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

James M. Stone, Fiona Pepper, Johnson Fam, Hannah Furby, Emer Hughes, Celia Morgan, Oliver D. Howes
2013 Psychopharmacology  
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 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
more » ... ncluded 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) was measured in 3 brain regionsanterior 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.
doi:10.1007/s00213-013-3354-8 pmid:24264567 fatcat:s4r6ce2pwfgc7hqepxij4byqdm