Proton Magnetic Resonance Spectroscopy as a Probe into the Pathophysiology of Autism Spectrum Disorders (ASD): A Review

Proton magnetic resonance spectroscopy (¹H-MRS) is a safe, noninvasive way of quantifying in vivo biochemical and metabolite concentration levels in individuals with Autism Spectrum Disorders (ASD). Findings to date suggest ASD is associated with widespread reduction in N-acetylaspartate (NAA), creatine plus phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol (mI), and glutamate plus glutamine plus gamma-Aminobutyric Acid (Glx); however, variable findings, and even substantial increases, are not uncommon depending on the study and/or region-of-interest. Widespread reduction of NAA, Cr, Cho, mI, and Glx in ASD likely reflects impaired neuronal function and/or metabolism related to abnormal neurodevelopmental processes. Future studies should attempt to relate ¹H-MRS findings to histological findings and control for variability in subject age and functioning level; this would assist in evaluating the relationship between ¹H-MRS metabolic levels and neuronal and glial cell densities, as well as neurodevelopmental process associated with ASD. Furthermore, more longitudinal ¹H-MRS studies are needed in both control and ASD subjects to attempt to standardize metabolite levels across different developmental periods in well-defined endophenotypes. This will provide for a standard rubric for which metabolic aberrations (as well as treatment responses) can be measured. With higher magnetic field strengths and spectral-editing techniques capable of quantifying less-concentrated metabolites, ¹H-MRS will continue to be an important tool in ASD research. Autism Res 2013, 6: 119-133.