Increased glutamate concentration in the auditory cortex of persons with autism and first-degree relatives: a (1)H-MRS study

Abstract

Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy ((1)H-MRS). Although autism spectrum disorders (ASDs) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism. Single-voxel, point-resolved spectroscopy data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was glutamate + glutamine (Glx). Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI), and creatine (Cr). The autism group had significantly higher Glx, NAA, and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures, and MRS variables were seen after Bonferroni correction for multiple comparisons. The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample-specific limitations such as the participation of singleton families.

Figure 1

¹H-MRS example. Image on left is axial localizer image illustrating voxel of interest (rectangle) and prescription plane for additional localizer (not shown) for spectroscopy voxel. Voxel is aligned with first transverse temporal gyrus (Heschl’s gyrus). Spectrum obtained from the prescribed voxel is shown on the right, with arrows showing the signals of interest in the study.

Figure 2

Mean +/− SD ¹H-MRS Metabolite Concentrations. Cho = choline; Cr = creatine; Glx = Glutamate + Glutamine; mI = myo inositol; NAA = n-acetyl-aspartate.

Figure 3

Glx concentration dot plots for left (top) and right (bottom) auditory voxels. Individuals taking various medications at the time of scan are identified. Dots are semi-transparent so that no medicated subjects are hidden by overlap with another dot.