Increased prefrontal and hippocampal glutamate concentration in schizophrenia: evidence from a magnetic resonance spectroscopy study.
BACKGROUND
Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. However, so far there is limited direct evidence of altered in vivo glutamate concentrations in the brains of patients with schizophrenia. To test the hypothesis that altered glutamatergic neurotransmission might play a role in the pathogenesis of schizophrenia, we measured glutamate and glutamine concentrations in the prefrontal cortex and the hippocampus of patients with chronic schizophrenia using high-field magnetic resonance spectroscopy.


METHODS
Twenty-one patients with schizophrenia and 32 healthy volunteers were examined clinically and by means of short echo time single voxel magnetic resonance spectroscopy of the dorsolateral prefrontal cortex and the hippocampus. Absolute concentrations of neurometabolites were calculated.


RESULTS
Absolute concentrations of glutamate were significantly higher in the prefrontal cortex and the hippocampus in the patient group. Factorial analysis of variance (ANOVA) revealed no significant interactions between duration of schizophrenia, number of hospitalizations, or type of antipsychotic medication and glutamate concentrations. Increased prefrontal glutamate concentrations were associated with poorer global mental functioning.


CONCLUSIONS
This is the first study that reports increased levels of glutamate in prefrontal and limbic areas in patients with schizophrenia. Our data support the hypothesis of glutamatergic dysfunction in schizophrenia.
van Elst
Ludger Tebartz
LT
Department for Psychiatry, Albert-Ludwigs-University, Freiburg, Germany. ludger_vanelst@psyallg.ukl.uni-freiburg.de
Valerius
Gabi
G
Büchert
Martin
M
Thiel
Thorsten
T
Rüsch
Nicholas
N
Bubl
Emanuel
E
Hennig
Jürgen
J
Ebert
Dieter
D
Olbrich
Hans M
HM
D000328:Adult; D000704:Analysis of Variance; D002908:Chronic Disease; D004569:Electroencephalography; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000378:metabolism*; D012565:Schizophrenic Psychology; D013569:Synapses / Q000378:metabolism
D005973:Glutamine; D018698:Glutamic Acid