Lithium and haloperidol treatments differently affect the mononuclear leukocyte Galphas protein levels in bipolar...

Despite numerous suggestions of the involvement of GTP-binding proteins in the mechanisms of action of psychoactive drugs in bipolar affective disorder, few studies have been conducted during the drug treatment of patients. The aim of the present study was to investigate the effects of a mood stabilizer and an antipsychotic drug on Galphas proteins. Patients with bipolar affective disorder under lithium treatment with or without haloperidol were assessed with respect to their mononuclear leukocyte (MNL) Galphas subunit protein. Galphas-45 protein subunit levels were analyzed by the Western immunoblot method. The subjects consisted of a group of 20 patients, all diagnosed as euthymic bipolars, and a comparison group of 15 drug-free healthy subjects. Results showed that Galphas levels were significantly decreased 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 factorial analysis of variance and showed significant differences between groups (Kruskal-Wallis H test, p < 0.02). Lithium-treated patients displayed the most decreased Galphas levels (normalized mean values 53.2 +/- 31 vs. 122 +/- 45% for BP and controls, respectively, p < 0.001), while no change was observed in Galphas levels of haloperidol-treated patients compared to controls (mean values: 124.9 +/- 37%; NS). The data indicate that lithium and haloperidol affect the mechanism of Galphas protein signal transduction differently, consistent with previous animal studies.