Scientists have identified the molecular mechanism behind lithium’s effectiveness in treating bipolar disorder in an international study published in Proceedings of the National Academy of Sciences (PNAS). Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP), Yokohama School of Medicine, Harvard Medical School, and UC San Diego collaborated on the study, which used human induced pluripotent stem cells (hiPS cells) to map lithium’s response pathway.
Lithium is a salt which has long been considered the gold-standard for bipolar treatment. The side effects–such as nausea, weight gain, and birth defects–are a trial for many people who take the drug. Only about one-third of people who suffer from bipolar disorder respond to lithium treatment. Before researchers at the Salk institute developed a test to predict who will respond to lithium with 92 percent accuracy, there was no test, and the drug’s effect was only found through a trial-and-error process which could take months or years.
In the study, scientists used hiPs cells created from lithium-responsive and non-responsive patience to observe a physiological difference in a protein called CRMP2: the protein was in a much more inactive state in responsive patients. However, when the researchers applied lithium, CRMP2 worked properly. So the study shows that bipolar disorder has a physiological–not necessarily genetic–cause.
This study is the first to explain the molecular basis of bipolar disorder. Scientists hope to use the results to develop a blood test for the disease, as well as further tests that can predict whether people who suffer from bipolar disorder will respond to lithium. Research leading from this study may also discover safer and more effective drugs to treat the disorder.
Edited to Add: Here is the link to the study, as requested.