back to indexThe 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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First of all, their supplements
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are of the absolute highest quality.
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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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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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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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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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If you'd like to try InsideTracker,
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you can visit insidetracker.com slash Huberman
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That's insidetracker.com slash Huberman to get 20% off.
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Today's episode is also brought to us by Roca.
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Roca makes eyeglasses and sunglasses
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that are of the absolute highest quality.
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The company was founded
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and everything about Roca eyeglasses and sunglasses
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I've spent a lifetime working on the biology
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Let's talk about bipolar disorder.
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And today I'm going to refer to bipolar disorder
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interchangeably with bipolar depression.
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Although, as you will soon learn,
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not everyone with bipolar disorder
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necessarily goes through highs and lows.
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There is a subset of people who suffer from bipolar disorder
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who experienced the manic phases,
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the highly elevated mood and energy,
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and then dropped down to so-called baseline.
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So they don't necessarily go down into a depressive state.
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They often will return to a somewhat normal state.
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In fact, we will talk about the percentage of time
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that people with bipolar disorder
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tend to be symptom-free, manic, or depressed
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in the context of the different categories
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of bipolar disorder.
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But as we wade into this topic that is bipolar disorder,
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I just want to give you a little bit
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of the background statistics to anchor us
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in just how serious and prevalent bipolar disorder is.
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So bipolar disorder impacts about 1% of people.
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That might seem like a small percentage,
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but if you think about a room of 100 people,
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that means that at least one of them
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is very likely to have bipolar disorder.
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And as I mentioned earlier in the introduction,
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bipolar disorder is very serious.
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It has a 20 to 30% greater incidence of suicide
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than the general population,
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which is, first of all,
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extremely tragic and extremely concerning.
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So anyone that thinks they might have bipolar disorder
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or who knows someone with bipolar disorder
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should be especially vigilant about this.
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And we'll talk about some of the signs and risk factors,
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age of onset, et cetera, as we move forward.
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So 1% of people have bipolar disorder.
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The typical age of onset is anywhere from 20 to 25 years old
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although it can be much earlier.
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And the earlier the onset of a bipolar episode,
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which we will define in a few minutes,
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the earlier the onset of that episode,
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the higher likelihood that the bipolar disorder
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is going to be a stable feature
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of that person's psychology going forward.
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And yet, I also want to point out
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that there are some very good treatments
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for bipolar disorder
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that those people could still benefit from.
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There are basically two kinds of bipolar disorder
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referred to as bipolar I and bipolar II.
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So let's just talk about bipolar I first.
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Bipolar I is characterized
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by a fairly extended period of mania.
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Mania is a period of very elevated mood, energy,
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distractibility, impulsivity, and some other symptomology
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that we'll talk about going forward.
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But this manic episode is extreme.
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This is a condition in which the energy lift,
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the mood lift, and the sort of impulsivity
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and actions and words of the person
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suffering from manic bipolar disorder
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are very noticeable and very extreme.
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Now, a key thing, however,
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is that it's not always noticeable
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to the person suffering from it
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that they are in this mode.
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Sometimes they recognize that, sometimes they don't,
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but it's always highly recognizable to other people
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that the person suffering from manic bipolar disorder
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is not like other people.
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So let's talk about bipolar I in a little bit more depth.
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One of the key clinical criteria
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or diagnostic criteria for bipolar I
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is that a person suffer from these manic episodes
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or display these manic episodes for seven days or more.
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That turns out to be very key.
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The stability of that manic episode for seven days or more
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turns out to be very important.
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And for those seven days,
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the person is in an elevated mood, expansive thought
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all day, every day for those seven days.
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Now, there are a lot of reasons
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why somebody could be in a manic mode.
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It doesn't necessarily mean
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that somebody has bipolar disorder.
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In fact, someone could be in a manic mode
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for seven days or more
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and still not be diagnosed with bipolar disorder.
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Well, there are other things
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that can create manic episodes,
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things like traumatic brain injury,
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things like seizure,
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things like various prescription drugs or illicit drugs,
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things like amphetamine and cocaine.
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That is not the same as bipolar disorder,
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even though from a symptomology perspective,
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they might look even identical.
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So let's think about these symptoms
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and the diagnostic criteria that a psychiatrist would use
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in order to ask whether or not someone is manic
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because they have manic bipolar disorder
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or whether or not that person is manic
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for some other reason,
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such as traumatic brain injury, illicit drugs, et cetera.
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So typically a person will be brought into a clinic
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or a person would bring themselves to a clinic
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or meet with a psychiatrist.
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It seems more likely that they would be directed
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toward a psychiatrist
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because oftentimes people who are in a manic episode
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just simply won't have the perspective
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or the foresight to bring themselves into the clinic.
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And the psychiatrist is going to start to evaluate
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for a couple of different things.
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But first of all, what they're going to try and figure out
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is whether or not the person has at least three
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of the following symptoms.
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The first symptom is distractibility.
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Is the person distractible?
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Are they going from one thing to the next?
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People who are in a manic episode
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will be talking about a pen
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and then they'll be talking about, you know,
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something they saw the other day
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and then something they want to purchase
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and then a place they're going to travel to, et cetera.
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But they are also very prone to any stimulus
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within the room, meaning, you know, a bell could go off
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or there could be a sound out in the hallway
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and they'll orient to that.
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And then they'll orient to the clinician
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and then they'll orient to something in their pocket.
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So they're all over the place.
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You could think of this a little bit like ADHD
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or attention deficit disorder, but it's very extreme.
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So highly distractible, highly impulsive.
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Impulsivity relates to actions.
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So the person might be fidgeting with something
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and then they might try and leave the room
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or the person might, if they were out in the real world,
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somebody might notice that the person is going
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and purchasing, you know, multiples of something
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that would be unusual for someone to purchase.
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So for instance, I happen to know someone
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whose ex-spouse had bipolar disorder
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and their ex-spouse went out
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and bought 10 plus air fryers, right?
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I mean, I think unless you're a restaurant
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that's using a lot of air fryers,
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the idea that you would need more than one
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or two air fryers might just seem
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a little bit out of the norm.
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And so that impulsivity can be purchasing.
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It can be other things as well.
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It could be booking, you know, 12 international trips
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in one afternoon or going and buying three cars, et cetera.
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The other is grandiosity.
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People who have manic bipolar disorder
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who are in a manic episode will often display words of
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or actions of grandiosity.
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And keep in mind, these are not lies
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in the sense that the person isn't lying
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in order to try and pull one over on anybody.
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These are actual beliefs that the person comes to have
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about their grandiose position in the world
link |
or grandiose opportunities or potential in the world.
link |
Typical forms of grandiosity in manic episodes would be
link |
that the person suddenly decides
link |
that they are going to win a Pulitzer Prize.
link |
They are the person selected to win a Pulitzer Prize.
link |
They're going to write a novel that afternoon
link |
and they're going to win a Pulitzer Prize that year,
link |
which is more or less a delusion of grandeur, right?
link |
The idea that someone could do that in one afternoon,
link |
I suppose it is possible in the realm of all possibilities,
link |
but it's extremely unlikely.
link |
Other forms of grandiosity that often present themselves
link |
in people suffering from a manic episode
link |
will be that they're going to run for president
link |
or that they are the person that they believe is selected
link |
by the citizens of a given country
link |
or by the universe to be the president of that country
link |
or to be president of the universe, right?
link |
It sounds ridiculous, but those sorts of delusions
link |
of grandiosity are one condition that often presents itself
link |
or one set of symptoms that presents itself.
link |
Flight of ideas are also typical of manic episodes.
link |
So this is a little bit like distractibility,
link |
but this would be people talking extensively about one thing
link |
and then switching and talking extensively
link |
about something else.
link |
It would be as if I was doing this podcast,
link |
talking about manic bipolar disorder,
link |
and then suddenly switching to OCD
link |
and then to deliberate cold exposure
link |
and then to the role of sugar
link |
and its impact on the brain, et cetera.
link |
So essentially a random selection
link |
of the different topics that exist in science,
link |
all of which I happen to be very interested in
link |
and curious about, but just as we have episodes
link |
of the podcast that are about one or two topics
link |
and we focus on those in a fairly narrow trench
link |
of discussion, somebody who has a flight of ideas
link |
would be jumping between categories and topics
link |
in a kind of pseudo random way.
link |
So they might take off down a path of one thing
link |
and then switch to another without any transition
link |
or with transitions that don't have
link |
any logical structure to them.
link |
The other aspect of manic bipolar disorder
link |
that often presents itself in the manic episodes
link |
are agitation, people feeling extremely physically agitated,
link |
so a lot of shaking and moving about.
link |
This can venture into the realm of paranoia,
link |
but a lot of agitation, a difficulty sitting down
link |
and being still, a difficulty in just looking,
link |
feeling and acting calm.
link |
And then another condition is no sleep.
link |
And when I say no sleep, I mean no sleep
link |
or very minimal sleep.
link |
As incredible as it sounds, people who are in a manic episode
link |
can often go seven days or more with zero sleep.
link |
And a key feature of this zero sleep
link |
is that they're not troubled by it.
link |
They're not thinking, oh, I'm suffering from insomnia
link |
and I really, really want to sleep.
link |
Sometimes that's the case, but more often than not,
link |
they are simply not sleeping.
link |
They're staying up 24 hours, then another 24 hours,
link |
it just continues for an entire week.
link |
Again, inconceivable to those of us
link |
that don't suffer from manic episodes,
link |
can only imagine how pulled apart most of us would feel
link |
under those conditions and yet they are just going
link |
and going and going with no sleep up all hours,
link |
shopping, talking, running,
link |
doing all sorts of different things
link |
in the categories of other symptoms
link |
that we talked about before.
link |
And it doesn't bother them that they're not sleeping.
link |
And then the last sort of category of symptoms
link |
that the psychiatrist is evaluating for
link |
and seeing if they present is rapid pressured speech.
link |
The rapid pressured speech is something
link |
that when you hear it, you recognize it.
link |
This is somebody that almost seems to be hitting you
link |
a speech like machine gun fire.
link |
It's coming at you, coming at you, coming at you,
link |
and there's really no room for conversation.
link |
They're not offering any opportunity for a back and forth,
link |
or if there is a back and forth,
link |
they might ask you how you feel about something
link |
and then you started, well, then they're going to hit you
link |
with another barrage or a paragraph of information
link |
or of just speech that's pseudo random.
link |
So we've got distractibility, impulsivity, grandiosity,
link |
flight of ideas, agitation, no sleep,
link |
and rapid pressured speech.
link |
For someone to be diagnosed as in a manic episode,
link |
they do not have to be engaging in
link |
or displaying all of those symptoms.
link |
They do, however, need to present
link |
at least three of those symptoms.
link |
And then in order to meet the condition of bipolar I,
link |
they have to be presenting those three symptoms
link |
for at least seven days.
link |
It could be longer, but at least seven days.
link |
Now, this seems pretty straightforward, right?
link |
At one level, the way that I describe this
link |
and the way that it exists in the clinical literature,
link |
you could think, well, this should be pretty easy
link |
to diagnose, and yet there's a complication there
link |
or a challenge there because the psychiatrist, again,
link |
has to determine that these manic episodes
link |
are not due to something other than bipolar disorder.
link |
For instance, again, it could be TBI, traumatic brain injury,
link |
it could be seizures or meds or other sorts of drugs.
link |
Corticosteroids, which are often prescribed
link |
for a number of immune conditions or for wound healing,
link |
can also cause manic episodes.
link |
So they have to determine that everything that's happening
link |
meets the criteria I described before,
link |
three out of seven of these symptom categories
link |
for seven days or more,
link |
and that it can't be better explained
link |
by something else going on in that person's life
link |
or immediate medical history.
link |
That's very important.
link |
Now, the other challenge,
link |
and this is something that's going to come up
link |
again and again today,
link |
not just in the description of the biology
link |
of bipolar disorder, but also in the description
link |
of different treatments and treatment approaches,
link |
is that typically when somebody is sitting
link |
in front of a psychiatrist,
link |
in particular for the first time,
link |
those two people are interacting,
link |
the psychiatrist is just getting one snapshot
link |
of the person at that moment, right?
link |
So the person could be on day one of a manic episode,
link |
the person might be on day six of a manic episode,
link |
the person could be transitioning out of a manic episode,
link |
or the person could be suffering
link |
from a combination of manic episode
link |
where because of the impulsivity of bipolar disorder,
link |
they went out and used illicit drugs,
link |
they also used cocaine.
link |
So the psychiatrist has a serious challenge.
link |
The psychiatrist has to determine
link |
based on a conversation, right?
link |
This isn't a blood test,
link |
this isn't a measurement that you can take on a scale
link |
or with a biomarker,
link |
they have to use language,
link |
a conversation with somebody who by all accounts
link |
is pretty impaired at conversation
link |
to determine whether or not
link |
they're suffering from a manic episode
link |
that is the consequence of bipolar disorder.
link |
You can imagine this in the real world as somebody says,
link |
well, how long has it been since you slept?
link |
And the person starts to answer,
link |
oh, well, the other day I went down to the basement,
link |
I was going to get something out of the refrigerator
link |
and I thought I might take a nap
link |
and then all of a sudden
link |
they're talking about something completely different.
link |
So they might not even have an answer.
link |
So the psychiatrist has to be a really good detective,
link |
a benevolent detective, but a detective nonetheless
link |
in determining whether or not
link |
these symptoms have existed for seven days or more
link |
and whether or not they meet at least three,
link |
it could be more, but at least three of the criteria
link |
of symptom categories I talked about before.
link |
Now, assuming that they do,
link |
assuming that the patient meets those criteria,
link |
they are likely to be diagnosed with bipolar I.
link |
Now bipolar I disorder
link |
means they're having these extended manic episodes,
link |
seven days or more,
link |
but it does not necessarily mean that they are dropping
link |
into a depressive episode as well.
link |
This is a common misconception about bipolar disorder
link |
because as it's often called,
link |
bipolar disorder is referred to as bipolar depression
link |
and yet many people with bipolar disorder
link |
don't necessarily experience the deep depressive episodes.
link |
Many of them do, but many of them do not.
link |
So somebody can truly be diagnosed accurately
link |
even though they're only experiencing manic episodes
link |
and then dropping down to baseline.
link |
Manic episode, then dropping down to baseline.
link |
That's very important to understand.
link |
Now, the second category of bipolar disorder is bipolar II.
link |
So BP2 or bipolar disorder II
link |
is somewhat different than bipolar disorder I.
link |
First of all, it's characterized most often
link |
by the presence of both manic episodes,
link |
mania and depressive episodes,
link |
or what's referred to as hypomania.
link |
Now, anytime in biology or in medicine you hear hypo,
link |
it's the opposite of hyper, okay?
link |
So we've got normal, hyper and hypo.
link |
Hypomania is a somewhat suppressed level of mania.
link |
So this is not going to be as extreme as the mania
link |
that we typically think of.
link |
And yet the hypo can be due to the duration,
link |
not the intensity of mania.
link |
Hypomania can mean a lessened intensity of mania,
link |
but it can also be used
link |
to refer to a shorter duration of mania.
link |
In fact, that's one of the key criteria for bipolar II.
link |
Bipolar II is often diagnosed
link |
on the basis of the presence of manic episodes
link |
that are lasting four days or even less.
link |
So someone with BP2 might have four days
link |
of this increased energy, goal-directed activity.
link |
They're irritable, they're euphoric,
link |
they're not sleeping, et cetera,
link |
but it's only lasting for about four days.
link |
Or they could be having longer extended periods of mania,
link |
but they are hypomanic episodes.
link |
They're not quite as intense.
link |
So the pressured speech isn't quite as pressured.
link |
The impulsivity isn't quite as severe, et cetera, et cetera.
link |
The other aspect of bipolar II
link |
is one that I had mentioned briefly a moment ago,
link |
which is that it's often associated
link |
with the drops into the depressive episodes.
link |
So people are going from manic episodes
link |
for four days or less,
link |
then they're dropping into a depression,
link |
going back to normal, manic again.
link |
I do want to point out, however,
link |
that people who have bipolar I
link |
can indeed go from manic episodes
link |
to severe what we call major depression.
link |
So they can oscillate like a sine wave,
link |
really high highs, really low lows.
link |
And very important to understand
link |
in terms of understanding both bipolar I and bipolar II
link |
is that it's not always a sine wave.
link |
This is really important.
link |
And it's something that frankly I did not know
link |
until I started researching this episode
link |
and talking to some psychiatrists.
link |
I should mention I've talked
link |
to several board-certified psychiatrists
link |
in preparation for this episode.
link |
I'll give some references to them.
link |
And in fact, some of them are going to be coming
link |
on the podcast as guests in the future
link |
for a more in-depth discussion about bipolar
link |
and other psychiatric disorders.
link |
But all of the psychiatrists I spoke to
link |
confirmed what the other was saying,
link |
which was that the way that bipolar disorder can present
link |
can vary tremendously between individuals.
link |
One person might go from very high highs
link |
that last seven days or more to very low lows,
link |
bouts of depression, major depression
link |
that could last two weeks or more.
link |
Other people are rapid cycling by way of three days manic,
link |
three days normal, three days manic,
link |
and then dropping into three days depression.
link |
So you want to erase that picture in your mind
link |
that manic bipolar disorder is this sine wave,
link |
this cycling up and down between mania and depression.
link |
It can take a lot of different forms.
link |
And again, this is a serious challenge
link |
for the psychiatrist to diagnose people
link |
because of that fact
link |
that they're only getting a snapshot of the person
link |
unless they've known them for some time
link |
and are working with them for some time.
link |
But this is also especially important for those of you
link |
that either have bipolar depression
link |
or suspect that you might,
link |
or that know someone with bipolar depression
link |
or suspect somebody might have bipolar depression,
link |
AKA bipolar disorder.
link |
Because if you're noticing that somebody
link |
is very manic and then normal,
link |
well, that's a very different picture
link |
than somebody who's going from very manic
link |
to very deep bouts of depression.
link |
The very manic to deep bouts of depression
link |
is easier to recognize
link |
because of the extremes of those highs and lows.
link |
Now, this might seem somewhat obvious to all of you
link |
And yet it's very important as a, frankly,
link |
a citizen of the planet who knows other human beings
link |
to keep an eye out for these manic episodes
link |
because again, whether or not it's four days or less
link |
or whether or not it's seven days or more,
link |
these manic episodes really are the defining criteria
link |
of bipolar disorder, AKA bipolar depression.
link |
There are a couple other key features
link |
about bipolar I and bipolar II
link |
that can allow us to get better insight
link |
into whether or not somebody has bipolar I or bipolar II.
link |
And that's the percentage of time
link |
that people with bipolar I versus bipolar II
link |
spend in a manic state, a depressed state,
link |
or a symptom-free state.
link |
And this is also important to discuss
link |
because it turns out that people with genuine,
link |
diagnosed bipolar I or bipolar II are often symptom-free,
link |
which again can make it difficult
link |
for us as people that know them
link |
or for people that are treating people
link |
with bipolar disorder to identify
link |
whether or not somebody is in a manic episode
link |
or a depressive episode,
link |
or whether or not they are headed
link |
into a manic or depressive episode.
link |
So the numbers on this have been studied.
link |
It's from a paper, actually two papers,
link |
first author Judd, J-U-D-D et al,
link |
published some years ago, 20 years ago,
link |
but the data hold up really nicely over time.
link |
These were both published
link |
in Journal of American Medical Association Psychiatry.
link |
So JAMA Psychiatry is a superb journal.
link |
And basically people who have bipolar I on average
link |
spend about 50%, it's actually 53%
link |
was the number that was eventually converged upon,
link |
but about 50% of their time symptom-free.
link |
That's interesting, right?
link |
Somebody who has genuine bipolar I disorder
link |
can spend as much as half of their life symptom-free,
link |
sleeping normally, speaking normally, et cetera,
link |
about 32% of the time depressed.
link |
And when we say depressed, we mean major depression.
link |
So severe challenges with waking up
link |
at two or three in the morning
link |
and having trouble falling back asleep,
link |
that's one of the defining characteristics of depression
link |
or sleeping far too much,
link |
having a hard time getting out of bed in the morning,
link |
suppressed appetite, suppressed libido,
link |
suppressed motivation, all the general symptoms
link |
of major depression,
link |
which we'll talk about a little bit more later
link |
and in an upcoming episode
link |
about major depression in particular.
link |
And then about 15% of their time
link |
in this kind of manic state or mixed manic state
link |
where they are showing long,
link |
again, seven days or more bouts of sleeplessness,
link |
irritability, pressured speech, grandiosity, et cetera.
link |
Contrast that with people who have bipolar II disorder
link |
who are spending about half of their time
link |
in a depressed state.
link |
So that's interesting.
link |
People with bipolar II disorder,
link |
while not always displaying depressed states
link |
or oscillations between mania or hypomania
link |
and depressed states,
link |
they tend to be in a depressed state more often.
link |
And again, this is major depression.
link |
This isn't just a little bit of a low.
link |
This is a serious depression of their nervous system,
link |
their mood, and as we say, their affect,
link |
their outlook on life.
link |
And that's one of the key distinguishing features
link |
of major depression is that people's outlook on life
link |
becomes very diminished in the sense
link |
that they don't see a future.
link |
You ask them about, you know, how's work going?
link |
How are relationships?
link |
And it's not just that they feel that that's going poorly.
link |
They really feel as if there's no opportunity
link |
for those things to improve.
link |
Those people with bipolar II tend to be symptom-free
link |
about 45% of the time.
link |
Again, these are averages.
link |
So about 45% of the time.
link |
That's a considerable amount of the time.
link |
And they tend to be in these hypomanic states
link |
only about four or 5% of the time.
link |
Again, the criteria for BP2, bipolar II,
link |
is these four days or less of mania or hypomania.
link |
But only 4% of the time or 5% of the time
link |
is a small enough sliver of the pie
link |
that is these people's existence
link |
that you can imagine why it would be easy
link |
for them or other people to overlook the fact
link |
that they have bipolar disorder and not major depression.
link |
This is a person who, or I should say a collection of people
link |
who are spending about half of their time depressed,
link |
close to half, 45% of their time symptom-free,
link |
and then about 5% of their time in a hypomanic state.
link |
So either shortened bouts of high intensity mania
link |
or hypomania that is of reduced intensity.
link |
One of the reasons that I mentioned these percentages
link |
of time spent in a symptom-free depressed manic
link |
or hypomanic state is because one of my major goals
link |
for today's episode is that it will increase awareness
link |
of whether or not you or somebody you know,
link |
could be a coworker, could be a family member, et cetera,
link |
might be suffering from bipolar I or bipolar II.
link |
I think it's fair to say that if somebody is suffering
link |
from bipolar I, that is likely to be revealed
link |
or to reveal itself before too long
link |
because of the fact that people have these extended periods
link |
of mania and mania is such an extreme state,
link |
not just for the person who's experiencing it,
link |
but the way that it presents is just so extreme
link |
and out of the ordinary.
link |
But bipolar II, you can imagine,
link |
could really duck under the radar of our awareness.
link |
And you could imagine that we might just think
link |
somebody is low or depressed,
link |
especially if that person tends to self-medicate
link |
with alcohol or other substances.
link |
We might think, oh, well, they're drinking more than often,
link |
more than usual, excuse me,
link |
or they're spending more time alone and isolating.
link |
But then when they're in their hypomanic state,
link |
that might actually present as normal to us
link |
because they were in such a depressed state before.
link |
So it's very important that we dial up our awareness,
link |
that we can tune our antennae to the possibility
link |
that people out there who might appear depressed
link |
or that we haven't heard from in a while
link |
might actually be suffering from bipolar II disorder.
link |
Before we move into a in-depth discussion
link |
about the different kinds of treatments
link |
for bipolar disorder,
link |
I'd like to touch on just a few additional aspects
link |
of what bipolar disorder can do
link |
in terms of its negative consequences
link |
and also talk about some of the inherited risk,
link |
that is the genetic factors and the environmental factors
link |
that can contribute to bipolar disorder.
link |
In terms of the burden,
link |
the very real emotional and occupational
link |
and educational burden
link |
that can occur for somebody with bipolar disorder,
link |
that's actually been studied.
link |
There's a measure of this, it's called global burden,
link |
which is defined as the years lost
link |
in engaging in normal life due to some disability.
link |
So that disability could be cancer,
link |
that disability in this case is bipolar disorder.
link |
And basically the way this sort of study is done
link |
is that through questionnaires,
link |
I should say quite in-depth questionnaires,
link |
there's a probing for whether or not somebody
link |
has lost two consecutive weeks or more
link |
of interest in normal activities.
link |
Now, for people who have depression,
link |
that's a kind of straightforward thing to address, right?
link |
You ask somebody, when was the last time you ate?
link |
Or when was the last time that you went a few days
link |
without food or lost interest in relationships
link |
or work or sex or things of that sort?
link |
And they answer and you can figure out
link |
the amount of time that you've essentially been withdrawn
link |
from normal levels of activity for them.
link |
With bipolar disorder, what it turns out
link |
is that the global burden of having bipolar I
link |
and even bipolar II is massive.
link |
In fact, having bipolar disorder sits
link |
as one of the highest risk factors
link |
for being in the top 10 of all categories of disabilities
link |
leading to global burden.
link |
Put in plain English, what that means is having bipolar I
link |
or bipolar II disorder is extremely debilitating.
link |
It really slows down one's life trajectory
link |
unless it's treated properly.
link |
Now, the other aspect of bipolar disorder
link |
is its heritability.
link |
And this gets into a little bit of some tricky science
link |
related to heritability versus the genetic contribution
link |
of a given disease.
link |
So that might sound like the same thing.
link |
You think, okay, genes relate to heritability,
link |
heritability relates to genes,
link |
but of course everything about the way
link |
that our nervous system works and functions
link |
and expresses itself, healthy or otherwise,
link |
is an interaction between our genes and our environment.
link |
And so typically the way these studies are done
link |
is you address what is the risk of somebody
link |
having a given condition in the general population?
link |
We talked about that before.
link |
Bipolar disorder is a 1% of the world's population.
link |
Compare that to people who have only major depression.
link |
So this would be repeated bouts of two weeks or more
link |
of serious depression, not just low mood
link |
or something due to a life loss, but major depression,
link |
which is 10 to 17% of people have major depression.
link |
Okay, they suffer from major depressive disorder
link |
compared to bipolar disorder, which again is 1%.
link |
Now you can address how much of the 1% of bipolar disorder
link |
that exists is due to genes versus environment
link |
in a somewhat exact way.
link |
This is never an exact science.
link |
And the way that this is typically done
link |
is to look at concordance, that is the likelihood
link |
that two identical twins will both have a given condition
link |
as opposed to two fraternal twins,
link |
which have more different genes
link |
than identical twins, of course.
link |
And then two siblings who have similar genes, of course,
link |
but less similar than identical or fraternal twins
link |
and so on and so forth.
link |
So what you basically do is you evaluate the probability
link |
that two people in the general population
link |
who are completely unrelated will have the same condition
link |
versus two people in the general population
link |
who are very related identical twins.
link |
And what you find is that in identical twins,
link |
if one identical twin has true major depression
link |
or major depressive disorder,
link |
there's a 20 to 45% chance that their identical twin
link |
will also have major depressive disorder.
link |
Now that tells you right there that it can't all be genes.
link |
That is not a gene for major depression per se,
link |
or if it is a gene or a collection of genes,
link |
that those genes are also subject to environmental
link |
influences, either prenatal within the womb
link |
or after children are born.
link |
Now, the large range there of 20 to 45%
link |
could be due to any number of things.
link |
It could be experimental,
link |
meaning the techniques that were used in experiments.
link |
It could be due to regional differences, right?
link |
One part of the world versus another.
link |
There are a lot of different factors.
link |
Right now, we probably shouldn't delve into all that.
link |
At some point, we'll probably do an episode
link |
all about the genetics of nervous system heritability
link |
and heritability of features and mental health, et cetera.
link |
But we can compare major depression and the heritability
link |
or the genetic concordance between identical twins
link |
in major depression and bipolar disorder and ask,
link |
if one twin of an identical twin pair
link |
has bipolar depression,
link |
what is the likelihood that the other twin will have it?
link |
And it turns out that number is much higher.
link |
It's 40 to 70% likelihood or probability
link |
that if one twin has bipolar disorder,
link |
that their identical twin will also have bipolar disorder.
link |
So again, the total incidence of bipolar disorder
link |
in the general population is much lower
link |
than it is for major depression.
link |
It's 1% for bipolar versus 10 to 17% for major depression.
link |
But the genetic component is much higher,
link |
40 to 70% for bipolar disorder versus 20 to 45%
link |
for major depression.
link |
I know I'm throwing a lot of numbers out there,
link |
but basically what this means is that researchers
link |
have been able to take those numbers
link |
and filter them through a number of different risk factors
link |
that are related to early development,
link |
ask questions like if two twins were raised separately
link |
or together in one part of the world versus another,
link |
or had a two-parent household versus one-parent household,
link |
evaluate a lot of different variables.
link |
What they were able to discover,
link |
and this has been shown again and again,
link |
is that the genetic contribution to bipolar disorder
link |
is very, very high.
link |
That is the heritability of bipolar disorder is 85%.
link |
Okay, so again, I want to be really clear what this means.
link |
The total occurrence in the general population, fairly low.
link |
Still serious, 1%, but fairly low
link |
compared to other things like major depression.
link |
However, if someone has bipolar disorder,
link |
it's very likely that they inherited some gene
link |
or sets of genes or more accurately a susceptibility
link |
within their genes to environmental influences
link |
that can trigger bipolar disorder.
link |
There are a lot of different ways to discuss
link |
and to conceptualize heritability.
link |
So I want to be very careful
link |
with the way that I'm wording this.
link |
What this means is that people with bipolar disorder
link |
very likely have a gene or more typically
link |
it's going to be a set of genes that creates a susceptibility
link |
for bipolar disorder to present itself.
link |
Now, what environmental factors trigger
link |
or increase that susceptibility is not entirely clear.
link |
This always seems to center back onto the same sets of things
link |
like early life stress, trauma, et cetera.
link |
Certainly those are going to exacerbate the likelihood
link |
that someone who has a genetic propensity
link |
for bipolar disorder will express that bipolar disorder
link |
in its full array of symptomology,
link |
but 85% while very, very high is not 100%.
link |
Again, 85%, while a very high number for heritability
link |
What that means is that there is no single gene
link |
or identified gene cluster for bipolar disorder.
link |
The reason I keep drilling into this over and over
link |
is that I think we can confidently say
link |
that if someone has bipolar disorder,
link |
that there was something in their genetic lineage
link |
that led to that, or that very likely led to that.
link |
And yet it's not like eye color
link |
or some other physical feature
link |
which we can actually do the direct,
link |
so it's called Mendelian genetics
link |
and figure out whether or not somebody directly inherited
link |
that gene from one parent or the other parent.
link |
So the takeaway here is that
link |
if you have certainly an identical twin
link |
or a fraternal twin or a sibling or a parent
link |
or even a cousin or an uncle that has bipolar disorder
link |
in particular bipolar one,
link |
well then you need to be on the lookout
link |
for bipolar disorder perhaps in yourself
link |
and for the family members of that person.
link |
My goal within this episode up until now
link |
has been to provide a clear and detailed picture
link |
of bipolar disorder and its various forms.
link |
Before we start to talk about treatments
link |
for bipolar disorder
link |
and some of the neural circuit basis for bipolar disorder,
link |
I want to make sure that I distinguish bipolar disorder
link |
from borderline personality disorder.
link |
We will do an entire episode
link |
or maybe even several episodes
link |
about borderline personality disorder.
link |
Borderline personality disorder can indeed present itself
link |
in ways that resemble bipolar disorder and vice versa,
link |
but there are some key distinctions that need to be made
link |
because it turns out that bipolar disorder
link |
and borderline personality disorder are quite distinct
link |
in terms of their defining criteria.
link |
The key distinction between somebody
link |
with borderline personality disorder and bipolar disorder
link |
is that in borderline personality disorder,
link |
there can be episodes that can resemble mania or hypomania.
link |
So periods of flights of ideas
link |
or where people are spending money excessively
link |
or sexually promiscuous in ways that seem manic
link |
or could even be a little bit manic or a lot manic.
link |
And yet more often than not,
link |
there is an environmental trigger for those manic episodes.
link |
That is distinctly different from bipolar disorder
link |
where the person will have manic episodes
link |
without any need for a trigger.
link |
There doesn't need to be a call from someone saying,
link |
hey, let's go on a vacation together
link |
or there's something coming up this Friday
link |
that's really exciting
link |
or let's enter a relationship together
link |
of one form or another.
link |
The person with bipolar disorder will have episodes of mania
link |
or episodes of major depression
link |
without any need for an external stimulus
link |
or environmental trigger.
link |
But the person with borderline personality disorder
link |
almost always, again,
link |
there's never an always in biology and psychiatry,
link |
but almost always is going to exhibit flights of mania
link |
or depressive episodes or other types of mood shifts
link |
that are dramatic and maladaptive in response to things
link |
that are coming in through the external environment
link |
or relationships of some kind.
link |
In fact, one of the defining characteristics
link |
of borderline personality disorder
link |
is this thing that's referred to as splitting.
link |
A good example of splitting
link |
in the person with borderline personality disorder
link |
is that they will feel that they absolutely adore you
link |
and want to spend all their time with you
link |
and just think the world of you, you can do no wrong.
link |
And in fact, they genuinely can feel that way
link |
and can genuinely think that way about you.
link |
And then for whatever reason,
link |
it could be a perception of something that you did
link |
or something that you said
link |
or suspicion that you're thinking something about them,
link |
they can suddenly shift or split their emotions
link |
and what's called move you from a good object
link |
or a can do no wrong object to a bad object.
link |
They'll suddenly decide that you are cheating on them
link |
or that you are being mean to them
link |
or that you're insulting them
link |
or that something that you're doing
link |
is in violation to their self-worth,
link |
their wellbeing, et cetera.
link |
And that can send them down a pathway
link |
of being very angry, very depressed, et cetera.
link |
As I described the contour of a person
link |
with borderline personality disorder
link |
as somebody who splits very suddenly
link |
in response to some environmental trigger,
link |
real or perceived, there's the risk, of course,
link |
that it makes the person with borderline personality disorder
link |
sound like a bad person, that they're very volatile.
link |
And while they can be volatile,
link |
I want to be very careful to point out
link |
that the person with borderline personality disorder
link |
is also suffering in this context.
link |
So while those sorts of relationships
link |
with people with borderline personality disorder,
link |
whether or not they're romantic relationships
link |
or familial or coworkers, et cetera,
link |
can be very challenged, can be very high friction
link |
because of the good object, bad object shifts, et cetera,
link |
it's bi-directional, meaning the person
link |
with borderline personality disorder, as you can imagine,
link |
is also going through a lot of suffering.
link |
At one moment, they feel as if someone is wonderful
link |
and can do no wrong to them
link |
and they want to be so strongly affiliated with them.
link |
And then in the next moment,
link |
they feel as if that person is attacking them
link |
through their actions or even through their non-actions.
link |
So again, we will return
link |
to borderline personality disorder in a separate episode.
link |
It's a serious disorder, both for the person that has it
link |
and for people around them.
link |
Fortunately, there are some emerging treatments
link |
that are showing promise,
link |
and it's a fairly common disorder,
link |
but it's important that we distinguish
link |
borderline personality disorder from bipolar disorder,
link |
mostly on the basis of this need for a trigger.
link |
Again, in bipolar disorder,
link |
there is no need for a trigger to create a manic episode
link |
or a major depressive episode.
link |
They just happen, or they can just happen.
link |
Whereas in borderline personality disorder,
link |
almost always there's an external trigger
link |
or a perception that something happened in the environment
link |
or that somebody is behaving a certain way
link |
that dramatically shifts the person
link |
with borderline personality disorder
link |
from one mode to the next.
link |
As we move into our discussion about the treatments for
link |
and neural circuits underlying bipolar disorder,
link |
I want to just nail down one more key point.
link |
This is a very brief point,
link |
but it's perhaps the most important point,
link |
which is the highs and lows,
link |
or we should say the highs,
link |
these manic episodes and sometimes lows,
link |
because again, not everybody with bipolar disorder one or two
link |
suffers from depressive episodes.
link |
Sometimes yes, sometimes no.
link |
In particular in bipolar II, yes,
link |
but people with bipolar I can have extreme manic episodes
link |
and then just return to normal, as you recall.
link |
Well, those extreme lows and or extreme highs
link |
of people with bipolar disorder
link |
impact their lives in very negative ways.
link |
This is essential.
link |
And it's something that we're going to return to
link |
a little bit later when we talk about the relationship
link |
between bipolar disorder and creativity,
link |
because it turns out that there's
link |
a quite strong association there,
link |
one that would almost lead you to believe
link |
that being bipolar can be beneficial in certain contexts.
link |
And yet on whole, having bipolar disorder
link |
is extremely detrimental
link |
and challenging to the person suffering from it.
link |
And it's something that we want to keep in mind
link |
as we think about treatments and the underlying biology.
link |
Now I'd like to talk about some of the treatments
link |
for bipolar disorder.
link |
And in the discussion of those treatments,
link |
there's an absolutely incredible history
link |
of the discovery of one particular treatment
link |
that still shows great success in many patients,
link |
although some people can't take it
link |
for reasons that we'll talk about.
link |
And in the description of the discovery of this treatment
link |
for bipolar disorder,
link |
it also reveals to us that sometimes
link |
treatments come to the profession of medicine
link |
and through science in ways that precede
link |
the discovery of the underlying biology.
link |
Every once in a while,
link |
someone will discover a treatment for a disease
link |
without any understanding
link |
about the underlying biological basis of that disease.
link |
And in fact, that is the case for bipolar disorder.
link |
And the treatment that we're referring to is lithium.
link |
Lithium, as some of you know,
link |
is on the periodic table of elements.
link |
It is indeed a naturally occurring substance.
link |
It actually arrived on earth by way of stardust.
link |
Yes, we are talking about stardust on this podcast.
link |
But if you'd like to learn more
link |
about the origins of lithium
link |
and how lithium arrived here on earth
link |
for its discovery and applications in psychiatry,
link |
there's a beautiful talk that exists on YouTube.
link |
And we'll provide a link to this in the show note captions
link |
that describes the history of lithium
link |
in terms of its interplanetary travels
link |
and arrival on earth.
link |
This is a talk delivered by a physicist
link |
who's expert in quantum mechanics
link |
and is expert in lithium.
link |
And it's a just wonderful talk that I can refer you to.
link |
Less on the biology in that talk,
link |
but certainly a lot about lithium as an element.
link |
So for those of you nerds like me
link |
that love to know how things came to be here on the planet
link |
in one form or another,
link |
I'll encourage you to take a brief listen to that talk.
link |
We are going to discuss lithium
link |
in the context of its applications
link |
for treatment of bipolar disorder.
link |
And the discovery of lithium
link |
as a treatment for bipolar disorder
link |
is truly a miraculous story
link |
that I think everyone should know.
link |
The key player in this story is a physician
link |
by the last name Cade.
link |
He was an Australian physician.
link |
And Cade has a very interesting story in his own right.
link |
Cade was an Australian psychiatrist
link |
or Australian psychiatrist who also was a soldier.
link |
And during World War II,
link |
after the fall of Singapore to Japan,
link |
he became a prisoner of war
link |
and he was a prisoner of war from 1942 until 1945.
link |
So he had some time for observation.
link |
And during his imprisonment,
link |
he observed some of his fellow inmates
link |
as going through pretty wild vacillations
link |
in mood and energy,
link |
essentially going from manic episodes to depressed episodes
link |
or from manic to normal episodes.
link |
And for one reason or another,
link |
we don't know why,
link |
because I couldn't find any report
link |
as to why he hypothesized this,
link |
but he hypothesized that there was some buildup
link |
of some chemical in these people's brains
link |
that then they would urinate out
link |
and that urinating out of whatever chemical was in there
link |
would allow them to be more relaxed and not manic.
link |
Cade hypothesized that there's a buildup of a chemical
link |
in certain people's brains that makes them manic
link |
and they urinate that chemical out.
link |
So eventually he got out of this prison,
link |
as we mentioned, in 1945,
link |
and he started doing experiments
link |
in addition to seeing patients in his clinic.
link |
And what he did is he started to take urine
link |
from people who exhibited mania
link |
and urine from people who were not manic.
link |
And he took that urine
link |
and he would inject it into guinea pigs
link |
as an experimental model.
link |
And his general observation
link |
was that there was something in the urine
link |
that was indeed making the guinea pigs more manic
link |
if they were injected with urine from a manic patient.
link |
The exact measures that he was taking in these guinea pigs
link |
wasn't exactly clear.
link |
This is at a time or an era in science
link |
when you could just sort of report things
link |
a little bit more subjectively.
link |
Although there were still numbers and statistics,
link |
it was a little bit more of like case studies
link |
but it turns out that even though
link |
that all seems a little bit loose,
link |
it led to some incredible and still important discoveries
link |
for psychiatric health.
link |
So what he figured out
link |
was that the urine from manic patients
link |
seemed to be more toxic for these guinea pigs.
link |
And he also knew that there are two toxic substances
link |
in urine, urea and uric acid.
link |
So he was able to separate the urea and uric acid
link |
from people with mania and patients that did not have mania.
link |
And he figured out that the urea was the same
link |
in both these mentally ill manic patients
link |
and the non-manic patients.
link |
So it did not seem that urea was the compound
link |
that was creating these manic episodes
link |
or related to manic episodes or held the toxicity.
link |
So instead he focused on the uric acid.
link |
Now, in order to put the uric acid into solution
link |
so that he could inject it into these guinea pigs,
link |
he had to try a number of different compounds
link |
in order to dilute it.
link |
It just so happens that,
link |
and you chemists will be familiar with this,
link |
but there's certain things
link |
that just don't go into solution easily.
link |
You put the powder in a vial,
link |
you add some water or a saline or another solution,
link |
you mix it up and the powder stays suspended in there.
link |
It just doesn't actually ever become a clear liquid
link |
that you can inject.
link |
So in order to try injecting different strengths
link |
of uric acid, he ended up using lithium
link |
to assist in the dilution and lithium worked.
link |
So what he basically was doing, again for you chemists,
link |
is he was taking uric acid, he was adding lithium
link |
and making a solution of lithium urate, okay?
link |
This is a lot of details, but this is important
link |
because what he eventually found
link |
is that when he diluted the uric acid with lithium
link |
and created lithium urate,
link |
lithium urate could actually calm down these guinea pigs
link |
that were injected with the toxic urea.
link |
He also found that lithium urate
link |
had a generally calming effect on these guinea pigs.
link |
So now we're really off in crazy territory, right?
link |
We're talking about urine from patients
link |
that's separating out urea and uric acid.
link |
We're adding lithium to the uric acid.
link |
We're injecting this into guinea pigs.
link |
This is getting pretty wild and pretty weird,
link |
but this is medicine and from time to time,
link |
this is medicine and science.
link |
Cade was a good scientist
link |
in addition to being a good physician.
link |
And by good scientists,
link |
I mean that he did control experiments.
link |
Here he was injecting lithium urate
link |
into animals and seeing an effect,
link |
but he knew that that solution of lithium urate
link |
contained not just the uric acid,
link |
but it also contained lithium.
link |
And so he quite appropriately asked,
link |
maybe the lithium alone is having this calming effect
link |
on these guinea pigs.
link |
And indeed that was the case.
link |
When he did the proper control experiment
link |
and injected only lithium solution into these guinea pigs,
link |
From there, he in sort of 1940s style medicine,
link |
this would not happen now,
link |
he very quickly moved from that animal model
link |
into human patients and started injecting human patients
link |
with lithium or providing lithium orally to those patients.
link |
And lo and behold, found an absolutely profound
link |
and positive effect of lithium
link |
in reducing symptoms of mania.
link |
And as all good physician scientists do,
link |
he wrote up his results.
link |
And he wrote it up in a paper entitled
link |
Lithium Salts in the Treatment of Psychotic Excitement.
link |
Okay, back then they didn't call it mania,
link |
they called it psychotic excitement.
link |
This is a paper that was published September 3rd, 1949
link |
in the Medical Journal of Australia.
link |
We will provide a link to this study
link |
is now a classic study in the field of psychiatry.
link |
It's a really wonderful paper to read.
link |
And actually I encourage people,
link |
even if you're not a scientist or a clinician
link |
to just take a quick look at the second page in this paper
link |
that we've made available to you,
link |
where he describes each of the various case studies
link |
or the individuals that he looked at.
link |
I'm not going to read these in detail now
link |
because it would take a lot of unnecessary time,
link |
but things like case seven, MC, aged 40 years old,
link |
suffering from manic recurrent mania.
link |
In this episode, he'd been excited,
link |
restless and violent for over two months
link |
and was interfering so often
link |
that he had to be confined to a single room during the day.
link |
So this is very debilitating,
link |
what we now know to be bipolar depression.
link |
He commenced taking lithium citrate 20 grains,
link |
that's a measure of the amount of lithium,
link |
three times a day.
link |
In four days, he was distinctly quieter.
link |
And by February 13th, 1949 appeared practically normal.
link |
He continued well and on February 20th, 1949,
link |
the dose of citrate was reduced to 10 grains,
link |
et cetera, et cetera.
link |
He left the hospital.
link |
There are numerous descriptions of this sort
link |
within this paper, including some descriptions of patients
link |
that did not see such success
link |
and including some descriptions of patients
link |
that suffered from some negative side effects.
link |
So that's important to point out as well,
link |
but it's an absolutely wonderful paper
link |
and it's an absolutely wonderful voyage
link |
into the history of psychiatry,
link |
right down to the discussion
link |
where in just three short paragraphs,
link |
Cade really lays out the case for why lithium
link |
is such an important discovery in the treatment
link |
of what at that time they were calling psychotic excitement
link |
and what we now know to be manic bipolar depression.
link |
Lithium, I should mention,
link |
has a number of important features,
link |
but also a number of important side effects
link |
that need to be considered.
link |
First of all, it does have a certain toxicity
link |
and so levels of lithium in the blood
link |
need to be monitored extremely carefully.
link |
So it's not the sort of thing
link |
that people can just take at a given dose
link |
and every patient responds the same.
link |
There's a lot of oversight
link |
and a lot of blood tests that have to be done,
link |
especially in the first three months of lithium treatment.
link |
I should mention that lithium treatment is still used
link |
to some great degree of success in many,
link |
not all people suffering from bipolar depression
link |
or bipolar disorder rather,
link |
but there are a number of important things that happen
link |
between 1949 and present day that prevented lithium
link |
from reaching patients that really needed it.
link |
And that all can be summarized
link |
in two or three short sentences,
link |
basically by virtue of the fact
link |
that lithium is a naturally occurring element,
link |
it could not be patented.
link |
And as a consequence of that,
link |
there wasn't a lot of potential profit for drug companies
link |
to produce lithium, in fact, still to this day,
link |
it's very low cost.
link |
And still to this day,
link |
no one really owns the patent for lithium
link |
in its purest form.
link |
So that made it unattractive.
link |
It turns out that the FDA in the United States
link |
didn't allow lithium to be used as a treatment
link |
for manic bipolar disorder until 1970.
link |
So we're talking about a full 21 years
link |
from the publication of this paper
link |
by Cade in the Medical Journal of Australia
link |
showing quite beautifully the great potential
link |
and use of lithium for quelling the symptoms
link |
of bipolar disorder until the first patients
link |
in the United States were starting
link |
to access lithium regularly.
link |
And nowadays, of course, lithium is available,
link |
but still not able to be patented
link |
because it's element number three on the periodic table,
link |
it's naturally occurring.
link |
It's not literally falling down from the stars
link |
as stardust and going into pill form,
link |
but rather it can be synthesized in laboratories,
link |
but it is available.
link |
It does show not only great potential in many patients,
link |
but great application in many patients
link |
despite its side effects.
link |
So lithium really stands as this kind of golden example
link |
of a treatment that works, at least in many individuals,
link |
prior to an understanding of the biological basis
link |
of the disease for which that treatment is needed.
link |
Now, with that said, scientists and clinicians
link |
have been quite rigorous in trying to understand
link |
why and how lithium works in order to understand
link |
the why and how of bipolar disorder.
link |
This is the way that proper medicine and science is done.
link |
Even if there's an excellent treatment for something,
link |
it's important to understand why that treatment works
link |
because first of all, not everyone responds
link |
to that treatment.
link |
Second of all, scientists and physicians understand
link |
that just because we have one treatment that works,
link |
if it has any side effects at all,
link |
there is the possibility for better treatments.
link |
So it's not just about trying to bypass a drug
link |
that doesn't make much money for drug companies.
link |
I know a lot of people think in those terms,
link |
they think, oh, well, you know,
link |
there's this continued search for better treatments
link |
for bipolar disorder, even though lithium works
link |
because lithium doesn't allow drug companies
link |
to make much money.
link |
That's not really the case.
link |
The fact of the matter is, is that the toxicity,
link |
some of the other issues that are created with lithium,
link |
the fact that people need the ongoing blood testing,
link |
et cetera, really stimulates the need,
link |
really an urgent need for new and better treatments
link |
for bipolar disorder.
link |
And only by understanding how lithium works
link |
at the cellular level, at the neural circuit level,
link |
et cetera, do we really stand to find those new discoveries.
link |
If you were to do a literature search
link |
on the actions and mechanisms of lithium
link |
in terms of how it can calm people down
link |
and reduce their manic episodes,
link |
you would find an enormous array of papers,
link |
literally thousands of scientific studies
link |
in animals and in humans, which, for instance,
link |
will tell you that lithium treatment
link |
will increase so-called BDNF,
link |
brain-derived neutrophic factor.
link |
BDNF is often talked about
link |
in the context of neuroplasticity,
link |
the brain and nervous system's ability to change
link |
in response to experience.
link |
And indeed, it does seem that ingesting lithium
link |
BDNF is what we call permissive for neuroplasticity.
link |
It doesn't create specific changes in the brain,
link |
meaning it's not going to make your memory better
link |
or your coordination better
link |
or your emotional state better per se.
link |
What BDNF does is it permits the neurons, the nerve cells,
link |
and their connections in the brain
link |
to be more likely to change
link |
if the proper environmental conditions are met.
link |
That is, BDNF creates a kind of buoyancy
link |
to neuroplasticity.
link |
It opens the gates to neuroplasticity.
link |
So lithium does increase BDNF.
link |
We'll talk about why that's important
link |
in the context of the neural circuits involved
link |
with bipolar disorder in a few minutes.
link |
It also seems to be a potent anti-inflammatory.
link |
Now, inflammation is one of those words
link |
that's thrown around extensively nowadays,
link |
especially on social media
link |
and especially as it relates to any health condition.
link |
It's like inflammation, inflammation, inflammation
link |
always seems to be discussed
link |
in the context of inflammation being bad.
link |
But I do want to point out
link |
that inflammation is a natural adaptive response
link |
to physical injury to a cell or organ or tissue of any kind.
link |
Inflammation is the basis
link |
by which adaptations occur to exercise.
link |
So for instance, you were to weight train
link |
and use a heavier than normal weight
link |
and do a set to failure
link |
or create some little micro tears in the muscle
link |
that are healthy in the sense
link |
that they would create adaptations
link |
and make that muscle stronger, maybe even grow that muscle.
link |
There's an inflammatory response associated with that
link |
that is critical to the positive adaptation.
link |
So inflammation isn't always bad,
link |
although excessive or as we say, runaway inflammation is bad.
link |
Lithium seems to be able to suppress inflammation
link |
and importantly, it can suppress inflammation
link |
in neural tissues and within the brain in particular.
link |
That is important and we will return to that
link |
and why it's important in a little bit.
link |
The other thing about lithium
link |
is that lithium is neuroprotective.
link |
That is, it can prevent neurons from dying
link |
under certain conditions.
link |
Why would neurons die?
link |
Well, there are a lot of reasons why neurons can die.
link |
There can be a physical insult to the neurons.
link |
You can get hit really hard in the head.
link |
A bullet, God forbid, can enter the skull and kill neurons.
link |
There are a lot of reasons why neurons can die.
link |
Neuroprotection is a situation
link |
in which a neuron is given some sort of chemical
link |
or physical resiliency
link |
that allows it to suffer an insult and yet bounce back.
link |
So it's very similar to the way
link |
that we think about psychological resiliency.
link |
Neuroprotection is an ability for neurons
link |
to be better able to handle stress of different kinds.
link |
In particular, excitotoxicity.
link |
There's a phenomenon in bipolar disorder
link |
and a lot of other psychiatric conditions
link |
in which hyperactivity of certain brain areas
link |
actually starts to kill off neurons.
link |
Hyperactivity doesn't always do this,
link |
but it turns out that if certain brain circuits
link |
are too active for too long,
link |
some of the chemicals associated with neuronal activity,
link |
things like calcium and neurotransmitters like glutamate,
link |
can actually kill the very neurons that are active.
link |
So it seems that lithium can prevent
link |
some of that neurotoxicity.
link |
Now, this turns out to be particularly important
link |
for this discussion about bipolar disorder
link |
and the neural circuit basis of bipolar disorder,
link |
because if we were to just take a step back and ask,
link |
what's different in the brains
link |
of people with bipolar disorder?
link |
There are some very interesting answers that start to emerge.
link |
There are basically two main neural circuits
link |
that are present in normal individuals.
link |
I say normal, I say that respectfully
link |
to the people with bipolar disorder
link |
by referring to people who do not suffer
link |
from manic episodes or from manic depression.
link |
There are circuits that are present
link |
in people with bipolar disorder
link |
and in people that do not suffer from bipolar disorder.
link |
Both of those circuits do the same thing
link |
in both sets of individuals.
link |
And yet in people with bipolar disorder,
link |
there seems to be an atrophy
link |
or a removal of certain neural connections over time
link |
that leads to a situation
link |
in which people with bipolar disorder become very poor
link |
at registering their own internal state,
link |
in particular, their emotional states
link |
and their somatic states.
link |
What we're referring to here
link |
is something called interoception.
link |
I've talked about this a little bit
link |
on the Huberman Lab podcast before,
link |
but there are two modes of perception.
link |
Perception, of course, is a attention
link |
to something that's happening in our environment
link |
or to us on or within our body.
link |
Exteroception is literally an attention
link |
to things that are happening beyond the confines
link |
So seeing that person's face over there
link |
or seeing that color of leaf over there
link |
or hearing a sound over to my left.
link |
That is exteroception,
link |
perception of things beyond the confines of one's skin.
link |
Then there's interoception,
link |
which is perception of things that are happening internally,
link |
like how full does my gut feel?
link |
How fast is my heart beating?
link |
Some people can measure that quite accurately
link |
just by thinking about it.
link |
Other people can't.
link |
How energetic am I?
link |
How lethargic am I?
link |
Et cetera, et cetera.
link |
So we are always existing in a balance
link |
between exteroception and interoception.
link |
But as it turns out,
link |
people with bipolar disorder over time,
link |
and especially into the second and third decade
link |
of having bipolar disorder,
link |
seem to have progressively diminished levels
link |
And that very likely is important
link |
in their inability to register, for instance,
link |
that, wow, they are talking at an excessive rate
link |
or they haven't slept in five or even 10 days,
link |
or they haven't eaten in a long period of time.
link |
This atrophy of neural circuits for interoception
link |
is starting to emerge
link |
as one of the defining neural circuit characteristics
link |
or underpinnings of bipolar.
link |
Now, I bridged to this conversation about neural circuits
link |
from the statement that lithium can protect
link |
against some of the neurotoxic effects
link |
of neural circuits being very active.
link |
Now, this can get a little bit complicated,
link |
but I promise I'm going to make it clear
link |
for any of you that are watching and or listening.
link |
The reality is that people with bipolar depression
link |
very likely have a hyperactivity,
link |
that is an increased level of activity
link |
in certain circuits within the brain
link |
early in the expression of their disease.
link |
And that typically, as I mentioned earlier,
link |
sets in around the early 20s,
link |
although sometimes that can be even earlier
link |
in the teens and so forth.
link |
But that hyperactivity, we think, leads to a toxicity,
link |
an excitotoxicity of certain elements of the neural circuits
link |
that are responsible for interoception.
link |
In other words, the overuse of certain circuits
link |
can lead to a diminishing, an atrophy,
link |
or even a death of certain elements within those circuits.
link |
And it appears that lithium,
link |
through its anti-inflammatory and neuroprotective effects,
link |
and through its ability to increase BDNF,
link |
very likely protects us against some of that atrophy
link |
of those circuits for interoception.
link |
So this isn't a case in which, you know,
link |
people with bipolar have a neural circuit
link |
or lack a neural circuit,
link |
and people without bipolar are the opposite.
link |
This is a case in which everyone
link |
more or less starts out the same,
link |
but it seems that there's a hyperactivity
link |
of certain neural circuits in people with bipolar disorder
link |
that over time actually causes those circuits to diminish.
link |
Now, this is very important
link |
because some of the more recent longitudinal studies
link |
doing brain imaging on people with bipolar disorder
link |
and those without, and doing that over time
link |
in patients starting as early as their teens,
link |
but into their 20s and 30s,
link |
reveals just that,
link |
that there can be hyperactivity of circuits early on,
link |
but then hypo, reduced activity of those very same circuits
link |
at a time five or 10 years later.
link |
Again, this speaks to the complicated nature
link |
of bipolar disorder and the complicated nature of psychiatry
link |
and linking specific psychiatric disorders
link |
to neural circuits in general.
link |
Because if you have a situation in which, you know,
link |
in one disease, let's just hypothesize here for a second
link |
that for instance, in certain forms of schizophrenia,
link |
there's elevated dopamine,
link |
and were we to just reduce the amount of dopamine
link |
that they would receive relief
link |
from those schizophrenic symptoms?
link |
Well, that's all pretty straightforward on the face of it.
link |
But in this situation with bipolar disorder,
link |
what we're talking about is hyperactivity, too much activity,
link |
leading to hypoactivity through death
link |
of those very circuits.
link |
And so now you can especially appreciate why
link |
when the patient shows up to the psychiatrist
link |
or when the psychiatrist shows up to the patient
link |
in the total course of their disease
link |
is going to be very important.
link |
And then layer on top of that the complexity of the fact
link |
that the very defining characteristic of bipolar disorder
link |
is that there are oscillations in mood.
link |
So now we need to think about treatments
link |
not just for the manic episodes,
link |
but also treatments for the depressive episodes.
link |
And that's in fact what psychiatrists do.
link |
Turns out that they apply different treatments
link |
or combinations of treatments
link |
for patients that are in manic episodes
link |
versus depressive episodes.
link |
And they have to infer all that from discussions.
link |
Again, just exchange of words,
link |
depending on when that person walked into their office,
link |
where they are in terms of manic episodes,
link |
no symptomology or depressive symptomology,
link |
and whether or not they've had that symptomology
link |
for an extended period of time.
link |
And then just to make the situation even more complicated,
link |
the very circuits that atrophy
link |
that start to wane and disappear
link |
in people with bipolar disorder
link |
are the circuits for interoception,
link |
for understanding of what's going on in one's own body.
link |
So you can imagine if you sit down and ask somebody,
link |
well, how long has it been since you slept?
link |
That person may genuinely not know.
link |
Or if you ask the very depressed person,
link |
how depressed are you?
link |
That person may not be able to articulate that.
link |
So fortunately, there are solutions to this.
link |
And the solution is that more often than not,
link |
the accurate understanding of whether or not
link |
someone has bipolar depression or not,
link |
and what stage of the illness they might be in or not
link |
is going to depend on the reports of people around them
link |
and not the patient themselves.
link |
Hence, the importance of having a rather detailed
link |
and admittedly a rather intense discussion
link |
about the symptomology of bipolar disorder
link |
so that you can have an understanding
link |
of the people around you and have an eye and an ear
link |
to whether or not those people
link |
might be suffering from bipolar,
link |
and if so, at what stage of the disease
link |
they might happen to be at.
link |
Now I'd like to talk a little bit more
link |
about what is known about the neural circuits
link |
that lead to the manic states,
link |
as well as the depressive states,
link |
but mainly the manic states of bipolar disorder.
link |
We already discussed the fact that interoception,
link |
registering of one's own internal emotions
link |
and bodily states is diminished
link |
in people with bipolar disorder,
link |
but we haven't really talked about the neural circuits
link |
that are responsible for that lack of recognition.
link |
For that reason, I'd like to point out a paper.
link |
This is a fairly recent paper, just came out this year,
link |
but it's an excellent one
link |
looking at the changes over time in neural circuitry
link |
in people with high genetic risk for bipolar disorder,
link |
and in particular, in young people.
link |
And studies of this sort are rare,
link |
but are exceedingly important because of the fact
link |
that they track individuals over time.
link |
The title of this paper is
link |
Longitudinal Changes in Structural Connectivity
link |
in Young People at High Genetic Risk for Bipolar Disorder.
link |
We will provide a link to this study
link |
in the show note captions.
link |
There are a lot of data in this paper,
link |
in particular, neuroimaging data,
link |
and it's quite extensive in terms of analyzing
link |
the so-called connectomics.
link |
You've probably heard of genomics,
link |
which is the analysis of genes and their display
link |
in different individuals or different animals, et cetera.
link |
You have proteomics, which is the display of
link |
or the existence of different proteins.
link |
So omics is a big thing now in science.
link |
You kind of throw omics behind anything
link |
and it becomes its own Wikipedia page,
link |
which means it becomes its own thing.
link |
So to speak, I say that only partially in jest.
link |
Nonetheless, connectomics is the analysis of connections
link |
between different neurons and neural circuit elements.
link |
And what this paper really showed
link |
by analyzing the connectomics of neural circuits
link |
in the brains of many different people
link |
with different categories of and onset of
link |
and severity of bipolar disorder,
link |
as well as controls in different age groups, et cetera,
link |
is that people who are a particularly high risk
link |
for having bipolar disorder
link |
or that have full-blown bipolar disorder
link |
have deficits and actually reductions
link |
in the amount of connectivity
link |
between what are called the parietal brain regions
link |
and the limbic system.
link |
Now, the limbic system I've talked about before
link |
in this podcast, if you're not familiar with it,
link |
I'll explain what it is in a moment.
link |
It's simply a collection of brain structures,
link |
not one brain structure,
link |
but a collection of brain structures
link |
that generally are responsible
link |
for shifting the overall state that we're in
link |
from states of more relaxed and calm
link |
to states of more alert and focused.
link |
The limbic system is intimately related
link |
to the so-called autonomic nervous system,
link |
which regulates our sleep-wake cycles
link |
and a number of other things like our digestion, et cetera,
link |
our level of hunger and on and on.
link |
So the limbic system is really kind of like a volume control
link |
or as nerd scientists like to say,
link |
a kind of game control on the overall level
link |
or amplitude of alertness or calmness.
link |
In fact, if we're very, very calm,
link |
we are asleep or even more calm, we can be in a coma.
link |
If we are very alert, we can be wide awake
link |
and ready to work and run, et cetera.
link |
Or if we are very, very, very alert
link |
by way of limbic autonomic interactions,
link |
well, then we can be in anxiety,
link |
we can be in full-blown panic attack, or we can be in mania.
link |
We can have so much energy
link |
that we feel like we don't need to sleep.
link |
And in fact, disruptions in the circuitry
link |
really seems to be what's going on
link |
in people who have bipolar disorder.
link |
Now, if disruptions in the circuitry
link |
are present in the limbic system,
link |
that doesn't necessarily mean that the limbic system
link |
is at fault because the way that neural circuits work
link |
is that different brain areas are talking to one another
link |
through electrical chemical signaling
link |
and they are regulating one another.
link |
And what this paper really tells us
link |
is that there are elements within the parietal lobe,
link |
which is a kind of a section of the brain
link |
that sits off to the side.
link |
It's not really off to the side,
link |
but in neuroanatomical nomenclature,
link |
the parietal lobe is connected in two ways, bidirectionally.
link |
So parietal lobe is connecting to limbic system
link |
and limbic system is connecting to parietal lobe.
link |
And in people with bipolar disorder,
link |
it seems that the parietal lobe
link |
is able to exert less top-down control,
link |
that is less suppression
link |
of certain elements of the limbic system,
link |
which at least right now is leading researchers
link |
to hypothesize that the limbic system
link |
is sort of revving at higher levels.
link |
It's kind of like RPM in your cars
link |
or kind of redlining at times and for durations
link |
that are inappropriate or at least abnormal.
link |
So we have two major sets of neural circuit deficits
link |
or changes in people with bipolar.
link |
Their lack of internal awareness is reduced
link |
and that turns out to be by way of neural structures
link |
like the insula, which is a brain region
link |
that is connected in a very direct way
link |
to our somatosensory cortex,
link |
so the part of our cortex that registers how we feel,
link |
literally, sense of touch and internal state.
link |
So those circuits, excuse me,
link |
for those of you listening, I just bumped the microphone,
link |
excuse me, those circuits are disrupted
link |
in people with bipolar and the top-down control,
link |
the kind of accelerator and brake
link |
on our overall levels of energy are also disrupted.
link |
Now, that's all fine and good because, well, it's true,
link |
at least according to what the data
link |
at this point in time tell us,
link |
there may be new discoveries to come,
link |
but that all seems to be the case,
link |
but it doesn't tell us how to modulate
link |
or change that circuitry.
link |
It also doesn't tell us how something like lithium
link |
can actually benefit a large number of patients
link |
or how a good number of the other treatments
link |
for bipolar disorder, which we'll talk about going forward,
link |
can benefit patients with bipolar.
link |
So it appears that lithium is exerting its positive effects
link |
on bipolar depression treatment, at least in part,
link |
by preventing the loss of certain neural circuits,
link |
namely the neural circuits for interoception
link |
and the top-down control over the limbic system.
link |
Now, it turns out that by examining lithium's effects
link |
at an even more reductionist level,
link |
we can gain really important insight
link |
into what's going on in bipolar depression
link |
and some of the other treatments for bipolar depression,
link |
including behavioral treatments,
link |
things like transcranial magnetic stimulation,
link |
and even some of the more natural
link |
or so-called nutraceutical treatments,
link |
including things like high-dose omega-3 supplementation,
link |
which we're going to talk about extensively.
link |
Now, in order to understand
link |
what we're going to talk about next,
link |
it's important that everybody understand
link |
a key concept of neuroplasticity.
link |
And this is a key concept,
link |
regardless of whether or not
link |
one is talking about bipolar depression.
link |
In fact, it's something I think everybody,
link |
every citizen of Earth should know about,
link |
and that's called homeostatic plasticity.
link |
Homeostatic plasticity is a particular form
link |
of neuroplasticity in which if a neural circuit
link |
is overactive for a period of time,
link |
there are changes that occur at the cellular level
link |
that lead to a balance or a homeostatic regulation
link |
of that circuit so that it's no longer overactive.
link |
Conversely, if a neural circuit is underactive
link |
for a period of time,
link |
certain changes happen within the cells of that circuit
link |
to ramp up their activity
link |
or make them more likely to be active.
link |
And whether or not a neural circuit
link |
and the neurons within it become more active
link |
or less active in the context of homeostatic plasticity
link |
largely depends on one mechanism,
link |
and it's a beautiful mechanism
link |
that I'll make very clear to you right now
link |
even if you don't have a background in biology.
link |
Neurons communicate with one another
link |
by releasing so-called neurotransmitters,
link |
which are just chemicals.
link |
Those neurotransmitters are vomited out.
link |
They're not actually vomited,
link |
but they're spit out into the so-called synaptic cleft,
link |
often called the synapse.
link |
The synapse is just a little gap between neurons.
link |
And when they are released into the synapse,
link |
they don't just stay there.
link |
They actually park or bind to receptors
link |
on what's called the postsynaptic neuron.
link |
And depending on how many receptors they bind to
link |
and how many receptors are available, et cetera,
link |
they can have a greater or lesser effect
link |
on the postsynaptic neuron.
link |
This scenario of neurotransmitters
link |
being released into synapses,
link |
then binding to receptors on postsynaptic neurons
link |
and influencing the electrical excitability
link |
of those postsynaptic neurons,
link |
sits central to not just the treatment of bipolar disorder,
link |
but to all treatments of all psychiatric conditions
link |
and indeed to things like neuropathic pain as well.
link |
For example, the so-called SSRIs,
link |
Prozac, Zoloft, and others, et cetera,
link |
stands for selective serotonin reuptake inhibitor.
link |
What does that mean?
link |
Well, serotonin is a neurotransmitter.
link |
It's actually a neuromodulator
link |
that's released into the synapse.
link |
And then the SSRI,
link |
the selective serotonin reuptake inhibitor,
link |
allows more of that serotonin
link |
to sit within the synapse for longer, right?
link |
It's a reuptake inhibitor.
link |
It prevents reuptake by the presynaptic neuron.
link |
And that serotonin therefore can park in
link |
or dock in the receptors, as it's called,
link |
of the postsynaptic neuron in greater numbers
link |
and have a greater impact on that postsynaptic neuron.
link |
So the drugs that are used to treat depression
link |
or other things of that sort, things like SSRIs,
link |
work by changing the availability
link |
of neurotransmitter in the synapse.
link |
Other things like MAO inhibitors,
link |
monoamine oxidase inhibitors, work a different way.
link |
They inhibit the enzyme.
link |
Anytime you hear ASE in biology,
link |
it's very likely an enzyme which breaks things down.
link |
So MAO inhibitors prevent the breakdown,
link |
not the reuptake, but the breakdown of neurotransmitter,
link |
and therefore allow more neurotransmitter
link |
to be available in the synapse
link |
and influence the postsynaptic cell.
link |
Homeostatic plasticity is a form of neuroplasticity
link |
in which overall circuits can become much more excitable
link |
or much less excitable
link |
by the addition of more receptors in the postsynaptic neuron
link |
or by the removal of more receptors
link |
from the postsynaptic neuron.
link |
And the way this happens is just beautiful.
link |
It was first discovered in the visual system,
link |
and the person primarily responsible
link |
for the discovery of homeostatic plasticity,
link |
although there are several,
link |
is a woman by the name of Gina Turgiano.
link |
She's a professor at Brandeis University.
link |
And what the Turgiano laboratory showed was that,
link |
for instance, if we are in the dark
link |
for a long period of time,
link |
literally, we're not seeing much for a long period of time,
link |
there's an increase in the number of receptors
link |
in the postsynaptic neurons
link |
so that a smaller amount of light
link |
and excitability within the visual system
link |
can lead to greater amounts of activity
link |
in the visual system.
link |
Conversely, if there's an overactivity
link |
or an increase in the activity in the visual system
link |
for some period of time,
link |
then a number of receptors in the postsynaptic neuron
link |
are removed from that postsynaptic neuron surface,
link |
making any neurotransmitter that's available
link |
only able to bind the receptors that are left
link |
and have less of an influence on those cells.
link |
In other words, keeping a circuit
link |
in so-called homeostatic balance
link |
in a particular range of excitability.
link |
Now, while that's a mouthful and an earful
link |
and a conceptful, I don't know if a conceptful is a word,
link |
but in any case, that's a lot to think about,
link |
but all you need to know is that if a neural circuit
link |
is very active for a period of time,
link |
in normal individuals,
link |
there will be a reduction in the amount of activity
link |
by way of removing receptors that bind neurotransmitter.
link |
Whereas if a neural circuit is very quiet,
link |
it's not activated for a period of time,
link |
maybe your leg is in a cast, for instance,
link |
and you're not activating your quadricep and calves
link |
very much well, when that cast comes off,
link |
sure, the muscle might be atrophied,
link |
but the nerves that connect to that muscle
link |
are actually in a position to influence that muscle
link |
even more once you start using that muscle or those muscles,
link |
because whatever neurotransmitter is released
link |
now has the opportunity to bind to more receptors,
link |
in that case, in muscle,
link |
or in the case of brain circuits in postsynaptic neurons.
link |
So homeostatic plasticity is this beautiful
link |
balancing mechanism that makes sure that neural circuits
link |
are never too active nor too quiet for too long.
link |
And in a beautiful display of how treatments
link |
can lead to a better understanding of biology,
link |
which can lead to the discovery of even better treatments,
link |
lithium and another compound,
link |
which we'll talk about ketamine,
link |
seem to exert their actions largely through effects
link |
on homeostatic neuroplasticity.
link |
There's a wonderful paper that describes
link |
all the nitty gritty of this.
link |
Certainly most people listening, I'm guessing,
link |
are not going to be interested in all this detail,
link |
but for those of you that you are,
link |
and you want to delve deep into this,
link |
this paper was published in Neuron, Cell Press Journal,
link |
excellent journal.
link |
It's titled Targeting Homeostatic Plasticity
link |
for the Treatment of Mood Disorders.
link |
And there's one particular figure in this paper
link |
that I'll just describe to you
link |
in which measurements were made from neurons
link |
and the number of receptors in those neurons.
link |
It's done somewhat indirectly through a method
link |
that's detailed and neuroscientists are familiar with.
link |
Basically what it measures is how excited a given neuron is,
link |
electrically excited a given neuron is
link |
to a given amount of neurotransmitter, okay?
link |
So the amount of neurotransmitter
link |
that's vomited onto a neuron
link |
is essentially kept constant,
link |
and then the response of the postsynaptic neuron
link |
So it can be of one level or higher or lower
link |
depending on homeostatic plasticity.
link |
And what this paper shows,
link |
and what's been shown over and over again,
link |
is that when neurons are exposed to lithium
link |
for a period of time,
link |
there is a reduction in the excitability
link |
of the postsynaptic neuron.
link |
That is, neurons within the brain become less excitable
link |
over time if lithium is present,
link |
whereas ketamine, which is now a common FDA approved,
link |
at least in the US,
link |
it's approved for the treatment of major depression,
link |
ketamine does the opposite.
link |
Ketamine seems to increase the number of receptors
link |
in the postsynaptic neuron
link |
and lead to greater levels of excitability
link |
and electrical activity within neural circuits
link |
to a given fixed amount of neurotransmitter.
link |
So this is super interesting
link |
because what it means is that lithium
link |
is causing circuits to be less active.
link |
Ketamine is causing circuits to be more active.
link |
And we know from excellent clinical data now
link |
that ketamine seems to be a very effective treatment
link |
for major depression
link |
and for the major depressive episodes
link |
of people that suffer from bipolar depression
link |
that includes these major depressive episodes
link |
of two weeks or longer of suppressed mood,
link |
appetite, sleep issues, et cetera.
link |
Now, the key thing about ketamine
link |
that's often not discussed
link |
is that while its effects are very potent,
link |
they are transient.
link |
So one major drawback to ketamine therapy for depression
link |
is that it has to be done repeatedly.
link |
And how repeatedly or how often rather depends, of course,
link |
on a discussion between the psychiatrist and the patient.
link |
This is not something to cowboy on your own.
link |
I know that, and many of you are probably familiar
link |
with the fact that ketamine also is abused recreationally.
link |
It is a so-called NMDA,
link |
N-methyl-D-aspartate receptor antagonist.
link |
So it blocks the very receptor
link |
that's responsible for neuroplasticity
link |
for changes in neural circuits.
link |
It also changes excitability in neurons,
link |
as I just described.
link |
So ketamine is a very potent chemical
link |
that has been shown over and over again
link |
and is now FDA approved for the treatment
link |
of major depression,
link |
but its effects seem to be transient.
link |
Lithium, as I described earlier,
link |
seems to reduce the manic episodes
link |
or the intensity of manic episodes and symptomology
link |
in people with bipolar disorder.
link |
It's doing that through neural protection.
link |
So protecting neural circuits from dying away
link |
that initially are overactive
link |
and that overactivity causing excitotoxicity.
link |
It blocks that excitotoxicity, we believe.
link |
And it seems to do that in part
link |
by diminishing the amount of activity in those circuits.
link |
So this is a beautiful mechanistic story,
link |
and it's the sort of story that you'd love to have
link |
for a great number of psychiatric illnesses.
link |
And fortunately, we have for bipolar disorder.
link |
Overactivity of a given circuit
link |
eventually leads to neurotoxicity, excuse me.
link |
Lithium is preventing that neurotoxicity
link |
by reducing the number of receptors
link |
in certain elements within those circuits,
link |
so-called homeostatic scaling.
link |
It's down-regulating the number of receptors,
link |
leading to less excitability
link |
and preventing, we think, excitotoxicity.
link |
And in that sense,
link |
you can see exactly why it's important
link |
to get lithium treatment in there early
link |
for people with bipolar disorder.
link |
Ketamine as a treatment for major depression
link |
seems to be effective but transient.
link |
And you can also see why it would be important
link |
not just to reduce the manic episodes
link |
for people with bipolar disorder
link |
but to also treat the depressive episodes.
link |
So this is a key feature of the treatment
link |
for bipolar depression and for bipolar disorder.
link |
There needs to be treatment both of the mania
link |
and of the depressive episodes if they're present.
link |
And fortunately, there are excellent drugs to do that.
link |
And I should mention that ketamine and lithium
link |
are just two of the drugs within the kit
link |
that psychiatrists have access to.
link |
There are many things, olanzapines
link |
and a number of different things, including clozapine.
link |
Clozapine is an antipsychotic,
link |
which is commonly prescribed as a sedative in some cases
link |
that allows people in manic episodes to sleep.
link |
It's classically described
link |
as so-called dopamine receptor four antagonist,
link |
although it does other things as well.
link |
Clozapine has a number of side effect features
link |
related to white blood cell and things of that sort
link |
that require careful monitoring.
link |
So there are an enormous number now,
link |
literally dozens and dozens of different drugs,
link |
each designed to target either the manic phase,
link |
the depressive phase, or some what we call acute,
link |
sort of early phases versus ongoing treatments.
link |
This is a vast galaxy of drug treatments
link |
that really should be navigated,
link |
I should say absolutely should be navigated
link |
by a board certified psychiatrist.
link |
And of course, in close discussion
link |
with both the person suffering from bipolar disorder,
link |
but also ideally the family members
link |
of the person suffering from bipolar disorder.
link |
But I think at least up until now,
link |
we've focused on the two major pathways for treatment,
link |
lithium and ketamine.
link |
And we talked about why lithium and ketamine work,
link |
that they're working on opposite ends
link |
of this homeostatic scaling.
link |
We talked a bit about the circuits that are involved
link |
in generating what we think are the manic symptomology
link |
and the lack of interoception,
link |
why people can just persist in staying awake,
link |
awake, awake, not eating, et cetera.
link |
Now you have in mind how all that is put together.
link |
And I think you have in mind
link |
some of the well-demonstrated treatments
link |
for the different component parts of bipolar disorder,
link |
which now I'm hoping you're also well versed in
link |
based on our early, early discussion
link |
of what constitutes bipolar one and bipolar two.
link |
Now I would like to also talk about
link |
some of the not so typical therapeutics
link |
for bipolar disorder,
link |
and also point to the things that have been tried and failed
link |
for successful treatment of bipolar disorder,
link |
because some of those things are often talked about
link |
and suggested, especially in online communities.
link |
And while it's not clear that any of them
link |
are particularly hazardous on their own,
link |
although some of them do carry some hazards,
link |
I do think it's important
link |
because of the critical time-sensitive nature
link |
of bipolar disorder and the urgency
link |
of getting treatments early
link |
to try and prevent some of the longer lasting
link |
neural circuit changes,
link |
that if people can avoid some of the less effective
link |
or demonstrated to be ineffective treatments,
link |
that they stand to combat bipolar disorder
link |
much more successfully.
link |
First of all, a key point about drug therapies
link |
versus non-drug therapies or talk therapies.
link |
drug therapies are going to be most effective
link |
when done also with talk therapies.
link |
And we'll talk about which talk therapies
link |
have been demonstrated to be most effective.
link |
There is some argument about what I'm about to say next,
link |
but in general, most psychiatrists will tell you,
link |
or certainly the ones I've spoken to have told me,
link |
that talk therapy on its own is rarely, if ever,
link |
effective for bipolar depression and bipolar disorder,
link |
whether or not it's BP1 or BP2.
link |
That's just the reality of it.
link |
Contrast that with our discussion
link |
about obsessive compulsive disorder,
link |
which we talked about a few episodes ago.
link |
If you haven't seen that episode,
link |
we have an in-depth episode all about OCD
link |
and obsessive compulsive personality disorder.
link |
There, it seems that drug therapies and talk therapies
link |
can be done independently or in combination.
link |
As expected, combined drug and talk therapies
link |
are more effective there than either one alone,
link |
but there are pretty impressive effects
link |
of talk therapy alone,
link |
provided that they are initiated at the right time
link |
and it's the right form of talk therapy.
link |
That's OCD, but in terms of bipolar disorder,
link |
it really seems that the drug therapies are necessary,
link |
at least in most all cases.
link |
That said, talk therapies are a terrific augment
link |
or support for those drug therapies
link |
and sometimes can allow people to take lower doses
link |
of those drug therapies,
link |
which turns out to be important
link |
because of the side effect profiles
link |
of a lot of drug therapies
link |
and sometimes the cost as well.
link |
I guess we can think of cost
link |
just as another side effect, really.
link |
There are both established and more novel forms
link |
of talk therapy being used, again,
link |
in concert with drug treatments for bipolar disorder.
link |
Cognitive behavioral therapy is the one
link |
that seems to be best,
link |
at least by way of the statistics and papers that exist.
link |
It's also the one that's been explored the most.
link |
So one of the reasons why it's often considered
link |
the most popular or effective
link |
is because it's also been around longer
link |
and it's been explored the most cognitive behavioral therapy
link |
in general is a progressive exposure of the patient
link |
in a very controlled way in a clinical setting
link |
to some of the triggers or the conditions
link |
that would exacerbate bipolar disorder.
link |
Now, earlier I said borderline personality disorder
link |
has all these triggers and triggered elements
link |
from the external environment,
link |
whereas bipolar disorder does not.
link |
And that's still true,
link |
but it is the case that somebody with bipolar
link |
can have worse symptoms
link |
if life conditions get worse or more stressful.
link |
So cognitive behavioral therapy in the discussion about,
link |
and sometimes the direct exposure
link |
to anxiety provoking elements of life
link |
can be very helpful for adjusting the responses
link |
to those otherwise triggering events
link |
and sometimes making the drug treatments more effective
link |
even at lower doses.
link |
There are also forms of therapy
link |
including family focused therapy,
link |
which is especially important in terms of bipolar disorder
link |
because family members,
link |
provided that they are not themselves in a manic episode
link |
due to the close heritability of bipolar disorder,
link |
but family members can often be excellent windows
link |
into whether or not somebody is doing well or poorly
link |
or is veering toward or is emerging
link |
from a manic or depressive episode
link |
because they understand that person.
link |
They have a lot of data.
link |
It could be purely subjective data,
link |
but they have a lot of exposure
link |
to how long or well somebody has been sleeping
link |
or eating, et cetera.
link |
So family focused therapy involves other members
link |
of the person suffering from bipolar disorders family,
link |
as well as conversations about family members
link |
in a way that helps patients with bipolar disorder navigate
link |
not just through manic episodes and depressive episodes,
link |
but start to learn to predict what are the conditions,
link |
psychological, physical, and otherwise,
link |
that can trigger bipolar episodes.
link |
And then there's a category of therapy
link |
called interpersonal and social rhythm therapy.
link |
This is deserving of its own entire episode, really.
link |
Interpersonal and social rhythm therapy
link |
is sort of an expansion on family focused therapy,
link |
although it's distinct in certain ways as well,
link |
and really focuses on how people are relating
link |
to others in their life and in the workplace
link |
and in the school environment
link |
and also within the family, et cetera.
link |
And I should say that a overall theme
link |
that's emerging in psychiatry and psychology
link |
is to start wherever possible
link |
to incorporate more of the social aspects
link |
and the interpersonal aspects.
link |
In other words, not just talking to and examining a patient
link |
as one biological system, one nervous system,
link |
one set of chemicals and one life,
link |
but rather a set of chemicals, neural circuits,
link |
and a life that's embedded in the chemicals
link |
and neural circuits and lives of other people.
link |
Just by way of example, you can imagine that
link |
if somebody is in a very healthy relationship
link |
or a very abusive relationship,
link |
that that's going to strongly impact
link |
the outcomes of manic episodes.
link |
You can imagine that if the financial situation
link |
is one in which people can recover from manic episodes,
link |
I did mention this earlier, but I should have, forgive me,
link |
that oftentimes people who are in a manic episode
link |
will go out and spend immense amounts of money
link |
that they simply cannot afford to lose.
link |
And then the depressive episodes that in many cases follow
link |
are made far worse by the financial anxiety
link |
and the financial stress that results
link |
from those manic episodes of spending, et cetera.
link |
And then of course, this carries over to sexual promiscuity
link |
where people might be dealing with unwanted pregnancy
link |
or STIs or very fractured interpersonal dynamics
link |
with existing or new relationships.
link |
I mean, you can imagine how these manic episodes
link |
as well as the depressive episodes can really wick out
link |
into an enormous amount of destruction,
link |
which brings us back to the initial criteria of BP1 and BP2
link |
is that these manic episodes are not a good thing.
link |
These depressive episodes are not a good thing.
link |
They create this sense of euphoria
link |
in the person experiencing mania,
link |
or they create the sense that anything is possible,
link |
but at the end of the day, and actually every day,
link |
these episodes are quite maladaptive.
link |
They really destroy people's lives
link |
and it's not just the life of the person
link |
that's suffering from bipolar disorder.
link |
And so hence, cognitive behavioral therapy,
link |
family-focused therapy,
link |
and interpersonal and social rhythm therapies
link |
are the primary three talk therapies
link |
that are most often combined with drug therapies
link |
in order to try and really reduce the harm.
link |
It's really all about harm reduction
link |
from manic episodes and depressive episodes.
link |
One very exciting and emerging treatment
link |
that does show great promise,
link |
and in some cases, great outcomes for bipolar disorder
link |
is, believe it or not, electric shock therapy.
link |
Electric shock therapy may sound barbaric,
link |
and in fact, it tends to look barbaric,
link |
although this is done in the controlled setting
link |
If any of you have seen One Flew Over the Cuckoo's Nest,
link |
the final scene or near final scene in that movie
link |
was Jack Nicholson with the sort of bite protector
link |
in his mouth and getting electric shock therapy,
link |
and it's, as the name suggests,
link |
it's kind of inducing a global seizure,
link |
either low-level or grand mal-type seizure
link |
in the patient's brain and nervous system.
link |
You might ask, well, why would one want to do that?
link |
Well, it turns out that this is a well-established
link |
and in many cases, very effective treatment
link |
for major depression.
link |
Electric shock therapy is generally used
link |
for treatment-resistant depression,
link |
so these are people that have no positive response
link |
or ongoing positive response to drug therapies
link |
or other therapies.
link |
Electric shock therapy is thought to work primarily
link |
by stimulating the massive kind of indiscriminate release
link |
of things like serotonin, dopamine, acetylcholine,
link |
a huge variety of neuromodulators,
link |
as well as things like BDNF,
link |
brain-derived neurotrophic factor,
link |
which then allows neuroplasticity to take place.
link |
Again, BDNF being permissive for neuroplasticity.
link |
The problem with ECT is that it's really only useful
link |
for treatment-resistant depression.
link |
It doesn't actually target the manic aspects
link |
of bipolar depression and bipolar disorder,
link |
but nonetheless is used when drug treatments don't work.
link |
Some of the negatives of electric shock therapy
link |
or electroconvulsive therapy, ECT,
link |
is the proper acronym and way it's described,
link |
is that it's quite invasive, right?
link |
This is something that you need to go to the hospital for
link |
and oftentimes there's some inpatient care required
link |
after the electric shock convulsive therapy.
link |
It's a fairly high cost,
link |
especially for those that don't have insurance.
link |
And of course it requires anesthesia.
link |
For most people, that's not going to be a problem,
link |
but for many people that could be a problem.
link |
And there's often some associated memory loss.
link |
And so the memory loss,
link |
the invasive nature of ECT and the cost
link |
oftentimes rule out ECT for most patients.
link |
And that's why it's sort of a late stage
link |
or kind of last resort type thing
link |
for treatment-resistant depression.
link |
Nowadays, ketamine type therapy is done repeatedly
link |
or other treatments.
link |
For instance, transcranial magnetic stimulation,
link |
which is basically noninvasive.
link |
It's a coil that's placed on the outside of the skull,
link |
And we can more accurately refer to it as repetitive
link |
or RTMS, repetitive transcranial magnetic stimulation.
link |
Transcranial magnetic stimulation is a tool
link |
that allows researchers and clinicians
link |
to reduce the amount of activity in specific neural circuits.
link |
So they can actually target the magnetic field
link |
to particular neural circuits
link |
to reduce activity in those neural circuits.
link |
Again, it's minimally invasive.
link |
It has been shown to be effective
link |
in both increasing neuroplasticity in positive ways,
link |
as well as reducing depressive episodes.
link |
And in a few instances in reducing the amplitude
link |
or the intensity of manic episodes
link |
in people with bipolar disorder.
link |
The problem is it's still a very early technique.
link |
There aren't a lot of clinics and labs doing it.
link |
I'm starting to see more advertisements,
link |
literally commercial clinics that are advertising RTMS or TMS
link |
I encourage you to approach those clinics with caution.
link |
I'm of the mind that if those clinics
link |
are not either closely or maybe even distantly associated
link |
with a research institution
link |
that's really up on the latest of RTMS,
link |
you'd be wise to at least do your research, right?
link |
And explore, talk to other patients
link |
who've done these treatments.
link |
But certainly in university hospitals
link |
and in clinical settings and research settings,
link |
RTMS is being used as a way to, for instance,
link |
reduce the activity of certain limbic circuitries
link |
so that people are just overall less excitable and manic.
link |
because it can also be used for activation now,
link |
certain neural circuits activate, for instance,
link |
the parietal inputs,
link |
the top-down control over the limbic system.
link |
This is all happening right now.
link |
So we have ECT, repetitive TMS or RTMS.
link |
And then as I mentioned earlier, ketamine therapies,
link |
most of those are targeted
link |
toward the depressive aspects of manic depression.
link |
So for people with bipolar disorder
link |
that doesn't include depression,
link |
those are going to be less effective.
link |
But overall, it's going to be the talk therapies
link |
of the sort that we discussed earlier or a moment ago,
link |
plus drug treatments,
link |
almost always lithium will be explored,
link |
plus some treatments for the depressive episodes,
link |
in particular, if those depressive episodes are present.
link |
Nowadays, there's a lot of excitement about psilocybin,
link |
which is a psychedelic.
link |
In the US, psilocybin is still illegal.
link |
meaning you can get in a lot of trouble for possessing it,
link |
certainly for selling it, et cetera.
link |
But psilocybin is being explored as a clinical therapy
link |
in certain laboratory settings,
link |
in particular, at Johns Hopkins School of Medicine.
link |
It's being explored in human patients
link |
for the treatment of major depression,
link |
for OCD, I believe, as well,
link |
but certainly for major depression
link |
and for eating disorders.
link |
And it seems from the initial wave of publications
link |
from that work done by the incredible Matthew Johnson
link |
or Dr. Matthew Johnson,
link |
who was a guest on this podcast before.
link |
He's also been on the Tim Ferriss podcast.
link |
He's been on the Lex Friedman podcast.
link |
Dr. Matthew Johnson came on this podcast
link |
and talked about some of the work with psilocybin
link |
for the treatment of depression.
link |
Very impressive results there.
link |
And as you can imagine,
link |
very impressive results
link |
for the major depressive episodes for bipolar.
link |
However, at least to my knowledge,
link |
again, to my knowledge,
link |
there have not been any controlled clinical trials
link |
exploring psilocybin
link |
for the mania associated with bipolar disorder.
link |
If someone out there is aware of those clinical trials,
link |
please let me know.
link |
I'll do an update in a future podcast.
link |
But right now, no knowledge from me
link |
about psilocybin clinical trials
link |
for the manic component of bipolar disorder.
link |
A number of people are probably also going to wonder
link |
about whether or not cannabis or medical marijuana
link |
is useful for bipolar disorder.
link |
To address this, I looked to some previous lectures
link |
and some clinicians at Stanford Psychiatry.
link |
This question was asked of them.
link |
And as it turns out,
link |
cannabis does not seem to be effective
link |
for the treatment of the manic phases of bipolar disorder
link |
or for the treatment of the major depressive component.
link |
The only treatment perhaps,
link |
or I should say the only situation perhaps
link |
in which it might be useful,
link |
and this is what was relayed to me,
link |
is that it may help with sleep
link |
in certain people that are having trouble with insomnia.
link |
Although nowadays it's far more common
link |
for people in manic episodes
link |
to prescribe things like trazodone or other benzos,
link |
in order to try and get sleep within the manic episodes.
link |
And benzodiazepines and trazodone, et cetera,
link |
work largely through the so-called GABA system.
link |
This is a neurotransmitter
link |
that causes reductions in excitability of neurons,
link |
hence why it's being used to try and calm people down
link |
and allow them to sleep during their manic episodes.
link |
So not a lot, or essentially no data,
link |
supporting the use of cannabis
link |
for the treatment of bipolar disorder per se,
link |
nor data supporting the use of psilocybin
link |
for the treatment of bipolar disorder per se.
link |
But I realized as I say that,
link |
that there are going to be a number of people
link |
that may have had positive
link |
or negative experiences with cannabis or psilocybin
link |
as they relate to bipolar disorder.
link |
So please, if you're willing or comfortable,
link |
put that if you're comfortable
link |
into the comment section on YouTube.
link |
And of course, if you are aware of any studies
link |
on cannabis or psilocybin showing positive outcomes
link |
for the treatment of bipolar disorder,
link |
please provide links or PubMed ideas to those.
link |
I'd love to peruse those studies.
link |
There are two naturopathic,
link |
or I should say nutrition supplement-based approaches
link |
to bipolar disorder they get talked about a lot.
link |
And one of them shows some interesting promise
link |
or effectiveness even in a limited context.
link |
Before marching into this description
link |
of these two compounds,
link |
in fact, before even mentioning these two compounds,
link |
I do want to emphasize what's been said
link |
and written about over and over again,
link |
and what was relayed to me from expert psychiatrists.
link |
It is not wise to rely purely on talk therapy
link |
or on natural approaches
link |
to the treatment of bipolar disorder,
link |
given the intensity of the disorder
link |
and the high propensity for suicide risk
link |
in people with bipolar disorder.
link |
It is a chemical and neural circuit disruption,
link |
and it needs to be dealt with head on
link |
through the appropriate chemistry
link |
and prescription drug approaches
link |
from a board certified psychiatrist.
link |
I don't say this to protect me.
link |
I say this truly to protect those who either suffer from
link |
or think they may suffer from bipolar disorder
link |
if you know someone who you think might suffer
link |
from bipolar disorder.
link |
Now, all that is not to say
link |
that there aren't useful lifestyle interventions
link |
that can support people with bipolar disorder.
link |
So I just briefly want to mention those.
link |
And again, I'm lifting the statements I'm about to make
link |
from some excellent online lectures
link |
from psychiatrists at Stanford and elsewhere,
link |
which essentially say that of course, of course, of course,
link |
getting better sleep, getting adequate exercise,
link |
getting proper nutrition,
link |
having quality, healthy social interactions,
link |
even getting regular sunlight in the day
link |
and avoiding bright light at night,
link |
all of those things are going to braid together
link |
to support the nervous system
link |
and the psyche of somebody with bipolar disorder,
link |
but they braid together to support the psyche
link |
and the neurochemistry and the neural circuits
link |
of anybody and everybody.
link |
So they have generally a modulatory effect.
link |
That is they're indirectly shifting the likelihood
link |
that somebody might have an episode
link |
or the intensity of an episode,
link |
in particular, the depressive episodes, right?
link |
You can imagine how someone
link |
who's heading into a depressive episode,
link |
maybe they're on a lower amount of medication
link |
or they haven't yet medicated
link |
for the depressive episode of bipolar.
link |
And now they're making sure,
link |
or their family is making sure
link |
that they're getting exercise, sunshine,
link |
eating correctly, social engagement, et cetera.
link |
Of course, it makes perfect sense
link |
why they would have perhaps a shallower drop into depression
link |
or maybe even offset a depressive episode.
link |
That said, most all, if not all people
link |
with bipolar disorder are likely to need
link |
some sort of drug therapy intervention
link |
in order to help them.
link |
So lifestyle factors are always important
link |
in all individuals,
link |
those suffering from psychiatric conditions or not.
link |
But in some conditions of the mind and body,
link |
those lifestyle interventions can have a greater effect
link |
in offsetting symptoms.
link |
Whereas in bipolar disorder,
link |
I think it's naive and in fact wrong
link |
to say that lifestyle interventions alone
link |
are going to prevent especially the extreme forms
link |
of mania and depression.
link |
Again, bipolar disorder being so serious
link |
and carrying such high suicide risk,
link |
we just have to point this out again and again.
link |
Now, with that said, there are two substances
link |
generally found as supplements,
link |
although there are other sources of them as well,
link |
including within nutritional sources that have been shown,
link |
at least in some studies, to be pretty effective
link |
in adjusting the symptoms of bipolar disorder.
link |
And those two things are inositol and omega-3 fatty acids.
link |
Now, inositol is a compound
link |
that is taken for a variety of reasons.
link |
It's something we've talked about on the podcast before.
link |
I personally take inositol
link |
not because I have bipolar disorder.
link |
In fact, I am quite lucky that I don't have bipolar disorder,
link |
but I take inositol at 900 milligrams of myo-inositol
link |
every third night or so in order to improve my sleep.
link |
It's something that I've added to my sleep stack.
link |
It's something that I found greatly enhances
link |
the depth and quality of my sleep.
link |
And if I wake up in the middle of the night
link |
to use the bathroom, et cetera,
link |
it's greatly enhanced my ability to fall back asleep
link |
when I want to go back to sleep.
link |
It also seems to have a fairly potent anti-anxiety effect
link |
And as I discussed in our episode
link |
about obsessive compulsive disorder,
link |
inositol has been used at high dosages.
link |
Again, I should say myo-inositol
link |
has been used at high dosages,
link |
levels of even 10, 18 grams.
link |
Those are massive dosages, by the way,
link |
to deal with certain symptoms of OCD to limited success.
link |
And I should mention that high dosages
link |
of 10 or 18 grams of inositol
link |
can cause a lot of gastric discomfort, et cetera.
link |
If you want to learn more about inositol
link |
and its various uses,
link |
I encourage you to go to examine.com
link |
where there's the so-called human effect matrix
link |
and that human effects matrix will describe the many places
link |
in which myo-inositol and other forms of inositol
link |
have been shown to be effective in, for instance,
link |
reducing anxiety, enhancing sleep, and on and on.
link |
Myo-inositol is important because myo-inositol,
link |
and we can just say inositol,
link |
is related to so-called second messenger pathways.
link |
I don't want to get too deep
link |
into second messenger pathways,
link |
but when certain substances bind like neurotransmitters
link |
to a receptor on a cell surface,
link |
oftentimes those receptors themselves will open
link |
and allow the passage of ions and other things into a cell.
link |
Oftentimes they will engage
link |
what are called second messenger systems.
link |
That is, they will trigger mechanisms within the cell
link |
to then go do other things.
link |
This is probably something we should get into
link |
in real detail in a future episode
link |
for those of you that really want to nerd out
link |
on cell-cell signaling, which is a favorite topic of mine.
link |
In any case, inositol is related
link |
to a number of so-called second messenger systems,
link |
this handoff or this kind of stimulating
link |
of changes within a cell that can inspire changes
link |
in what's called a membrane fluidity,
link |
can actually make the membranes of cells,
link |
the outside fence around a cell,
link |
which is made up of fatty stuff,
link |
it can change the fluidity,
link |
meaning how readily things can float around in the membrane.
link |
We think of cells as very rigid,
link |
like there's a cell, there's a neuron,
link |
or there's a immune cell,
link |
but actually those cells have a fatty outside,
link |
in particular neurons have a fatty outside,
link |
it's a thin fatty outside,
link |
and it's called the cell membrane.
link |
And things are floating around in that cell membrane,
link |
but it's kind of like jello that hasn't quite fixed.
link |
And so things like receptors moving into the synapse
link |
or moving out of the synapse for homeostatic plasticity,
link |
things like the ability for certain genes
link |
to be turned on in a cell or not turned on
link |
can depend a lot on things that are happening
link |
in that cell membrane
link |
and how readily things move around in the cell membrane.
link |
One way to think about this whole picture
link |
of membrane fluidity is that just imagine
link |
that every one of your cells has this layer,
link |
it's kind of a gelatinous-like layer,
link |
and there are lots of little rafts floating around in there,
link |
but those rafts are able to move more quickly
link |
from one place to another,
link |
or get more stuck in one place or another,
link |
depending on how set that jello is.
link |
Inositol and lithium, and as we'll talk about next,
link |
omega-3 fatty acids seem to change
link |
the fluidity of those membranes.
link |
In other words, they allow things to move
link |
in and out of those membranes more readily or not.
link |
And this is no surprise,
link |
given that those membranes are made out of fatty stuff.
link |
In particular, the membranes of neurons
link |
are called a lipid bilayer.
link |
It's two layers of fat, okay, bi means two, lipid fat,
link |
and omega-3 fatty acids of the sort
link |
that are found in certain fish,
link |
and fatty fish in particular,
link |
and that are found in fish oil and cod liver oil, et cetera.
link |
Omega-3 fatty acids, when we ingest them,
link |
are used for a lot of different things,
link |
but they can be readily incorporated into pathways
link |
or directly incorporated into cell membranes,
link |
changing the way those cell membranes work,
link |
and if those cell membranes are the cell membranes
link |
of neurons, changing the way that neurons work.
link |
So the ability for fish oil, and in particular,
link |
the omega-3 fatty acids, which come in varieties
link |
like EPA and DHA, we'll talk about that in a moment,
link |
have been explored at relatively high dosages
link |
for their ability to offset some of the effects of mania
link |
and to offset the effects of depressive episodes
link |
in bipolar disorder.
link |
And actually, the data there are pretty impressive,
link |
although they are varied,
link |
meaning you will find several studies,
link |
and I'll mention a few, that found no effect
link |
of omega-3 supplementation through fish oil.
link |
Usually it's capsuled fish oil,
link |
although fish oil can also be taken in liquid form.
link |
Oftentimes, taking in liquid form
link |
is the more cost-efficient way to do it.
link |
Taking in capsule form is the more palatable way to do it,
link |
because fish oil, for a lot of people, doesn't taste good.
link |
But nonetheless, there are several studies that have shown
link |
that supplementing with fish oil or omega-3 fatty acids
link |
at levels of, for instance, four grams per day
link |
for a period of time,
link |
this is a study that we will link in the show notes.
link |
This is Murphy et al. 2012.
link |
This is a fatty acid supplementation of 70% EPA to DHA,
link |
actually worsened symptoms of mania
link |
over a period of about 16 weeks,
link |
which on the face of it makes it seem like, okay,
link |
omega-3 fatty acid supplementation,
link |
very likely to not be good for bipolar disorder.
link |
And yet, that was the manic phase.
link |
When one looks at some of the other studies
link |
of omega-3 fatty acid supplementation,
link |
there is, for instance, a study published in 1999.
link |
This is a much higher dosage supplementation
link |
with omega-3 fatty acid.
link |
This is a 9.6 grams of fish oil per day for four months.
link |
And that actually greatly reduced symptoms
link |
of bipolar depression compared to the control group,
link |
which received olive oil.
link |
Olive oil is a different form of fat,
link |
monounsaturated fat,
link |
but doesn't contain as much of the omega-3 fatty acids
link |
So 9.6 grams of fish oil per day over four months
link |
is a lot of fish oil to be ingesting on a given day.
link |
This was a double-blind study.
link |
This was only carried out, I should mention, in 30 subjects,
link |
but it was males and females.
link |
And the age range was pretty broad,
link |
anywhere from 18 all the way up to 64 years of age,
link |
which is important given the sort of longitudinal
link |
or changes over time that one sees in bipolar disorder.
link |
Here's the major takeaway.
link |
Supplementing with high-dose omega-3s
link |
does seem to be beneficial for a good number of people
link |
with bipolar disorder.
link |
However, again, I want to highlight,
link |
however, it should not be viewed
link |
as the only treatment approach for bipolar disorder.
link |
This goes back to what I was saying before
link |
about the essential need in most every case
link |
for high potency prescription drug treatments
link |
prescribed by a board-certified psychiatrist
link |
for bipolar disorder.
link |
However, omega-3 supplementation does seem to improve
link |
or reduce the depressive symptoms
link |
in the major depressive episodes of bipolar.
link |
And there are a couple of studies,
link |
and we'll link to these in the show notes as well,
link |
that show that it may even improve
link |
some of the manic episodes as well,
link |
meaning it reduces some of the manic symptoms.
link |
Now, I say all this from a place of great caution
link |
because I know, especially for listeners of this podcast,
link |
there's a lot of interest in the behavioral tools,
link |
the supplement-based tools, the nutrition tools
link |
that can support bipolar disorder.
link |
But I don't think I can overemphasize enough
link |
that especially for bipolar disorder
link |
and the great risk of suicide and suffering
link |
and inappropriate spending,
link |
or I should say maladaptive spending and impulsivity
link |
that's associated with bipolar disorder,
link |
that it's hard to imagine a scenario
link |
in which just talk therapy and fish oil
link |
and lifestyle interventions are going to completely suppress
link |
or treat bipolar disorder.
link |
People with bipolar disorder really need to consider
link |
the full picture of treatments, the drug treatments,
link |
the talk therapy treatments and lifestyle treatments
link |
and nutraceutical, or we can say supplement-based treatments
link |
such as omega-3 supplementation,
link |
as a full and necessary picture
link |
for dealing with their illness.
link |
I'd be remiss, however, if I didn't emphasize
link |
that the omega-3 fatty acid supplementation
link |
is very interesting,
link |
not just in terms of the subjective effects,
link |
people saying they feel less depressed
link |
or able to sleep better,
link |
or maybe even some reduction in manic symptoms.
link |
There's actually been some really good brain imaging
link |
to try and understand how omega-3 fatty acid treatments
link |
are actually changing the brains and neural circuits
link |
of people with bipolar.
link |
And I will put a reference to this.
link |
This is a paper that was published
link |
in the American Journal of Psychiatry.
link |
It's entitled Omega-3 Fatty Acid Treatment
link |
and T2 Whole-Brain Relaxation Times in Bipolar Disorder.
link |
I don't have the opportunity to go into a lot of detail
link |
right now about what T2 whole-brain relaxation times are,
link |
but basically when people go into a MRI
link |
or F, functional MRI scanner,
link |
magnetic resonance imaging scanner,
link |
what they're getting essentially
link |
is pulses of magnetic fields.
link |
And the way that brain structures and neural activity
link |
can be evaluated has a lot to do
link |
with the sort of spinning or not sort of,
link |
it has to do with the spinning and the relaxation times
link |
of different elements,
link |
literally the protons and electrons within the neuron.
link |
So it gets really detailed there.
link |
And the relaxation time is essentially looking
link |
at how quickly some of that spinning returns to rest.
link |
And in particular, the fact that the relaxation times
link |
are different for aqueous, that is liquid,
link |
versus lipid, fatty, versus other components of brain tissue.
link |
And basically what this study shows
link |
is that the membranes of neurons within the brains
link |
of these people with bipolar disorder
link |
showed more fluidity, more ability of things
link |
to move in and around the membranes,
link |
which we know is an important component
link |
of neuroplasticity in bipolar subjects
link |
that were treated with omega-3 fatty acids
link |
as compared to bipolar subjects
link |
that did not receive omega-3 fatty acids.
link |
And fortunately, this study also include
link |
a healthy comparison group
link |
where they could essentially find
link |
that people with bipolar disorder
link |
who supplemented with omega-3s
link |
had changes at the cellular level
link |
and the neural circuit level
link |
that brought their brains and neural circuits
link |
closer to that of the healthy comparison subjects.
link |
So while I don't want to point
link |
to omega-3 fatty acid supplementation
link |
as the be all end all of treatment for bipolar disorder,
link |
certainly it is not,
link |
it does have a strong mechanistic basis
link |
for its possible support of neural circuitry,
link |
of neuroplasticity, and in particular,
link |
the ability to make changes in cell membranes
link |
that are very reminiscent
link |
of some of the neural circuit changes
link |
and changes in membrane fluidity
link |
that are seen with lithium treatment
link |
and other known prescription drug treatments
link |
that have been established now for decades
link |
to be very effective for bipolar disorder.
link |
So what that says is that omega-3 supplementation,
link |
while not the only intervention that one should consider,
link |
is something to consider and talk about with your doctor.
link |
And it's operating in powerful ways.
link |
It's not just that it's changing, for instance,
link |
your gut microbiome, which is powerful,
link |
but is indirect to the brain.
link |
It does seem to be having direct effects
link |
on neurons and neural circuits.
link |
Before we begin to conclude our discussion
link |
about bipolar disorder,
link |
I want to talk a little bit about this word disorder.
link |
And this is a theme that doesn't just relate
link |
to bipolar disorder,
link |
but other psychiatric disorders as well.
link |
And when we think of a disorder,
link |
we think of something that is really detrimental to us,
link |
something that really impairs our ability
link |
to function in work and school and relationships
link |
and really starts to pull down our health status
link |
in a variety of ways.
link |
And certainly bipolar disorder meets those criteria.
link |
However, there is this idea
link |
that things like bipolar disorder,
link |
even things like schizophrenia in some cases,
link |
are responsible for some of the creative aspects
link |
or the creative works that have been observed
link |
and carried out by human beings for many centuries.
link |
And believe it or not,
link |
there are good data to support the fact
link |
that certain aspects of mania
link |
are associated with creativity.
link |
Now, we are long overdue for an episode about creativity,
link |
its neural circuit basis, its chemical basis,
link |
here on the Huberman Lab Podcast.
link |
And certainly we will have that conversation.
link |
But in the meantime,
link |
I'd like to just briefly touch upon this idea
link |
that certain occupations are associated
link |
with a higher incidence of bipolar depression.
link |
And in fact, it's been explored at a research level.
link |
Really, there are data pointed to the fact
link |
that certain individuals of certain occupations
link |
tend to be more creative
link |
and that creativity is associated with,
link |
again, associated, this isn't causal,
link |
it's associated or correlated with higher levels
link |
or incidents of bipolar depression
link |
and maybe even other forms of depression.
link |
So this is a study looking at mood disorders
link |
in eminent individuals.
link |
So these are people that are not just good at what they do,
link |
but are exceptional at what they do
link |
and explored the percentage of people in given professions
link |
with either depression or mania.
link |
And this was actually a data set gleaned
link |
from more than 1,000 20th century Westerners
link |
based on their biographies
link |
that were reviewed by other people.
link |
So it's a bit of an indirect measurement.
link |
This isn't psychiatrist data.
link |
This is data, or I should say these are data
link |
that were compiled from self-reports
link |
or from reads of self-reports.
link |
And they explored a number of different professions.
link |
So for instance, they looked at people in the military
link |
or people who were professional athletes
link |
or natural scientists or social scientists,
link |
people who occupied positions in public office
link |
or were musical performers, artists, nonfiction writers,
link |
poetry, et cetera.
link |
There are a lot of professions here.
link |
I will post this, or I'll post a link to it
link |
in the show note captions for you to peruse,
link |
but I'll just give you a sense of the extremes
link |
on this graph because they're very interesting.
link |
It turns out that if you were to look at the profession,
link |
or I should say among the professions
link |
that they looked at in this study,
link |
cause they didn't look at all professions,
link |
those in the military and those who are professional athletes
link |
or had jobs in the social or natural sciences had the,
link |
of those, there was a lower percentage of those
link |
that had depression or mania.
link |
In some cases like those who were professional athletes
link |
didn't seem to have, there was no incidents of mania,
link |
at least in this data set.
link |
Whereas at the opposite extreme of the graph,
link |
those that were poets, so these are eminent individuals,
link |
people that were exceptional poets,
link |
exceptional fiction writers, exceptional artists
link |
or nonfiction writers.
link |
Well, they're especially for the poets.
link |
You find that as many as 90% of these very successful poets
link |
had either depression or mania, as high as 90%.
link |
That's incredible.
link |
Contrast that with military, where it's as few as 10%
link |
or professional athletes, where it's as few as 20%
link |
and for the professional athletes, as I mentioned before,
link |
none of them had mania.
link |
So does this mean that being a poet
link |
will make you manic or depressed?
link |
Well, first of all, let's look at the poetry category.
link |
It turns out that 75% of these eminent poets,
link |
these highly accomplished poets had major depression.
link |
Whereas only about 20% of those poets had manic episodes.
link |
So again, it's not that being a poet
link |
is going to give you mania, certainly we're not saying that,
link |
it's not that being a poet is going to give you depression,
link |
but it turns out that people with depression
link |
and people with depression and mania
link |
seem to gravitate towards poetry
link |
or at least are very successful at poetry.
link |
Again, associative, correlative,
link |
no causal relationship here,
link |
but it is really striking to see how
link |
the creative occupations, poetry, fiction, art,
link |
nonfiction writing,
link |
even though nonfiction writing is about nonfiction,
link |
it's still creative, music, composition, theater,
link |
much higher incidents of things like mania.
link |
And in fact, for the people in theater, the actors,
link |
even though the overall occurrence of depression and mania
link |
is lower than that in poets,
link |
the fraction of those individuals that have mania
link |
is exceedingly high.
link |
It's about 30% of those that they looked at
link |
who are actors have manic episodes or have full-blown mania.
link |
So I'm referring to these data because first of all,
link |
I find them incredibly interesting, right?
link |
Up until now, we've been talking about bipolar disorder
link |
and other mood disorders for their maladaptive effects.
link |
And again, they're extremely maladaptive,
link |
much, much higher instance of suicide, et cetera.
link |
But we'd be wrong to say that certain aspects
link |
of manic episodes don't lend themselves well to creativity
link |
or that certain aspects of major depression
link |
don't lend themselves well to creativity
link |
or to the performing arts or to poetry.
link |
That said, in no way, shape, or form,
link |
do I believe that being depressed is a good thing
link |
or that being manic is a good thing.
link |
Again, we return to the basic foundational criteria
link |
for bipolar disorder and major depression,
link |
which is that the pressured speech, the not sleeping,
link |
the incredible increases in energy and the flights of ideas
link |
are generally not going to lead,
link |
or I think it's fair to say
link |
are not going to lead to good places.
link |
In fact, often lead to bad places.
link |
But we would also be wrong if we didn't consider the fact
link |
that there is a somewhat inextricable relationship
link |
between mania and creativity.
link |
And it could be that hypomania or brief periods of mania,
link |
maybe even an hour a day or 30 minutes a day
link |
of composing or writing poetry,
link |
maybe even some of the lows that we feel,
link |
some of the sadness, some of the grief,
link |
some of the nostalgia that we feel,
link |
provided that it's not pathologic,
link |
that it's not persistent for the four or seven days
link |
that are diagnostic of bipolar II
link |
and bipolar I disorder respectively.
link |
Well, then we can start to view emotional states
link |
as something that can actually lend themselves
link |
to positive outcomes and maybe even to creativity
link |
and to improved occupations.
link |
So it's important that we have a nuanced view
link |
of what sadness versus depression
link |
versus major depression are.
link |
It's important that we distinguish between being erratic,
link |
being very energized and full-blown bipolar disorder.
link |
And I raise this for another reason as well.
link |
Nowadays, it's very common to hear people saying,
link |
oh, you know, that person is OCD.
link |
Well, on the episode about OCD that I did a few weeks back,
link |
that you can find if you like at hubermanlab.com,
link |
in that episode, I pointed out that OCD,
link |
obsessive compulsive disorder, is very maladaptive, right?
link |
I think it's number seven, as I recall,
link |
on the list of debilitating diseases,
link |
all diseases in terms of lost time at work,
link |
suffering relationships, et cetera.
link |
So it's a really serious condition, and yet we often hear,
link |
oh, that person is obsessive.
link |
And as I pointed out,
link |
there is obsessive compulsive personality disorder,
link |
and then there is obsessive compulsive tendencies
link |
which actually benefit people.
link |
But that is distinct from obsessive compulsive disorder
link |
as a clinically diagnosed thing.
link |
Similarly, we hear that, oh, somebody's being bipolar,
link |
you know, they're all over the place, they're bipolar.
link |
Well, that's a very subjective and kind of label
link |
that people give one another in passing.
link |
More and more often I'm hearing this,
link |
and yet bipolar disorder, whether or not it's BP1 or BP2,
link |
are extremely maladaptive and extremely associated
link |
with high suicide risk.
link |
So while I'm not here to police people,
link |
I'm certainly not the word police
link |
or the nomenclature police,
link |
I do think that whether or not you refer to people as OCD
link |
or as bipolar, et cetera, that's up to you, all right?
link |
It's not my place to say,
link |
but I do think it's important
link |
that all of us understand that these psychiatric conditions
link |
carry with them tremendous maladaptive weight.
link |
So today we've really done a deep dive
link |
into bipolar disorder and to both the manic
link |
and the depressive components that are present
link |
or can be present in bipolar disorder
link |
and the different forms of bipolar disorder
link |
and some of the major treatments for bipolar disorder,
link |
in particular lithium and its underlying mechanisms
link |
and some of the neural circuit and chemical basis
link |
and neuroplasticity basis of the treatments
link |
for bipolar disorder,
link |
in particular homeostatic scaling
link |
or homeostatic plasticity.
link |
All of that, of course, is relevant to bipolar disorder
link |
and I hope will be useful in your understanding
link |
and maybe even in your pursuit of treatments
link |
for bipolar depression,
link |
bipolar disorder for you or other people.
link |
I also hope that it will be useful in your understanding
link |
of how brain circuits work in normal conditions
link |
or in conditions where there is no disease state
link |
or maladaptive conditions.
link |
Homeostatic plasticity is present in all of us.
link |
Membrane fluidity due to how easily things move around
link |
in the surface, the fatty layers on the outside of neurons
link |
and the movement of receptors in and out of neurons,
link |
that is present in all of us.
link |
The influence of omega-3 fatty acids
link |
is central to that discussion,
link |
as is the discussion about various drug treatments
link |
because even if you're not somebody
link |
who's taking a drug treatment
link |
or who is pursuing a drug treatment for bipolar disorder
link |
or another psychiatric condition,
link |
your serotonin levels, your dopamine levels,
link |
your acetylcholine levels,
link |
all of these play into what we call
link |
your mental and physical health.
link |
In fact, if any of you are interested
link |
in the various categories of neuromodulators
link |
and tools to adjust those neuromodulators
link |
under more standard non-disease conditions,
link |
we did an episode on neurochemicals and how to control them.
link |
You can find that at hubermanlab.com
link |
along with all other episodes of the Huberman Lab Podcast.
link |
I should mention everything is timestamped
link |
so you can navigate to the specific topics
link |
and tools of interest to you.
link |
And meanwhile, I just want to thank all of you
link |
for joining me on this voyage through the biology
link |
and the treatments for bipolar disorder.
link |
I do hope you found it beneficial
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both for yourself and for others.
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I just want to remind people that bipolar disorder
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is an extremely serious condition.
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If you suspect that you have bipolar disorder
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or you know somebody who does,
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please make sure that you or they
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talk to a qualified health professional.
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If you're learning from and are enjoying this podcast,
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please subscribe to our YouTube channel.
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That's a terrific zero cost way to support us.
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In addition, please subscribe to the podcast
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And on both Spotify and Apple,
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you can leave us up to a five-star review.
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If you have suggestions about topics you'd like us to cover
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or guests you'd like us to interview
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We do read all the comments.
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In addition, please check out the sponsors mentioned
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That's the best way to support this podcast.
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During today's episode and certainly
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on many previous episodes of the Huberman Lab Podcast,
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we talk about supplements.
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Once again, while supplements
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aren't necessary for everybody,
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many people derive tremendous benefit from them
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for things like enhancing sleep and focus
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and hormone support and other aspects
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of mental and physical health and performance.
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As I mentioned at the beginning of today's episode,
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the Huberman Lab Podcast is happy to announce
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that we partnered with Momentous Supplements.
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If you'd like to see our supplements
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Please also check out Huberman Lab on social media.
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In both places, I cover science and science related tools,
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but much of which is distinct from the information covered
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on the Huberman Lab Podcast.
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We also have a newsletter.
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It's called the Neural Network Newsletter.
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It's completely zero cost
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You can sign up for it by going to HubermanLab.com,
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go to the menu and click on Neural Network Newsletter.
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And again, it is completely zero cost.
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So once again, thank you for joining me today
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for our discussion about the biology
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and treatment of bipolar disorder.
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And last, but certainly not least,
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thank you for your interest in science.
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And I'll see you in the next one.