cAMP-dependent protein kinase activity in major depression

• Published in: The American journal of psychiatry Vol. 153; no. 8; p. 1037
• Main Authors: Shelton, R C, Mainer, D H, Sulser, F
• Format: Journal Article
• Language: English
• Published: United States 01.08.1996
• Subjects: Adult; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases - metabolism; Depressive Disorder - diagnosis; Depressive Disorder - enzymology; Depressive Disorder - physiopathology; Diagnosis, Differential; Female; Fibroblasts - enzymology; Humans; Male; Psychiatric Status Rating Scales; Receptors, Adrenergic, beta - metabolism; Receptors, Adrenergic, beta - physiology; Signal Transduction; Skin - enzymology
• ISSN: 0002-953X
• DOI: 10.1176/ajp.153.8.1037

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. 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. 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. 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.