Cyclic AMP-mediated signaling components are upregulated in the prefrontalcortex of depressed suicide victims

The components of cyclic AMP signaling cascade (catalytic (C alpha) subunit of cyclic AMP-dependent protein kinase (PKA) and cyclic AMP response eleme nt binding protein (CREB)) were quantitated by Western blotting in the pref rontal cortex of depressed suicide victims (n=23) and their matched control s (n=14). There was a significant increase in the levels of CREB, both in t otal (tCREB; 121+/-8% (mean+/-S.E.M.), P<0.02) and phosphorylated (pCREB; 1 28+/-9%, P<0.01) forms, but not in PKA C alpha levels (109+/-9%, ns), in br ains of depressed suicides compared to those in control subjects. The incre ases in CREB were specifically observed in antidepressant drug-free subject s (tCREB: 137+/-11%, P<0.01, pCREB: 136+/-12%, P<0.02; n=9), but not in the antidepressant-treated subjects tCREB: 108+/-18%, ns; pCREB: 111+/-17%, ns ; n=8). There were significant correlations between the levels of PKA and t hose of tCREB and pCREB in the prefrontal cortex of depressed suicides. The se results indicate that the components of cyclic AMP signaling are upregul ated in a coordinated manner in brains of depressed suicides and that this alteration is not related to antidepressant treatment. (C) 2001 Published b y Elsevier Science B.V.