In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder.
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-HT(2A)) and dopamine (D(2)) receptor distribution. For this, we used [11C]MDL and [11C]Raclopride, highly selective antagonists of 5-HT(2A) and D(2) 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-HT(2A) 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-HT(2A) 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.
Vita-Salute San Raffaele University, Milan, Italy.
Daniela
D
Perani
Valentina
V
Garibotto
Alessandra
A
Gorini
Rosa Maria
RM
Moresco
Marta
M
Henin
Andrea
A
Panzacchi
Mario
M
Matarrese
Assunta
A
Carpinelli
Laura
L
Bellodi
Ferruccio
F
Fazio
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists; D014018:Tissue Distribution; D055815:Young Adult
D065127:Dopamine D2 Receptor Antagonists; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; D058830:Serotonin 5-HT2 Receptor Antagonists