title: Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei.
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.
authors.affiliation: Neurobiology Research Unit (NRU), University Hospital of Copenhagen, Denmark.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Adams
authors.forename: Elsebeth S
authors.initials: ES
authors.lastname: Hansen
authors.forename: Lars H
authors.initials: LH
authors.lastname: Pinborg
authors.forename: Steen G
authors.initials: SG
authors.lastname: Hasselbalch
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: Søren
authors.initials: S
authors.lastname: Holm
authors.forename: Tom G
authors.initials: TG
authors.lastname: Bolwig
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D005462:Fluorine Radioisotopes; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin