Altered brain protein kinase C in depression: a post-mortem study

[(3)H]Phorbol 12,13-dibutyrate (PDBu) binding was measured in soluble and particulate fractions of frontal cortex and hippocampus from suicides, with a firm retrospective diagnosis of depression, and individually matched controls. Suicides were divided into those who had been free of antidepressant drugs for at least 3 months and those in whom prescription of antidepressants was clearly documented. In frontal cortex, there was a significantly higher number (by 75%) of [(3)H]PDBu binding sites in the soluble fraction in antidepressant-free suicides compared to controls; significant differences were also seen in the proportion of sites in the soluble and particulate fractions. Higher numbers of [(3)H]PDBu binding sites in the particulate fraction of hippocampus in antidepressant-free suicides was restricted to those who died by violent means. No significant differences in the number of [(3)H]PDBu binding sites were found in antidepressant-treated suicides compared to controls. This study provides evidence for the involvement of protein kinase C in the pathophysiology of depression.