Scientists find a main cause of mood swings in bipolar disorder

People with bipolar disorder experience dramatic shifts in mood, oscillating between often debilitating periods of mania and depression.

While a third of people with bipolar disorder can be successfully treated with the drug lithium, the majority of patients struggle to find treatment options that work.

In a new study, researchers found previously unknown details explaining why some neurons in bipolar patients swing between being overly or under excited.

The research was conducted by a team at Salk Institute.

The team used experimental and computational techniques to describe how variations in potassium and sodium currents in the brain cells of people with bipolar disorder may help to further explain why some patients respond to lithium and others do not.

In 2015, the team discovered for the first time the initial differences between brain cells of patients who respond to lithium and those who don’t.

In both cases, neurons from the brain’s dentate gyrus (DG) region were hyperexcitable—more easily stimulated—compared to DG neurons from people without bipolar disorder.

But when exposed to lithium, only the cells from known lithium-responders were calmed by the drug.

In the new research, the team conducted similar experiments but with more in-depth probes and using a different type of neuron than before.

They grew the neurons—called CA3 pyramidal neurons—from six people with bipolar disorder, three of whom responded to lithium.

The team found that these cells had higher than usual numbers of potassium channels as well as stronger potassium currents through these channels.

The increased potassium currents, the scientists showed, were responsible for the hyperactivity of the CA3 neurons: when they exposed the cells to a potassium channel blocker, the hyperactivity disappeared.

Intriguingly, when they exposed the cells to lithium, the drug not only reversed the hyperactivity but reduced potassium currents at the same time.

In addition, the team initially observed that the CA3 neurons from lithium non-responders, on average, had normal excitability. But when they looked more closely at individual cells over time, they found a different story.

The findings strengthened the evidence that potassium currents play a role in bipolar disorder—in both lithium responders and non-responders—and can help researchers understand how to better target drugs.

The team is planning to see if these shifts may be driving the manic and depressive moods seen in bipolar disorder.

One author of the study is Salk Professor Rusty Gage, the president of the Institute.

The study is published in the journal Biological Psychiatry.

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