Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei

Int J Neuropsychopharmacol. 2005 Sep;8(3):391-401. doi: 10.1017/S1461145705005055. Epub 2005 Apr 1.

Abstract

The pharmacological efficacy of serotonergic-acting drugs suggest that patients with obsessive-compulsive disorder (OCD) may have alterations in their cerebral serotonergic (5-HT) receptor system, and previous neuroimaging studies of OCD patients have shown abnormalities in several fronto-subcortical regions. In this study we investigated cerebral 5-HT(2A) receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [(18)F]altanserin positron emission tomography (PET). Eleven of the patients were rescanned with PET after receiving treatment with a selective serotonin reuptake inhibitor (SSRI). The distribution volumes of specific tracer binding (DV(3)') were calculated for 12 brain regions, and comparisons were made between: (1) healthy volunteers vs. untreated OCD patients, (2) healthy volunteers vs. treated OCD patients, and (3) OCD patients before and during treatment. When comparing the distribution volume for specific fronto-subcortical brain regions, significantly higher values were recorded in the caudate nuclei in OCD patients (DV(3)': 0.24+/-0.14) compared to the healthy control group (DV(3)': 0.15+/-0.13) (p<0.05, Wilcoxon matched-pairs test). This difference between groups was not present after treatment with SSRIs. There was no correlation between the severity of OCD symptoms and 5-HT(2A )receptor binding. An increase in 5-HT(2A) receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT(2A) receptors might be compensatory for a lack of serotonin in the feedback loop between the thalamus and orbito-frontal cortex, the caudate nuclei, and the globus pallidus.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Brain Mapping
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism*
  • Caudate Nucleus / pathology
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Ketanserin / analogs & derivatives
  • Ketanserin / pharmacokinetics
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / metabolism*
  • Obsessive-Compulsive Disorder / pathology
  • Positron-Emission Tomography / methods
  • Protein Binding / drug effects
  • Protein Binding / physiology
  • Receptor, Serotonin, 5-HT2A / metabolism*

Substances

  • Antidepressive Agents
  • Fluorine Radioisotopes
  • Receptor, Serotonin, 5-HT2A
  • altanserin
  • Ketanserin