Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder.
In this study, we examined the amounts of cAMP-responsive element binding protein (CREB) and its phosphorylated form in homogenate preparations from postmortem orbitofrontal cortices of antidepressant drug-free patients with major depressive disorder and age-matched controls by immunoblotting. Immunoreactivies of both CREB and phosphorylated CREB were significantly decreased in depressive subjects compared to controls. The immunoreactivity of phosphorylated CREB was diminished to a greater extent than that of CREB in depressive patients. It has been indicated from animal studies that a transcription factor likely mediates neural plasticity in the mammalian brain and neural tissues. Our results suggest that alterations in the cAMP signaling system, especially in CREB, may be involved in the pathophysiology of depression and be potential targets for antidepressant treatment.
Yamada
S
S
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Yamamoto
M
M
Ozawa
H
H
Riederer
P
P
Saito
T
T
D000368:Aged; D000369:Aged, 80 and over; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP