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

Stone, James M., Pepper, Fiona, Fam, Johnson, Furby, Hannah ORCID: https://orcid.org/0000-0002-7279-1812, Hughes, Emer, Morgan, Celia and Howes, Oliver D. 2014. Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users. Psychopharmacology 231 (10) , pp. 2107-2116. 10.1007/s00213-013-3354-8

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Glutamate; N-Acetyl aspartate; Psychotic symptoms; Ketamine
Additional Information:	Published online November 2013.
Publisher:	Springer
ISSN:	0033-3158
Date of Acceptance:	4 November 2013
Last Modified:	25 Oct 2022 09:03
URI:	https://orca.cardiff.ac.uk/id/eprint/57027

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