Glutamate in dorsolateral prefrontal cortex and auditory verbal hallucinations in patients with schizophrenia: A 1H MRS study

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Purpose:Glutamatergic models of psychosis propose that dysfunction of N-methyl-d-aspartate (NMDA) receptors, and associated excess of glutamate, may underlie psychotic experiences in people with schizophrenia. However, little is known about the specific relation between glutamate and auditory verbal hallucinations (AVH) in patients with psychosis. In this study, levels of glutamate + glutamine (Glx) in the left lateral prefrontal lobe were determined using proton magnetic resonance spectroscopy (1H MRS) to calculate their association with AVH.Methods:Sixty-seven patients with schizophrenia and thirty healthy control participants (HC) underwent magnetic resonance spectroscopy (MRS) to estimate levels of Glx in the white matter of the left prefrontal lobe. The spectrum was estimated from an 8 mm3 voxel placed in the left lateral prefrontal region, belonging to both the cingulum and forceps minor. Patients with lifetime AVH (AVH group; n = 45) and patients without lifetime AVH were compared (NoAVH group; n = 22) to control participants.Results:Levels of Glx were significantly different between the groups (F(2,94) = 5.27, p = 0.007). Planned comparisons showed that higher Glx levels were found in control participants than in the total patient group (p = 0.010). However, patients with lifetime AVH had higher levels of Glx compared to patients without lifetime AVH (p = 0.019). Creatin levels were similar in all three groups. We found no association between Glx and the severity of symptoms (item P3 of the PANSS or PANSS positive subscale).Conclusion:The higher Glx levels in patients with lifetime AVH as compared to patients without lifetime AVH suggest a mediating role for Glx in AVH. Our results are consistent with a previous study that found similar decreased levels of Glx in patients with schizophrenia, and increased levels in an AVH group as compared to a NoAVH group. The role of the glutamatergic system deserves further investigation, for example in different brain regions and in relation to clinical variables.HIGHLIGHTWe examined glutamate + glutamine (Glx) levels in the left prefrontal tracts of patients with schizophrenia.Schizophrenia patients have lower levels of Glx than healthy controls in this specific region.Patients with AVH experience have Glx levels closer to healthy controls compared to patients who have never experienced AVH.Results point toward a mediating role of Glx in auditory verbal hallucinations.Future studies should investigate Glx levels in association to AVH in different brain areas.Further investigations should be directed towards illuminating cellular mechanisms of Glx dysfunction.

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