DYNAMICS OF ECT NORMALIZATION OF LOW G-PROTEIN FUNCTION AND IMMUNOREACTIVITY IN MONONUCLEAR LEUKOCYTES OF PATIENTS WITH MAJOR DEPRESSION

Objective: Heterotrimeric G proteins were Previously implicated in the biochemical mechanisms underlying the pathophysiology and treatment o f 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: Repented G protein measure ments in mononuclear leukocytes of 10 patients with major depression w ere made. Each patient was examined while untreated and after successi ve sessions of ECT; 14 normal subjects were also studied. G protein fu nction was evaluated through beta-adrenergic- and muscarinic-agonist-e nhanced guanine nucleotide binding capacity, substantiated by quantita tive measures of G proteins through immunoblot analyses using polyclon al antibodies against G(s) alpha, G(i) alpha, and G beta proteins. Res ults: Mononuclear leukocytes of patients with depression showed immuno reactive levels of G(s) alpha and G(i) alpha that were significantly l ower than those of normal subjects; the depressed patients also had ma rkedly hypofunctional G(s) and G(i). The low levels of G protein funct ion and immunoreactivity were alleviated by ECT. Repeated measurements in the same patients after successive ECT sessions showed that the no rmalization of G protein measures preceded, and thus predicted, clinic al improvement. The function and quantity of G(s) and G(i) 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 wi th depression may potentially serve not only as a biochemical marker f or affective state but also for biochemical prediction and evaluation of responses to ECT.