Reduced phosphorylation of cyclic AMP-responsive element binding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder

• Published in: Journal of Neural Transmission Vol. 110; no. 6; pp. 671 - 680
• Main Authors: Yamada, S., Yamamoto, M., Ozawa, H., Riederer, P., Saito, T.
• Format: Journal Article
• Language: English
• Published: Wien Springer 01.06.2003; New York, NY Springer Nature B.V
• Subjects: Aged; Aged, 80 and over; Biological and medical sciences; Cyclic AMP - metabolism; Cyclic AMP Response Element-Binding Protein - drug effects; Cyclic AMP Response Element-Binding Protein - metabolism; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Depressive Disorder, Major - physiopathology; Down-Regulation - drug effects; Down-Regulation - physiology; Fundamental and applied biological sciences. Psychology; Humans; Middle Aged; Neurons - drug effects; Neurons - metabolism; Phosphorylation - drug effects; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Prefrontal Cortex - physiopathology; Signal Transduction - drug effects; Signal Transduction - physiology; Subcellular Fractions - drug effects; Subcellular Fractions - metabolism; transcription factor; phosphorylation; Major depressive disorder; postmortem human brain; antidepressant; cAMP-responsive element binding protein (CREB)
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-002-0810-8

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.