The International Journal of Neuropsychopharmacology

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

Karen H. Adams a1, Elsebeth S. Hansen a2, Lars H. Pinborg a1, Steen G. Hasselbalch a1, Claus Svarer a1, Søren Holm a3, Tom G. Bolwig a2 and Gitte M. Knudsen a1c1
a1 Neurobiology Research Unit (NRU), University Hospital of Copenhagen, Denmark
a2 The Department of Psychiatry, University Hospital of Copenhagen, Denmark
a3 PET and Cyclotron Unit, University Hospital of Copenhagen, Denmark

Article author query
adams kh   [PubMed][Google Scholar] 
hansen es   [PubMed][Google Scholar] 
pinborg lh   [PubMed][Google Scholar] 
hasselbalch sg   [PubMed][Google Scholar] 
svarer c   [PubMed][Google Scholar] 
holm s   [PubMed][Google Scholar] 
bolwig tg   [PubMed][Google Scholar] 
knudsen gm   [PubMed][Google Scholar] 


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-HT2A receptor binding in 15 untreated OCD patients and in 15 age- and gender-matched healthy volunteers by magnetic resonance imaging and [18F]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 (DV3′) 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 (DV3′: 0.24±0.14) compared to the healthy control group (DV3′: 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-HT2A receptor binding. An increase in 5-HT2A receptor binding is found in the caudate nuclei of untreated patients with OCD. The up-regulation in 5-HT2A 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.

(Received March 17 2004)
(Reviewed June 20 2004)
(Revised September 15 2004)
(Accepted October 5 2004)

Key Words: OCD; positron emission tomography (PET); serotonin 5-HT2A receptors.

c1 Neurobiology Research Unit N9201, University Hospital of Copenhagen, 9 Blegdamsvej, Copenhagen, DK-2100 Denmark. Tel.: (+45) 3545 6720 Fax: (+45) 3545 6713 E-mail: