Scientists Discover How Lithium Works, Finally
For 40 years, lithium has been approved in the United States for the treatment of bipolar disorder, and although it often provides satisfying results, one fundamental question has been, how does lithium work? A team of scientists has come up with an answer.
Lithium is prescribed to treat the manic episodes of bipolar disorder, also known as manic depression, a condition that affects an estimated 5.7 million adults in the United States. Manic symptoms include hyperactivity, aggression, hostility, rushed speech, a reduced need for sleep, and poor judgment. Scientists have believed that lithium has an impact on bipolar disorder because it reduces inflammation in the brain that occurs during the manic phase, but they have not been sure exactly how the drug works.
A research team from the National Institute of Aging and University of Colorado, Denver, tackled the mystery by using mass spectrometry to evaluate the chemical makeup of brain samples obtained from rats stressed by brain inflammation that were treated with lithium compared with those that were not. As seen in previous studies, the rats that received lithium for six weeks demonstrated lower levels of arachidonic acid, which contributes to inflammation.
Mireille Basselin and colleagues also found, however, that lithium increased levels of 17-OH-DHA in response to inflammation. 17-OH-DHA is a metabolite of the omega-3 fatty acid DHA (docosahexaenoic acid) and is the precursor to many anti-inflammatory substances called docosanoids. Because the concentration of DHA did not increase, the scientists believe lithium may raise 17-OH-DHA levels by having an impact on the enzyme that changes DHA to its metabolite.
According to the National Alliance on Mental Health, lithium is also sometimes prescribed to people with depression who have not responded to antidepressants alone, even though they have never experienced a manic episode. Lithium is also sometimes prescribed for individuals who have schizophrenia.
This study indicates that lithium delivers a two-fisted punch: it reduces pro-inflammatory arachidonic acid products while increasing anti-inflammatory DHA products. This is the first study to bring scientists to a closer understanding of how lithium works, and the new information may lead researchers to find new applications for the drug in conditions characterized by inflammation in the brain.
Basselin M et al. Journal of Lipid Research 2010; 51: 1049-56
National Alliance on Mental Health
National Institute of Mental Health