In vivo PET study of 5HT2A serotonin and D2 dopamine dysfunction in drug-naive obsessive-compulsive disorder

Daniela Perani, Valentina Garibotto, Alessandra Gorini, Rosa Maria Moresco, Marta Henin, Andrea Panzacchi, Mario Matarrese, Assunta Carpinelli, Laura Bellodi, Ferruccio Fazio

Research output: Contribution to journalArticlepeer-review

Abstract

There are several lines of evidence, the majority indirect, suggesting that changes in serotonergic or dopaminergic neurotransmission may contribute to the pathogenesis of obsessive-compulsive disorder (OCD). We evaluated the co-occurrence of serotonergic and dopaminergic dysfunctions in OCD subjects, all drug-naive, with no co-morbidity and homogeneous for symptoms. Each subject underwent two positron emission tomography (PET) scans to measure in vivo both serotonin (5-HT2A) and dopamine (D2) receptor distribution. For this, we used [11C]MDL and [11C]Raclopride, highly selective antagonists of 5-HT2A and D2 receptors, respectively. The comparison with a control group was carried out using both voxel-wise (SPM2) and regions of interest (ROI) approaches. There was a significant reduction of 5-HT2A receptor availability in frontal polar, dorsolateral, and medial frontal cortex, as well as in parietal and temporal associative cortex of OCD patients. We also found a significant correlation between 5-HT2A receptor availability in orbitofrontal and dorsolateral frontal cortex and clinical severity, suggesting a specific role for serotonin in determining the OCD symptoms. There was also a significant reduction of [11C]Raclopride uptake in the whole striatum, particularly in the ventral portion, possibly reflecting endogenous dopaminergic hyperactivity. The co-existence of serotonergic and dopaminergic dysfunction in the same homogeneous group of drug-naive OCD patients provides in vivo evidence for the complex molecular mechanisms of OCD, and represents the basis for further studies on the effect of therapeutic agents with specific modulatory effects on these neurotransmission systems.

Original languageEnglish
Pages (from-to)306-314
Number of pages9
JournalNeuroImage
Volume42
Issue number1
DOIs
Publication statusPublished - Aug 1 2008

Keywords

  • 5HT
  • D
  • Dopamine
  • Obsessive-compulsive disorder
  • PET
  • Serotonin

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

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