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A Positron Emission Tomography Study of the 5-Ht1A Receptor in Schizophrenia and during Clozapine TreatmentCyclotron Unit, CSC, The Hammersmith Hospital, Imperial College London, London, UKrabantick{at}doctors.org.uk
Cyclotron Unit, CSC, The Hammersmith Hospital, Imperial College London, London, UK
Community Mental Health Resource Centre, Southall/Norwood Hospital, Southall, Middlesex, UK
CPRS, Fulbourn Hospital, Fulbourn, Cambridge, UK
City Central CMHT, Warneford Hospital, Oxford, UK
Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK
Cyclotron Unit, CSC, The Hammersmith Hospital, Imperial College London, London, UK Several post-mortem studies have identified increases of 5-HT1A receptor density in frontal cortical areas in schizophrenic patients, and one has found increases in the cerebellar vermis. Clozapine has moderate affinity at the 5-HT1A receptor, and this may be of therapeutic importance. This positron emission tomography (PET) study attempted to replicate the post-mortem findings in vivo and sought an occupancy effect of clozapine at the 5-HT1A receptor. We recruited healthy controls, and patients with schizophrenia who were divided into those receiving clozapine and those receiving neuroleptics lacking 5-HT1A receptoraffinity. Each volunteer received a PET scan, using the 5-HT1A receptor radioligand [carbonyl-11C]WAY-100635, and a magnetic resonanceimaging scan. The cerebellar vermis was examined by comparing time-activity data between groups. For other brain regions (the raphe and subdivisions of the cerebral cortex), binding potential images weregenerated to reflect receptor density, then analysed using ‘region of interest’ and voxel-by-voxel methods. No significant changes of 5-HT1A receptor density were found in schizophrenic patients compared tocontrols. Two other PET studies, containing drug naïve rather thanmedicated schizophrenic patients, have also reported no increase in 5-HT1A receptor density in the frontal cortex. The results obtained in vivo bring into question the importance of the receptor in thepathophysiology of the illness. Clozapine did not occupy the 5-HT1A receptor at clinical doses. This is consistent with recent related PET results: 5-HT1A agonists do not appear to measurably block the binding of antagonist radiotracers in man at doses that are pharmacologically active but which are limited by tolerability.
Key Words: clozapine • emission-computed tomography • 5-HT1A receptor • 5-HT1 receptor agonist • schizophrenia • WAY-100635
Journal of Psychopharmacology, Vol. 18, No. 3,
346-354 (2004) This article has been cited by other articles:
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