Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Tauscher, J. et al.

Tauscher, Kapur, Verhoeff, Hussey, Daskalakis, Tauscher-Wisniewski, Wilson, Houle, Kasper, Zipursky,

Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635.

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-(11)C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide ([(11)C]WAY-100635). METHODS: The 5-HT(1A) binding potential of 14 antipsychotic drug-naÃ¯ve 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 medio temporal cortex (F = 4.453; P =.045). There were no significant differences in regional tracer delivery or cerebellar [(11)C]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.[1]

References

Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635. Tauscher, J., Kapur, S., Verhoeff, N.P., Hussey, D.F., Daskalakis, Z.J., Tauscher-Wisniewski, S., Wilson, A.A., Houle, S., Kasper, S., Zipursky, R.B. Arch. Gen. Psychiatry (2002) [Pubmed]

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