1H-MRS in autism spectrum disorders: a systematic meta-analysis

We conducted a systematic review and meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies comparing autism spectrum disorder (ASD) patients with healthy controls, with the aim of profiling ASD-associated changes in the metabolites N-acetyl-aspartate (NAA) and Creatine (Cr). Meta-regression models of NAA and Cr levels were employed, using data from 20 eligible studies (N = 852), to investigate age-dependent differences in both global brain and region-specific metabolite levels, while controlling for measurement method (Cr-ratio versus absolute concentrations). Decreased NAA concentrations that were specific to children were found for whole-brain grey and white matter. In addition, a significant decrease in NAA was evident across age categories in the parietal cortex, the cerebellum, and the anterior cingulate cortex. Higher levels of Cr were observed for ASD adults than children in global grey matter, with specific increases for adults in the temporal lobe and decreased Cr in the occipital lobe in children. No differences were found for either NAA or Cr in the frontal lobes. These data provide some evidence that ASD is characterized by age-dependent fluctuations in metabolite levels across the whole brain and at the level of specific regions thought to underlie ASD-associated behavioural and affective deficits. Differences in Cr as a function of age and brain region suggests caution in the interpretation of Cr-based ratio measures of metabolites. Despite efforts to control for sources of heterogeneity, considerable variability in metabolite levels was observed in frontal and temporal regions, warranting further investigation.