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First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients

Molecular Psychiatry volume 11, pages 118–119 (2006)Cite this article

Evidence suggests a deficit in NMDA receptor function is one underlying cause for schizophrenia.1 We tested this hypothesis using the highly selective single photon emission tomography (SPET) NMDA receptor tracer, [123I]CNS-1261. Significant reductions in relative NMDA receptor binding in left hippocampal medication-free, but not antipsychotic-treated, schizophrenic patients compared to healthy subjects were found.

[123I]CNS-1261 is an intrachannel NMDA receptor SPET probe that has been extensively developed with quantitative kinetic modeling methods in humans.2 Direct challenge with ketamine has revealed a displacement greater than test–retest in all brain regions (max 20%).3 We have recently reported the results of a study examining the impact of schizophrenia and antipsychotic treatment on [123I]CNS-1261 binding.4 Total volume of distribution (VT) was the main outcome measure. VT is a measure that is linearly proportional to Bmax/Kd, but does not control for f1 and f2 (free fractions of tracer in plasma and in tissue, respectively). We now extend the analysis using normalized-to-cortex binding indices to evaluate regional NMDA receptor binding incorporating the effects of nonspecific binding.

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References

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Acknowledgements

RA Bressan was financially supported by research grants from CAPES (Brazil), Janssen Pharmaceutica Inc., and Sanofi-Syntelabo, LS Pilowsky was financially supported by a UK Medical Research Council (MRC) Senior Clinical Research Fellowship. K Erlandsson and RS Mulligan were financially supported on a UK MRC Senior clinical research fellowship. JH Krystal was funded by NIH: KO5 AA 014906-02, Department of Veterans Affairs: VA Alcohol Research Center, VA Schizophrenia Biological Research Center. LSP, RAB, JMS, KE, RSM, PJE contributed to the study execution, analysis and writing up of the data. JHK contributed to the interpretation and writing up of the data.

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Authors and Affiliations

  1. King's College London, Institute of Psychiatry, London, UK

    L S Pilowsky, R A Bressan & J M Stone

  2. Institute of Nuclear Medicine, University College London, London, UK

    L S Pilowsky, K Erlandsson, R S Mulligan & P J Ell

  3. Department of Psychiatry, Yale University, New Haven, CT, USA

    J H Krystal

  4. VA Connecticut Healthcare System, West Haven, CT, USA

    J H Krystal

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  1. L S Pilowsky
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  2. R A Bressan
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  3. J M Stone
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  7. P J Ell
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Pilowsky, L., Bressan, R., Stone, J. et al. First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients. Mol Psychiatry 11, 118–119 (2006). https://doi.org/10.1038/sj.mp.4001751

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