CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY IN MAJOR DEPRESSION

Objective: The authors' intent was to evaluate the activity of the bet a-adrenoceptor-linked, cAMP-dependent protein kinase (protein Kinase A ) in patients with major depression compared with a group of nondepres sed volunteer subjects. Method: Skin fibroblast samples were obtained by 2-mm punch biopsy from 12 patients (11 were women) who had major de pression diagnosed according to the Structured Clinical Interview for DSM-III-R and from 10 nondepressed volunteers (seven were women). Fibr oblasts were cultured in Dulbecco's modified Eagle medium. Baseline an d cAMP-stimulated activities of protein kinase A were determined in bo th particulate and supernatant fractions (900 g). Linkage of the findi ng to beta adrenergic receptor function was evaluated by determination of protein Kinase A activity after incubation of the confluent cultur es for 30 minutes with 10 mu M isoproterenol. Results: There were sign ificant 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 nor mal subjects. The reductions in protein kinase A activity support the significance of beta-receptor-mediated events in depression.