Journal article
cAMP Signaling in Brain is Decreased in Unmedicated Depressed Patients and Increased by Treatment with a Selective Serotonin Reuptake Inhibitor
Molecular psychiatry, Vol.22(5), pp.754-759
05/2017
DOI: 10.1038/mp.2016.171
PMCID: PMC5388600
PMID: 27725657
Abstract
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 approximately eight weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).
11
C-(
R
)-rolipram 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 approximately eight 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 to controls (P=0.001). SSRI treatment significantly increased rolipram binding (12%, P<0.001) with significantly greater increases observed in older patients (P<0.001). Rolipram binding did not correlate with severity of baseline symptoms, and increased rolipram binding during treatment did not correlate with symptom improvement. In brief, consistent with the results of basic studies, PDE4 was decreased in unmedicated MDD patients and increased after SSRI treatment. The lack of correlation between PDE4 binding and depressive symptoms could reflect the heterogeneity of the disease and/or the heterogeneity of the target, given that PDE4 has four subtypes. These results suggest that PDE4 inhibitors, which increase cAMP cascade activity, may have antidepressant effects.
Details
- Title: Subtitle
- cAMP Signaling in Brain is Decreased in Unmedicated Depressed Patients and Increased by Treatment with a Selective Serotonin Reuptake Inhibitor
- Creators
- Masahiro Fujita - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesErica M Richards - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesMark J Niciu - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesDawn F Ionescu - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesSami S Zoghbi - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesJinsoo Hong - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesSanjay Telu - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesChristina S Hines - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesVictor W Pike - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesCarlos A Zarate - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United StatesRobert B Innis - Experimental Therapeutics & Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.22(5), pp.754-759
- DOI
- 10.1038/mp.2016.171
- PMID
- 27725657
- PMCID
- PMC5388600
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Language
- English
- Date published
- 05/2017
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984003956302771
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