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There’s no doubt that lithium has a diverse list of uses. But the way that it interacts with our bodies to help treat bipolar disorder is aiding us in better understanding the disorder and potentially developing new drugs to combat it.

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[♪ INTRO].

Lithium is the third element  on the periodic table. But it’s also so much more than that.

Lithium and its compounds are used  to make everything from cell phone   batteries to airplane parts to pacemakers.   And one compound, lithium carbonate,  is also used in psychiatric medicine, most commonly, to treat  patients with bipolar disorder. If it’s surprising that the same element used  in batteries would be good for your brain… yes. But the stranger thing is, even though  we’ve been using this treatment for   decades, we’re still learning  exactly how and why it works.  Doctors started using lithium compounds to treat  neurological conditions way back in the mid-1800s.

Then, in 1949, an Australian  psychiatrist named John Cade   discovered that lithium carbonate in particular could treat the extreme mood swings  symptomatic of bipolar disorder.  Over the next 70 years, this compound, which   we’ll just call “lithium” from now on,  went on to become a first-line treatment. And now, the World Health Organization considers  it one of the world’s most essential medicines!    Having an effective drug treatment  for bipolar disorder is great. Researchers estimate that around 45  million people worldwide have it.

And while there are a few slightly  different subtypes of bipolar disorder,   it can cause someone’s mood to fluctuate  between depression and euphoric mania. Or between depression and a  slightly less extreme manic episode. All in all, though, this can  be disruptive to everyday life,   and on average, it can also shorten  someone’s life expectancy by 9 to 17 years.

So having a drug like lithium  is incredibly important. But unfortunately, it doesn’t work for everyone. A 2017 study found that only one-third of patients  can be treated effectively with lithium alone.

For everyone else, it either doesn’t work or has  to be paired with another drug to get results.  And for the longest time, we just didn’t  know why. Or why lithium works, period. But finally, we’ve started  to put the pieces together.

For one, starting around the 1970s, research has   gradually revealed that lithium can help  stabilize magnesium levels in our bodies.  Magnesium plays an important role in neurological   health by helping electrical signals  move from one neuron to another. And studies show that patients  with bipolar disorder symptoms   often have irregular levels of it. So, the fact that lithium can stabilize  magnesium levels means it could improve   how signals are transmitted  through the nervous system!

But that doesn’t seem to be the only way it works. Like, the authors of a more recent 2018  study discovered that while lithium may   play nice with magnesium, it  gets competitive with sodium. Normally, sodium binds with certain types  of G-protein coupled receptors, or GPCRs, which are proteins found on cell membranes  that help activate cell responses.  Humans have more than 1000 types of GPCRs,  and they help regulate everything from our sense of taste to the levels of  serotonin and dopamine in our brains.   But in the 2018 study, scientists found  that lithium can give sodium the boot.

It turns out that when lithium binds  with compatible GPCRs instead of sodium, it can deactivate them. But that can actually be a good thing. We’re still learning a lot about how  these receptors work, but we do know   that they can be hyperactive in  patients with bipolar disorder.

And some GPCRs in our brain control levels of  chemicals like serotonin and noradrenaline, which scientists believe are  key players in bipolar disorder. So if lithium can inactivate some  of these hyperactive receptors,   that might be another reason  it can treat symptoms so well. So, overall, there are still  some things to pin down,   but we’re finally starting to get a  sense of why lithium works at all.

And in 2017, another study came out that might   even shed some light on why  it only helps in some cases. In this paper, the researchers focused on  mapping how lithium works on a molecular level.  And in doing so, they discovered that bipolar  disorder can be caused by a protein involved   in nerve cell communication, called CRMP2.  In patients with bipolar disorder that  didn’t respond to lithium treatment, researchers found that. CRMP2 was much more active than in  patients who did respond to lithium.

This matters for a couple of reasons. For one, by understanding how lithium  interacts with these proteins, doctors could better predict which patients  might respond well to lithium treatment.  But also, these results could mean  that bipolar disorder isn’t always   caused by changes to someone’s genetic code:. It could also be the result of how proteins  like CRMP2 are treated inside cells.

In the future, information like this could  lead to the development of new drugs, and even diagnostic tests.  And since it takes the average person eight  years to get diagnosed with bipolar disorder,   a diagnostic test could really speed things up! Of course, this wouldn’t apply to all cases. And it wouldn’t address other  complications with diagnoses, like the stigma around bipolar disorder.

But for some people, it would be  a step in the right direction. Even though we’ve been studying  lithium carbonate for decades,   we’ve only finally begun to  figure out some of its secrets. But the more we learn about this compound, the  more we can understand how bipolar disorder works and how to develop effective  treatments for those who need them.

Thanks for watching this episode of SciShow Psych! And a huge shoutout to the patrons on  Patreon who make this show possible. Our patrons decided we should make  SciShow Psych a few years ago, and now,   they’re the ones helping us explore  the complexities of the human brain.

So to all our patrons: Thank you! And if you’d like to learn more  about what it means to be a patron, you can go to [♪ OUTRO] .