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Am J Psychiatry 1997; 154:211-217
Copyright © 1997 by American Psychiatric Association
Reduced G protein functions and immunoreactive levels in mononuclear leukocytes of patients with depression
S Avissar, Y Nechamkin, G Roitman and G Schreiber
Department of Clinical Pharmacology, Faculty of Health Sciences, Ben- Gurion University of the Negev, Beer-Sheva, Israel.
OBJECTIVE: Heterotrimeric G proteins play a pivotal role in postreceptor
information transduction. These proteins were previously implicated in the
biochemical mechanism underlying lithium action and in the pathophysiology
of mood disorders. The present study sought to quantitatively and
functionally evaluate G proteins in patients with major depression. METHOD:
G proteins were measured in mononuclear leukocytes of 37 untreated patients
with major depression and 31 comparison subjects. Receptor-coupled G
protein function was evaluated through beta-adrenergic and
muscarinic-agonist-induced increases in guanine nucleotide binding
capacity, which were substantiated by quantitative measures of G proteins
through immunoblot analyses that used polyclonal antibodies against
stimulatory (Gs alpha) and inhibitory (Gi alpha) G proteins. RESULTS:
Mononuclear leukocytes of depressed patients showed significantly reduced
immunoreactive quantities of Gs alpha and Gi alpha together with markedly
hypofunctional Gs and Gi. The reductions in both function and quantity of
Gs and Gi were significantly correlated with the severity of depressive
symptoms. Moreover, simultaneous quantitative and functional measurements
in a large number of patients showed significant correlations between the
function and the quantity of mononuclear leukocyte Gs and Gi proteins:
CONCLUSIONS: These findings lend further support to the implication of G
proteins in the pathophysiology of mood disorders. G protein functional and
quantitative measurements in mononuclear leukocytes of patients with mood
disorders may potentially serve as a biochemical marker for the affective
state of these patients.
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