Increased cyclic AMP-dependent protein kinase activity in postmortem brainfrom patients with bipolar affective disorder

Previous observations of reduced [H-3]cyclic AMP binding in postmortem brai n regions from bipolar affective disorder subjects imply cyclic AMP-depende nt protein kinase function may be altered in this illness. To test this hyp othesis, basal and stimulated cyclic AMP-dependent protein kinase activity was determined in cytosolic and particulate fractions of postmortem brain f rom bipolar disorder patients and matched controls, Maximal enzyme activity was significantly higher (104%) in temporal cortex cytosolic fractions fro m bipolar disorder brain compared with matched controls. In temporal cortex particulate fractions and in the cytosolic and particulate fractions of ot her brain regions, smaller but statistically nonsignificant increments in m aximal enzyme activity were detected. Basal cyclic AMP-dependent protein ki nase activity was also significantly higher (40%) in temporal cortex cytoso lic fractions of bipolar disorder brain compared with controls. Estimated E C50 values for cyclic AMP activation of this kinase were significantly lowe r (70 and 58%, respectively) in both cytosolic and particulate fractions of temporal cortex from bipolar disorder subjects compared with controls. The se findings suggest that higher cyclic AMP-dependent protein kinase activit y in bipolar disorder brain may be associated with a reduction of regulator y subunits of this enzyme, reflecting a possible adaptive response of this transducing enzyme to increased cyclic AMP signaling in this disorder.