REDUCED G-PROTEIN FUNCTIONS AND IMMUNOREACTIVE LEVELS IN MONONUCLEAR LEUKOCYTES OF PATIENTS WITH DEPRESSION

Objective: Heterotrimeric G proteins play a pivotal role in postrecept or information transduction. These proteins were previously implicated in the biochemical mechanism underlying lithium action and in the pat hophysiology of mood disorders. The present study sought to quantitati vely and functionally evaluate G proteins in patients with major depre ssion. Method: G proteins were measured in mononuclear leukocytes of 3 7 untreated patients with major depression and 31 comparison subjects. Receptor-coupled G protein function was evaluated through beta-adrene rgic and muscarinic-agonist-induced increases in guanine nucleotide bi nding capacity, which were substantiated by quantitative measures of G proteins through immunoblot analyses that used polyclonal antibodies against stimulatory (G(s) alpha) and inhibitory (G(i) alpha) G protein s. Results: Mononuclear leukocytes of depressed patients showed signif icantly reduced immunoreactive quantities of G(s) alpha and G(i) alpha together with markedly hypofunctional G(s) and G(i). The reductions i n both function and quantity of G(s) and G(i) were significantly corre lated with the severity of depressive symptoms. Moreover, simultaneous quantitative and functional measurements in a large number of patient s showed significant correlations between the Junction and the quantit y of mononuclear leukocyte G(s) and G(i) proteins. Conclusions: These findings lend further support to the implication of G proteins in the pathophysiology of mood disorders. G protein functional and quantitati ve measurements in mononuclear leukocytes of patients with mood disord ers may potentially serve as a biochemical marker for the affective st ate of these patients.