Numerous findings indicate alterations in brain serotonin systems in obsessive-compulsive disorder (OCD). We investigated the in vivo availability of thalamus-hypothalamus serotonin transporters (SERT) in patients with DSM-IV OCD who displayed prominent behavioral checking compulsions (OC-checkers). Four hours after injection of [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]-beta-CIT), single photon emission computed tomography (SPECT) scans were performed in 24 medication-free non-depressed OC-checkers and 24 age- and gender-matched healthy controls. For quantification of brain serotonin transporter availability, a ratio of specific to non-displaceable [(123)I]-beta-CIT brain binding was used (V""(3)=(thalamus and hypothalamus-cerebellum)/cerebellum). Drug-free non-depressed OC-checkers showed an 18% reduced brain serotonin transporter availability in the thalamus and hypothalamus, as compared with healthy control subjects (1.38+/-0.19 vs 1.69+/-0.21; p<0.001). There was a strong negative correlation between severity of OC symptomatology (Y-BOCS scores) and SERT availability (r=-0.80; p<0.001). Moreover, we found a significant positive correlation between illness duration and serotonin transporter availability (r=0.43; p<0.05). This first report of significantly reduced [(123)I]-beta-CIT binding in the thalamus-hypothalamus region in OC-checkers suggests reduced brain serotonin transporter availability, which is more pronounced with increased severity of OC symptomatology and short duration of illness. The results provide direct evidence for an involvement of the serotonergic system in the pathophysiology of OCD.
Adult Case-Control Studies Cocaine/analogs & derivatives Cocaine/diagnostic use Cocaine/pharmacokinetics Female Humans Hypothalamus/drug effects Hypothalamus/metabolism Hypothalamus/radionuclide imaging* Male Middle Aged Obsessive-Compulsive Disorder*/diagnosis Obsessive-Compulsive Disorder*/pathology Obsessive-Compulsive Disorder*/radionuclide imaging Protein Binding/drug effects Radiopharmaceuticals/diagnostic use Radiopharmaceuticals/pharmacokinetics Serotonin Plasma Membrane Transport Proteins/metabolism* Statistics, Nonparametric Thalamus/drug effects Thalamus/metabolism Thalamus/radionuclide imaging* Tomography, Emission-Computed, Single-Photon/methods*