cAMP-dependent protein kinase activity in major depression.
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.


METHODS
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.
Shelton
R C
RC
Psychopharmacology Division, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
Mainer
D H
DH
Sulser
F
F
D000328:Adult; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D003866:Depressive Disorder / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D003937:Diagnosis, Differential; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology
D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases