Neurometabolite differences in Autism as assessed with Magnetic Resonance Spectroscopy: a systematic review and meta-analysis

Abstract

Abstract1H-Magnetic Resonance Spectroscopy (MRS)is a non-invasive technique that can be used to quantify the concentrations of metabolites in the brain in vivo. MRS findings in the context of autism are inconsistent and conflicting. We performed asystematic review and meta-analysisof MRS studies observing glutamate and gamma-aminobutyric acid (GABA), as well as brain metabolites involved in energy metabolism (glutamine, creatine), neural integrity (e.g. n-acetyl aspartate (NAA), choline, myo-inositol) and neuro-inflammation (glutathione) in autism cohorts. Data were extracted and grouped by metabolite, brain region and several other factors before calculation of standardised effect sizes. Overall, we find significantly lower concentrations of GABA and NAA in autism, indicative of disruptions to the balance between excitation/inhibition within brain circuits, as well as neural integrity. Further analysis found these alterations are most pronounced in autistic children and in limbic brain regions relevant to autism phenotypes. Additionally, we show how study outcome varies due to demographic and methodological factors (e.g. medication use), emphasising the importance of conforming with consensus study designs and transparent reporting.HighlightsWe performed a meta-analysis ofMagnetic Resonance Spectroscopyfindings in autism.We find significantly lower concentrations of GABA and NAA in children with autism.These alterations were most pronounced in limbic brain regions.Demographic factors (including sex) contribute to MRS study outcome variation.