Investigating neuroinflammation in schizophrenia: a proton magnetic resonance spectroscopy (1H-MRS) and cytokine study

Burger, Antoinette

Investigating neuroinflammation in schizophrenia: a proton magnetic resonance spectroscopy (1H-MRS) and cytokine study

Doctoral Thesis

2022

Abstract

Introduction: There are similarities in the phenomenology and psychobiology of schizophrenia and methamphetamine psychosis, with evidence of alterations in glutamatergic function in both conditions, and of involvement of inflammatory pathways in schizophrenia and methamphetamine abuse. Few studies have directly compared glutamatergic and inflammatory metabolites in thalamo-cortical circuitry across schizophrenia and methamphetamine-induced psychosis or assessed the relationship between such metabolites and inflammatory markers in either disorder. This study aimed to 1) compare glutamatergic and neuroinflammatory metabolites in thalamo-cortical circuitry in schizophrenia and methamphetamine-induced psychosis, and 2) to investigate associations between glutamatergic metabolites, neuroinflammatory metabolites, and peripheral cytokine levels in both disorders. Methods: One hundred and sixteen participants were recruited – 44 with schizophrenia, 34 with methamphetamine-induced psychosis, and 38 healthy controls. All participants underwent a magnetic resonance imaging scan, which included magnetic resonance spectroscopy with voxels located in the anterior cingulate cortex (ACC) and left thalamus as well as a chemical-shift imaging 2-dimensional slice. Neurometabolites obtained included glutamatergic metabolites (glutamate (Glu), glutamine (Gln) and glutamate plus glutamine (Glx)) and neuroinflammatory metabolites (myo-inositol (mI), n-acetyl-aspartate (NAA), and n-acetyl aspartate plus n-acetyl-aspartyl glutamate (NAA+NAAG)). Absolute metabolite concentrations are reported. Serum cytokine concentrations were measured. For group differences, parametric data were analysed with one-way analysis of variance and nonparametric data analysed with Kruskal Wallis tests, followed by relevant post-hoc tests. Associations were determined using Spearman's rank-order coefficient. Significant associations were followed by comparison of correlations of independent samples. Results: There were no differences between neurometabolites in schizophrenia and healthy controls. The methamphetamine-induced psychotic disorder group had lower relative nacetyl-aspartate plus n-acetyl-aspartyl glutamate in left dorsolateral prefrontal cortex and left frontal white matter, compared to healthy controls. In schizophrenia, positive associations were found between absolute glutamatergic metabolites and absolute inflammatory metabolites in the anterior cingulate cortex (n-acetyl-aspartate with glutamate, lower n-acetylaspartate with n-acetyl-aspartyl glutamate plus glutamate, myo-inositol with glutamate, myoinositol with glutamate plush glutamine). Several positive relationships were found in mI between different brain areas of the thalamo-cortical circuitry in the methamphetamineinduced psychosis group. Conclusion: In schizophrenia, the associations between lower glutamatergic and lower neuroinflammatory metabolites suggest dysfunction in neuronal tissues in the glutamateglutamine cycle within the thalamo-cortical circuit. In methamphetamine-induced psychosis, lower NAA+NAAG/Cr+PCr in the left dorsolateral prefrontal cortex and left frontal white mattersuggest compromised neuronal integrity associated with chronic disease progression. Furthermore, in this group the associations of mI between brain areas in the thalamo-cortical 6 circuit suggest that neuroinflammatory pathways in this circuit are dysfunctional. Taken together, there may be important differences in the neurobiology of schizophrenia and methamphetamine-induced psychosis.

Keywords

health sciences

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PhD / Doctoral

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