cAMP signaling in brain is decreased in unmedicated depressed patients and increased by treatment with a selective serotonin reuptake inhibitor

• Published in: Molecular psychiatry 2017-05, Vol.22 (5), p.754-759
• Main Authors: Fujita, M, Richards, E M, Niciu, M J, Ionescu, D F, Zoghbi, S S, Hong, J, Telu, S, Hines, C S, Pike, V W, Zarate, C A, Innis, R B
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - metabolism; 59/78; 631/378; 692/699/476/1414; Adenosine; Adult; Antidepressants; Antidepressive Agents - therapeutic use; Behavioral Sciences; Biological Psychology; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Carbon Radioisotopes; Case-Control Studies; Cyclic AMP; Cyclic AMP - metabolism; Depression - diagnostic imaging; Depression - drug therapy; Depression - metabolism; Depressive Disorder, Major - diagnostic imaging; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - metabolism; Enzymes; Female; Humans; Kinases; Male; Medicine; Medicine & Public Health; Mental depression; Mental health; Middle Aged; Neurosciences; original-article; Patients; Pharmacotherapy; Phosphodiesterase; Phosphodiesterase 4 Inhibitors - pharmacokinetics; Positron emission tomography; Positron-Emission Tomography - methods; Psychiatry; Rolipram; Rolipram - pharmacokinetics; Serotonin; Serotonin uptake inhibitors; Serotonin Uptake Inhibitors - therapeutic use; Signal Transduction - drug effects
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2016.171

Basic studies exploring the importance of the cyclic adenosine monophosphate (cAMP) cascade in major depressive disorder (MDD) have noted that the cAMP cascade is downregulated in MDD and upregulated by antidepressant treatment. We investigated cAMP cascade activity by using 11 C-( R )-rolipram to image phosphodiesterase-4 (PDE4) in unmedicated MDD patients and after ~8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI). 11 C-( R )-rolipram positron emission tomographic (PET) scans were performed in 44 unmedicated patients during a major depressive episode and 35 healthy controls. Twenty-three of the 44 patients had a follow-up 11 C-( R )-rolipram PET scan ~8 weeks after treatment with an SSRI. Patients were moderately depressed (Montgomery–Åsberg Depression Rating Scale=30±6) and about half were treatment naïve. 11 C-( R )-rolipram binding was measured using arterial sampling to correct for individual differences in radioligand metabolism. We found in unmedicated MDD patients widespread, ~20% reductions in 11 C-( R )-rolipram binding compared with controls ( P =0.001). SSRI treatment significantly increased rolipram binding (12%, P