Brain Cells May Predict Bipolar Patients' Response to Lithium

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Brain cells in those with bipolar disorder are more sensitive to stimuli than people without the condition, a discovery researchers say provides an explanation for why some bipolar patients respond to lithium treatment while others don’t.

Rusty Gage, PhD, of the Salk Institute for Biological Studies in La Jolla, Calif., and colleagues collected skin cells from six bipolar patients. Three of the patients responded well to lithium, while the other three didn’t.

The researchers then reprogrammed the cells to become stem cells, then worked the stem cells to develop into neurons. These neurons were then compared to ones from healthy people.

Next, they tested how the cells reacted to lithium. The team let some of the neurons grow in liquid containing lithium and then remeasured how sensitive the cells were. The neurons behaved differently when exposed to the lithium. Cells from lithium responder patients showed weakened excitability after growing in the lithium, but cells from patients who hadn’t seen any benefit from the drug remained hyperexcitable, the researchers reported in the journal Nature.

The findings offers a starting point to probe why lithium works for some bipolar disorder patients but not others by examining what the differences between the cells are.

“After a few months, it's possible that this hyperexcitability becomes too much for the cell to handle and it crashes into a less excitable state,” Gage said in a statement. “That could signal the shift between the depression and mania that patients experience.”

bipolar brain cells
Brain cells from lithium responder patients showed weakened excitability after being treated with lithium.

The brain cells of patients with bipolar disorder, characterized by severe swings between depression and elation, are more sensitive to stimuli than other people's brain cells, researchers have discovered.

The finding, published in the journal Nature, is among the first to show at a cellular level how the disorder affects the brain. Moreover, it reveals why some patients respond to treatment with lithium while others don't.

Bipolar disorder affects more than five million Americans and is often a challenge to treat. If patients' severe mood swings aren't helped with lithium, doctors often piece together treatment plans with antipsychotic drugs, antidepressants and mood stabilizers. But they often help only the depressive swings of bipolar or the opposing manic swings, not both.

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