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Johannes Tauscher, MD; Shitij Kapur, MD, PhD, FRCPC; N. Paul L. G. Verhoeff, MD, PhD, FRCPC; Douglas F. Hussey, BSc; Zafiris J. Daskalakis, MD, FRCPC; Sitra Tauscher-Wisniewski, MD; Alan A. Wilson, PhD; Sylvain Houle, MD, PhD, FRCPC; Siegfried Kasper, MD; Robert B. Zipursky, MD, FRCPC

Arch Gen Psychiatry. 2002;59:514-520.

Background  Results of postmortem studies show an elevation in serotonin-1A (5-hydroxytryptamine-1A [5-HT_1A]) receptor density in the prefrontal and temporal cortices of patients with schizophrenia. This study examined 5-HT_1A receptors in vivo in patients with schizophrenia using positron emission tomography and [carbonyl-¹¹C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-
N-(2-pyridinyl)cyclohexane carboxamide ([¹¹C]WAY-100635).

Methods  The 5-HT_1A binding potential of 14 antipsychotic drug–naïve patients with a DSM-IV diagnosis of schizophrenia was compared with that of 14 age-matched healthy controls. Positron emission tomography data were analyzed using 9 cortical regions of interest, which were delineated on a coregistered magnetic resonance image and transferred to the positron emission tomographic image, with the cerebellum as the reference region for a simplified reference tissue model. We also performed a voxel-wise comparison using statistical parametric mapping.

Results  The region of interest–based analysis revealed a significant mean ± SD cortical 5-HT_1A receptor binding potential increase of 7.1% ± 6.4% in patients with schizophrenia (F = 2.975; P = .02); local differences were +20% in the left medial temporal cortex (F = 9.339;P = .005) and +13% in the right mediotemporal cortex (F = 4.453; P = .045). There were no significant differences in regional tracer delivery or cerebellar [¹¹C]WAY-100635 uptake. The voxel-based analysis also confirmed a group difference in the left medial temporal cortex.

Conclusions  The biological significance of elevated 5-HT_1A receptor density in schizophrenia remains unclear. Given the location of 5-HT_1A receptors on pyramidal cells, this elevation may reflect an abnormal glutamatergic network. Our finding needs to be viewed in light of preclinical evidence supporting a role for 5-HT_1A receptors in mediating antipsychotic action and extrapyramidal adverse effects of drugs.

From the PET Centre (Drs Tauscher, Kapur, Verhoeff, Wilson, and Houle and Mr Hussey) and the Schizophrenia and Continuing Care Program (Drs Daskalakis, Tauscher-Wisniewski, and Zipursky), Centre for Addiction and Mental Health and the Department of Psychiatry, University of Toronto (Drs Kapur, Verhoeff, Daskalakis, Tauscher-Wisniewski, Wilson, Houle and Zipursky), Toronto Ontario; and the Department of General Psychiatry, University of Vienna, Vienna, Austria (Drs Tauscher and Kasper).

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