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Abstract
There is an established relationship between the monoaminergic neurotransmitter system
and mood disorders. In an attempt to define further the pathophysiology of mood disorders,
research is focussing on intracellular second messenger 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 disorder
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 patients with mood disorders. The relations between
changes in second messenger systems, gene transcription, and clinical effects of current
therapeutic regimens has implications for development of novel treatments of mood
disorders.