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Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.

ABSTRACT: RATIONALE:N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brain glutamate levels in schizophrenia have not been evaluated. OBJECTIVES:The aim of this study was to examine whether a single dose of NAC can alter brain glutamate levels. A secondary aim was to characterise its effects on regional brain perfusion. METHODS:In a double-blind placebo-controlled crossover study, 19 patients with a diagnosis of schizophrenia underwent two MRI scans, following oral administration of 2400 mg NAC or matching placebo. Proton magnetic resonance spectroscopy was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling was used to assess the effects of NAC on resting cerebral blood flow (rCBF) in the same regions. RESULTS:Relative to the placebo condition, the NAC condition was associated with lower levels of Glx/Cr, in the ACC (P?

SUBMITTER: McQueen G

PROVIDER: S-EPMC6182588 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.

McQueen Grant G Lally John J Collier Tracy T Zelaya Fernando F Lythgoe David J DJ Barker Gareth J GJ Stone James M JM McGuire Philip P MacCabe James H JH Egerton Alice A

Psychopharmacology 20180823 10

<h4>Rationale</h4>N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brain glutamate levels in schizophrenia have not been evaluated.<h4>Objectives</h4>The aim of this study was to examine whether a single dose of NAC can alter brain glutamate levels. A secondary aim was to characterise its effects on regional brain perfusion.<h4>Methods</h4>I ...[more]

PMID: 30141055

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Project description:Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p < 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p < 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = -0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = -0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = -0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p < 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p < 0.001). Proportion of males was negatively associated with MFC glutamate (z = -0.02, p < 0.001) and frontal white matter Glx (z = -0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies.

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Dataset Information

Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.

Publications

Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.

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