Dynamics of ECT Normalization of Low G Protein Function and Immunoreactivity in Mononuclear Leukocytes of Patients With Major Depression

Abstract

These findings support the implication of G proteins in the pathophysiology and treatment of mood disorders. G protein measurements in patients with depression may potentially serve not only as a biochemical marker for affective state but also for biochemical prediction and evaluation of responses to ECT.

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.…”

“…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. 32 This study attempts to characterize G protein levels in peripheral blood elements of patients with SAD by addressing the following questions: (1) Do reduced G protein levels, which are characteristic of MNLs of patients with nonseasonal, typical depression, also appear in patients with SAD, whose depressive symptoms are generally described as atypical?…”

“…We have discussed this issue at length previously. 30 As we use a mixed-cell MNL preparation for our assays, the possibility remains that the alterations observed in G protein immunoreactivity reflect, at least in part, alteration in a white cell subpopulation induced by the depressive state and/or by light therapy. While G s ␣ and G i ␣ levels were reduced in the group of depressed patients with SAD, the G␤ levels remained similar to the control group.…”

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression

“…[30][31][32][33][34][35][36][37][38][39] Alternatively, the observed modifications may reflect adaptive responses to other reported dysfunctions in cell signaling of depressed patients such as Ca 2+ signaling and the phosphoinositides cycle, including protein kinase C. [40][41][42][43][44][45][46] These findings alone or in combination may contribute to explain the reason why PKA and Rap1 are altered in major depression, but the molecular mechanisms by which these modifications occur remain unknown.…”