Abstract | CONTEXT: OBJECTIVE: DESIGN: The M2 receptor binding was compared between unmedicated subjects with major depressive disorder or bipolar disorder during depression vs healthy controls, using positron emission tomography and [18F] FP-TZTP ( fluorodopa F 18 [3-(3-[3-fluoroproply]thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine), a selective M2 receptor radioligand. SETTING: Outpatients at the National Institutes of Health. PARTICIPANTS: MAIN OUTCOME MEASURES: The primary outcome parameter was [(18)F] FP-TZTP distribution volume, which is proportional to the product of receptor density and affinity and, in the case of [(18)F] FP-TZTP, is known to be sensitive to endogenous acetylcholine concentrations. The relationship between illness severity, as rated using the Montgomery-Asberg Depression and Hamilton Anxiety Rating scales, and distribution volume also was assessed. RESULTS: The mean anterior cingulate cortex distribution volume differed across groups (F55 = 3.4; P = .04), and this difference was accounted for by significantly lower binding in bipolar disorder compared with both major depressive disorder and control groups. CONCLUSIONS: The mean M2 receptor binding in subjects with bipolar disorder was reduced relative to both healthy controls and subjects with major depressive disorder, to an extent that correlated with depressive symptoms. The reduction in the bipolar disorder group could be accounted for either by a reduction in M2 receptor density or affinity or an elevation in endogenous acetylcholine levels. To our knowledge, these data provide the first direct evidence that altered M2 receptor function contributes to mood dysregulation in bipolar disorder.
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Authors | Dara M Cannon, Richard E Carson, Allison C Nugent, William C Eckelman, Dale O Kiesewetter, Joan Williams, Denise Rollis, Michele Drevets, Shilpa Gandhi, Gerardo Solorio, Wayne C Drevets |
Journal | Archives of general psychiatry
(Arch Gen Psychiatry)
Vol. 63
Issue 7
Pg. 741-7
(Jul 2006)
ISSN: 0003-990X [Print] United States |
PMID | 16818863
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Pyridines
- Receptor, Muscarinic M2
- Thiazoles
- Fluorodeoxyglucose F18
- FP-TZTP
- Acetylcholine
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Topics |
- Acetylcholine
(metabolism)
- Adult
- Ambulatory Care
- Bipolar Disorder
(diagnosis, metabolism)
- Brain
(diagnostic imaging, metabolism)
- Depressive Disorder, Major
(diagnosis, metabolism)
- Female
- Fluorodeoxyglucose F18
(metabolism)
- Gyrus Cinguli
(diagnostic imaging, metabolism)
- Humans
- Image Processing, Computer-Assisted
- Imaging, Three-Dimensional
- Magnetic Resonance Imaging
- Male
- Positron-Emission Tomography
(statistics & numerical data)
- Pyridines
(metabolism)
- Radioligand Assay
- Receptor, Muscarinic M2
(metabolism)
- Synapses
(diagnostic imaging, metabolism)
- Thiazoles
(metabolism)
- Tissue Distribution
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