Research Gives Clues to Why Some Benefit More From Drug for Bipolar Disorder

Key brain cell differences could play a role in lithium's effectiveness, researchers say

By Robert Preidt

Wednesday, October 28, 2015

WEDNESDAY, Oct. 28, 2015 (HealthDay News) -- Some people with bipolar disorder do not respond as well as others to the standby drug lithium, and a new study hints at why that may be so.

The research also brings scientists closer to understanding the origins of the psychiatric illness, which causes severe mood swings that include emotional highs and lows.

Specifically, the brain cells of people with bipolar disorder seem to be more sensitive than brain cells of people without the mental illness, the small study suggests.

"Researchers hadn't all agreed that there was a cellular cause to bipolar disorder," study senior author Rusty Gage, a professor in the genetics lab at the Salk Institute in La Jolla, Calif., said in an institute news release. "So our study is important validation that the [brain] cells of these patients really are different."

Gage and his colleagues took skin cells from six people with bipolar disorder, reprogrammed the cells to become stem cells, and then coaxed them to develop into brain cells (neurons), which were compared with brain cells from healthy people.

"Neurons are normally activated by a stimuli and respond," study first author Jerome Mertens, a postdoctoral research fellow, said in the news release. "The cells we have from all six patients are much more sensitive in that you don't need to activate them very strongly to see a response."

The researchers also found that the brain cells from the bipolar disorder patients had more active mitochondria, which is the energy source in cells.

The findings may give insight into current treatment, as well. Lithium is used to treat bipolar disorder, but the Salk team noted that not all patients respond to the drug.

Three of the patients in the study benefited from lithium, while three others did not. The neurons from the three who responded to lithium became less sensitive when exposed to the drug, while the neurons from non-responders remained highly sensitive after exposure to lithium, the research showed.

The findings don't explain why lithium benefits some patients but not others, but does provide a starting point to investigate differences in neurons between the two groups of patients and to test new drugs, the researchers said.

The study was published in the Oct. 28 issue of the journal Nature.

Bipolar disorder affects more than 5 million Americans, according to background information in the news release.

SOURCE: Salk Institute, news release, Oct. 28, 2015

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