Reduced β-adrenergic receptor-coupled Gs protein function and Gsα immunoreactivity in mononuclear leukocytes of patients with depression

The Effects of Seasons and Light Therapy on G Protein Levels in Mononuclear Leukocytes of Patients With Seasonal Affective Disorder

“…24,[28][29][30] The G protein abnormalities detected in this study in depressed patients with SAD seem to be a state rather than a trait marker of SAD since (1) the same patients examined for their MNL G proteins levels in the summer, while in remission, did not show statistically significant alterations when compared with healthy control subjects; and (2) light therapy resulted in normalization of the reduced G protein immunoreactivity detected in the same patients while depressed. The results of this study are consistent with our earlier reports of MNL G protein measures as a state characteristic of mood disorders: (1) inverse picture of MNL G protein measures in bipolar mood disorder with respective increases in mania and decreases in bipolar depression 23,24,28,30 ; and (2) normalization of MNL G protein measures in patients with mood disorders with lithium, 23 antidepressants, and electroconvulsive therapy. 35 The mechanisms underlying the alterations in G protein levels in MNL of depressed patients with SAD and their normalization by light are still unknown.…”

“…[25][26][27] Reduced functional measures of G proteins were found in MNLs of patients with major depressive disorder. 24,[28][29][30] Although conflicting results were obtained concerning G protein immunoreactive levels in MNLs of patients with major depression, 31 a larger study has detected reduced levels of G s ␣ and G i ␣ proteins in MNLs of depressed patients that correlated with the severity of depression and with reductions in the functional measures of these proteins. 30 Quantitative and functional measures of G proteins in human MNLs were found to be age independent.…”

Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression

“…Isoproterenol-induced increases in GppNHp binding capacity were blockable by pretreatment with cholera toxin, with no effect of pertussis toxin, which indicates a specific effect through G s protein. Carbamylcholine exerted its effects on guanine nucleotide binding in a specific pertussis toxin-sensitive manner, which suggests coupling with non-G s proteins (e.g., G i ) (15,16,25,26). Figure 1 shows the functional measures of G s and G i following agonist stimulation for the normal and depressed subjects.…”

“…Indeed, lithium-sensitive hyperfunctional stimulatory (G s ) and in-hibitory (G i ) G proteins were detected in mononuclear leukocytes of patients with mania (15,25), while in a preliminary study (26) decreases in the function and level of G s protein have been found in mononuclear leukocytes of patients with major depressive disorder. In accordance with our findings, Friedman et al (27,28) have shown that lithium inhibits the association of various receptors with membrane G proteins, and binding of labeled GTPγS enhanced by agonists is elevated in postmortem cerebral cortical membranes of patients with bipolar disorder.…”

Heterotrimeric G Proteins: Insights into the Neurobiology of Mood Disorders

“…On the contrary, increased levels of G i have been found in mononuclear leukocytes of patients with bipolar disorder [188]. In platelets of patients with mood disorders (both major depression and bipolar disorder), decreased densities of 45 kDa G s [11], and unaltered levels of G i/o have been reported [140].…”