S Avissar1, Y Nechamkin, G Roitman, G Schreiber. 1. Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. sofia@bgu-mail.bgu.ac.il
Abstract
OBJECTIVE: Heterotrimeric G proteins were previously implicated in the biochemical mechanisms underlying the pathophysiology and treatment of mood disorders. Low function and immunoreactivity of G proteins were observed in patients with major depression. In the present study the authors evaluated the effects of ECT on the low measures of G proteins in patients with major depression. METHOD: Repeated G protein measurements in mononuclear leukocytes of 10 patients with major depression were made. Each patient was examined while untreated and after successive sessions of ECT; 14 normal subjects were also studied. G protein function was evaluated through beta-adrenergic- and muscarinic-agonist-enhanced guanine nucleotide binding capacity, substantiated by quantitative measures of G proteins through immunoblot analyses using polyclonal antibodies against Gs alpha, Gi alpha, and G beta proteins. RESULTS: Mononuclear leukocytes of patients with depression showed immunoreactive levels of Gs alpha and Gi alpha that were significantly lower than those of normal subjects; the depressed patients also had markedly hypofunctional Gs and Gi. The low levels of G protein function and immunoreactivity were alleviated by ECT. Repeated measurements in the same patients after successive ECT sessions showed that the normalization of G protein measures preceded, and thus predicted, clinical improvement. The function and quantity of Gs and Gi proteins in patients given ECT were significantly correlated. CONCLUSIONS: 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.
OBJECTIVE: Heterotrimeric G proteins were previously implicated in the biochemical mechanisms underlying the pathophysiology and treatment of mood disorders. Low function and immunoreactivity of G proteins were observed in patients with major depression. In the present study the authors evaluated the effects of ECT on the low measures of G proteins in patients with major depression. METHOD: Repeated G protein measurements in mononuclear leukocytes of 10 patients with major depression were made. Each patient was examined while untreated and after successive sessions of ECT; 14 normal subjects were also studied. G protein function was evaluated through beta-adrenergic- and muscarinic-agonist-enhanced guanine nucleotide binding capacity, substantiated by quantitative measures of G proteins through immunoblot analyses using polyclonal antibodies against Gs alpha, Gi alpha, and G beta proteins. RESULTS: Mononuclear leukocytes of patients with depression showed immunoreactive levels of Gs alpha and Gi alpha that were significantly lower than those of normal subjects; the depressedpatients also had markedly hypofunctional Gs and Gi. The low levels of G protein function and immunoreactivity were alleviated by ECT. Repeated measurements in the same patients after successive ECT sessions showed that the normalization of G protein measures preceded, and thus predicted, clinical improvement. The function and quantity of Gs and Gi proteins in patients given ECT were significantly correlated. CONCLUSIONS: 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.
Authors: S Anttila; K Huuhka; M Huuhka; R Rontu; K M Mattila; E Leinonen; T Lehtimäki Journal: J Neural Transm (Vienna) Date: 2006-10-27 Impact factor: 3.575