Reduced GABA and altered somatosensory function in children with autism spectrum disorder.
BACKGROUND
Abnormal responses to tactile stimuli are a common feature of autism spectrum disorder (ASD). Several lines of evidence suggest that GABAergic function, which has a crucial role in tactile processing, is altered in ASD. In this study, we determine whether in vivo GABA levels are altered in children with ASD, and whether alterations in GABA levels are associated with abnormal tactile function in these children.


METHODS
GABA-edited magnetic resonance spectroscopy was acquired in 37 children with Autism and 35 typically developing children (TDC) from voxels over primary sensorimotor and occipital cortices. Children performed tactile tasks previously shown to be altered in ASD, linked to inhibitory mechanisms. Detection threshold was measured with- and without the presence of a slowly increasing sub-threshold stimulus. Amplitude discrimination was measured with- and without the presence of an adapting stimulus, and frequency discrimination was measured.


RESULTS
Sensorimotor GABA levels were significantly reduced in children with autism compared to healthy controls. Occipital GABA levels were normal. Sensorimotor GABA levels correlated with dynamic detection threshold as well as with the effect of sub-threshold stimulation. Sensorimotor GABA levels also correlated with amplitude discrimination after adaptation (an effect absent in autism) and frequency discrimination in controls, but not in children with autism.


CONCLUSIONS
GABA levels correlate with behavioral measures of inhibition. Children with autism have reduced GABA, associated with abnormalities in tactile performance. We show here that altered in vivo GABA levels might predict abnormal tactile information processing in ASD and that the GABA system may be a future target for therapies. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, Maryland, 21287.|F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway Street, Baltimore, Maryland, 21205.
Nicolaas A J
NAJ
Puts
Center for Neurocognitive and Imaging Research, Kennedy Krieger Institute, 716 N Broadway, Baltimore, Maryland, 21205.|Center for Autism and Related Disorders, Kennedy Krieger Institute, 3901 Greenspring Ave, Baltimore, Maryland, 21211.|Department of Behavioral Science and Psychiatry, Johns Hopkins University, School of Medicine, 600 N Wolfe Street, Baltimore, Maryland, 21287.
Ericka L
EL
Wodka
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, Maryland, 21287.|F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway Street, Baltimore, Maryland, 21205.|Radiology, University of Calgary, 1403 - 29th Street N.W, Calgary, AB, T2N 2T9, Canada.|CAIR Program, Alberta Children's Hospital Research Institute, University of Calgary, 1403 - 29th Street N.W, Calgary, AB, T2N 2T9, Canada.|Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.
Ashley D
AD
Harris
F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway Street, Baltimore, Maryland, 21205.|Center for Neurocognitive and Imaging Research, Kennedy Krieger Institute, 716 N Broadway, Baltimore, Maryland, 21205.
Deana
D
Crocetti
Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599.
Mark
M
Tommerdahl
Center for Neurocognitive and Imaging Research, Kennedy Krieger Institute, 716 N Broadway, Baltimore, Maryland, 21205.|Center for Autism and Related Disorders, Kennedy Krieger Institute, 3901 Greenspring Ave, Baltimore, Maryland, 21211.|Department of Neurology, Johns Hopkins School of Medicine, 600 N Wolfe Street, Baltimore, Maryland, 21287.
Stewart H
SH
Mostofsky
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore, Maryland, 21287.|F.M. Kirby Center for Functional Brain Imaging, Kennedy Krieger Institute, 707 N Broadway Street, Baltimore, Maryland, 21205.
Richard A E
RAE
Edden
D000067877:Autism Spectrum Disorder / Q000175:diagnosis / Q000503:physiopathology*; D002648:Child; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009433:Neural Inhibition / Q000502:physiology; D009778:Occipital Lobe / Q000503:physiopathology*; D012016:Reference Values; D013003:Somatosensory Cortex / Q000503:physiopathology*; D013223:Statistics as Topic; D055698:Touch Perception / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid
GABA; MRS; autism; magnetic resonance spectroscopy; somatosensory; tactile; touch