Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuropsychobiology 2006;53:157–168 DOI: 10.1159/000093342 Positron Emission Tomography Imaging of Risperidone Augmentation in Serotonin Reuptake Inhibitor-Refractory Patients Monte S. Buchsbaum Eric Hollander Stefano Pallanti Nicolò Baldini Rossi Jimcy Platholi Randall Newmark Rachel Bloom Erica Sood Mount Sinai School of Medicine, New York, N.Y., USA Introduction Functional neuroimaging of obsessive-compulsive dis- order (OCD) has most often identified differences from normal controls in the orbital prefrontal cortex, striatum, and cingulate gyrus. Positron emission tomography with FDG showed increased metabolic rates in the orbitofron- tal and cingulate gyrus region in patients with OCD [1–4]. SPECT studies have supported these patient hyperactivity findings in some [5, 6] but not all studies [7, 8]. The effect was more marked in more ventral areas than dorsal areas in one study that presented this dimension [9] and more marked in medial frontal cortex in one study [10]. Low metabolic rates assessed by positron emission tomogra- phy with 18 F-deoxyglucose (FDG-PET) in the striatum or thalamus [2, 3, 11–13] may also characterize the disorder (although high values in cingulate, pallidum/putamen and thalamus have also been reported [14]). SPECT stud- ies, consistent with FDG-PET studies, also found low flow in the caudate [15–17] as did some fMRI studies [18]. SPECT studies found both reduced [17] and high flow [6] in the thalamus, however. Lastly, event-related brain po- tential measures of components associated with the ante- rior cingulate [19] and frontostriatal systems [20, 21] have had enhanced amplitudes in OCD patients and subjects with obsessive-compulsive characteristics. A recent and useful meta-analysis confirmed orbitofrontal gyrus and caudate activation abnormalities in OCD [22] . These findings taken together have suggested a circuit alteration Key Words Obsessive-compulsive disorder  18 F-deoxyglucose  Caudate  Putamen  Cingulate gyrus Abstract We studied 15 nondepressed patients with obsessive-com- pulsive disorder (OCD) who were nonresponders to sero- tonin reuptake inhibitors with an additive trial of risperidone. Positron emission tomography with 18 F-deoxyglucose and magnetic resonance imaging was obtained at baseline and following 8 weeks of either risperidone or placebo in a dou- ble-blind parallel group design. Risperidone treatment was associated with significant increases in relative metabolic rate in the striatum, cingulate gyrus, the prefrontal cortex, especially in the orbital region, and the thalamus. Four of 9 patients who received risperidone showed clinical improve- ment (CGI score of 1 or 2 at 8 weeks) while none of the 6 pa- tients who received placebo showed improvement. Patients with low relative metabolic rates in the striatum and high relative metabolic rates in the anterior cingulate gyrus were more likely to show a clinical response. These metabolic pre- dictors of clinical response are consistent with earlier PET studies showing similar prediction when either neuroleptics or serotonin reuptake inhibitor treatments are administered individually. Our results are consistent with a frontostriatal circuit change related to both dopaminergic and serotoner- gic systems and with the presence of psychopharmacologi- cal subtypes within OCD. Copyright © 2006 S. Karger AG, Basel Received: June 9, 2005 Accepted after revision: March 2, 2006 Published online: May 16, 2006 Monte S. Buchsbaum Mount Sinai School of Medicine 1 Gustave Levy Place, Box 1505 New York, NY 10029 (USA) Tel. +1 212 241 5294, Fax +1 212 423 0819, E-Mail monte.buchsbaum@mssm.edu © 2006 S. Karger AG, Basel 0302–282X/06/0533–0157$23.50/0 Accessible online at: www.karger.com/nps