Christopher Pittenger1, Thomas G Adams2, Jean-Dominique Gallezot3, Michael J Crowley4, Nabeel Nabulsi3, Hong Gao5, Stephen A Kichuk2, Ryan Simpson2, Eileen Billingslea2, Jonas Hannestad2, Michael Bloch6, Linda Mayes7, Zubin Bhagwagar2, Richard E Carson8. 1. Department of Psychiatry, Yale University School of Medicine, USA; Department of Psychology, Yale University School of Medicine, USA; Child Study Center, Yale University School of Medicine, USA; Interdepartmental Neuroscience Program, Yale University School of Medicine, USA. Electronic address: Christopher.pittenger@yale.edu. 2. Department of Psychiatry, Yale University School of Medicine, USA. 3. Department of Diagnostic Radiology, Yale University School of Medicine, USA; Yale PET Center, Yale University School of Medicine, USA. 4. Department of Psychology, Yale University School of Medicine, USA. 5. Yale PET Center, Yale University School of Medicine, USA. 6. Department of Psychiatry, Yale University School of Medicine, USA; Child Study Center, Yale University School of Medicine, USA. 7. Department of Psychology, Yale University School of Medicine, USA; Child Study Center, Yale University School of Medicine, USA. 8. Department of Diagnostic Radiology, Yale University School of Medicine, USA; Department of Biomedical Engineering, Yale University School of Medicine, USA; Yale PET Center, Yale University School of Medicine, USA.
Abstract
Obsessive-compulsive disorder (OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using (11)C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCD patients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability ((11)C-P943 BPND); however, the relationship between PPI and (11)C-P943 BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCD patients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.
pan class="Disease">Obsessive-compulsive disorder (n>n class="Disease">OCD) is characterized by impaired sensorimotor gating, as measured using prepulse inhibition (PPI). This effect may be related to abnormalities in the serotonin (5-HT) system. 5-HT1B agonists can impair PPI, produce OCD-like behaviors in animals, and exacerbate OCD symptoms in humans. We measured 5-HT1B receptor availability using (11)C-P943 positron emission tomography (PET) in unmedicated, non-depressed OCDpatients (n=12) and matched healthy controls (HC; n=12). Usable PPI data were obtained from 20 of these subjects (10 from each group). There were no significant main effects of OCD diagnosis on 5-HT1B receptor availability ((11)C-P943BPND); however, the relationship between PPI and (11)C-P943BPND differed dramatically and significantly between groups. 5-HT1B receptor availability in the basal ganglia and thalamus correlated positively with PPI in controls; these correlations were lost or even reversed in the OCD group. In cortical regions there were no significant correlations with PPI in controls, but widespread positive correlations in OCDpatients. Positive correlations between 5-HT1B receptor availability and PPI were consistent across diagnostic groups only in two structures, the orbitofrontal cortex and the amygdala. Differential associations of 5-HT1B receptor availability with PPI in patients suggest functionally important alterations in the serotonergic regulation of cortical/subcortical balance in OCD.
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