N-Acetyl-Aspartate in the dorsolateral prefrontal cortex in men with schizophrenia and auditory verbal hallucinations: A 1.5\u2009T Magnetic Resonance Spectroscopy Study

Marion Psomiades,Remy Bation,Marie-Françoise Suaud-Chagny,Marine Mondino,Frederic Haesebaert,Jerome Brunelin,Clara Fonteneau

doi:10.1038/s41598-018-22597-y

Abstract

Auditory verbal hallucinations (AVH) in patients with schizophrenia are linked to abnormalities within a large cerebral network including frontal and temporal regions. Whilst abnormalities of frontal speech production and temporal speech perception regions have been extensively studied, alterations of the dorsolateral prefrontal cortex (DLPFC), a region critically involved in the pathophysiology of schizophrenia, have rarely been studied in relation to AVH. Using 1.5 T proton magnetic resonance spectroscopy, this study examined the relationship between right and left DLPFCs N-AcetylAspartate (NAA) levels and the severity of AVH in patients with schizophrenia. Twenty-seven male patients with schizophrenia were enrolled in this study, 15 presented daily treatment-resistant AVH (AVH+) and 12 reported no AVH (no-AVH). AVH+ patients displayed higher NAA levels in the right DLPFC than no-AVH patients (p = 0.033). In AVH+ patients, NAA levels were higher in the right DLPFC than in the left (p = 0.024). No difference between the right and left DLPFC was observed in no-AVH patients. There was a positive correlation between NAA levels in the right DLPFC and the severity of AVH (r = 0.404, p = 0.037). Despite limited by magnetic field strength, these results suggest that AVH may be associated with increased NAA levels in the right DLPFC in schizophrenia.

Highlights

Auditory verbal hallucinations (AVH) have been linked to abnormal activities within bilateral inferior frontal and temporal regions associated with speech generation and speech perception[1,2]
The final analyzed samples consisted of 15 AVH+ patients with daily AVH (Positive and Negative Syndrome Scale (PANSS) P3 item > 3), and 12 no AVH (no-AVH) patients with no current or past history of AVH (PANSS P3 item ≤ 3)
NAA levels in the right dorsolateral prefrontal cortex (DLPFC) were higher in AVH+ patients than in no-AVH patients (6.67 ± 1.02)

Summary

Introduction

AVH have been linked to abnormal activities within bilateral inferior frontal and temporal regions associated with speech generation and speech perception[1,2]. Only few studies have explored the functional connectivity of the right DLPFC by comparing patients with AVH (AVH+patients) and patients with no AVH (no-AVH patients) In this line, measuring local neuronal activity by regional homogeneity analysis of BOLD, Cui et al.[8] put forward an increased contribution of the right DLPFC in AVH+ patients compared to no-AVH patients. P measured by in vivo 1H-MRS, Glx is an index of glutamate and glutamine levels This result suggested a relationship between high glutamatergic neurotransmission in the left DLPFC and AVH in schizophrenia. Another important brain metabolite that is often investigated using 1H-MRS is N-AcetylAspartate (NAA). As an exploratory outcome, we conducted correlation analyses to investigate the relationship between AVH severity and left and right DLPFC NAA levels

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