Abnormalities in the cAMP signaling pathway in post-mortem brain tissue from the Stanley Neuropathology Consortium.
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.
Stewart
R J
RJ
Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada.
Chen
B
B
Dowlatshahi
D
D
MacQueen
G M
GM
Young
L T
LT
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000928:Antidepressive Agents / Q000494:pharmacology; D001109:Archives; D001714:Bipolar Disorder / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008094:Lithium / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014015:Tissue Banks
D000928:Antidepressive Agents; D017362:Cyclic AMP Response Element-Binding Protein; D008094:Lithium; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases