Increased prefrontal and hippocampal glutamate concentration in first episode paranoid-hallucinatory schizophrenia: evidence from a magnetic resonance spectroscopy study

Background: Glutamatergic dysfunction has been implicated in the pathophysiology of 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 first-episode paranoid-hallucinatory schizophrenia using high-field magnetic resonance spectroscopy. Methods: Nine patients with first-episode 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: We found increased levels of glutamate in prefrontal and limbic areas in patients with schizophrenia. Our data support the hypothesis of glutamatergic dysfunction in schizophrenia. A modell illustrating a possible glutamatergic pathogenesis of schizophrenia will be presented.