Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium

There is an established relationship between the monoaminergic neurotransmi tter system and mood disorders. In an attempt to define further the pathoph ysiology of mood disorders, research is focussing on intracellular second m essenger systems, including cyclic adenosine 3 ' ,5 ' -monophosphate (cAMP) and the polyphosphoinositol generated second messengers. The availability of tissue from the Stanley Foundation Neuropathology Consortium has offered us the opportunity to make a number of observations with respect to these second messenger systems in tissue from patients with major depressive diso rder and bipolar affective disorder. There is evidence that antidepressants stimulate components of the cAMP pathway in patients with depression while mood stabilizers blunt the same pathway in patients with bipolar disorder. Furthermore, downstream targets of this pathway appear to be altered in pa tients with mood disorders. The relations between changes in second messeng er systems, gene transcription, and clinical effects of current therapeutic regimens has implications for development of novel treatments of mood diso rders. (C) 2001 Elsevier Science Inc.