The effects of seasons and light therapy on G protein levels in mononuclear leukocytes of patients with seasonal affective disorder

Background: Information-transducing heterotrimeric G proteins have been imp licated previously in the mechanism of action of mood stabilizers and in th e pathophysiology of mood disorders. Mononuclear leukocytes of patients wit h unipolar and bipolar depression have been characterized by reduced measur es of the stimulatory and inhibitory G proteins. In this study, patients wi tt; seasonal affective disorder (SAD) were measured for mononuclear leukocy te G protein levels while depressed during the winter, following light ther apy, and in remission during the summer. Methods: Twenty-six patients with SAD and 28 healthy subjects were assessed in the study. The immunoreactivities of G(5)alpha, G(i)alpha, and G beta s ubunit proteins were de termined by Western blot analysis of mononuclear le ukocyte membranes with selective polyclonal antibodies for the various G su bunit proteins, followed by densitometric quantitation using an image analy sis system. Results: Untreated patients with SAD and winter, atypical-type depression s howed significantly reduced mononuclear leukocyte immunoreactive levels of G(s)alpha and G(i)alpha proteins, similar to previous observations in patie nts with nonseasonal major depression. The reduced G protein levels were no rmalized with 2 weeks of light therapy. The same patients while in remissio n during the summer had G protein levels that were similar to those of heal thy subjects. Conclusions: G protein-immunoreactive measures in patients with SAD are sug gested as a state marker for winter depression, which is normalized by ligh t treatment and during the summer. We speculate that light may ex ert its e ffects via normalization of transducin (G, protein) levels, which are thoug ht to be reduced in winter depression.