Is lithium response related to G(s)alpha levels in transformed lymphoblasts from subjects with bipolar disorder?

A series of studies from independent laboratories have found increased levels of G(s)alpha in bipolar disorder in postmortem brain and peripheral blood cells. Long-term lithium administration blunts G-protein coupled cAMP signaling and may regulate G(s)alpha levels.

We measured G(s)alpha 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.

We found no differences in G(s)alpha protein levels measured with immunoblotting. G(s)alpha levels did not correlate with age, age of onset or duration of lithium therapy.

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.

These results are consistent with recent observations suggesting that mood state and treatment effects may account at least in part for increased G(s)alpha levels in bipolar disorder.

This study suggests a need to further characterize biological phenotypes in subjects with mood disorders to enhance genetic studies.