Increased cerebral lactate levels in adults with autism spectrum disorders compared to non-autistic controls: a magnetic resonance spectroscopy study

Introduction: Autism Spectrum Disorder (ASD) encompasses a heterogeneous group with varied phenotypes and etiologies. Identifying pathogenic subgroups could facilitate targeted treatments. One promising avenue is investigating energy metabolism, as mitochondrial dysfunction has been implicated in a subgroup of ASD. Lactate, an indicator of energy metabolic anomalies, may serve as a potential biomarker for this subgroup. This study aimed to examine cerebral lactate (Lac+) levels in high-functioning adults with ASD, hypothesizing elevated mean Lac+ concentrations in contrast to neurotypical controls (NTCs). Materials: and Methods: Magnetic resonance spectroscopy (MRS) was used to study cerebral Lac+ in 71 adults with ASD and NTC, focusing on the posterior cingulate cortex (PCC). After quality control, 64 ASD and 58 NTC participants remained. Lac+ levels two standard deviations above the mean of the control group were considered elevated. Results: : Mean PCC Lac+ levels were significantly higher in the ASD group than in the NTC group (p=0.028; Cohen's d = 0.404), and 9.4% of the ASD group had elevated levels as compared to 0% of the NTCs (p=0.029). No significant correlation was found between blood serum lactate levels and MRS-derived Lac+ levels. Limitations: A cautious interpretation of our results is warranted due to a p-value of 0.028. In addition, a higher than anticipated proportion of data sets had to be excluded due to poor spectral quality. Conclusion: This study confirms the presence of elevated cerebral Lac+ levels in a subgroup of adults with ASD, suggesting the potential of lactate as a biomarker for mitochondrial dysfunction in a subgroup of ASD. The lower-than-expected prevalence (20% was expected) and moderate increase require further investigation to elucidate the underlying mechanisms and relationships with mitochondrial function.