Is lithium response related to Gsα levels in transformed lymphoblasts from subjects with bipolar disorder?

Background: A series of studies from independent laboratories have found increased levels of Gsα in bipolar disorder in postmortem brain and peripheral blood cells. Long-term lithium administration blunts G-protein coupled cAMP signaling and may regulate Gsα levels. Methods: We measured Gsα in transformed lymphoblasts obtained from subjects with bipolar disorder and compared the findings with 23 age- and sex-matched controls. To reduce patient heterogeneity, we included only patients with an excellent response to lithium prophylaxis. Results: We found no differences in Gsα protein levels measured with immunoblotting. Gsα levels did not correlate with age, age of onset or duration of lithium therapy. Limitations: This study made use of transformed lymphoblasts, which may not fully represent changes that occur in regionalized brain tissue. Furthermore, the transformed lymphoblasts used in this study were acquired from a select group of bipolar disorder subjects that responded to lithium treatment. Lastly, consideration has to be given to the small sample size of the study. Conclusions: These results are consistent with recent observations suggesting that mood state and treatment effects may account at least in part for increased Gsα levels in bipolar disorder. Clinical relevance: This study suggests a need to further characterize biological phenotypes in subjects with mood disorders to enhance genetic studies.