Glutamate Dysfunction in the Basal Ganglia of Autism Spectrum Disorders : An MRS Study

Background: Glutamate (Glu), the major excitatory neurotransmitter, is highly concentrated throughout the brain and is crucial to neuronal plasticity and the maintenance of cognitive functioning. The concentration of Glu in the human brain can be quantified with a technique of Proton Magnetic Resonance Spectroscopy (MRS). There are only a few MRS studies in relation to autism or autism spectrum disorders (ASD) with conflicting results. It is thus unclear whether abnormality in Glu plays a pathophysiological role in the condition.

Objectives: We aimed to examine Glu and other metabolites abnormalities in the brain (the cerebellar vermis, the right prefrontal cortex white matter, the right hippocampal-amygdala complex and the right basal ganglia) of individuals with ASD using the proton MRS

Methods: Twenty four (six females) individuals with ASD (age, mean ± SD; 26.0 ± 3.8 years) and 25 (six females) controls (age; 26.1 ± 3.5) were recruited. All the participants were right-handed. All the subjects with ASD were diagnosed based on the Autism Diagnostic Interview (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in addition to DSM-IV criteria. The mean ± SD score of ADIR social, communication and repetitive behavior for the ASD was 20.6 ± 5.8, 15.1 ± 4.5 and 4.4 ± 2.6, respectively. The mean ± SD ADOS score of social, communication and repetitive behavior was 8.9 ± 2.5, 4.9 ± 2.2 and 0.8 ± 1.0, respectively. IQ was assessed with the Wechsler Abbreviated Scale of Intelligence (WASI). There was no significant difference in full IQ between the ASD (88.8 ± 19.1) and control (96.8 ± 14.1) groups. Four ASD participants received medication and two ASD participants smoked at assessment. As for MRI data, all participants were scanned using a 3-T GE Signa System. As Volumes of interest (VOIs), we selected four brain regions, i.e. the cerebellar vermis, the right prefrontal cortex white matter, the right hippocampal-amygdala complex and the right basal ganglia. We employed the point resolved spectroscopy (PRESS) spectrum [TE=35, TR=3000 and NEX=128] for data acquisition. The metabolites examined were myo-inositol (mI), choline (Cho), creatine (Cr), glutamate (Glu), glutamate+glutamine (Glx) and N-acetylaspartate (NAA) and the concentration of CSF within the VOI was controlled for. Data analysis was performed by the software of SPM5 and FSL.   

Results: The level of Glu in the right basal ganglia in the ASD group was significantly decreased (p =0.03) compared with that of the control group. Even if medicated individuals and smokers among the ASD were excluded from the analysis, the level of Glu in the right basal ganglia in individuals with ASD remained significant (p =0.04). Other metabolites did not differ between the two groups. Glu levels in the basal ganglia were not correlated with symptom severity.

Conclusions: We found a reduction of glutamate in the basal ganglia in individuals with ASD. Glutamate dysfunction in the basal ganglia may be associated with ASD.