G protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: Effects of diagnosis, suicide, and treatment at the time of death

Components of cyclic AMP (cAMP) signaling were examined in postmortem cereb ral cortex of a well characterized group of patients with mood disorders an d nonpsychiatric control subjects. We measured G protein levels, adenylyl c yclase (AC) activity, and CREB levels in cerebral cortex of the subjects wi th respect to diagnosis, treatment, and suicide. There was no effect of dia gnosis on any measure, except for a trend toward decreased stimulated AC ac tivity in subjects with mood disorders relative to control subjects. We als o detected a significant effect of suicide on temporal cortex CREB levels i n subjects that died as a result of suicide relative to those that did not, which was more evident in patients with major depressive disorder. Bipolar disorder (BD) subjects treated with anticonvulsants at the time of death h ad decreased temporal cortex CREB levels relative to those not receiving an ticonvulsants. Furthermore, we found a trend toward decreased occipital cor tex G alpha(s) (short) levels in ED subjects treated with lithium. These re sults support the hypothesis of altered cAMP signaling in mood disorders an d raise the possibility that factors other than diagnosis, such as treatmen t and suicide, may be relevant to cell-signaling abnormalities reported in the literature.