Lithium and haloperidol treatments differently affect the mononuclear leukocyte G alpha s protein levels in bipolar affective disorder

Despite numerous suggestions of the involvement of GTP-binding proteins in the mechanisms of action of psychoactive drugs in bipolar affective disorde r, few studies have been conducted during the drug treatment of patients. T he aim of the present study was to investigate the effects of a mood stabil izer and an antipsychotic drug on G alpha s proteins. Patients with bipolar affective disorder under lithium treatment with or without haloperidol wer e assessed with respect to their mononuclear leukocyte (MNL) G alpha s subu nit protein. G alpha s-45 protein subunit levels were analyzed by the Weste rn immunoblot method. The subjects consisted of a group of 20 patients, all diagnosed as euthymic bipolars, and a comparison group of 15 drug-free hea lthy subjects. Results showed that G alpha s levels were significantly decr eased in the bipolar patients (BP) compared to drug-free healthy subjects ( Mann-Whitney U test, p < 0.002). The drug effect was evaluated by a factori al analysis of variance and showed significant differences between groups ( Kruskal-Wallis H test, p < 0.02). Lithium-treated patients displayed the mo st decreased G alpha s levels (normalized mean values 53.2 +/- 31 vs. 122 /- 45% for BP and controls, respectively, p < 0.001), while no change was o bserved in G alpha s levels of haloperidol-treated patients compared to con trols (mean values: 124.9 +/- 37%; NS). The data indicate that lithium and haloperidol affect the mechanism of G alpha s protein signal transduction d ifferently, consistent with previous animal studies.