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The Journal of Neuroscience, January 21, 2004, 24(3):589-591; doi:10.1523/JNEUROSCI.4921-03.2004
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Reduced Serotonin Type 1A Receptor Binding in Panic Disorder
Alexander Neumeister,1 Earle Bain,2 Allison C. Nugent,2 Richard E. Carson,3 Omer Bonne,1 David A. Luckenbaugh,1 William Eckelman,3 Peter Herscovitch,3 Dennis S. Charney,1 * andWayne C. Drevets2 * National Institutes of Health (NIH), National Institute of Mental Health, Mood and Anxiety Disorders Program, 1Section on Experimental Therapeutics, and 2Section on Neuroimaging in Mood and Anxiety Disorders, and 3NIH, Positron Emission Tomography Imaging Center, Bethesda, Maryland 20892-2670
Recent animal models suggest that disturbances in serotonin type-1A receptor (5-HT1AR) function may contribute to chronic anxiety, although it is not clear at all whether such models constitute relevant models for panic disorder (PD) in humans. The selective 5-HT1AR radioligand [18F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (FCWAY) permits in vivo assessment of central 5-HT1AR binding using positron emission tomography (PET). We studied 16 unmedicated symptomatic outpatients with PD and 15 matched healthy controls. Seven patients had an additional diagnosis of a current major depressive episode, however PD was the primary diagnosis. A 120 min PET study of 5-HT1AR binding was acquired using a GE Advance scanner in three-dimensional mode. Using quantitative PET image analysis, regional values were obtained for [18F]-FCWAY volume of distribution (DV), corrected for plasma protein binding, and K1, the delivery rate of [18F]-FCWAY from plasma to tissue. MRI scanning was performed using a GE Signa Scanner (3.0 Tesla) to provide an anatomical framework for image analysis and partial volume correction of PET data. PD patients showed lower DV in the anterior cingulate (t = 4.3; p < 0.001), posterior cingulate (t = 4.1; p < 0.001), and raphe (t = 3.1; p = 0.004). Comparing patients with PD, patients with PD and comorbid depression, and healthy controls revealed that DVs did not differ between PD patients and PD patients with comorbid depression, whereas both patient groups differed significantly from controls. These results provide for the first time in vivo evidence for the involvement of 5-HT1ARs in the pathophysiology of PD.
Key words: anxiety; imaging; neuron; neurotransmitter; positron emission tomography; serotonin
Received Nov 3, 2003; revised November 17, 2003; accepted November 20, 2003.
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