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

1H-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 a systematic review and meta-analysis of 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. Highlights ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement TA was supported by an MRC Clinician Scientist Fellowship and Transition Support Award. AT and NP and TA received support from the Medical Research Council Centre for Neurodevelopmental Disorders at Kings College London. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: These data from this meta-analysis are from previously published studies. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data and analysis files are available