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Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users

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An Erratum to this article was published on 11 December 2013

Abstract

Rationale

Ketamine, a non-competitive NMDA receptor antagonist, induces acute effects resembling the positive, negative and cognitive symptoms of schizophrenia. Chronic use has been suggested to lead to persistent schizophrenia-like neurobiological changes.

Objectives

This study aims to test the hypothesis that chronic ketamine users have changes in brain neurochemistry and increased subthreshold psychotic symptoms compared to matched poly-drug users.

Methods

Fifteen ketamine users and 13 poly-drug users were included in the study. Psychopathology was assessed using the Comprehensive Assessment of At-Risk Mental State. Creatine-scaled glutamate (Glu/Cr), glutamate + glutamine (Glu + Gln/Cr) and N-acetyl aspartate (NAA/Cr) were measured in three brain regions—anterior cingulate, left thalamus and left medial temporal cortex using proton magnetic resonance spectroscopy.

Results

Chronic ketamine users had higher levels of subthreshold psychotic symptoms (p < 0.005, Cohen’s d = 1.48) and lower thalamic NAA/Cr (p < 0.01, d = 1.17) compared to non-users. There were no differences in medial temporal cortex or anterior cingulate NAA/Cr or in Glu/Cr or Glu + Gln/Cr in any brain region between the two groups. In chronic ketamine users, CAARMS severity of abnormal perceptions was directly correlated with anterior cingulate Glu/Cr (p < 0.05, r = 0.61—uncorrected), but NAA/Cr was not related to any measures of psychopathology.

Conclusions

The finding of lower thalamic NAA/Cr in chronic ketamine users may be secondary to the effects of ketamine use compared to other drugs of abuse and resembles previous reports in individuals at genetic or clinical risk of schizophrenia.

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Funding source

This work was supported by an MRC grant to Oliver Howes (grant code: MC_A656_5QD30).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Experimental Medicine, Imperial College London, London, UK

    James M. Stone, Johnson Fam & Oliver D. Howes

  2. Clinical Psychopharmacology Unit, University College London, London, UK

    Fiona Pepper, Hannah Furby & Celia Morgan

  3. Robert Steiner MRI Unit, Imaging Sciences Unit, Hammersmith Hospital, Imperial College London, London, UK

    Emer Hughes

  4. MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK

    Fiona Pepper & Oliver D. Howes

  5. Department of Psychosis Studies, Institute of Psychiatry, King’s College London, London, UK

    James M. Stone & Oliver D. Howes

  6. Centre for Neuroimaging Sciences, Institute of Psychiatry, King’s College London, London, UK

    James M. Stone

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  1. James M. Stone
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  2. Fiona Pepper
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  3. Johnson Fam
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Correspondence to James M. Stone.

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Celia Morgan and Oliver D. Howes contributed equally to this work.

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Stone, J.M., Pepper, F., Fam, J. et al. Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users. Psychopharmacology 231, 2107–2116 (2014). https://doi.org/10.1007/s00213-013-3354-8

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  • DOI: https://doi.org/10.1007/s00213-013-3354-8

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