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Am J Psychiatry 1996; 153:1037-1042
Copyright © 1996 by American Psychiatric Association
cAMP-dependent protein kinase activity in major depression
RC Shelton, DH Mainer and F Sulser
Psychopharmacology Division, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
OBJECTIVE: The author's intent was to evaluate the activity of the beta-
adrenoceptor-linked, cAMP-dependent protein kinase (protein kinase A) in
patients with major depression compared with a group of nondepressed
volunteer subjects. METHOD: Skin fibroblast samples were obtained by 2- mm
punch biopsy from 12 patients (11 were women) who had major depression
diagnosed according to the Structured Clinical Interview for DSM-III-R and
from 10 nondepressed volunteers (seven were women). Fibroblasts were
cultured in Dulbecco's modified Eagle medium. Baseline and cAMP-stimulated
activities of protein kinase A were determined in both particulate and
supernatant fractions (900g). Linkage of the finding to beta adrenergic
receptor function was evaluated by determination of protein kinase A
activity after incubation of the confluent cultures for 30 minutes with 10
microM isoproterenol. RESULTS: There were significant differences between
groups in the baseline and cAMP-stimulated phosphorylation in the
supernatant fraction. Moreover, the attenuated protein kinase A response
was accompanied by a blunted isoproterenol response. CONCLUSIONS: Patients
with depression exhibit significantly less activity of beta-
adrenoceptor-linked protein kinase A than do normal subjects. The
reductions in protein kinase A activity support the significance of
beta-receptor-mediated events in depression.
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