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 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.


METHODS
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.
Avissar
S
S
Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. sofia@bgu-mail.bgu.ac.il
Nechamkin
Y
Y
Roitman
G
G
Schreiber
G
G
D015415:Biomarkers; D002217:Carbachol / Q000494:pharmacology; D003866:Depressive Disorder / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D004565:Electroconvulsive Therapy; D019204:GTP-Binding Proteins / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007545:Isoproterenol / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000276:immunology
D015415:Biomarkers; D006165:Guanylyl Imidodiphosphate; D002217:Carbachol; D019204:GTP-Binding Proteins; D007545:Isoproterenol