Serotonin 2A receptors in obsessive-compulsive disorder: A positron emission tomography study with [ ¹¹C]MDL 100907

Background: Serotonergic abnormalities are hypothesized to contribute to obsessive-compulsive disorder (OCD). This study used positron emission tomography with the radioligand [ ¹¹C]MDL 100907 to examine whether the distribution of serotonin 2A (5-HT _2A) receptors is altered in OCD. Methods: Nineteen OCD subjects, free of psychiatric medications and depression, and 19 matched healthy subjects underwent positron emission tomography scans following injection of [ ¹¹C]MDL 100907. Total distribution volumes were derived by kinetic analysis using the arterial input function. Two measures of 5-HT _2A availability were computed: the ratio at equilibrium of specifically bound radiotracer either to nondisplaceable radiotracer in tissue (BP _ND) or to unmetabolized tracer in arterial plasma (BP _p). Groups were compared using a region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps. ROIs included cortical (orbitofrontal, dorsolateral prefrontal, medial prefrontal, anterior cingulate, temporal, parietal, occipital, and insular cortex) and limbic (entorhinal cortex, parahippocampal gyrus, and medial temporal lobe) regions. Results: No significant group differences were observed in [ ¹¹C]MDL 100907 BP _ND or BP _p in the ROIs or in the voxelwise analysis of BP _ND maps. There was a significant correlation in the orbitofrontal cortex between [ ¹¹C]MDL 100907 binding and age of onset, with earlier age of onset associated with higher binding. Conclusions: Adults with OCD are not characterized as a group by major changes in 5-HT _2A availability in cortical or limbic brain regions. Further research is warranted to examine potential differences in 5-HT _2A availability between early- and late-onset OCD and to assess 5-HT _2A function in relation to other neurotransmitter systems implicated in OCD.