link |
00:43:13.120
if one twin of an identical twin pair
link |
00:43:16.860
has bipolar depression,
link |
00:43:19.780
what is the likelihood that the other twin will have it?
link |
00:43:22.300
And it turns out that number is much higher.
link |
00:43:25.700
It's 40 to 70% likelihood or probability
link |
00:43:29.000
that if one twin has bipolar disorder,
link |
00:43:32.800
that their identical twin will also have bipolar disorder.
link |
00:43:35.580
So again, the total incidence of bipolar disorder
link |
00:43:39.420
in the general population is much lower
link |
00:43:42.520
than it is for major depression.
link |
00:43:43.780
It's 1% for bipolar versus 10 to 17% for major depression.
link |
00:43:48.140
But the genetic component is much higher,
link |
00:43:51.260
40 to 70% for bipolar disorder versus 20 to 45%
link |
00:43:55.860
for major depression.
link |
00:43:56.860
I know I'm throwing a lot of numbers out there,
link |
00:44:00.260
but basically what this means is that researchers
link |
00:44:03.580
have been able to take those numbers
link |
00:44:05.540
and filter them through a number of different risk factors
link |
00:44:08.820
that are related to early development,
link |
00:44:10.900
ask questions like if two twins were raised separately
link |
00:44:13.700
or together in one part of the world versus another,
link |
00:44:16.340
or had a two-parent household versus one-parent household,
link |
00:44:19.140
evaluate a lot of different variables.
link |
00:44:21.200
What they were able to discover,
link |
00:44:23.100
and this has been shown again and again,
link |
00:44:25.100
is that the genetic contribution to bipolar disorder
link |
00:44:30.140
is very, very high.
link |
00:44:32.020
That is the heritability of bipolar disorder is 85%.
link |
00:44:37.660
Okay, so again, I want to be really clear what this means.
link |
00:44:41.740
The total occurrence in the general population, fairly low.
link |
00:44:46.020
Still serious, 1%, but fairly low
link |
00:44:49.020
compared to other things like major depression.
link |
00:44:51.100
However, if someone has bipolar disorder,
link |
00:44:55.100
it's very likely that they inherited some gene
link |
00:44:58.500
or sets of genes or more accurately a susceptibility
link |
00:45:02.780
within their genes to environmental influences
link |
00:45:05.740
that can trigger bipolar disorder.
link |
00:45:08.240
There are a lot of different ways to discuss
link |
00:45:10.420
and to conceptualize heritability.
link |
00:45:12.340
So I want to be very careful
link |
00:45:13.460
with the way that I'm wording this.
link |
00:45:15.380
What this means is that people with bipolar disorder
link |
00:45:18.540
very likely have a gene or more typically
link |
00:45:21.540
it's going to be a set of genes that creates a susceptibility
link |
00:45:24.680
for bipolar disorder to present itself.
link |
00:45:27.520
Now, what environmental factors trigger
link |
00:45:30.380
or increase that susceptibility is not entirely clear.
link |
00:45:34.480
This always seems to center back onto the same sets of things
link |
00:45:37.220
like early life stress, trauma, et cetera.
link |
00:45:40.020
Certainly those are going to exacerbate the likelihood
link |
00:45:42.660
that someone who has a genetic propensity
link |
00:45:44.660
for bipolar disorder will express that bipolar disorder
link |
00:45:47.900
in its full array of symptomology,
link |
00:45:50.300
but 85% while very, very high is not 100%.
link |
00:45:55.940
Again, 85%, while a very high number for heritability
link |
00:45:59.060
is not 100%.
link |
00:46:00.180
What that means is that there is no single gene
link |
00:46:03.600
or identified gene cluster for bipolar disorder.
link |
00:46:07.260
The reason I keep drilling into this over and over
link |
00:46:09.260
is that I think we can confidently say
link |
00:46:11.260
that if someone has bipolar disorder,
link |
00:46:12.800
that there was something in their genetic lineage
link |
00:46:15.160
that led to that, or that very likely led to that.
link |
00:46:18.220
And yet it's not like eye color
link |
00:46:22.380
or some other physical feature
link |
00:46:24.620
which we can actually do the direct,
link |
00:46:27.300
so it's called Mendelian genetics
link |
00:46:28.700
and figure out whether or not somebody directly inherited
link |
00:46:32.540
that gene from one parent or the other parent.
link |
00:46:34.420
So the takeaway here is that
link |
00:46:36.980
if you have certainly an identical twin
link |
00:46:39.140
or a fraternal twin or a sibling or a parent
link |
00:46:41.460
or even a cousin or an uncle that has bipolar disorder
link |
00:46:44.640
in particular bipolar one,
link |
00:46:46.900
well then you need to be on the lookout
link |
00:46:49.340
for bipolar disorder perhaps in yourself
link |
00:46:51.840
and for the family members of that person.
link |
00:46:53.840
My goal within this episode up until now
link |
00:46:56.340
has been to provide a clear and detailed picture
link |
00:46:59.700
of bipolar disorder and its various forms.
link |
00:47:03.040
Before we start to talk about treatments
link |
00:47:04.780
for bipolar disorder
link |
00:47:05.780
and some of the neural circuit basis for bipolar disorder,
link |
00:47:09.460
I want to make sure that I distinguish bipolar disorder
link |
00:47:12.180
from borderline personality disorder.
link |
00:47:15.260
We will do an entire episode
link |
00:47:16.740
or maybe even several episodes
link |
00:47:18.160
about borderline personality disorder.
link |
00:47:20.520
Borderline personality disorder can indeed present itself
link |
00:47:25.020
in ways that resemble bipolar disorder and vice versa,
link |
00:47:29.500
but there are some key distinctions that need to be made
link |
00:47:32.340
because it turns out that bipolar disorder
link |
00:47:34.460
and borderline personality disorder are quite distinct
link |
00:47:38.240
in terms of their defining criteria.
link |
00:47:40.120
The key distinction between somebody
link |
00:47:42.820
with borderline personality disorder and bipolar disorder
link |
00:47:47.220
is that in borderline personality disorder,
link |
00:47:50.340
there can be episodes that can resemble mania or hypomania.
link |
00:47:54.360
So periods of flights of ideas
link |
00:47:56.540
or where people are spending money excessively
link |
00:47:59.080
or sexually promiscuous in ways that seem manic
link |
00:48:02.400
or could even be a little bit manic or a lot manic.
link |
00:48:05.960
And yet more often than not,
link |
00:48:08.280
there is an environmental trigger for those manic episodes.
link |
00:48:12.280
That is distinctly different from bipolar disorder
link |
00:48:16.000
where the person will have manic episodes
link |
00:48:18.320
without any need for a trigger.
link |
00:48:20.340
There doesn't need to be a call from someone saying,
link |
00:48:23.360
hey, let's go on a vacation together
link |
00:48:25.280
or there's something coming up this Friday
link |
00:48:27.480
that's really exciting
link |
00:48:28.760
or let's enter a relationship together
link |
00:48:31.160
of one form or another.
link |
00:48:32.400
The person with bipolar disorder will have episodes of mania
link |
00:48:35.440
or episodes of major depression
link |
00:48:37.600
without any need for an external stimulus
link |
00:48:40.480
or environmental trigger.
link |
00:48:42.160
But the person with borderline personality disorder
link |
00:48:44.960
almost always, again,
link |
00:48:46.240
there's never an always in biology and psychiatry,
link |
00:48:48.460
but almost always is going to exhibit flights of mania
link |
00:48:53.040
or depressive episodes or other types of mood shifts
link |
00:48:55.800
that are dramatic and maladaptive in response to things
link |
00:48:59.360
that are coming in through the external environment
link |
00:49:02.280
or relationships of some kind.
link |
00:49:03.840
In fact, one of the defining characteristics
link |
00:49:05.720
of borderline personality disorder
link |
00:49:07.840
is this thing that's referred to as splitting.
link |
00:49:10.080
A good example of splitting
link |
00:49:11.420
in the person with borderline personality disorder
link |
00:49:14.120
is that they will feel that they absolutely adore you
link |
00:49:17.820
and want to spend all their time with you
link |
00:49:19.640
and just think the world of you, you can do no wrong.
link |
00:49:22.240
And in fact, they genuinely can feel that way
link |
00:49:25.380
and can genuinely think that way about you.
link |
00:49:27.760
And then for whatever reason,
link |
00:49:30.020
it could be a perception of something that you did
link |
00:49:32.880
or something that you said
link |
00:49:34.280
or suspicion that you're thinking something about them,
link |
00:49:37.120
they can suddenly shift or split their emotions
link |
00:49:41.200
and what's called move you from a good object
link |
00:49:45.040
or a can do no wrong object to a bad object.
link |
00:49:48.240
They'll suddenly decide that you are cheating on them
link |
00:49:50.760
or that you are being mean to them
link |
00:49:53.220
or that you're insulting them
link |
00:49:54.520
or that something that you're doing
link |
00:49:56.720
is in violation to their self-worth,
link |
00:49:59.560
their wellbeing, et cetera.
link |
00:50:00.640
And that can send them down a pathway
link |
00:50:02.560
of being very angry, very depressed, et cetera.
link |
00:50:04.960
As I described the contour of a person
link |
00:50:06.800
with borderline personality disorder
link |
00:50:08.760
as somebody who splits very suddenly
link |
00:50:11.020
in response to some environmental trigger,
link |
00:50:12.680
real or perceived, there's the risk, of course,
link |
00:50:16.160
that it makes the person with borderline personality disorder
link |
00:50:18.860
sound like a bad person, that they're very volatile.
link |
00:50:22.080
And while they can be volatile,
link |
00:50:23.800
I want to be very careful to point out
link |
00:50:25.400
that the person with borderline personality disorder
link |
00:50:27.640
is also suffering in this context.
link |
00:50:30.280
So while those sorts of relationships
link |
00:50:33.200
with people with borderline personality disorder,
link |
00:50:35.800
whether or not they're romantic relationships
link |
00:50:37.620
or familial or coworkers, et cetera,
link |
00:50:39.680
can be very challenged, can be very high friction
link |
00:50:42.040
because of the good object, bad object shifts, et cetera,
link |
00:50:46.480
it's bi-directional, meaning the person
link |
00:50:48.380
with borderline personality disorder, as you can imagine,
link |
00:50:50.720
is also going through a lot of suffering.
link |
00:50:52.320
At one moment, they feel as if someone is wonderful
link |
00:50:54.880
and can do no wrong to them
link |
00:50:55.920
and they want to be so strongly affiliated with them.
link |
00:50:57.960
And then in the next moment,
link |
00:50:59.240
they feel as if that person is attacking them
link |
00:51:01.400
through their actions or even through their non-actions.
link |
00:51:04.040
So again, we will return
link |
00:51:05.640
to borderline personality disorder in a separate episode.
link |
00:51:08.540
It's a serious disorder, both for the person that has it
link |
00:51:11.200
and for people around them.
link |
00:51:12.620
Fortunately, there are some emerging treatments
link |
00:51:14.480
that are showing promise,
link |
00:51:16.200
and it's a fairly common disorder,
link |
00:51:18.540
but it's important that we distinguish
link |
00:51:20.600
borderline personality disorder from bipolar disorder,
link |
00:51:23.840
mostly on the basis of this need for a trigger.
link |
00:51:25.980
Again, in bipolar disorder,
link |
00:51:28.200
there is no need for a trigger to create a manic episode
link |
00:51:31.160
or a major depressive episode.
link |
00:51:32.480
They just happen, or they can just happen.
link |
00:51:35.680
Whereas in borderline personality disorder,
link |
00:51:38.320
almost always there's an external trigger
link |
00:51:40.560
or a perception that something happened in the environment
link |
00:51:43.720
or that somebody is behaving a certain way
link |
00:51:45.940
that dramatically shifts the person
link |
00:51:47.560
with borderline personality disorder
link |
00:51:49.600
from one mode to the next.
link |
00:51:51.500
As we move into our discussion about the treatments for
link |
00:51:53.800
and neural circuits underlying bipolar disorder,
link |
00:51:56.560
I want to just nail down one more key point.
link |
00:51:59.960
This is a very brief point,
link |
00:52:01.480
but it's perhaps the most important point,
link |
00:52:03.960
which is the highs and lows,
link |
00:52:07.120
or we should say the highs,
link |
00:52:09.160
these manic episodes and sometimes lows,
link |
00:52:11.480
because again, not everybody with bipolar disorder one or two
link |
00:52:14.140
suffers from depressive episodes.
link |
00:52:15.900
Sometimes yes, sometimes no.
link |
00:52:17.600
In particular in bipolar II, yes,
link |
00:52:19.840
but people with bipolar I can have extreme manic episodes
link |
00:52:22.760
and then just return to normal, as you recall.
link |
00:52:25.040
Well, those extreme lows and or extreme highs
link |
00:52:28.460
of people with bipolar disorder
link |
00:52:30.520
impact their lives in very negative ways.
link |
00:52:34.000
This is essential.
link |
00:52:35.320
And it's something that we're going to return to
link |
00:52:37.040
a little bit later when we talk about the relationship
link |
00:52:39.020
between bipolar disorder and creativity,
link |
00:52:41.600
because it turns out that there's
link |
00:52:42.800
a quite strong association there,
link |
00:52:45.480
one that would almost lead you to believe
link |
00:52:47.200
that being bipolar can be beneficial in certain contexts.
link |
00:52:49.640
And yet on whole, having bipolar disorder
link |
00:52:54.220
is extremely detrimental
link |
00:52:56.120
and challenging to the person suffering from it.
link |
00:52:58.320
And it's something that we want to keep in mind
link |
00:52:59.960
as we think about treatments and the underlying biology.
link |
00:53:03.440
Now I'd like to talk about some of the treatments
link |
00:53:05.240
for bipolar disorder.
link |
00:53:06.920
And in the discussion of those treatments,
link |
00:53:08.880
there's an absolutely incredible history
link |
00:53:11.820
of the discovery of one particular treatment
link |
00:53:14.280
that still shows great success in many patients,
link |
00:53:18.120
although some people can't take it
link |
00:53:19.780
for reasons that we'll talk about.
link |
00:53:21.560
And in the description of the discovery of this treatment
link |
00:53:24.680
for bipolar disorder,
link |
00:53:26.280
it also reveals to us that sometimes
link |
00:53:29.080
treatments come to the profession of medicine
link |
00:53:32.800
and through science in ways that precede
link |
00:53:36.620
the discovery of the underlying biology.
link |
00:53:39.520
That's right.
link |
00:53:40.360
Every once in a while,
link |
00:53:41.620
someone will discover a treatment for a disease
link |
00:53:44.400
without any understanding
link |
00:53:46.300
about the underlying biological basis of that disease.
link |
00:53:49.940
And in fact, that is the case for bipolar disorder.
link |
00:53:52.800
And the treatment that we're referring to is lithium.
link |
00:53:56.600
Lithium, as some of you know,
link |
00:53:59.020
is on the periodic table of elements.
link |
00:54:01.480
It is indeed a naturally occurring substance.
link |
00:54:04.400
It actually arrived on earth by way of stardust.
link |
00:54:08.240
Yes, we are talking about stardust on this podcast.
link |
00:54:11.040
But if you'd like to learn more
link |
00:54:12.000
about the origins of lithium
link |
00:54:13.520
and how lithium arrived here on earth
link |
00:54:15.780
for its discovery and applications in psychiatry,
link |
00:54:18.960
there's a beautiful talk that exists on YouTube.
link |
00:54:21.640
And we'll provide a link to this in the show note captions
link |
00:54:24.720
that describes the history of lithium
link |
00:54:27.480
in terms of its interplanetary travels
link |
00:54:29.920
and arrival on earth.
link |
00:54:31.280
This is a talk delivered by a physicist
link |
00:54:34.120
who's expert in quantum mechanics
link |
00:54:36.400
and is expert in lithium.
link |
00:54:38.280
And it's a just wonderful talk that I can refer you to.
link |
00:54:40.720
Less on the biology in that talk,
link |
00:54:42.380
but certainly a lot about lithium as an element.
link |
00:54:44.380
So for those of you nerds like me
link |
00:54:46.840
that love to know how things came to be here on the planet
link |
00:54:50.820
in one form or another,
link |
00:54:52.360
I'll encourage you to take a brief listen to that talk.
link |
00:54:55.280
We are going to discuss lithium
link |
00:54:56.600
in the context of its applications
link |
00:54:58.620
for treatment of bipolar disorder.
link |
00:55:00.520
And the discovery of lithium
link |
00:55:01.820
as a treatment for bipolar disorder
link |
00:55:04.160
is truly a miraculous story
link |
00:55:05.940
that I think everyone should know.
link |
00:55:07.540
The key player in this story is a physician
link |
00:55:11.400
by the last name Cade.
link |
00:55:12.560
He was an Australian physician.
link |
00:55:14.880
And Cade has a very interesting story in his own right.
link |
00:55:18.200
Cade was an Australian psychiatrist
link |
00:55:20.080
or Australian psychiatrist who also was a soldier.
link |
00:55:24.800
And during World War II,
link |
00:55:27.280
after the fall of Singapore to Japan,
link |
00:55:29.120
he became a prisoner of war
link |
00:55:31.340
and he was a prisoner of war from 1942 until 1945.
link |
00:55:35.560
So he had some time for observation.
link |
00:55:37.800
And during his imprisonment,
link |
00:55:39.440
he observed some of his fellow inmates
link |
00:55:41.740
as going through pretty wild vacillations
link |
00:55:44.600
in mood and energy,
link |
00:55:46.240
essentially going from manic episodes to depressed episodes
link |
00:55:49.520
or from manic to normal episodes.
link |
00:55:51.820
And for one reason or another,
link |
00:55:54.880
we don't know why,
link |
00:55:55.800
because I couldn't find any report
link |
00:55:57.080
as to why he hypothesized this,
link |
00:55:59.040
but he hypothesized that there was some buildup
link |
00:56:01.600
of some chemical in these people's brains
link |
00:56:05.400
that then they would urinate out
link |
00:56:08.000
and that urinating out of whatever chemical was in there
link |
00:56:12.520
would allow them to be more relaxed and not manic.
link |
00:56:15.600
In other words,
link |
00:56:16.820
Cade hypothesized that there's a buildup of a chemical
link |
00:56:19.240
in certain people's brains that makes them manic
link |
00:56:21.240
and they urinate that chemical out.
link |
00:56:23.620
So eventually he got out of this prison,
link |
00:56:27.120
as we mentioned, in 1945,
link |
00:56:29.040
and he started doing experiments
link |
00:56:30.960
in addition to seeing patients in his clinic.
link |
00:56:33.860
And what he did is he started to take urine
link |
00:56:36.060
from people who exhibited mania
link |
00:56:38.280
and urine from people who were not manic.
link |
00:56:41.000
And he took that urine
link |
00:56:42.240
and he would inject it into guinea pigs
link |
00:56:44.400
as an experimental model.
link |
00:56:46.440
And his general observation
link |
00:56:49.000
was that there was something in the urine
link |
00:56:51.480
that was indeed making the guinea pigs more manic
link |
00:56:55.160
if they were injected with urine from a manic patient.
link |
00:56:59.680
The exact measures that he was taking in these guinea pigs
link |
00:57:02.260
wasn't exactly clear.
link |
00:57:03.280
This is at a time or an era in science
link |
00:57:06.180
when you could just sort of report things
link |
00:57:08.260
a little bit more subjectively.
link |
00:57:09.720
Although there were still numbers and statistics,
link |
00:57:12.240
it was a little bit more of like case studies
link |
00:57:14.560
and descriptions,
link |
00:57:15.600
but it turns out that even though
link |
00:57:16.960
that all seems a little bit loose,
link |
00:57:18.280
it led to some incredible and still important discoveries
link |
00:57:21.940
for psychiatric health.
link |
00:57:23.680
So what he figured out
link |
00:57:25.460
was that the urine from manic patients
link |
00:57:27.080
seemed to be more toxic for these guinea pigs.
link |
00:57:29.840
And he also knew that there are two toxic substances
link |
00:57:33.420
in urine, urea and uric acid.
link |
00:57:36.800
So he was able to separate the urea and uric acid
link |
00:57:40.160
from people with mania and patients that did not have mania.
link |
00:57:44.580
And he figured out that the urea was the same
link |
00:57:47.800
in both these mentally ill manic patients
link |
00:57:50.840
and the non-manic patients.
link |
00:57:52.640
So it did not seem that urea was the compound
link |
00:57:56.200
that was creating these manic episodes
link |
00:57:58.680
or related to manic episodes or held the toxicity.
link |
00:58:02.840
So instead he focused on the uric acid.
link |
00:58:05.800
Now, in order to put the uric acid into solution
link |
00:58:09.520
so that he could inject it into these guinea pigs,
link |
00:58:11.760
he had to try a number of different compounds
link |
00:58:13.920
in order to dilute it.
link |
00:58:14.820
It just so happens that,
link |
00:58:16.460
and you chemists will be familiar with this,
link |
00:58:18.200
but there's certain things
link |
00:58:19.540
that just don't go into solution easily.
link |
00:58:21.180
You put the powder in a vial,
link |
00:58:23.140
you add some water or a saline or another solution,
link |
00:58:25.440
you mix it up and the powder stays suspended in there.
link |
00:58:27.800
It just doesn't actually ever become a clear liquid
link |
00:58:32.600
that you can inject.
link |
00:58:33.940
So in order to try injecting different strengths
link |
00:58:36.920
of uric acid, he ended up using lithium
link |
00:58:40.520
to assist in the dilution and lithium worked.
link |
00:58:43.760
So what he basically was doing, again for you chemists,
link |
00:58:46.120
is he was taking uric acid, he was adding lithium
link |
00:58:49.440
and making a solution of lithium urate, okay?
link |
00:58:52.780
This is a lot of details, but this is important
link |
00:58:55.440
because what he eventually found
link |
00:58:57.520
is that when he diluted the uric acid with lithium
link |
00:59:01.520
and created lithium urate,
link |
00:59:02.880
lithium urate could actually calm down these guinea pigs
link |
00:59:07.160
that were injected with the toxic urea.
link |
00:59:10.280
He also found that lithium urate
link |
00:59:13.160
had a generally calming effect on these guinea pigs.
link |
00:59:16.880
So now we're really off in crazy territory, right?
link |
00:59:19.560
We're talking about urine from patients
link |
00:59:21.720
that's separating out urea and uric acid.
link |
00:59:24.920
We're adding lithium to the uric acid.
link |
00:59:27.020
We're injecting this into guinea pigs.
link |
00:59:28.640
This is getting pretty wild and pretty weird,
link |
00:59:30.760
but this is medicine and from time to time,
link |
00:59:33.400
this is medicine and science.
link |
00:59:36.160
Cade was a good scientist
link |
00:59:37.880
in addition to being a good physician.
link |
00:59:39.880
And by good scientists,
link |
00:59:41.520
I mean that he did control experiments.
link |
00:59:43.440
Here he was injecting lithium urate
link |
00:59:47.440
into animals and seeing an effect,
link |
00:59:49.620
but he knew that that solution of lithium urate
link |
00:59:52.720
contained not just the uric acid,
link |
00:59:55.480
but it also contained lithium.
link |
00:59:57.040
And so he quite appropriately asked,
link |
01:00:00.040
maybe the lithium alone is having this calming effect
link |
01:00:04.080
on these guinea pigs.
link |
01:00:05.560
And indeed that was the case.
link |
01:00:07.280
When he did the proper control experiment
link |
01:00:09.240
and injected only lithium solution into these guinea pigs,
link |
01:00:14.280
they calmed down.
link |
01:00:15.520
From there, he in sort of 1940s style medicine,
link |
01:00:20.080
this would not happen now,
link |
01:00:21.800
he very quickly moved from that animal model
link |
01:00:24.000
into human patients and started injecting human patients
link |
01:00:27.720
with lithium or providing lithium orally to those patients.
link |
01:00:31.640
And lo and behold, found an absolutely profound
link |
01:00:36.120
and positive effect of lithium
link |
01:00:38.880
in reducing symptoms of mania.
link |
01:00:41.360
And as all good physician scientists do,
link |
01:00:44.020
he wrote up his results.
link |
01:00:45.720
And he wrote it up in a paper entitled
link |
01:00:48.960
Lithium Salts in the Treatment of Psychotic Excitement.
link |
01:00:52.360
Okay, back then they didn't call it mania,
link |
01:00:53.640
they called it psychotic excitement.
link |
01:00:55.880
This is a paper that was published September 3rd, 1949
link |
01:00:58.720
in the Medical Journal of Australia.
link |
01:01:00.640
We will provide a link to this study
link |
01:01:02.180
is now a classic study in the field of psychiatry.
link |
01:01:05.520
It's a really wonderful paper to read.
link |
01:01:07.240
And actually I encourage people,
link |
01:01:09.240
even if you're not a scientist or a clinician
link |
01:01:12.680
to just take a quick look at the second page in this paper
link |
01:01:15.640
that we've made available to you,
link |
01:01:17.800
where he describes each of the various case studies
link |
01:01:21.400
or the individuals that he looked at.
link |
01:01:23.840
I'm not going to read these in detail now
link |
01:01:25.160
because it would take a lot of unnecessary time,
link |
01:01:27.120
but things like case seven, MC, aged 40 years old,
link |
01:01:31.660
suffering from manic recurrent mania.
link |
01:01:33.640
In this episode, he'd been excited,
link |
01:01:34.820
restless and violent for over two months
link |
01:01:36.920
and was interfering so often
link |
01:01:37.960
that he had to be confined to a single room during the day.
link |
01:01:40.520
So this is very debilitating,
link |
01:01:42.800
what we now know to be bipolar depression.
link |
01:01:45.960
He commenced taking lithium citrate 20 grains,
link |
01:01:48.340
that's a measure of the amount of lithium,
link |
01:01:50.360
three times a day.
link |
01:01:51.200
In four days, he was distinctly quieter.
link |
01:01:53.760
And by February 13th, 1949 appeared practically normal.
link |
01:01:58.440
He continued well and on February 20th, 1949,
link |
01:02:00.940
the dose of citrate was reduced to 10 grains,
link |
01:02:03.080
et cetera, et cetera.
link |
01:02:03.920
He left the hospital.
link |
01:02:05.360
There are numerous descriptions of this sort
link |
01:02:07.900
within this paper, including some descriptions of patients
link |
01:02:10.340
that did not see such success
link |
01:02:12.860
and including some descriptions of patients
link |
01:02:15.240
that suffered from some negative side effects.
link |
01:02:18.200
So that's important to point out as well,
link |
01:02:20.000
but it's an absolutely wonderful paper
link |
01:02:22.280
and it's an absolutely wonderful voyage
link |
01:02:24.720
into the history of psychiatry,
link |
01:02:26.300
right down to the discussion
link |
01:02:27.560
where in just three short paragraphs,
link |
01:02:30.300
Cade really lays out the case for why lithium
link |
01:02:34.240
is such an important discovery in the treatment
link |
01:02:36.680
of what at that time they were calling psychotic excitement
link |
01:02:39.480
and what we now know to be manic bipolar depression.
link |
01:02:43.300
Lithium, I should mention,
link |
01:02:44.800
has a number of important features,
link |
01:02:46.420
but also a number of important side effects
link |
01:02:48.680
that need to be considered.
link |
01:02:49.720
First of all, it does have a certain toxicity
link |
01:02:53.160
and so levels of lithium in the blood
link |
01:02:55.180
need to be monitored extremely carefully.
link |
01:02:57.700
So it's not the sort of thing
link |
01:02:58.680
that people can just take at a given dose
link |
01:03:00.820
and every patient responds the same.
link |
01:03:02.480
There's a lot of oversight
link |
01:03:03.760
and a lot of blood tests that have to be done,
link |
01:03:05.560
especially in the first three months of lithium treatment.
link |
01:03:08.840
I should mention that lithium treatment is still used
link |
01:03:11.600
to some great degree of success in many,
link |
01:03:14.160
not all people suffering from bipolar depression
link |
01:03:17.840
or bipolar disorder rather,
link |
01:03:20.360
but there are a number of important things that happen
link |
01:03:23.840
between 1949 and present day that prevented lithium
link |
01:03:28.240
from reaching patients that really needed it.
link |
01:03:31.480
And that all can be summarized
link |
01:03:33.140
in two or three short sentences,
link |
01:03:35.140
basically by virtue of the fact
link |
01:03:37.360
that lithium is a naturally occurring element,
link |
01:03:39.840
it could not be patented.
link |
01:03:41.360
And as a consequence of that,
link |
01:03:43.100
there wasn't a lot of potential profit for drug companies
link |
01:03:46.120
to produce lithium, in fact, still to this day,
link |
01:03:48.400
it's very low cost.
link |
01:03:50.680
And still to this day,
link |
01:03:52.160
no one really owns the patent for lithium
link |
01:03:54.680
in its purest form.
link |
01:03:56.280
So that made it unattractive.
link |
01:03:57.760
It turns out that the FDA in the United States
link |
01:04:00.080
didn't allow lithium to be used as a treatment
link |
01:04:02.560
for manic bipolar disorder until 1970.
link |
01:04:06.720
So we're talking about a full 21 years
link |
01:04:08.840
from the publication of this paper
link |
01:04:11.120
by Cade in the Medical Journal of Australia
link |
01:04:13.100
showing quite beautifully the great potential
link |
01:04:16.680
and use of lithium for quelling the symptoms
link |
01:04:19.760
of bipolar disorder until the first patients
link |
01:04:23.680
in the United States were starting
link |
01:04:24.840
to access lithium regularly.
link |
01:04:26.560
And nowadays, of course, lithium is available,
link |
01:04:28.280
but still not able to be patented
link |
01:04:30.480
because it's element number three on the periodic table,
link |
01:04:32.800
it's naturally occurring.
link |
01:04:34.180
It's not literally falling down from the stars
link |
01:04:36.120
as stardust and going into pill form,
link |
01:04:37.740
but rather it can be synthesized in laboratories,
link |
01:04:41.940
but it is available.
link |
01:04:43.400
It does show not only great potential in many patients,
link |
01:04:47.040
but great application in many patients
link |
01:04:49.200
despite its side effects.
link |
01:04:51.120
So lithium really stands as this kind of golden example
link |
01:04:55.200
of a treatment that works, at least in many individuals,
link |
01:04:58.680
prior to an understanding of the biological basis
link |
01:05:01.960
of the disease for which that treatment is needed.
link |
01:05:04.920
Now, with that said, scientists and clinicians
link |
01:05:07.040
have been quite rigorous in trying to understand
link |
01:05:09.760
why and how lithium works in order to understand
link |
01:05:13.080
the why and how of bipolar disorder.
link |
01:05:15.240
This is the way that proper medicine and science is done.
link |
01:05:17.560
Even if there's an excellent treatment for something,
link |
01:05:20.120
it's important to understand why that treatment works
link |
01:05:22.980
because first of all, not everyone responds
link |
01:05:25.320
to that treatment.
link |
01:05:26.160
Second of all, scientists and physicians understand
link |
01:05:29.400
that just because we have one treatment that works,
link |
01:05:31.960
if it has any side effects at all,
link |
01:05:34.280
there is the possibility for better treatments.
link |
01:05:36.720
So it's not just about trying to bypass a drug
link |
01:05:39.840
that doesn't make much money for drug companies.
link |
01:05:41.700
I know a lot of people think in those terms,
link |
01:05:43.360
they think, oh, well, you know,
link |
01:05:44.780
there's this continued search for better treatments
link |
01:05:46.680
for bipolar disorder, even though lithium works
link |
01:05:48.960
because lithium doesn't allow drug companies
link |
01:05:50.600
to make much money.
link |
01:05:51.640
That's not really the case.
link |
01:05:52.840
The fact of the matter is, is that the toxicity,
link |
01:05:55.240
some of the other issues that are created with lithium,
link |
01:05:58.600
the fact that people need the ongoing blood testing,
link |
01:06:01.560
et cetera, really stimulates the need,
link |
01:06:04.560
really an urgent need for new and better treatments
link |
01:06:07.280
for bipolar disorder.
link |
01:06:08.160
And only by understanding how lithium works
link |
01:06:10.360
at the cellular level, at the neural circuit level,
link |
01:06:12.880
et cetera, do we really stand to find those new discoveries.
link |
01:06:16.060
If you were to do a literature search
link |
01:06:18.320
on the actions and mechanisms of lithium
link |
01:06:22.000
in terms of how it can calm people down
link |
01:06:24.280
and reduce their manic episodes,
link |
01:06:26.320
you would find an enormous array of papers,
link |
01:06:29.040
literally thousands of scientific studies
link |
01:06:31.680
in animals and in humans, which, for instance,
link |
01:06:35.040
will tell you that lithium treatment
link |
01:06:37.240
will increase so-called BDNF,
link |
01:06:39.680
brain-derived neutrophic factor.
link |
01:06:42.320
BDNF is often talked about
link |
01:06:44.000
in the context of neuroplasticity,
link |
01:06:45.740
the brain and nervous system's ability to change
link |
01:06:48.080
in response to experience.
link |
01:06:49.440
And indeed, it does seem that ingesting lithium
link |
01:06:53.380
increases BDNF.
link |
01:06:54.960
BDNF is what we call permissive for neuroplasticity.
link |
01:06:59.320
It doesn't create specific changes in the brain,
link |
01:07:02.080
meaning it's not going to make your memory better
link |
01:07:04.400
or your coordination better
link |
01:07:06.360
or your emotional state better per se.
link |
01:07:08.800
What BDNF does is it permits the neurons, the nerve cells,
link |
01:07:13.560
and their connections in the brain
link |
01:07:15.040
to be more likely to change
link |
01:07:17.920
if the proper environmental conditions are met.
link |
01:07:21.600
That is, BDNF creates a kind of buoyancy
link |
01:07:25.200
to neuroplasticity.
link |
01:07:26.560
It opens the gates to neuroplasticity.
link |
01:07:28.960
So lithium does increase BDNF.
link |
01:07:31.200
We'll talk about why that's important
link |
01:07:32.480
in the context of the neural circuits involved
link |
01:07:34.880
with bipolar disorder in a few minutes.
link |
01:07:37.400
It also seems to be a potent anti-inflammatory.
link |
01:07:41.240
Now, inflammation is one of those words
link |
01:07:42.880
that's thrown around extensively nowadays,
link |
01:07:45.200
especially on social media
link |
01:07:46.440
and especially as it relates to any health condition.
link |
01:07:48.760
It's like inflammation, inflammation, inflammation
link |
01:07:50.940
always seems to be discussed
link |
01:07:52.620
in the context of inflammation being bad.
link |
01:07:54.440
But I do want to point out
link |
01:07:56.080
that inflammation is a natural adaptive response
link |
01:07:59.160
to physical injury to a cell or organ or tissue of any kind.
link |
01:08:03.220
Inflammation is the basis
link |
01:08:05.040
by which adaptations occur to exercise.
link |
01:08:08.240
So for instance, you were to weight train
link |
01:08:10.760
and use a heavier than normal weight
link |
01:08:12.680
and do a set to failure
link |
01:08:14.040
or create some little micro tears in the muscle
link |
01:08:16.240
that are healthy in the sense
link |
01:08:17.740
that they would create adaptations
link |
01:08:19.720
and make that muscle stronger, maybe even grow that muscle.
link |
01:08:22.400
There's an inflammatory response associated with that
link |
01:08:24.700
that is critical to the positive adaptation.
link |
01:08:27.400
So inflammation isn't always bad,
link |
01:08:29.480
although excessive or as we say, runaway inflammation is bad.
link |
01:08:33.920
Lithium seems to be able to suppress inflammation
link |
01:08:36.680
and importantly, it can suppress inflammation
link |
01:08:40.160
in neural tissues and within the brain in particular.
link |
01:08:43.160
That is important and we will return to that
link |
01:08:45.960
and why it's important in a little bit.
link |
01:08:48.360
The other thing about lithium
link |
01:08:49.880
is that lithium is neuroprotective.
link |
01:08:52.920
That is, it can prevent neurons from dying
link |
01:08:56.120
under certain conditions.
link |
01:08:57.280
Why would neurons die?
link |
01:08:58.400
Well, there are a lot of reasons why neurons can die.
link |
01:09:00.400
There can be a physical insult to the neurons.
link |
01:09:01.920
You can get hit really hard in the head.
link |
01:09:03.680
A bullet, God forbid, can enter the skull and kill neurons.
link |
01:09:07.680
There are a lot of reasons why neurons can die.
link |
01:09:10.520
Neuroprotection is a situation
link |
01:09:13.920
in which a neuron is given some sort of chemical
link |
01:09:16.560
or physical resiliency
link |
01:09:18.240
that allows it to suffer an insult and yet bounce back.
link |
01:09:21.920
So it's very similar to the way
link |
01:09:23.200
that we think about psychological resiliency.
link |
01:09:25.000
Neuroprotection is an ability for neurons
link |
01:09:28.200
to be better able to handle stress of different kinds.
link |
01:09:31.700
In particular, excitotoxicity.
link |
01:09:34.240
There's a phenomenon in bipolar disorder
link |
01:09:36.600
and a lot of other psychiatric conditions
link |
01:09:38.680
in which hyperactivity of certain brain areas
link |
01:09:41.720
actually starts to kill off neurons.
link |
01:09:44.440
Hyperactivity doesn't always do this,
link |
01:09:46.280
but it turns out that if certain brain circuits
link |
01:09:48.120
are too active for too long,
link |
01:09:49.800
some of the chemicals associated with neuronal activity,
link |
01:09:52.560
things like calcium and neurotransmitters like glutamate,
link |
01:09:55.360
can actually kill the very neurons that are active.
link |
01:09:57.840
So it seems that lithium can prevent
link |
01:09:59.600
some of that neurotoxicity.
link |
01:10:00.920
Now, this turns out to be particularly important
link |
01:10:03.800
for this discussion about bipolar disorder
link |
01:10:05.720
and the neural circuit basis of bipolar disorder,
link |
01:10:08.440
because if we were to just take a step back and ask,
link |
01:10:10.600
what's different in the brains
link |
01:10:12.000
of people with bipolar disorder?
link |
01:10:14.040
There are some very interesting answers that start to emerge.
link |
01:10:16.900
There are basically two main neural circuits
link |
01:10:19.400
that are present in normal individuals.
link |
01:10:22.600
I say normal, I say that respectfully
link |
01:10:24.720
to the people with bipolar disorder
link |
01:10:26.000
by referring to people who do not suffer
link |
01:10:29.000
from manic episodes or from manic depression.
link |
01:10:32.480
There are circuits that are present
link |
01:10:33.780
in people with bipolar disorder
link |
01:10:36.240
and in people that do not suffer from bipolar disorder.
link |
01:10:40.520
Both of those circuits do the same thing
link |
01:10:43.560
in both sets of individuals.
link |
01:10:45.360
And yet in people with bipolar disorder,
link |
01:10:47.840
there seems to be an atrophy
link |
01:10:49.960
or a removal of certain neural connections over time
link |
01:10:53.240
that leads to a situation
link |
01:10:55.200
in which people with bipolar disorder become very poor
link |
01:10:59.600
at registering their own internal state,
link |
01:11:02.240
in particular, their emotional states
link |
01:11:04.140
and their somatic states.
link |
01:11:05.840
What we're referring to here
link |
01:11:06.780
is something called interoception.
link |
01:11:08.480
I've talked about this a little bit
link |
01:11:09.460
on the Huberman Lab podcast before,
link |
01:11:11.260
but there are two modes of perception.
link |
01:11:13.780
Perception, of course, is a attention
link |
01:11:16.680
to something that's happening in our environment
link |
01:11:18.800
or to us on or within our body.
link |
01:11:21.940
Exteroception is literally an attention
link |
01:11:25.100
to things that are happening beyond the confines
link |
01:11:27.120
of our skin.
link |
01:11:27.960
So seeing that person's face over there
link |
01:11:29.960
or seeing that color of leaf over there
link |
01:11:32.660
or hearing a sound over to my left.
link |
01:11:34.660
That is exteroception,
link |
01:11:36.400
perception of things beyond the confines of one's skin.
link |
01:11:39.640
Then there's interoception,
link |
01:11:41.400
which is perception of things that are happening internally,
link |
01:11:44.240
like how full does my gut feel?
link |
01:11:46.160
How fast is my heart beating?
link |
01:11:48.540
Some people can measure that quite accurately
link |
01:11:50.500
just by thinking about it.
link |
01:11:51.520
Other people can't.
link |
01:11:53.300
How happy am I?
link |
01:11:54.480
How sad am I?
link |
01:11:55.680
How energetic am I?
link |
01:11:56.920
How lethargic am I?
link |
01:11:58.040
Et cetera, et cetera.
link |
01:11:59.020
So we are always existing in a balance
link |
01:12:00.720
between exteroception and interoception.
link |
01:12:03.440
But as it turns out,
link |
01:12:04.840
people with bipolar disorder over time,
link |
01:12:07.720
and especially into the second and third decade
link |
01:12:10.400
of having bipolar disorder,
link |
01:12:11.960
seem to have progressively diminished levels
link |
01:12:15.240
of interoception.
link |
01:12:16.480
And that very likely is important
link |
01:12:18.280
in their inability to register, for instance,
link |
01:12:20.520
that, wow, they are talking at an excessive rate
link |
01:12:23.760
or they haven't slept in five or even 10 days,
link |
01:12:27.280
or they haven't eaten in a long period of time.
link |
01:12:30.200
This atrophy of neural circuits for interoception
link |
01:12:35.240
is starting to emerge
link |
01:12:37.040
as one of the defining neural circuit characteristics
link |
01:12:40.020
or underpinnings of bipolar.
link |
01:12:42.120
Now, I bridged to this conversation about neural circuits
link |
01:12:44.880
from the statement that lithium can protect
link |
01:12:48.720
against some of the neurotoxic effects
link |
01:12:51.640
of neural circuits being very active.
link |
01:12:53.420
Now, this can get a little bit complicated,
link |
01:12:55.320
but I promise I'm going to make it clear
link |
01:12:57.060
for any of you that are watching and or listening.
link |
01:12:59.800
The reality is that people with bipolar depression
link |
01:13:03.900
very likely have a hyperactivity,
link |
01:13:06.280
that is an increased level of activity
link |
01:13:08.000
in certain circuits within the brain
link |
01:13:09.560
early in the expression of their disease.
link |
01:13:12.080
And that typically, as I mentioned earlier,
link |
01:13:14.300
sets in around the early 20s,
link |
01:13:15.920
although sometimes that can be even earlier
link |
01:13:18.040
in the teens and so forth.
link |
01:13:19.840
But that hyperactivity, we think, leads to a toxicity,
link |
01:13:25.560
an excitotoxicity of certain elements of the neural circuits
link |
01:13:29.160
that are responsible for interoception.
link |
01:13:31.640
In other words, the overuse of certain circuits
link |
01:13:34.440
can lead to a diminishing, an atrophy,
link |
01:13:37.480
or even a death of certain elements within those circuits.
link |
01:13:40.000
And it appears that lithium,
link |
01:13:41.560
through its anti-inflammatory and neuroprotective effects,
link |
01:13:45.420
and through its ability to increase BDNF,
link |
01:13:49.160
very likely protects us against some of that atrophy
link |
01:13:52.160
of those circuits for interoception.
link |
01:13:54.240
So this isn't a case in which, you know,
link |
01:13:56.400
people with bipolar have a neural circuit
link |
01:13:59.020
or lack a neural circuit,
link |
01:14:00.060
and people without bipolar are the opposite.
link |
01:14:02.200
This is a case in which everyone
link |
01:14:03.360
more or less starts out the same,
link |
01:14:05.080
but it seems that there's a hyperactivity
link |
01:14:07.240
of certain neural circuits in people with bipolar disorder
link |
01:14:09.840
that over time actually causes those circuits to diminish.
link |
01:14:13.440
Now, this is very important
link |
01:14:14.560
because some of the more recent longitudinal studies
link |
01:14:17.320
doing brain imaging on people with bipolar disorder
link |
01:14:19.400
and those without, and doing that over time
link |
01:14:21.960
in patients starting as early as their teens,
link |
01:14:23.840
but into their 20s and 30s,
link |
01:14:25.800
reveals just that,
link |
01:14:27.620
that there can be hyperactivity of circuits early on,
link |
01:14:29.920
but then hypo, reduced activity of those very same circuits
link |
01:14:33.800
at a time five or 10 years later.
link |
01:14:36.360
Again, this speaks to the complicated nature
link |
01:14:38.240
of bipolar disorder and the complicated nature of psychiatry
link |
01:14:41.840
and linking specific psychiatric disorders
link |
01:14:45.000
to neural circuits in general.
link |
01:14:46.880
Because if you have a situation in which, you know,
link |
01:14:49.840
in one disease, let's just hypothesize here for a second
link |
01:14:53.600
that for instance, in certain forms of schizophrenia,
link |
01:14:55.900
there's elevated dopamine,
link |
01:14:57.080
and were we to just reduce the amount of dopamine
link |
01:14:58.920
that they would receive relief
link |
01:15:00.140
from those schizophrenic symptoms?
link |
01:15:02.200
Well, that's all pretty straightforward on the face of it.
link |
01:15:04.440
But in this situation with bipolar disorder,
link |
01:15:06.440
what we're talking about is hyperactivity, too much activity,
link |
01:15:09.240
leading to hypoactivity through death
link |
01:15:12.000
of those very circuits.
link |
01:15:12.960
And so now you can especially appreciate why
link |
01:15:16.800
when the patient shows up to the psychiatrist
link |
01:15:19.080
or when the psychiatrist shows up to the patient
link |
01:15:20.800
in the total course of their disease
link |
01:15:23.200
is going to be very important.
link |
01:15:24.420
And then layer on top of that the complexity of the fact
link |
01:15:26.880
that the very defining characteristic of bipolar disorder
link |
01:15:30.160
is that there are oscillations in mood.
link |
01:15:31.860
So now we need to think about treatments
link |
01:15:33.760
not just for the manic episodes,
link |
01:15:35.600
but also treatments for the depressive episodes.
link |
01:15:38.060
And that's in fact what psychiatrists do.
link |
01:15:40.360
Turns out that they apply different treatments
link |
01:15:42.720
or combinations of treatments
link |
01:15:44.400
for patients that are in manic episodes
link |
01:15:46.540
versus depressive episodes.
link |
01:15:47.960
And they have to infer all that from discussions.
link |
01:15:51.460
Again, just exchange of words,
link |
01:15:53.140
depending on when that person walked into their office,
link |
01:15:56.740
where they are in terms of manic episodes,
link |
01:15:59.440
no symptomology or depressive symptomology,
link |
01:16:02.080
and whether or not they've had that symptomology
link |
01:16:04.500
for an extended period of time.
link |
01:16:06.000
And then just to make the situation even more complicated,
link |
01:16:08.640
the very circuits that atrophy
link |
01:16:10.300
that start to wane and disappear
link |
01:16:12.040
in people with bipolar disorder
link |
01:16:13.480
are the circuits for interoception,
link |
01:16:15.580
for understanding of what's going on in one's own body.
link |
01:16:17.800
So you can imagine if you sit down and ask somebody,
link |
01:16:20.280
well, how long has it been since you slept?
link |
01:16:23.400
That person may genuinely not know.
link |
01:16:26.120
Or if you ask the very depressed person,
link |
01:16:28.680
how depressed are you?
link |
01:16:29.720
That person may not be able to articulate that.
link |
01:16:32.560
So fortunately, there are solutions to this.
link |
01:16:34.920
And the solution is that more often than not,
link |
01:16:38.600
the accurate understanding of whether or not
link |
01:16:40.300
someone has bipolar depression or not,
link |
01:16:43.280
and what stage of the illness they might be in or not
link |
01:16:47.200
is going to depend on the reports of people around them
link |
01:16:50.320
and not the patient themselves.
link |
01:16:52.240
Hence, the importance of having a rather detailed
link |
01:16:55.400
and admittedly a rather intense discussion
link |
01:16:57.560
about the symptomology of bipolar disorder
link |
01:16:59.880
so that you can have an understanding
link |
01:17:03.440
of the people around you and have an eye and an ear
link |
01:17:06.160
to whether or not those people
link |
01:17:07.360
might be suffering from bipolar,
link |
01:17:08.720
and if so, at what stage of the disease
link |
01:17:10.680
they might happen to be at.
link |
01:17:11.960
Now I'd like to talk a little bit more
link |
01:17:13.240
about what is known about the neural circuits
link |
01:17:15.280
that lead to the manic states,
link |
01:17:17.380
as well as the depressive states,
link |
01:17:18.640
but mainly the manic states of bipolar disorder.
link |
01:17:22.320
We already discussed the fact that interoception,
link |
01:17:25.320
registering of one's own internal emotions
link |
01:17:27.520
and bodily states is diminished
link |
01:17:29.220
in people with bipolar disorder,
link |
01:17:31.160
but we haven't really talked about the neural circuits
link |
01:17:33.280
that are responsible for that lack of recognition.
link |
01:17:36.820
For that reason, I'd like to point out a paper.
link |
01:17:38.960
This is a fairly recent paper, just came out this year,
link |
01:17:41.720
but it's an excellent one
link |
01:17:43.520
looking at the changes over time in neural circuitry
link |
01:17:46.360
in people with high genetic risk for bipolar disorder,
link |
01:17:50.360
and in particular, in young people.
link |
01:17:51.840
And studies of this sort are rare,
link |
01:17:54.320
but are exceedingly important because of the fact
link |
01:17:56.640
that they track individuals over time.
link |
01:17:58.680
The title of this paper is
link |
01:17:59.920
Longitudinal Changes in Structural Connectivity
link |
01:18:02.400
in Young People at High Genetic Risk for Bipolar Disorder.
link |
01:18:05.880
We will provide a link to this study
link |
01:18:07.580
in the show note captions.
link |
01:18:09.200
There are a lot of data in this paper,
link |
01:18:12.080
in particular, neuroimaging data,
link |
01:18:14.840
and it's quite extensive in terms of analyzing
link |
01:18:17.520
the so-called connectomics.
link |
01:18:19.560
You've probably heard of genomics,
link |
01:18:21.080
which is the analysis of genes and their display
link |
01:18:24.000
in different individuals or different animals, et cetera.
link |
01:18:26.920
You have proteomics, which is the display of
link |
01:18:29.680
or the existence of different proteins.
link |
01:18:31.180
So omics is a big thing now in science.
link |
01:18:33.280
You kind of throw omics behind anything
link |
01:18:35.000
and it becomes its own Wikipedia page,
link |
01:18:37.320
which means it becomes its own thing.
link |
01:18:39.200
So to speak, I say that only partially in jest.
link |
01:18:42.400
Nonetheless, connectomics is the analysis of connections
link |
01:18:46.920
between different neurons and neural circuit elements.
link |
01:18:50.120
And what this paper really showed
link |
01:18:52.000
by analyzing the connectomics of neural circuits
link |
01:18:54.360
in the brains of many different people
link |
01:18:57.160
with different categories of and onset of
link |
01:19:01.840
and severity of bipolar disorder,
link |
01:19:05.400
as well as controls in different age groups, et cetera,
link |
01:19:11.160
is that people who are a particularly high risk
link |
01:19:14.920
for having bipolar disorder
link |
01:19:16.400
or that have full-blown bipolar disorder
link |
01:19:19.200
have deficits and actually reductions
link |
01:19:22.280
in the amount of connectivity
link |
01:19:23.720
between what are called the parietal brain regions
link |
01:19:25.920
and the limbic system.
link |
01:19:27.240
Now, the limbic system I've talked about before
link |
01:19:28.800
in this podcast, if you're not familiar with it,
link |
01:19:30.620
I'll explain what it is in a moment.
link |
01:19:32.900
It's simply a collection of brain structures,
link |
01:19:34.780
not one brain structure,
link |
01:19:35.800
but a collection of brain structures
link |
01:19:37.760
that generally are responsible
link |
01:19:39.600
for shifting the overall state that we're in
link |
01:19:43.240
from states of more relaxed and calm
link |
01:19:46.360
to states of more alert and focused.
link |
01:19:48.820
The limbic system is intimately related
link |
01:19:51.980
to the so-called autonomic nervous system,
link |
01:19:53.940
which regulates our sleep-wake cycles
link |
01:19:56.080
and a number of other things like our digestion, et cetera,
link |
01:19:59.000
our level of hunger and on and on.
link |
01:20:01.000
So the limbic system is really kind of like a volume control
link |
01:20:05.040
or as nerd scientists like to say,
link |
01:20:07.480
a kind of game control on the overall level
link |
01:20:11.120
or amplitude of alertness or calmness.
link |
01:20:13.960
In fact, if we're very, very calm,
link |
01:20:15.600
we are asleep or even more calm, we can be in a coma.
link |
01:20:18.620
If we are very alert, we can be wide awake
link |
01:20:20.960
and ready to work and run, et cetera.
link |
01:20:22.760
Or if we are very, very, very alert
link |
01:20:25.020
by way of limbic autonomic interactions,
link |
01:20:27.540
well, then we can be in anxiety,
link |
01:20:29.340
we can be in full-blown panic attack, or we can be in mania.
link |
01:20:33.380
We can have so much energy
link |
01:20:35.020
that we feel like we don't need to sleep.
link |
01:20:36.440
And in fact, disruptions in the circuitry
link |
01:20:38.780
really seems to be what's going on
link |
01:20:41.120
in people who have bipolar disorder.
link |
01:20:43.820
Now, if disruptions in the circuitry
link |
01:20:46.960
are present in the limbic system,
link |
01:20:48.300
that doesn't necessarily mean that the limbic system
link |
01:20:50.680
is at fault because the way that neural circuits work
link |
01:20:53.140
is that different brain areas are talking to one another
link |
01:20:55.500
through electrical chemical signaling
link |
01:20:57.060
and they are regulating one another.
link |
01:20:58.540
And what this paper really tells us
link |
01:21:01.060
is that there are elements within the parietal lobe,
link |
01:21:03.300
which is a kind of a section of the brain
link |
01:21:04.900
that sits off to the side.
link |
01:21:06.220
It's not really off to the side,
link |
01:21:07.380
but in neuroanatomical nomenclature,
link |
01:21:10.740
the parietal lobe is connected in two ways, bidirectionally.
link |
01:21:15.940
So parietal lobe is connecting to limbic system
link |
01:21:18.180
and limbic system is connecting to parietal lobe.
link |
01:21:20.660
And in people with bipolar disorder,
link |
01:21:21.980
it seems that the parietal lobe
link |
01:21:23.380
is able to exert less top-down control,
link |
01:21:26.580
that is less suppression
link |
01:21:28.540
of certain elements of the limbic system,
link |
01:21:30.740
which at least right now is leading researchers
link |
01:21:34.340
to hypothesize that the limbic system
link |
01:21:36.380
is sort of revving at higher levels.
link |
01:21:39.580
It's kind of like RPM in your cars
link |
01:21:41.260
or kind of redlining at times and for durations
link |
01:21:44.840
that are inappropriate or at least abnormal.
link |
01:21:47.240
So we have two major sets of neural circuit deficits
link |
01:21:51.700
or changes in people with bipolar.
link |
01:21:53.620
Their lack of internal awareness is reduced
link |
01:21:55.700
and that turns out to be by way of neural structures
link |
01:21:58.300
like the insula, which is a brain region
link |
01:22:00.940
that is connected in a very direct way
link |
01:22:03.580
to our somatosensory cortex,
link |
01:22:05.700
so the part of our cortex that registers how we feel,
link |
01:22:09.820
literally, sense of touch and internal state.
link |
01:22:13.100
So those circuits, excuse me,
link |
01:22:15.380
for those of you listening, I just bumped the microphone,
link |
01:22:17.740
excuse me, those circuits are disrupted
link |
01:22:20.780
in people with bipolar and the top-down control,
link |
01:22:24.260
the kind of accelerator and brake
link |
01:22:26.060
on our overall levels of energy are also disrupted.
link |
01:22:30.040
Now, that's all fine and good because, well, it's true,
link |
01:22:34.100
at least according to what the data
link |
01:22:35.740
at this point in time tell us,
link |
01:22:37.340
there may be new discoveries to come,
link |
01:22:38.760
but that all seems to be the case,
link |
01:22:40.620
but it doesn't tell us how to modulate
link |
01:22:42.340
or change that circuitry.
link |
01:22:43.980
It also doesn't tell us how something like lithium
link |
01:22:47.260
can actually benefit a large number of patients
link |
01:22:50.180
or how a good number of the other treatments
link |
01:22:53.060
for bipolar disorder, which we'll talk about going forward,
link |
01:22:56.000
can benefit patients with bipolar.
link |
01:22:58.060
So it appears that lithium is exerting its positive effects
link |
01:23:00.460
on bipolar depression treatment, at least in part,
link |
01:23:04.100
by preventing the loss of certain neural circuits,
link |
01:23:06.300
namely the neural circuits for interoception
link |
01:23:08.140
and the top-down control over the limbic system.
link |
01:23:10.900
Now, it turns out that by examining lithium's effects
link |
01:23:14.160
at an even more reductionist level,
link |
01:23:16.400
we can gain really important insight
link |
01:23:18.420
into what's going on in bipolar depression
link |
01:23:20.540
and some of the other treatments for bipolar depression,
link |
01:23:23.380
including behavioral treatments,
link |
01:23:25.380
things like transcranial magnetic stimulation,
link |
01:23:27.420
and even some of the more natural
link |
01:23:29.580
or so-called nutraceutical treatments,
link |
01:23:31.780
including things like high-dose omega-3 supplementation,
link |
01:23:35.360
which we're going to talk about extensively.
link |
01:23:37.440
Now, in order to understand
link |
01:23:38.700
what we're going to talk about next,
link |
01:23:40.060
it's important that everybody understand
link |
01:23:42.040
a key concept of neuroplasticity.
link |
01:23:44.040
And this is a key concept,
link |
01:23:45.540
regardless of whether or not
link |
01:23:46.460
one is talking about bipolar depression.
link |
01:23:48.440
In fact, it's something I think everybody,
link |
01:23:50.060
every citizen of Earth should know about,
link |
01:23:52.540
and that's called homeostatic plasticity.
link |
01:23:55.060
Homeostatic plasticity is a particular form
link |
01:23:57.740
of neuroplasticity in which if a neural circuit
link |
01:24:01.140
is overactive for a period of time,
link |
01:24:04.500
there are changes that occur at the cellular level
link |
01:24:07.500
that lead to a balance or a homeostatic regulation
link |
01:24:12.040
of that circuit so that it's no longer overactive.
link |
01:24:15.140
Conversely, if a neural circuit is underactive
link |
01:24:18.060
for a period of time,
link |
01:24:19.240
certain changes happen within the cells of that circuit
link |
01:24:22.160
to ramp up their activity
link |
01:24:23.620
or make them more likely to be active.
link |
01:24:26.140
And whether or not a neural circuit
link |
01:24:27.880
and the neurons within it become more active
link |
01:24:30.940
or less active in the context of homeostatic plasticity
link |
01:24:34.120
largely depends on one mechanism,
link |
01:24:36.200
and it's a beautiful mechanism
link |
01:24:37.580
that I'll make very clear to you right now
link |
01:24:38.980
even if you don't have a background in biology.
link |
01:24:41.300
Neurons communicate with one another
link |
01:24:43.000
by releasing so-called neurotransmitters,
link |
01:24:44.760
which are just chemicals.
link |
01:24:45.740
Those neurotransmitters are vomited out.
link |
01:24:48.300
They're not actually vomited,
link |
01:24:49.140
but they're spit out into the so-called synaptic cleft,
link |
01:24:51.480
often called the synapse.
link |
01:24:52.500
The synapse is just a little gap between neurons.
link |
01:24:54.980
And when they are released into the synapse,
link |
01:24:58.360
they don't just stay there.
link |
01:24:59.280
They actually park or bind to receptors
link |
01:25:01.840
on what's called the postsynaptic neuron.
link |
01:25:03.840
And depending on how many receptors they bind to
link |
01:25:07.120
and how many receptors are available, et cetera,
link |
01:25:09.220
they can have a greater or lesser effect
link |
01:25:10.820
on the postsynaptic neuron.
link |
01:25:12.300
This scenario of neurotransmitters
link |
01:25:14.240
being released into synapses,
link |
01:25:16.060
then binding to receptors on postsynaptic neurons
link |
01:25:18.720
and influencing the electrical excitability
link |
01:25:21.100
of those postsynaptic neurons,
link |
01:25:22.540
sits central to not just the treatment of bipolar disorder,
link |
01:25:25.680
but to all treatments of all psychiatric conditions
link |
01:25:28.780
and indeed to things like neuropathic pain as well.
link |
01:25:31.540
For example, the so-called SSRIs,
link |
01:25:35.000
Prozac, Zoloft, and others, et cetera,
link |
01:25:37.940
stands for selective serotonin reuptake inhibitor.
link |
01:25:41.280
What does that mean?
link |
01:25:42.120
Well, serotonin is a neurotransmitter.
link |
01:25:43.980
It's actually a neuromodulator
link |
01:25:45.020
that's released into the synapse.
link |
01:25:46.540
And then the SSRI,
link |
01:25:48.720
the selective serotonin reuptake inhibitor,
link |
01:25:51.380
allows more of that serotonin
link |
01:25:53.660
to sit within the synapse for longer, right?
link |
01:25:55.780
It's a reuptake inhibitor.
link |
01:25:57.380
It prevents reuptake by the presynaptic neuron.
link |
01:26:00.060
And that serotonin therefore can park in
link |
01:26:02.780
or dock in the receptors, as it's called,
link |
01:26:05.460
of the postsynaptic neuron in greater numbers
link |
01:26:08.080
and have a greater impact on that postsynaptic neuron.
link |
01:26:11.940
So the drugs that are used to treat depression
link |
01:26:14.340
or other things of that sort, things like SSRIs,
link |
01:26:18.020
work by changing the availability
link |
01:26:20.380
of neurotransmitter in the synapse.
link |
01:26:22.100
Other things like MAO inhibitors,
link |
01:26:24.380
monoamine oxidase inhibitors, work a different way.
link |
01:26:27.460
They inhibit the enzyme.
link |
01:26:28.660
Anytime you hear ASE in biology,
link |
01:26:30.460
it's very likely an enzyme which breaks things down.
link |
01:26:33.860
So MAO inhibitors prevent the breakdown,
link |
01:26:37.980
not the reuptake, but the breakdown of neurotransmitter,
link |
01:26:40.900
and therefore allow more neurotransmitter
link |
01:26:43.140
to be available in the synapse
link |
01:26:45.000
and influence the postsynaptic cell.
link |
01:26:47.500
Homeostatic plasticity is a form of neuroplasticity
link |
01:26:52.260
in which overall circuits can become much more excitable
link |
01:26:55.780
or much less excitable
link |
01:26:57.580
by the addition of more receptors in the postsynaptic neuron
link |
01:27:01.500
or by the removal of more receptors
link |
01:27:03.500
from the postsynaptic neuron.
link |
01:27:04.660
And the way this happens is just beautiful.
link |
01:27:06.660
It was first discovered in the visual system,
link |
01:27:09.260
and the person primarily responsible
link |
01:27:11.420
for the discovery of homeostatic plasticity,
link |
01:27:13.300
although there are several,
link |
01:27:14.460
is a woman by the name of Gina Turgiano.
link |
01:27:16.200
She's a professor at Brandeis University.
link |
01:27:18.700
And what the Turgiano laboratory showed was that,
link |
01:27:21.980
for instance, if we are in the dark
link |
01:27:25.220
for a long period of time,
link |
01:27:26.340
literally, we're not seeing much for a long period of time,
link |
01:27:28.840
there's an increase in the number of receptors
link |
01:27:31.020
in the postsynaptic neurons
link |
01:27:32.420
so that a smaller amount of light
link |
01:27:34.660
and excitability within the visual system
link |
01:27:36.700
can lead to greater amounts of activity
link |
01:27:39.240
in the visual system.
link |
01:27:40.480
Conversely, if there's an overactivity
link |
01:27:42.820
or an increase in the activity in the visual system
link |
01:27:45.020
for some period of time,
link |
01:27:46.640
then a number of receptors in the postsynaptic neuron
link |
01:27:49.900
are removed from that postsynaptic neuron surface,
link |
01:27:52.940
making any neurotransmitter that's available
link |
01:27:55.740
only able to bind the receptors that are left
link |
01:27:58.140
and have less of an influence on those cells.
link |
01:28:00.540
In other words, keeping a circuit
link |
01:28:02.380
in so-called homeostatic balance
link |
01:28:04.700
in a particular range of excitability.
link |
01:28:07.780
Now, while that's a mouthful and an earful
link |
01:28:10.180
and a conceptful, I don't know if a conceptful is a word,
link |
01:28:13.060
but in any case, that's a lot to think about,
link |
01:28:15.160
but all you need to know is that if a neural circuit
link |
01:28:17.360
is very active for a period of time,
link |
01:28:19.060
in normal individuals,
link |
01:28:20.540
there will be a reduction in the amount of activity
link |
01:28:23.260
by way of removing receptors that bind neurotransmitter.
link |
01:28:26.540
Whereas if a neural circuit is very quiet,
link |
01:28:29.280
it's not activated for a period of time,
link |
01:28:30.780
maybe your leg is in a cast, for instance,
link |
01:28:33.060
and you're not activating your quadricep and calves
link |
01:28:35.900
very much well, when that cast comes off,
link |
01:28:38.540
sure, the muscle might be atrophied,
link |
01:28:40.120
but the nerves that connect to that muscle
link |
01:28:41.980
are actually in a position to influence that muscle
link |
01:28:44.460
even more once you start using that muscle or those muscles,
link |
01:28:48.800
because whatever neurotransmitter is released
link |
01:28:51.220
now has the opportunity to bind to more receptors,
link |
01:28:54.820
in that case, in muscle,
link |
01:28:55.740
or in the case of brain circuits in postsynaptic neurons.
link |
01:28:59.220
So homeostatic plasticity is this beautiful
link |
01:29:01.940
balancing mechanism that makes sure that neural circuits
link |
01:29:04.380
are never too active nor too quiet for too long.
link |
01:29:08.260
And in a beautiful display of how treatments
link |
01:29:13.660
can lead to a better understanding of biology,
link |
01:29:15.860
which can lead to the discovery of even better treatments,
link |
01:29:19.240
lithium and another compound,
link |
01:29:22.380
which we'll talk about ketamine,
link |
01:29:24.660
seem to exert their actions largely through effects
link |
01:29:28.820
on homeostatic neuroplasticity.
link |
01:29:31.440
There's a wonderful paper that describes
link |
01:29:33.180
all the nitty gritty of this.
link |
01:29:34.860
Certainly most people listening, I'm guessing,
link |
01:29:37.180
are not going to be interested in all this detail,
link |
01:29:40.540
but for those of you that you are,
link |
01:29:41.720
and you want to delve deep into this,
link |
01:29:43.600
this paper was published in Neuron, Cell Press Journal,
link |
01:29:46.060
excellent journal.
link |
01:29:47.660
It's titled Targeting Homeostatic Plasticity
link |
01:29:50.040
for the Treatment of Mood Disorders.
link |
01:29:51.700
And there's one particular figure in this paper
link |
01:29:53.460
that I'll just describe to you
link |
01:29:54.900
in which measurements were made from neurons
link |
01:29:58.500
and the number of receptors in those neurons.
link |
01:30:00.540
It's done somewhat indirectly through a method
link |
01:30:02.340
that's detailed and neuroscientists are familiar with.
link |
01:30:05.020
Basically what it measures is how excited a given neuron is,
link |
01:30:08.720
electrically excited a given neuron is
link |
01:30:10.580
to a given amount of neurotransmitter, okay?
link |
01:30:13.400
So the amount of neurotransmitter
link |
01:30:15.420
that's vomited onto a neuron
link |
01:30:16.900
is essentially kept constant,
link |
01:30:18.600
and then the response of the postsynaptic neuron
link |
01:30:21.000
is measured.
link |
01:30:21.840
So it can be of one level or higher or lower
link |
01:30:24.400
depending on homeostatic plasticity.
link |
01:30:27.380
And what this paper shows,
link |
01:30:30.120
and what's been shown over and over again,
link |
01:30:31.960
is that when neurons are exposed to lithium
link |
01:30:36.660
for a period of time,
link |
01:30:37.700
there is a reduction in the excitability
link |
01:30:41.660
of the postsynaptic neuron.
link |
01:30:42.820
That is, neurons within the brain become less excitable
link |
01:30:46.900
over time if lithium is present,
link |
01:30:50.060
whereas ketamine, which is now a common FDA approved,
link |
01:30:53.840
at least in the US,
link |
01:30:54.680
it's approved for the treatment of major depression,
link |
01:30:57.500
ketamine does the opposite.
link |
01:30:59.240
Ketamine seems to increase the number of receptors
link |
01:31:01.680
in the postsynaptic neuron
link |
01:31:02.820
and lead to greater levels of excitability
link |
01:31:06.120
and electrical activity within neural circuits
link |
01:31:08.340
to a given fixed amount of neurotransmitter.
link |
01:31:11.340
So this is super interesting
link |
01:31:12.620
because what it means is that lithium
link |
01:31:14.140
is causing circuits to be less active.
link |
01:31:16.580
Ketamine is causing circuits to be more active.
link |
01:31:19.140
And we know from excellent clinical data now
link |
01:31:22.180
that ketamine seems to be a very effective treatment
link |
01:31:25.400
for major depression
link |
01:31:27.280
and for the major depressive episodes
link |
01:31:30.300
of people that suffer from bipolar depression
link |
01:31:33.100
that includes these major depressive episodes
link |
01:31:35.020
of two weeks or longer of suppressed mood,
link |
01:31:37.500
appetite, sleep issues, et cetera.
link |
01:31:39.860
Now, the key thing about ketamine
link |
01:31:42.100
that's often not discussed
link |
01:31:43.980
is that while its effects are very potent,
link |
01:31:47.440
they are transient.
link |
01:31:48.840
So one major drawback to ketamine therapy for depression
link |
01:31:52.820
is that it has to be done repeatedly.
link |
01:31:54.580
And how repeatedly or how often rather depends, of course,
link |
01:31:58.540
on a discussion between the psychiatrist and the patient.
link |
01:32:00.940
This is not something to cowboy on your own.
link |
01:32:04.520
I know that, and many of you are probably familiar
link |
01:32:07.060
with the fact that ketamine also is abused recreationally.
link |
01:32:11.180
It is a so-called NMDA,
link |
01:32:13.020
N-methyl-D-aspartate receptor antagonist.
link |
01:32:16.060
So it blocks the very receptor
link |
01:32:17.620
that's responsible for neuroplasticity
link |
01:32:19.700
for changes in neural circuits.
link |
01:32:21.660
It also changes excitability in neurons,
link |
01:32:23.340
as I just described.
link |
01:32:24.180
So ketamine is a very potent chemical
link |
01:32:26.300
that has been shown over and over again
link |
01:32:28.780
and is now FDA approved for the treatment
link |
01:32:30.580
of major depression,
link |
01:32:31.400
but its effects seem to be transient.
link |
01:32:33.640
Lithium, as I described earlier,
link |
01:32:35.540
seems to reduce the manic episodes
link |
01:32:39.540
or the intensity of manic episodes and symptomology
link |
01:32:41.760
in people with bipolar disorder.
link |
01:32:43.300
It's doing that through neural protection.
link |
01:32:45.140
So protecting neural circuits from dying away
link |
01:32:47.340
that initially are overactive
link |
01:32:48.980
and that overactivity causing excitotoxicity.
link |
01:32:50.940
It blocks that excitotoxicity, we believe.
link |
01:32:54.460
And it seems to do that in part
link |
01:32:58.200
by diminishing the amount of activity in those circuits.
link |
01:33:01.460
So this is a beautiful mechanistic story,
link |
01:33:04.020
and it's the sort of story that you'd love to have
link |
01:33:06.340
for a great number of psychiatric illnesses.
link |
01:33:08.820
And fortunately, we have for bipolar disorder.
link |
01:33:10.960
Overactivity of a given circuit
link |
01:33:12.400
eventually leads to neurotoxicity, excuse me.
link |
01:33:16.460
Lithium is preventing that neurotoxicity
link |
01:33:18.260
by reducing the number of receptors
link |
01:33:20.280
in certain elements within those circuits,
link |
01:33:22.340
so-called homeostatic scaling.
link |
01:33:24.380
It's down-regulating the number of receptors,
link |
01:33:26.820
leading to less excitability
link |
01:33:28.240
and preventing, we think, excitotoxicity.
link |
01:33:31.020
And in that sense,
link |
01:33:33.180
you can see exactly why it's important
link |
01:33:35.500
to get lithium treatment in there early
link |
01:33:37.260
for people with bipolar disorder.
link |
01:33:39.860
Ketamine as a treatment for major depression
link |
01:33:41.580
seems to be effective but transient.
link |
01:33:43.620
And you can also see why it would be important
link |
01:33:45.740
not just to reduce the manic episodes
link |
01:33:48.580
for people with bipolar disorder
link |
01:33:49.820
but to also treat the depressive episodes.
link |
01:33:52.180
So this is a key feature of the treatment
link |
01:33:53.840
for bipolar depression and for bipolar disorder.
link |
01:33:56.900
There needs to be treatment both of the mania
link |
01:33:59.080
and of the depressive episodes if they're present.
link |
01:34:01.660
And fortunately, there are excellent drugs to do that.
link |
01:34:04.540
And I should mention that ketamine and lithium
link |
01:34:07.420
are just two of the drugs within the kit
link |
01:34:10.380
that psychiatrists have access to.
link |
01:34:12.400
There are many things, olanzapines
link |
01:34:14.860
and a number of different things, including clozapine.
link |
01:34:18.260
Clozapine is an antipsychotic,
link |
01:34:20.300
which is commonly prescribed as a sedative in some cases
link |
01:34:24.700
that allows people in manic episodes to sleep.
link |
01:34:26.820
It's classically described
link |
01:34:28.420
as so-called dopamine receptor four antagonist,
link |
01:34:31.220
although it does other things as well.
link |
01:34:32.900
Clozapine has a number of side effect features
link |
01:34:35.780
related to white blood cell and things of that sort
link |
01:34:39.020
that require careful monitoring.
link |
01:34:40.620
So there are an enormous number now,
link |
01:34:44.180
literally dozens and dozens of different drugs,
link |
01:34:46.700
each designed to target either the manic phase,
link |
01:34:49.860
the depressive phase, or some what we call acute,
link |
01:34:53.700
sort of early phases versus ongoing treatments.
link |
01:34:56.260
This is a vast galaxy of drug treatments
link |
01:34:59.420
that really should be navigated,
link |
01:35:01.460
I should say absolutely should be navigated
link |
01:35:03.780
by a board certified psychiatrist.
link |
01:35:06.300
And of course, in close discussion
link |
01:35:08.700
with both the person suffering from bipolar disorder,
link |
01:35:11.800
but also ideally the family members
link |
01:35:14.360
of the person suffering from bipolar disorder.
link |
01:35:16.800
But I think at least up until now,
link |
01:35:19.940
we've focused on the two major pathways for treatment,
link |
01:35:23.940
lithium and ketamine.
link |
01:35:25.740
And we talked about why lithium and ketamine work,
link |
01:35:28.380
that they're working on opposite ends
link |
01:35:29.700
of this homeostatic scaling.
link |
01:35:30.900
We talked a bit about the circuits that are involved
link |
01:35:33.540
in generating what we think are the manic symptomology
link |
01:35:37.080
and the lack of interoception,
link |
01:35:38.340
why people can just persist in staying awake,
link |
01:35:40.440
awake, awake, not eating, et cetera.
link |
01:35:43.040
Now you have in mind how all that is put together.
link |
01:35:45.940
And I think you have in mind
link |
01:35:47.420
some of the well-demonstrated treatments
link |
01:35:49.920
for the different component parts of bipolar disorder,
link |
01:35:52.620
which now I'm hoping you're also well versed in
link |
01:35:54.700
based on our early, early discussion
link |
01:35:57.140
of what constitutes bipolar one and bipolar two.
link |
01:36:00.020
Now I would like to also talk about
link |
01:36:02.220
some of the not so typical therapeutics
link |
01:36:04.900
for bipolar disorder,
link |
01:36:06.460
and also point to the things that have been tried and failed
link |
01:36:10.260
for successful treatment of bipolar disorder,
link |
01:36:12.760
because some of those things are often talked about
link |
01:36:16.620
and suggested, especially in online communities.
link |
01:36:19.220
And while it's not clear that any of them
link |
01:36:21.220
are particularly hazardous on their own,
link |
01:36:24.300
although some of them do carry some hazards,
link |
01:36:26.960
I do think it's important
link |
01:36:28.140
because of the critical time-sensitive nature
link |
01:36:30.900
of bipolar disorder and the urgency
link |
01:36:32.940
of getting treatments early
link |
01:36:34.780
to try and prevent some of the longer lasting
link |
01:36:36.940
neural circuit changes,
link |
01:36:38.200
that if people can avoid some of the less effective
link |
01:36:40.660
or demonstrated to be ineffective treatments,
link |
01:36:43.860
that they stand to combat bipolar disorder
link |
01:36:46.420
much more successfully.
link |
01:36:47.580
First of all, a key point about drug therapies
link |
01:36:50.040
versus non-drug therapies or talk therapies.
link |
01:36:54.300
Without question,
link |
01:36:55.480
drug therapies are going to be most effective
link |
01:36:59.160
when done also with talk therapies.
link |
01:37:02.040
And we'll talk about which talk therapies
link |
01:37:03.400
have been demonstrated to be most effective.
link |
01:37:06.160
There is some argument about what I'm about to say next,
link |
01:37:08.540
but in general, most psychiatrists will tell you,
link |
01:37:12.000
or certainly the ones I've spoken to have told me,
link |
01:37:14.920
that talk therapy on its own is rarely, if ever,
link |
01:37:18.920
effective for bipolar depression and bipolar disorder,
link |
01:37:23.280
whether or not it's BP1 or BP2.
link |
01:37:25.680
That's just the reality of it.
link |
01:37:27.360
Contrast that with our discussion
link |
01:37:29.080
about obsessive compulsive disorder,
link |
01:37:30.780
which we talked about a few episodes ago.
link |
01:37:32.680
If you haven't seen that episode,
link |
01:37:33.940
we have an in-depth episode all about OCD
link |
01:37:36.600
and obsessive compulsive personality disorder.
link |
01:37:39.460
There, it seems that drug therapies and talk therapies
link |
01:37:42.620
can be done independently or in combination.
link |
01:37:45.720
As expected, combined drug and talk therapies
link |
01:37:49.120
are more effective there than either one alone,
link |
01:37:51.280
but there are pretty impressive effects
link |
01:37:53.520
of talk therapy alone,
link |
01:37:54.480
provided that they are initiated at the right time
link |
01:37:56.320
and it's the right form of talk therapy.
link |
01:37:58.520
That's OCD, but in terms of bipolar disorder,
link |
01:38:01.360
it really seems that the drug therapies are necessary,
link |
01:38:04.880
at least in most all cases.
link |
01:38:07.920
That said, talk therapies are a terrific augment
link |
01:38:12.000
or support for those drug therapies
link |
01:38:13.600
and sometimes can allow people to take lower doses
link |
01:38:15.800
of those drug therapies,
link |
01:38:16.680
which turns out to be important
link |
01:38:17.860
because of the side effect profiles
link |
01:38:19.240
of a lot of drug therapies
link |
01:38:20.240
and sometimes the cost as well.
link |
01:38:22.040
I guess we can think of cost
link |
01:38:22.960
just as another side effect, really.
link |
01:38:25.760
There are both established and more novel forms
link |
01:38:28.780
of talk therapy being used, again,
link |
01:38:31.520
in concert with drug treatments for bipolar disorder.
link |
01:38:35.600
Cognitive behavioral therapy is the one
link |
01:38:37.520
that seems to be best,
link |
01:38:38.740
at least by way of the statistics and papers that exist.
link |
01:38:41.660
It's also the one that's been explored the most.
link |
01:38:43.340
So one of the reasons why it's often considered
link |
01:38:45.460
the most popular or effective
link |
01:38:46.680
is because it's also been around longer
link |
01:38:48.120
and it's been explored the most cognitive behavioral therapy
link |
01:38:50.840
in general is a progressive exposure of the patient
link |
01:38:55.460
in a very controlled way in a clinical setting
link |
01:38:57.480
to some of the triggers or the conditions
link |
01:39:00.200
that would exacerbate bipolar disorder.
link |
01:39:02.780
Now, earlier I said borderline personality disorder
link |
01:39:05.400
has all these triggers and triggered elements
link |
01:39:07.880
from the external environment,
link |
01:39:08.940
whereas bipolar disorder does not.
link |
01:39:10.880
And that's still true,
link |
01:39:12.760
but it is the case that somebody with bipolar
link |
01:39:16.800
can have worse symptoms
link |
01:39:18.680
if life conditions get worse or more stressful.
link |
01:39:20.520
So cognitive behavioral therapy in the discussion about,
link |
01:39:24.080
and sometimes the direct exposure
link |
01:39:25.800
to anxiety provoking elements of life
link |
01:39:29.360
can be very helpful for adjusting the responses
link |
01:39:33.700
to those otherwise triggering events
link |
01:39:35.400
and sometimes making the drug treatments more effective
link |
01:39:37.440
even at lower doses.
link |
01:39:38.600
There are also forms of therapy
link |
01:39:40.480
including family focused therapy,
link |
01:39:42.800
which is especially important in terms of bipolar disorder
link |
01:39:46.520
because family members,
link |
01:39:49.740
provided that they are not themselves in a manic episode
link |
01:39:52.280
due to the close heritability of bipolar disorder,
link |
01:39:55.840
but family members can often be excellent windows
link |
01:39:59.640
into whether or not somebody is doing well or poorly
link |
01:40:02.760
or is veering toward or is emerging
link |
01:40:04.880
from a manic or depressive episode
link |
01:40:06.960
because they understand that person.
link |
01:40:08.200
They have a lot of data.
link |
01:40:09.760
It could be purely subjective data,
link |
01:40:11.180
but they have a lot of exposure
link |
01:40:12.280
to how long or well somebody has been sleeping
link |
01:40:14.200
or eating, et cetera.
link |
01:40:15.400
So family focused therapy involves other members
link |
01:40:17.400
of the person suffering from bipolar disorders family,
link |
01:40:20.240
as well as conversations about family members
link |
01:40:24.080
in a way that helps patients with bipolar disorder navigate
link |
01:40:27.600
not just through manic episodes and depressive episodes,
link |
01:40:29.800
but start to learn to predict what are the conditions,
link |
01:40:32.880
psychological, physical, and otherwise,
link |
01:40:35.040
that can trigger bipolar episodes.
link |
01:40:38.080
And then there's a category of therapy
link |
01:40:41.040
called interpersonal and social rhythm therapy.
link |
01:40:44.080
This is deserving of its own entire episode, really.
link |
01:40:48.120
Interpersonal and social rhythm therapy
link |
01:40:49.960
is sort of an expansion on family focused therapy,
link |
01:40:53.020
although it's distinct in certain ways as well,
link |
01:40:55.360
and really focuses on how people are relating
link |
01:40:58.280
to others in their life and in the workplace
link |
01:41:01.400
and in the school environment
link |
01:41:03.000
and also within the family, et cetera.
link |
01:41:05.000
And I should say that a overall theme
link |
01:41:07.880
that's emerging in psychiatry and psychology
link |
01:41:10.460
is to start wherever possible
link |
01:41:12.260
to incorporate more of the social aspects
link |
01:41:15.520
and the interpersonal aspects.
link |
01:41:17.080
In other words, not just talking to and examining a patient
link |
01:41:19.920
as one biological system, one nervous system,
link |
01:41:22.560
one set of chemicals and one life,
link |
01:41:24.560
but rather a set of chemicals, neural circuits,
link |
01:41:27.040
and a life that's embedded in the chemicals
link |
01:41:28.960
and neural circuits and lives of other people.
link |
01:41:31.720
Just by way of example, you can imagine that
link |
01:41:33.580
if somebody is in a very healthy relationship
link |
01:41:35.940
or a very abusive relationship,
link |
01:41:37.840
that that's going to strongly impact
link |
01:41:39.920
the outcomes of manic episodes.
link |
01:41:41.720
You can imagine that if the financial situation
link |
01:41:44.380
is one in which people can recover from manic episodes,
link |
01:41:47.600
I did mention this earlier, but I should have, forgive me,
link |
01:41:50.360
that oftentimes people who are in a manic episode
link |
01:41:52.480
will go out and spend immense amounts of money
link |
01:41:54.780
that they simply cannot afford to lose.
link |
01:41:56.920
And then the depressive episodes that in many cases follow
link |
01:42:00.880
are made far worse by the financial anxiety
link |
01:42:05.120
and the financial stress that results
link |
01:42:07.260
from those manic episodes of spending, et cetera.
link |
01:42:09.480
And then of course, this carries over to sexual promiscuity
link |
01:42:13.280
where people might be dealing with unwanted pregnancy
link |
01:42:15.820
or STIs or very fractured interpersonal dynamics
link |
01:42:20.760
with existing or new relationships.
link |
01:42:22.360
I mean, you can imagine how these manic episodes
link |
01:42:25.960
as well as the depressive episodes can really wick out
link |
01:42:28.600
into an enormous amount of destruction,
link |
01:42:31.100
which brings us back to the initial criteria of BP1 and BP2
link |
01:42:35.360
is that these manic episodes are not a good thing.
link |
01:42:39.160
These depressive episodes are not a good thing.
link |
01:42:42.640
They create this sense of euphoria
link |
01:42:44.640
in the person experiencing mania,
link |
01:42:46.360
or they create the sense that anything is possible,
link |
01:42:48.880
but at the end of the day, and actually every day,
link |
01:42:52.400
these episodes are quite maladaptive.
link |
01:42:54.720
They really destroy people's lives
link |
01:42:56.440
and it's not just the life of the person
link |
01:42:58.020
that's suffering from bipolar disorder.
link |
01:42:59.460
And so hence, cognitive behavioral therapy,
link |
01:43:01.720
family-focused therapy,
link |
01:43:02.920
and interpersonal and social rhythm therapies
link |
01:43:04.840
are the primary three talk therapies
link |
01:43:07.000
that are most often combined with drug therapies
link |
01:43:09.520
in order to try and really reduce the harm.
link |
01:43:12.860
It's really all about harm reduction
link |
01:43:15.780
from manic episodes and depressive episodes.
link |
01:43:18.260
One very exciting and emerging treatment
link |
01:43:20.220
that does show great promise,
link |
01:43:22.440
and in some cases, great outcomes for bipolar disorder
link |
01:43:26.220
is, believe it or not, electric shock therapy.
link |
01:43:29.180
Electric shock therapy may sound barbaric,
link |
01:43:31.280
and in fact, it tends to look barbaric,
link |
01:43:33.280
although this is done in the controlled setting
link |
01:43:34.900
of a hospital.
link |
01:43:35.760
If any of you have seen One Flew Over the Cuckoo's Nest,
link |
01:43:38.680
the final scene or near final scene in that movie
link |
01:43:41.640
was Jack Nicholson with the sort of bite protector
link |
01:43:45.360
in his mouth and getting electric shock therapy,
link |
01:43:47.560
and it's, as the name suggests,
link |
01:43:50.620
it's kind of inducing a global seizure,
link |
01:43:53.280
either low-level or grand mal-type seizure
link |
01:43:57.080
in the patient's brain and nervous system.
link |
01:43:59.760
You might ask, well, why would one want to do that?
link |
01:44:02.600
Well, it turns out that this is a well-established
link |
01:44:06.040
and in many cases, very effective treatment
link |
01:44:08.400
for major depression.
link |
01:44:09.640
Electric shock therapy is generally used
link |
01:44:12.440
for treatment-resistant depression,
link |
01:44:14.320
so these are people that have no positive response
link |
01:44:17.640
or ongoing positive response to drug therapies
link |
01:44:19.820
or other therapies.
link |
01:44:20.860
Electric shock therapy is thought to work primarily
link |
01:44:23.920
by stimulating the massive kind of indiscriminate release
link |
01:44:27.720
of things like serotonin, dopamine, acetylcholine,
link |
01:44:31.280
a huge variety of neuromodulators,
link |
01:44:33.840
as well as things like BDNF,
link |
01:44:35.560
brain-derived neurotrophic factor,
link |
01:44:36.800
which then allows neuroplasticity to take place.
link |
01:44:39.280
Again, BDNF being permissive for neuroplasticity.
link |
01:44:42.320
The problem with ECT is that it's really only useful
link |
01:44:45.160
for treatment-resistant depression.
link |
01:44:47.160
It doesn't actually target the manic aspects
link |
01:44:49.460
of bipolar depression and bipolar disorder,
link |
01:44:52.360
but nonetheless is used when drug treatments don't work.
link |
01:44:56.000
Some of the negatives of electric shock therapy
link |
01:44:59.740
or electroconvulsive therapy, ECT,
link |
01:45:02.560
is the proper acronym and way it's described,
link |
01:45:05.200
is that it's quite invasive, right?
link |
01:45:06.680
This is something that you need to go to the hospital for
link |
01:45:09.120
and oftentimes there's some inpatient care required
link |
01:45:11.560
after the electric shock convulsive therapy.
link |
01:45:14.100
It's a fairly high cost,
link |
01:45:15.420
especially for those that don't have insurance.
link |
01:45:17.820
And of course it requires anesthesia.
link |
01:45:20.160
For most people, that's not going to be a problem,
link |
01:45:21.640
but for many people that could be a problem.
link |
01:45:24.720
And there's often some associated memory loss.
link |
01:45:28.380
And so the memory loss,
link |
01:45:30.960
the invasive nature of ECT and the cost
link |
01:45:34.160
oftentimes rule out ECT for most patients.
link |
01:45:37.640
And that's why it's sort of a late stage
link |
01:45:39.200
or kind of last resort type thing
link |
01:45:41.080
for treatment-resistant depression.
link |
01:45:42.740
Nowadays, ketamine type therapy is done repeatedly
link |
01:45:45.600
or other treatments.
link |
01:45:46.800
For instance, transcranial magnetic stimulation,
link |
01:45:50.120
which is basically noninvasive.
link |
01:45:52.120
It's a coil that's placed on the outside of the skull,
link |
01:45:55.160
excuse me.
link |
01:45:56.000
And we can more accurately refer to it as repetitive
link |
01:46:00.920
or RTMS, repetitive transcranial magnetic stimulation.
link |
01:46:04.900
Transcranial magnetic stimulation is a tool
link |
01:46:07.640
that allows researchers and clinicians
link |
01:46:09.680
to reduce the amount of activity in specific neural circuits.
link |
01:46:12.500
So they can actually target the magnetic field
link |
01:46:15.160
to particular neural circuits
link |
01:46:16.160
to reduce activity in those neural circuits.
link |
01:46:18.360
Again, it's minimally invasive.
link |
01:46:20.020
It has been shown to be effective
link |
01:46:21.680
in both increasing neuroplasticity in positive ways,
link |
01:46:25.480
as well as reducing depressive episodes.
link |
01:46:27.560
And in a few instances in reducing the amplitude
link |
01:46:31.960
or the intensity of manic episodes
link |
01:46:33.620
in people with bipolar disorder.
link |
01:46:35.760
The problem is it's still a very early technique.
link |
01:46:39.080
There aren't a lot of clinics and labs doing it.
link |
01:46:41.080
I'm starting to see more advertisements,
link |
01:46:42.920
literally commercial clinics that are advertising RTMS or TMS
link |
01:46:48.120
I encourage you to approach those clinics with caution.
link |
01:46:50.600
I'm of the mind that if those clinics
link |
01:46:53.380
are not either closely or maybe even distantly associated
link |
01:46:57.000
with a research institution
link |
01:46:58.200
that's really up on the latest of RTMS,
link |
01:47:00.560
you'd be wise to at least do your research, right?
link |
01:47:03.400
And explore, talk to other patients
link |
01:47:05.920
who've done these treatments.
link |
01:47:07.360
But certainly in university hospitals
link |
01:47:09.540
and in clinical settings and research settings,
link |
01:47:11.640
RTMS is being used as a way to, for instance,
link |
01:47:15.180
reduce the activity of certain limbic circuitries
link |
01:47:17.760
so that people are just overall less excitable and manic.
link |
01:47:20.460
Or to activate,
link |
01:47:22.440
because it can also be used for activation now,
link |
01:47:24.280
certain neural circuits activate, for instance,
link |
01:47:26.040
the parietal inputs,
link |
01:47:27.180
the top-down control over the limbic system.
link |
01:47:29.180
This is all happening right now.
link |
01:47:30.960
So we have ECT, repetitive TMS or RTMS.
link |
01:47:34.960
And then as I mentioned earlier, ketamine therapies,
link |
01:47:36.980
most of those are targeted
link |
01:47:38.280
toward the depressive aspects of manic depression.
link |
01:47:41.400
So for people with bipolar disorder
link |
01:47:42.920
that doesn't include depression,
link |
01:47:44.320
those are going to be less effective.
link |
01:47:45.940
But overall, it's going to be the talk therapies
link |
01:47:48.500
of the sort that we discussed earlier or a moment ago,
link |
01:47:51.920
plus drug treatments,
link |
01:47:54.560
almost always lithium will be explored,
link |
01:47:56.280
plus some treatments for the depressive episodes,
link |
01:47:58.940
in particular, if those depressive episodes are present.
link |
01:48:01.920
Nowadays, there's a lot of excitement about psilocybin,
link |
01:48:04.960
which is a psychedelic.
link |
01:48:06.400
In the US, psilocybin is still illegal.
link |
01:48:09.160
It is not legal,
link |
01:48:10.740
meaning you can get in a lot of trouble for possessing it,
link |
01:48:14.120
certainly for selling it, et cetera.
link |
01:48:15.840
But psilocybin is being explored as a clinical therapy
link |
01:48:18.560
in certain laboratory settings,
link |
01:48:20.000
in particular, at Johns Hopkins School of Medicine.
link |
01:48:22.640
It's being explored in human patients
link |
01:48:24.240
for the treatment of major depression,
link |
01:48:25.760
for OCD, I believe, as well,
link |
01:48:28.440
but certainly for major depression
link |
01:48:30.120
and for eating disorders.
link |
01:48:31.200
And it seems from the initial wave of publications
link |
01:48:34.300
from that work done by the incredible Matthew Johnson
link |
01:48:37.860
or Dr. Matthew Johnson,
link |
01:48:38.960
who was a guest on this podcast before.
link |
01:48:40.640
He's also been on the Tim Ferriss podcast.
link |
01:48:43.320
He's been on the Lex Friedman podcast.
link |
01:48:45.540
Dr. Matthew Johnson came on this podcast
link |
01:48:48.080
and talked about some of the work with psilocybin
link |
01:48:49.720
for the treatment of depression.
link |
01:48:51.640
Very impressive results there.
link |
01:48:54.120
And as you can imagine,
link |
01:48:55.360
very impressive results
link |
01:48:56.320
for the major depressive episodes for bipolar.
link |
01:48:58.520
However, at least to my knowledge,
link |
01:49:01.120
again, to my knowledge,
link |
01:49:02.620
there have not been any controlled clinical trials
link |
01:49:05.000
exploring psilocybin
link |
01:49:06.240
for the mania associated with bipolar disorder.
link |
01:49:09.020
If someone out there is aware of those clinical trials,
link |
01:49:11.360
please let me know.
link |
01:49:12.200
I'll do an update in a future podcast.
link |
01:49:14.000
But right now, no knowledge from me
link |
01:49:16.940
about psilocybin clinical trials
link |
01:49:18.680
for the manic component of bipolar disorder.
link |
01:49:22.400
A number of people are probably also going to wonder
link |
01:49:24.440
about whether or not cannabis or medical marijuana
link |
01:49:28.400
is useful for bipolar disorder.
link |
01:49:31.060
To address this, I looked to some previous lectures
link |
01:49:34.260
and some clinicians at Stanford Psychiatry.
link |
01:49:37.640
This question was asked of them.
link |
01:49:39.040
And as it turns out,
link |
01:49:41.000
cannabis does not seem to be effective
link |
01:49:43.440
for the treatment of the manic phases of bipolar disorder
link |
01:49:47.040
or for the treatment of the major depressive component.
link |
01:49:50.360
The only treatment perhaps,
link |
01:49:52.780
or I should say the only situation perhaps
link |
01:49:55.200
in which it might be useful,
link |
01:49:56.140
and this is what was relayed to me,
link |
01:49:57.760
is that it may help with sleep
link |
01:49:59.920
in certain people that are having trouble with insomnia.
link |
01:50:03.480
Although nowadays it's far more common
link |
01:50:05.540
for people in manic episodes
link |
01:50:06.880
to prescribe things like trazodone or other benzos,
link |
01:50:10.400
benzodiazepines,
link |
01:50:11.800
in order to try and get sleep within the manic episodes.
link |
01:50:14.360
And benzodiazepines and trazodone, et cetera,
link |
01:50:17.000
work largely through the so-called GABA system.
link |
01:50:19.240
This is a neurotransmitter
link |
01:50:21.240
that causes reductions in excitability of neurons,
link |
01:50:25.160
hence why it's being used to try and calm people down
link |
01:50:27.800
and allow them to sleep during their manic episodes.
link |
01:50:29.880
So not a lot, or essentially no data,
link |
01:50:32.040
supporting the use of cannabis
link |
01:50:33.280
for the treatment of bipolar disorder per se,
link |
01:50:35.800
nor data supporting the use of psilocybin
link |
01:50:38.480
for the treatment of bipolar disorder per se.
link |
01:50:40.460
But I realized as I say that,
link |
01:50:43.040
that there are going to be a number of people
link |
01:50:44.420
that may have had positive
link |
01:50:46.900
or negative experiences with cannabis or psilocybin
link |
01:50:49.560
as they relate to bipolar disorder.
link |
01:50:51.000
So please, if you're willing or comfortable,
link |
01:50:53.840
put that if you're comfortable
link |
01:50:54.960
into the comment section on YouTube.
link |
01:50:57.680
And of course, if you are aware of any studies
link |
01:50:59.640
on cannabis or psilocybin showing positive outcomes
link |
01:51:03.060
for the treatment of bipolar disorder,
link |
01:51:04.920
please provide links or PubMed ideas to those.
link |
01:51:07.280
I'd love to peruse those studies.
link |
01:51:10.200
There are two naturopathic,
link |
01:51:12.300
or I should say nutrition supplement-based approaches
link |
01:51:15.720
to bipolar disorder they get talked about a lot.
link |
01:51:18.720
And one of them shows some interesting promise
link |
01:51:22.000
or effectiveness even in a limited context.
link |
01:51:26.160
Before marching into this description
link |
01:51:28.280
of these two compounds,
link |
01:51:29.860
in fact, before even mentioning these two compounds,
link |
01:51:32.200
I do want to emphasize what's been said
link |
01:51:35.460
and written about over and over again,
link |
01:51:37.480
and what was relayed to me from expert psychiatrists.
link |
01:51:41.120
It is not wise to rely purely on talk therapy
link |
01:51:45.720
or on natural approaches
link |
01:51:48.360
to the treatment of bipolar disorder,
link |
01:51:49.700
given the intensity of the disorder
link |
01:51:52.680
and the high propensity for suicide risk
link |
01:51:56.260
in people with bipolar disorder.
link |
01:51:57.820
It is a chemical and neural circuit disruption,
link |
01:52:00.600
and it needs to be dealt with head on
link |
01:52:02.260
through the appropriate chemistry
link |
01:52:05.020
and prescription drug approaches
link |
01:52:06.860
from a board certified psychiatrist.
link |
01:52:09.080
I don't say this to protect me.
link |
01:52:11.320
I say this truly to protect those who either suffer from
link |
01:52:14.760
or think they may suffer from bipolar disorder
link |
01:52:16.800
if you know someone who you think might suffer
link |
01:52:18.740
from bipolar disorder.
link |
01:52:20.820
Now, all that is not to say
link |
01:52:22.600
that there aren't useful lifestyle interventions
link |
01:52:24.960
that can support people with bipolar disorder.
link |
01:52:26.840
So I just briefly want to mention those.
link |
01:52:28.460
And again, I'm lifting the statements I'm about to make
link |
01:52:30.960
from some excellent online lectures
link |
01:52:33.760
from psychiatrists at Stanford and elsewhere,
link |
01:52:36.480
which essentially say that of course, of course, of course,
link |
01:52:41.960
getting better sleep, getting adequate exercise,
link |
01:52:45.120
getting proper nutrition,
link |
01:52:46.660
having quality, healthy social interactions,
link |
01:52:50.600
even getting regular sunlight in the day
link |
01:52:52.400
and avoiding bright light at night,
link |
01:52:53.720
all of those things are going to braid together
link |
01:52:57.000
to support the nervous system
link |
01:52:58.880
and the psyche of somebody with bipolar disorder,
link |
01:53:02.360
but they braid together to support the psyche
link |
01:53:04.880
and the neurochemistry and the neural circuits
link |
01:53:06.480
of anybody and everybody.
link |
01:53:08.380
So they have generally a modulatory effect.
link |
01:53:11.240
That is they're indirectly shifting the likelihood
link |
01:53:15.040
that somebody might have an episode
link |
01:53:17.200
or the intensity of an episode,
link |
01:53:19.240
in particular, the depressive episodes, right?
link |
01:53:21.160
You can imagine how someone
link |
01:53:22.000
who's heading into a depressive episode,
link |
01:53:23.800
maybe they're on a lower amount of medication
link |
01:53:25.560
or they haven't yet medicated
link |
01:53:27.160
for the depressive episode of bipolar.
link |
01:53:29.200
And now they're making sure,
link |
01:53:31.400
or their family is making sure
link |
01:53:32.500
that they're getting exercise, sunshine,
link |
01:53:34.040
eating correctly, social engagement, et cetera.
link |
01:53:36.780
Of course, it makes perfect sense
link |
01:53:38.080
why they would have perhaps a shallower drop into depression
link |
01:53:41.380
or maybe even offset a depressive episode.
link |
01:53:43.920
That said, most all, if not all people
link |
01:53:47.500
with bipolar disorder are likely to need
link |
01:53:49.840
some sort of drug therapy intervention
link |
01:53:52.620
in order to help them.
link |
01:53:53.880
So lifestyle factors are always important
link |
01:53:56.800
in all individuals,
link |
01:53:58.280
those suffering from psychiatric conditions or not.
link |
01:54:01.400
But in some conditions of the mind and body,
link |
01:54:05.460
those lifestyle interventions can have a greater effect
link |
01:54:08.140
in offsetting symptoms.
link |
01:54:09.560
Whereas in bipolar disorder,
link |
01:54:11.240
I think it's naive and in fact wrong
link |
01:54:13.540
to say that lifestyle interventions alone
link |
01:54:16.320
are going to prevent especially the extreme forms
link |
01:54:18.800
of mania and depression.
link |
01:54:20.600
Again, bipolar disorder being so serious
link |
01:54:23.120
and carrying such high suicide risk,
link |
01:54:25.420
we just have to point this out again and again.
link |
01:54:27.500
Now, with that said, there are two substances
link |
01:54:29.760
generally found as supplements,
link |
01:54:31.840
although there are other sources of them as well,
link |
01:54:33.780
including within nutritional sources that have been shown,
link |
01:54:37.400
at least in some studies, to be pretty effective
link |
01:54:39.760
in adjusting the symptoms of bipolar disorder.
link |
01:54:43.340
And those two things are inositol and omega-3 fatty acids.
link |
01:54:48.720
Now, inositol is a compound
link |
01:54:51.680
that is taken for a variety of reasons.
link |
01:54:53.400
It's something we've talked about on the podcast before.
link |
01:54:55.440
I personally take inositol
link |
01:54:56.760
not because I have bipolar disorder.
link |
01:54:58.120
In fact, I am quite lucky that I don't have bipolar disorder,
link |
01:55:02.120
but I take inositol at 900 milligrams of myo-inositol
link |
01:55:05.240
every third night or so in order to improve my sleep.
link |
01:55:07.780
It's something that I've added to my sleep stack.
link |
01:55:09.640
It's something that I found greatly enhances
link |
01:55:12.400
the depth and quality of my sleep.
link |
01:55:14.500
And if I wake up in the middle of the night
link |
01:55:16.100
to use the bathroom, et cetera,
link |
01:55:17.360
it's greatly enhanced my ability to fall back asleep
link |
01:55:20.620
when I want to go back to sleep.
link |
01:55:22.000
It also seems to have a fairly potent anti-anxiety effect
link |
01:55:25.880
during the day.
link |
01:55:26.800
And as I discussed in our episode
link |
01:55:29.180
about obsessive compulsive disorder,
link |
01:55:30.780
inositol has been used at high dosages.
link |
01:55:34.040
Again, I should say myo-inositol
link |
01:55:35.360
has been used at high dosages,
link |
01:55:37.680
levels of even 10, 18 grams.
link |
01:55:40.320
Those are massive dosages, by the way,
link |
01:55:42.440
to deal with certain symptoms of OCD to limited success.
link |
01:55:46.680
And I should mention that high dosages
link |
01:55:48.360
of 10 or 18 grams of inositol
link |
01:55:51.680
can cause a lot of gastric discomfort, et cetera.
link |
01:55:54.480
If you want to learn more about inositol
link |
01:55:57.240
and its various uses,
link |
01:55:58.280
I encourage you to go to examine.com
link |
01:56:00.920
where there's the so-called human effect matrix
link |
01:56:03.520
and that human effects matrix will describe the many places
link |
01:56:07.120
in which myo-inositol and other forms of inositol
link |
01:56:10.000
have been shown to be effective in, for instance,
link |
01:56:12.400
reducing anxiety, enhancing sleep, and on and on.
link |
01:56:15.780
Myo-inositol is important because myo-inositol,
link |
01:56:19.340
and we can just say inositol,
link |
01:56:21.440
is related to so-called second messenger pathways.
link |
01:56:24.160
I don't want to get too deep
link |
01:56:25.000
into second messenger pathways,
link |
01:56:26.240
but when certain substances bind like neurotransmitters
link |
01:56:29.680
to a receptor on a cell surface,
link |
01:56:31.640
oftentimes those receptors themselves will open
link |
01:56:34.180
and allow the passage of ions and other things into a cell.
link |
01:56:37.280
Oftentimes they will engage
link |
01:56:39.200
what are called second messenger systems.
link |
01:56:41.000
That is, they will trigger mechanisms within the cell
link |
01:56:43.880
to then go do other things.
link |
01:56:45.480
This is probably something we should get into
link |
01:56:47.040
in real detail in a future episode
link |
01:56:48.720
for those of you that really want to nerd out
link |
01:56:50.380
on cell-cell signaling, which is a favorite topic of mine.
link |
01:56:53.440
In any case, inositol is related
link |
01:56:56.040
to a number of so-called second messenger systems,
link |
01:56:58.360
this handoff or this kind of stimulating
link |
01:57:01.400
of changes within a cell that can inspire changes
link |
01:57:05.500
in what's called a membrane fluidity,
link |
01:57:07.600
can actually make the membranes of cells,
link |
01:57:10.360
the outside fence around a cell,
link |
01:57:12.860
which is made up of fatty stuff,
link |
01:57:16.060
it can change the fluidity,
link |
01:57:17.520
meaning how readily things can float around in the membrane.
link |
01:57:21.680
We think of cells as very rigid,
link |
01:57:23.160
like there's a cell, there's a neuron,
link |
01:57:24.760
or there's a immune cell,
link |
01:57:25.980
but actually those cells have a fatty outside,
link |
01:57:29.840
in particular neurons have a fatty outside,
link |
01:57:31.960
it's a thin fatty outside,
link |
01:57:33.480
and it's called the cell membrane.
link |
01:57:35.380
And things are floating around in that cell membrane,
link |
01:57:37.820
but it's kind of like jello that hasn't quite fixed.
link |
01:57:40.240
And so things like receptors moving into the synapse
link |
01:57:43.360
or moving out of the synapse for homeostatic plasticity,
link |
01:57:46.360
things like the ability for certain genes
link |
01:57:50.720
to be turned on in a cell or not turned on
link |
01:57:52.560
can depend a lot on things that are happening
link |
01:57:54.960
in that cell membrane
link |
01:57:55.920
and how readily things move around in the cell membrane.
link |
01:57:58.340
One way to think about this whole picture
link |
01:57:59.920
of membrane fluidity is that just imagine
link |
01:58:02.720
that every one of your cells has this layer,
link |
01:58:05.040
it's kind of a gelatinous-like layer,
link |
01:58:07.400
and there are lots of little rafts floating around in there,
link |
01:58:10.660
but those rafts are able to move more quickly
link |
01:58:15.280
from one place to another,
link |
01:58:16.280
or get more stuck in one place or another,
link |
01:58:18.520
depending on how set that jello is.
link |
01:58:21.040
Inositol and lithium, and as we'll talk about next,
link |
01:58:26.960
omega-3 fatty acids seem to change
link |
01:58:30.000
the fluidity of those membranes.
link |
01:58:32.120
In other words, they allow things to move
link |
01:58:34.000
in and out of those membranes more readily or not.
link |
01:58:37.360
And this is no surprise,
link |
01:58:40.320
given that those membranes are made out of fatty stuff.
link |
01:58:44.840
In particular, the membranes of neurons
link |
01:58:47.200
are called a lipid bilayer.
link |
01:58:49.240
It's two layers of fat, okay, bi means two, lipid fat,
link |
01:58:54.320
and omega-3 fatty acids of the sort
link |
01:58:57.000
that are found in certain fish,
link |
01:58:59.240
and fatty fish in particular,
link |
01:59:01.500
and that are found in fish oil and cod liver oil, et cetera.
link |
01:59:06.360
Omega-3 fatty acids, when we ingest them,
link |
01:59:09.080
are used for a lot of different things,
link |
01:59:11.200
but they can be readily incorporated into pathways
link |
01:59:14.580
or directly incorporated into cell membranes,
link |
01:59:17.600
changing the way those cell membranes work,
link |
01:59:19.680
and if those cell membranes are the cell membranes
link |
01:59:21.880
of neurons, changing the way that neurons work.
link |
01:59:24.360
So the ability for fish oil, and in particular,
link |
01:59:28.520
the omega-3 fatty acids, which come in varieties
link |
01:59:31.200
like EPA and DHA, we'll talk about that in a moment,
link |
01:59:34.100
have been explored at relatively high dosages
link |
01:59:36.800
for their ability to offset some of the effects of mania
link |
01:59:41.520
and to offset the effects of depressive episodes
link |
01:59:44.860
in bipolar disorder.
link |
01:59:46.080
And actually, the data there are pretty impressive,
link |
01:59:48.560
although they are varied,
link |
01:59:52.780
meaning you will find several studies,
link |
01:59:55.320
and I'll mention a few, that found no effect
link |
01:59:57.800
of omega-3 supplementation through fish oil.
link |
02:00:00.080
Usually it's capsuled fish oil,
link |
02:00:01.540
although fish oil can also be taken in liquid form.
link |
02:00:04.760
Oftentimes, taking in liquid form
link |
02:00:06.080
is the more cost-efficient way to do it.
link |
02:00:07.800
Taking in capsule form is the more palatable way to do it,
link |
02:00:10.920
because fish oil, for a lot of people, doesn't taste good.
link |
02:00:13.600
But nonetheless, there are several studies that have shown
link |
02:00:17.540
that supplementing with fish oil or omega-3 fatty acids
link |
02:00:21.560
at levels of, for instance, four grams per day
link |
02:00:25.040
for a period of time,
link |
02:00:25.920
this is a study that we will link in the show notes.
link |
02:00:27.660
This is Murphy et al. 2012.
link |
02:00:29.920
This is a fatty acid supplementation of 70% EPA to DHA,
link |
02:00:35.100
actually worsened symptoms of mania
link |
02:00:37.560
over a period of about 16 weeks,
link |
02:00:39.920
which on the face of it makes it seem like, okay,
link |
02:00:42.040
omega-3 fatty acid supplementation,
link |
02:00:43.800
very likely to not be good for bipolar disorder.
link |
02:00:47.140
And yet, that was the manic phase.
link |
02:00:50.440
When one looks at some of the other studies
link |
02:00:52.120
of omega-3 fatty acid supplementation,
link |
02:00:54.700
there is, for instance, a study published in 1999.
link |
02:00:58.080
This is a much higher dosage supplementation
link |
02:01:01.200
with omega-3 fatty acid.
link |
02:01:02.320
This is a 9.6 grams of fish oil per day for four months.
link |
02:01:06.800
And that actually greatly reduced symptoms
link |
02:01:10.320
of bipolar depression compared to the control group,
link |
02:01:14.800
which received olive oil.
link |
02:01:16.280
Olive oil is a different form of fat,
link |
02:01:18.080
monounsaturated fat,
link |
02:01:19.520
but doesn't contain as much of the omega-3 fatty acids
link |
02:01:22.320
and so forth.
link |
02:01:23.140
So 9.6 grams of fish oil per day over four months
link |
02:01:27.440
is a lot of fish oil to be ingesting on a given day.
link |
02:01:31.580
This was a double-blind study.
link |
02:01:33.920
This was only carried out, I should mention, in 30 subjects,
link |
02:01:36.760
but it was males and females.
link |
02:01:38.400
And the age range was pretty broad,
link |
02:01:39.880
anywhere from 18 all the way up to 64 years of age,
link |
02:01:42.520
which is important given the sort of longitudinal
link |
02:01:45.460
or changes over time that one sees in bipolar disorder.
link |
02:01:49.040
Here's the major takeaway.
link |
02:01:50.840
Supplementing with high-dose omega-3s
link |
02:01:52.840
does seem to be beneficial for a good number of people
link |
02:01:56.040
with bipolar disorder.
link |
02:01:57.600
However, again, I want to highlight,
link |
02:01:59.260
however, it should not be viewed
link |
02:02:01.560
as the only treatment approach for bipolar disorder.
link |
02:02:04.560
This goes back to what I was saying before
link |
02:02:06.360
about the essential need in most every case
link |
02:02:09.080
for high potency prescription drug treatments
link |
02:02:12.360
prescribed by a board-certified psychiatrist
link |
02:02:14.120
for bipolar disorder.
link |
02:02:15.000
However, omega-3 supplementation does seem to improve
link |
02:02:20.780
or reduce the depressive symptoms
link |
02:02:22.480
in the major depressive episodes of bipolar.
link |
02:02:24.400
And there are a couple of studies,
link |
02:02:25.880
and we'll link to these in the show notes as well,
link |
02:02:27.880
that show that it may even improve
link |
02:02:29.640
some of the manic episodes as well,
link |
02:02:31.980
meaning it reduces some of the manic symptoms.
link |
02:02:34.880
Now, I say all this from a place of great caution
link |
02:02:38.080
because I know, especially for listeners of this podcast,
link |
02:02:41.160
there's a lot of interest in the behavioral tools,
link |
02:02:42.920
the supplement-based tools, the nutrition tools
link |
02:02:44.560
that can support bipolar disorder.
link |
02:02:46.280
But I don't think I can overemphasize enough
link |
02:02:48.600
that especially for bipolar disorder
link |
02:02:50.560
and the great risk of suicide and suffering
link |
02:02:53.080
and inappropriate spending,
link |
02:02:55.120
or I should say maladaptive spending and impulsivity
link |
02:02:57.480
that's associated with bipolar disorder,
link |
02:02:59.300
that it's hard to imagine a scenario
link |
02:03:01.360
in which just talk therapy and fish oil
link |
02:03:03.440
and lifestyle interventions are going to completely suppress
link |
02:03:06.840
or treat bipolar disorder.
link |
02:03:08.280
People with bipolar disorder really need to consider
link |
02:03:10.840
the full picture of treatments, the drug treatments,
link |
02:03:13.840
the talk therapy treatments and lifestyle treatments
link |
02:03:18.160
and nutraceutical, or we can say supplement-based treatments
link |
02:03:22.800
such as omega-3 supplementation,
link |
02:03:24.800
as a full and necessary picture
link |
02:03:28.040
for dealing with their illness.
link |
02:03:29.880
I'd be remiss, however, if I didn't emphasize
link |
02:03:32.400
that the omega-3 fatty acid supplementation
link |
02:03:35.600
is very interesting,
link |
02:03:36.880
not just in terms of the subjective effects,
link |
02:03:40.240
people saying they feel less depressed
link |
02:03:41.760
or able to sleep better,
link |
02:03:42.760
or maybe even some reduction in manic symptoms.
link |
02:03:45.160
There's actually been some really good brain imaging
link |
02:03:47.080
to try and understand how omega-3 fatty acid treatments
link |
02:03:50.600
are actually changing the brains and neural circuits
link |
02:03:53.100
of people with bipolar.
link |
02:03:54.040
And I will put a reference to this.
link |
02:03:55.320
This is a paper that was published
link |
02:03:56.840
in the American Journal of Psychiatry.
link |
02:03:58.760
It's entitled Omega-3 Fatty Acid Treatment
link |
02:04:00.920
and T2 Whole-Brain Relaxation Times in Bipolar Disorder.
link |
02:04:05.780
I don't have the opportunity to go into a lot of detail
link |
02:04:08.140
right now about what T2 whole-brain relaxation times are,
link |
02:04:11.120
but basically when people go into a MRI
link |
02:04:13.880
or F, functional MRI scanner,
link |
02:04:16.340
magnetic resonance imaging scanner,
link |
02:04:22.320
what they're getting essentially
link |
02:04:23.360
is pulses of magnetic fields.
link |
02:04:25.800
And the way that brain structures and neural activity
link |
02:04:28.520
can be evaluated has a lot to do
link |
02:04:30.080
with the sort of spinning or not sort of,
link |
02:04:33.040
it has to do with the spinning and the relaxation times
link |
02:04:36.040
of different elements,
link |
02:04:38.340
literally the protons and electrons within the neuron.
link |
02:04:41.720
So it gets really detailed there.
link |
02:04:43.720
And the relaxation time is essentially looking
link |
02:04:46.200
at how quickly some of that spinning returns to rest.
link |
02:04:49.960
And in particular, the fact that the relaxation times
link |
02:04:55.120
are different for aqueous, that is liquid,
link |
02:04:58.420
versus lipid, fatty, versus other components of brain tissue.
link |
02:05:03.060
And basically what this study shows
link |
02:05:05.120
is that the membranes of neurons within the brains
link |
02:05:08.780
of these people with bipolar disorder
link |
02:05:10.560
showed more fluidity, more ability of things
link |
02:05:12.740
to move in and around the membranes,
link |
02:05:14.940
which we know is an important component
link |
02:05:16.760
of neuroplasticity in bipolar subjects
link |
02:05:20.080
that were treated with omega-3 fatty acids
link |
02:05:22.520
as compared to bipolar subjects
link |
02:05:24.380
that did not receive omega-3 fatty acids.
link |
02:05:27.320
And fortunately, this study also include
link |
02:05:29.480
a healthy comparison group
link |
02:05:31.220
where they could essentially find
link |
02:05:32.880
that people with bipolar disorder
link |
02:05:34.760
who supplemented with omega-3s
link |
02:05:36.160
had changes at the cellular level
link |
02:05:38.560
and the neural circuit level
link |
02:05:40.320
that brought their brains and neural circuits
link |
02:05:43.280
closer to that of the healthy comparison subjects.
link |
02:05:46.300
So while I don't want to point
link |
02:05:48.640
to omega-3 fatty acid supplementation
link |
02:05:50.680
as the be all end all of treatment for bipolar disorder,
link |
02:05:53.040
certainly it is not,
link |
02:05:54.280
it does have a strong mechanistic basis
link |
02:05:57.660
for its possible support of neural circuitry,
link |
02:06:03.040
of neuroplasticity, and in particular,
link |
02:06:05.360
the ability to make changes in cell membranes
link |
02:06:07.480
that are very reminiscent
link |
02:06:09.680
of some of the neural circuit changes
link |
02:06:11.320
and changes in membrane fluidity
link |
02:06:12.920
that are seen with lithium treatment
link |
02:06:14.700
and other known prescription drug treatments
link |
02:06:17.300
that have been established now for decades
link |
02:06:20.240
to be very effective for bipolar disorder.
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02:06:22.960
So what that says is that omega-3 supplementation,
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02:06:26.440
while not the only intervention that one should consider,
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02:06:30.000
is something to consider and talk about with your doctor.
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02:06:33.080
And it's operating in powerful ways.
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02:06:35.640
It's not just that it's changing, for instance,
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02:06:38.200
your gut microbiome, which is powerful,
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02:06:40.320
but is indirect to the brain.
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02:06:41.520
It does seem to be having direct effects
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02:06:43.180
on neurons and neural circuits.
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02:06:44.900
Before we begin to conclude our discussion
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02:06:46.520
about bipolar disorder,
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02:06:48.160
I want to talk a little bit about this word disorder.
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02:06:51.000
And this is a theme that doesn't just relate
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02:06:52.920
to bipolar disorder,
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02:06:54.280
but other psychiatric disorders as well.
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02:06:57.000
And when we think of a disorder,
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02:06:58.720
we think of something that is really detrimental to us,
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02:07:02.080
something that really impairs our ability
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02:07:04.560
to function in work and school and relationships
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02:07:06.760
and really starts to pull down our health status
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02:07:10.060
in a variety of ways.
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02:07:11.160
And certainly bipolar disorder meets those criteria.
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02:07:14.920
However, there is this idea
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02:07:17.800
that things like bipolar disorder,
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02:07:19.740
even things like schizophrenia in some cases,
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02:07:22.640
are responsible for some of the creative aspects
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02:07:25.560
or the creative works that have been observed
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02:07:27.840
and carried out by human beings for many centuries.
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02:07:31.120
And believe it or not,
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02:07:32.160
there are good data to support the fact
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02:07:34.160
that certain aspects of mania
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02:07:36.360
are associated with creativity.
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02:07:38.860
Now, we are long overdue for an episode about creativity,
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02:07:42.240
its neural circuit basis, its chemical basis,
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02:07:44.180
here on the Huberman Lab Podcast.
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02:07:45.800
And certainly we will have that conversation.
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02:07:48.260
But in the meantime,
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02:07:49.440
I'd like to just briefly touch upon this idea
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02:07:52.080
that certain occupations are associated
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02:07:54.880
with a higher incidence of bipolar depression.
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02:07:57.840
And in fact, it's been explored at a research level.
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02:08:02.160
Really, there are data pointed to the fact
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02:08:04.560
that certain individuals of certain occupations
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02:08:07.800
tend to be more creative
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02:08:09.520
and that creativity is associated with,
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02:08:11.640
again, associated, this isn't causal,
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02:08:13.720
it's associated or correlated with higher levels
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02:08:16.900
or incidents of bipolar depression
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02:08:19.080
and maybe even other forms of depression.
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02:08:21.120
So this is a study looking at mood disorders
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02:08:24.240
in eminent individuals.
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02:08:25.840
So these are people that are not just good at what they do,
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02:08:28.960
but are exceptional at what they do
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02:08:30.960
and explored the percentage of people in given professions
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02:08:35.680
with either depression or mania.
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02:08:39.040
And this was actually a data set gleaned
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02:08:41.440
from more than 1,000 20th century Westerners
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02:08:45.140
based on their biographies
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02:08:46.660
that were reviewed by other people.
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02:08:49.060
So it's a bit of an indirect measurement.
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02:08:50.600
This isn't psychiatrist data.
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02:08:52.600
This is data, or I should say these are data
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02:08:55.760
that were compiled from self-reports
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02:08:59.360
or from reads of self-reports.
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02:09:02.180
And they explored a number of different professions.
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02:09:03.900
So for instance, they looked at people in the military
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02:09:06.520
or people who were professional athletes
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02:09:08.480
or natural scientists or social scientists,
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02:09:11.100
people who occupied positions in public office
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02:09:13.400
or were musical performers, artists, nonfiction writers,
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02:09:17.240
poetry, et cetera.
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02:09:18.620
There are a lot of professions here.
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02:09:20.260
I will post this, or I'll post a link to it
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02:09:22.720
in the show note captions for you to peruse,
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02:09:25.000
but I'll just give you a sense of the extremes
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02:09:27.120
on this graph because they're very interesting.
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02:09:29.440
It turns out that if you were to look at the profession,
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02:09:32.520
or I should say among the professions
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02:09:34.120
that they looked at in this study,
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02:09:35.540
cause they didn't look at all professions,
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02:09:38.220
those in the military and those who are professional athletes
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02:09:42.020
or had jobs in the social or natural sciences had the,
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02:09:46.680
of those, there was a lower percentage of those
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02:09:49.720
that had depression or mania.
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02:09:52.000
In some cases like those who were professional athletes
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02:09:53.920
didn't seem to have, there was no incidents of mania,
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02:09:56.440
at least in this data set.
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02:09:58.200
Whereas at the opposite extreme of the graph,
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02:10:00.600
those that were poets, so these are eminent individuals,
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02:10:04.240
people that were exceptional poets,
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02:10:06.080
exceptional fiction writers, exceptional artists
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02:10:09.400
or nonfiction writers.
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02:10:11.360
Well, they're especially for the poets.
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02:10:14.120
You find that as many as 90% of these very successful poets
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02:10:20.520
had either depression or mania, as high as 90%.
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02:10:26.300
That's incredible.
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02:10:27.240
Contrast that with military, where it's as few as 10%
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02:10:30.280
or professional athletes, where it's as few as 20%
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02:10:32.520
and for the professional athletes, as I mentioned before,
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02:10:34.600
none of them had mania.
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02:10:36.260
So does this mean that being a poet
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02:10:39.080
will make you manic or depressed?
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02:10:40.640
Well, first of all, let's look at the poetry category.
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02:10:43.360
It turns out that 75% of these eminent poets,
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02:10:47.960
these highly accomplished poets had major depression.
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02:10:52.680
Whereas only about 20% of those poets had manic episodes.
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02:10:59.920
So again, it's not that being a poet
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02:11:02.720
is going to give you mania, certainly we're not saying that,
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02:11:04.640
it's not that being a poet is going to give you depression,
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02:11:06.480
but it turns out that people with depression
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02:11:09.640
and people with depression and mania
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02:11:12.260
seem to gravitate towards poetry
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02:11:14.200
or at least are very successful at poetry.
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02:11:17.320
Again, associative, correlative,
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02:11:20.000
no causal relationship here,
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02:11:22.520
but it is really striking to see how
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02:11:24.920
the creative occupations, poetry, fiction, art,
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02:11:29.200
nonfiction writing,
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02:11:30.360
even though nonfiction writing is about nonfiction,
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02:11:32.160
it's still creative, music, composition, theater,
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02:11:35.000
much higher incidents of things like mania.
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02:11:37.640
And in fact, for the people in theater, the actors,
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02:11:41.040
even though the overall occurrence of depression and mania
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02:11:44.880
is lower than that in poets,
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02:11:47.240
the fraction of those individuals that have mania
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02:11:51.000
is exceedingly high.
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02:11:52.560
It's about 30% of those that they looked at
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02:11:56.320
who are actors have manic episodes or have full-blown mania.
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02:12:02.280
So I'm referring to these data because first of all,
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02:12:04.900
I find them incredibly interesting, right?
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02:12:06.760
Up until now, we've been talking about bipolar disorder
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02:12:08.680
and other mood disorders for their maladaptive effects.
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02:12:11.680
And again, they're extremely maladaptive,
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02:12:13.360
much, much higher instance of suicide, et cetera.
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02:12:16.460
But we'd be wrong to say that certain aspects
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02:12:19.020
of manic episodes don't lend themselves well to creativity
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02:12:22.000
or that certain aspects of major depression
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02:12:23.900
don't lend themselves well to creativity
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02:12:26.960
or to the performing arts or to poetry.
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02:12:29.320
That said, in no way, shape, or form,
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02:12:32.920
do I believe that being depressed is a good thing
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02:12:36.280
or that being manic is a good thing.
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02:12:37.880
Again, we return to the basic foundational criteria
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02:12:40.940
for bipolar disorder and major depression,
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02:12:42.500
which is that the pressured speech, the not sleeping,
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