Decreased left perisylvian GABA concentration in children with autism and unaffected siblings.
Imbalanced levels of excitation and inhibition (E/I) have been proposed to account for various behavioral and electrophysiological phenotypes in autism. Although proton magnetic resonance spectroscopy ((1)H-MRS) studies have been published on various metabolite levels in autism, including glutamate, the major excitatory neurotransmitter, few (1)H-MRS studies have yet been conducted the major inhibitory neurotransmitter GABA. Seventeen individuals with autism spectrum disorders (ASD) participated in a single-voxel, point resolved spectroscopy (PRESS) study conducted on a 3T magnet. Data were also acquired on 14 unaffected siblings of children with autism, and 17 age- and gender-matched healthy control subjects. GABA concentration was measured along with Creatine (Cr) in a single voxel aligned with the auditory cortex in the perisylvian region of the left hemisphere. The ratio of GABA to Cr was significantly lower in the ASD group than the control subjects. Siblings also exhibited lower GABA/Cr ratios compared to controls. Cr concentration did not differ between groups. The volumes of gray matter, white matter and CSF did not differ between groups in the whole brain or within the spectroscopy voxel. Reduced auditory GABA concentration in ASD is consistent with one previous MRS study of GABA concentration in the frontal lobe in autism, suggesting that multiple neocortical areas may be involved. Lower GABA levels are consistent with theories of ASD as a disorder involving impaired inhibitory neurotransmission and E/I imbalance. The reduction in unaffected siblings suggests that it may be a heritable biomarker, or endophenotype, of autism.
Department of Psychiatry, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA; Colorado Translational Research Imaging Center, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA. Electronic address: don.rojas@ucdenver.edu.
Donald C
DC
Rojas
Department of Radiology, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA; Colorado Translational Research Imaging Center, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA.
Debra
D
Singel
Department of Psychiatry, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA.
Sarah
S
Steinmetz
Department of Psychiatry, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA; JFK Partners, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA.
Susan
S
Hepburn
Department of Radiology, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA; Colorado Translational Research Imaging Center, University of Colorado Denver Anschutz Medical Campus, 13001 E. 17th Avenue, Aurora, CO 80045, USA.
Mark S
MS
Brown
D001303:Auditory Cortex / Q000378:metabolism*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D035781:Siblings; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid
Auditory cortex; Creatine; GABA; J-editing; MEGA-PRESS; Spectroscopy