OCD is associated with an altered association between sensorimotor gating and cortical and subcortical 5-HT1b receptor binding

J Affect Disord. 2016 May 15;196:87-96. doi: 10.1016/j.jad.2016.02.021. Epub 2016 Feb 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Basal Ganglia / metabolism
  • Case-Control Studies
  • Female
  • Humans
  • Inhibition, Psychological
  • Male
  • Obsessive-Compulsive Disorder / metabolism*
  • Obsessive-Compulsive Disorder / physiopathology*
  • Positron-Emission Tomography
  • Prefrontal Cortex / metabolism*
  • Receptor, Serotonin, 5-HT1B / metabolism*
  • Sensory Gating*
  • Serotonin 5-HT1 Receptor Agonists / metabolism
  • Thalamus / metabolism

Substances

  • Receptor, Serotonin, 5-HT1B
  • Serotonin 5-HT1 Receptor Agonists