title: Glutamate, N-acetyl aspartate and psychotic symptoms in chronic ketamine users.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Experimental Medicine, Imperial College London, London, UK, james.m.stone@kcl.ac.uk.
authors.forename: James M
authors.initials: JM
authors.lastname: Stone
authors.forename: Fiona
authors.initials: F
authors.lastname: Pepper
authors.forename: Johnson
authors.initials: J
authors.lastname: Fam
authors.forename: Hannah
authors.initials: H
authors.lastname: Furby
authors.forename: Emer
authors.initials: E
authors.lastname: Hughes
authors.forename: Celia
authors.initials: C
authors.lastname: Morgan
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011618:Psychotic Disorders / Q000150:complications* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000150:complications* / Q000378:metabolism; D055815:Young Adult
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007649:Ketamine; C000179:N-acetylaspartate