Salk method predicts whether bipolar patients will respond to lithium therapy

LA JOLLA, Calif., March 21, 2017 /PRNewswire-USNewswire/ -- For roughly one-third of people diagnosed with bipolar disorder, lithium is a miracle drug, effectively treating both their mania and depression. But once someone is diagnosed, it can take up to a year to learn whether that person will be among the 30 percent who respond to lithium (the preferred drug to treat the disorder) or the 70 percent who do not.

Now, scientists at the Salk Institute report a way to predict, with 92 percent accuracy, whether an individual with bipolar disorder will be a lithium responder. The work, which appeared online in Molecular Psychiatry, could benefit not only those who will respond to lithium but also the vast majority who will not, sparing them an ineffective treatment.

"In 2015 we discovered that the brain cells of people with bipolar disorder are more sensitive to stimuli than those of other people," says Rusty Gage, a professor in Salk's Laboratory of Genetics and senior author of the new work. "Since then, we have been able to characterize that sensitivity in greater detail and discern clear patterns in the neurons of bipolar patients that allow us to predict who will respond to lithium and who will not."

The Gage team's previous breakthrough was published in Nature in October 2015. The new study sought to better understand why, despite seemingly equivalent hyperactivity, some bipolar patients' neurons respond to lithium while others' do not. This time, instead of using skin cells, the team reprogrammed lymphocytes (immune cells) from six entirely new bipolar patients, some of whom are known lithium responders.

The Salk team characterized the electrical firing patterns of all six patients' neuronal lines, measuring spike height, spike width, the threshold for evoking a reaction and other qualities. The overall patterns were noticeably different in responders versus nonresponders.

The team then trained a computer program to recognize the variations between the profiles of responders and nonresponders using the firing patterns of 450 total neurons over six independent training rounds. Using the firing patterns of just five of any patient's neurons, the system identified the person as a responder or nonresponder with 92 percent accuracy.

The team says their method could be applied to lymphocytes taken from bipolar patients' blood samples, to find out whether specific individuals would be good candidates for lithium therapy.

Contact: Salk Communications
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SOURCE Salk Institute for Biological Studies

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