title: Reduced serotonin type 1A receptor binding in panic disorder.
abstract: Recent animal models suggest that disturbances in serotonin type-1A receptor (5-HT(1A)R) 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-HT(1A)R 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-HT(1A)R 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-HT(1A)R 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-HT(1A)Rs in the pathophysiology of PD.
authors.affiliation: National Institutes of Health, National Institute of Mental Health, Mood and Anxiety Disorders Program, Bethesda, Maryland 20892-2670, USA. neumeisa@intra.nimh.nih.gov
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Earle
authors.initials: E
authors.lastname: Bain
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
authors.forename: Omer
authors.initials: O
authors.lastname: Bonne
authors.forename: David A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: William
authors.initials: W
authors.lastname: Eckelman
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D016584:Panic Disorder / Q000150:complications / Q000000981:diagnostic imaging* / Q000378:metabolism*; D010879:Piperazines; D011485:Protein Binding; D011725:Pyridines; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed
chemical_list: D008024:Ligands; C435829:N-(2-(4-(2-methoxyphenyl)piperazino)ethyl)-N-2-(pyridyl)-4-fluorocyclohexanecarboxamide; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A