title: OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding.
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.
authors.affiliation: 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.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Adams
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, USA; Yale PET Center, Yale University School of Medicine, USA.
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Gallezot
authors.affiliation: Department of Psychology, Yale University School of Medicine, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Crowley
authors.affiliation: Department of Diagnostic Radiology, Yale University School of Medicine, USA; Yale PET Center, Yale University School of Medicine, USA.
authors.forename: Nabeel
authors.initials: N
authors.lastname: Nabulsi
authors.affiliation: Yale PET Center, Yale University School of Medicine, USA.
authors.lastname: James Ropchan
authors.affiliation: Yale PET Center, Yale University School of Medicine, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kichuk
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Simpson
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Eileen
authors.initials: E
authors.lastname: Billingslea
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Hannestad
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA; Child Study Center, Yale University School of Medicine, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Bloch
authors.affiliation: Department of Psychology, Yale University School of Medicine, USA; Child Study Center, Yale University School of Medicine, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Mayes
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, USA.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Bhagwagar
authors.affiliation: 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.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Carson
mesh_terms: D000328:Adult; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism* / Q000503:physiopathology*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000378:metabolism*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D055139:Sensory Gating; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists