Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder

Allegra J Johnson; Eric Shankland; Todd Richards; Neva Corrigan; Dennis Shusterman; Richard Edden; Annette Estes; Tanya St John; Stephen Dager; Natalia M Kleinhans

doi:10.1016/j.pscychresns.2023.111745

Relationships between GABA, glutamate, and GABA/glutamate and social and olfactory processing in children with autism spectrum disorder

Psychiatry Res Neuroimaging. 2023 Dec:336:111745. doi: 10.1016/j.pscychresns.2023.111745. Epub 2023 Nov 4.

Authors

Affiliations

¹ Department of Radiology, University of Washington, USA; Integrated Brain Imaging Center (IBIC), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98195, USA.
² Department of Radiology, University of Washington, USA.
³ Institute on Human Development and Disability (IHDD), University of Washington, USA.
⁴ Department of Medicine, University of California, San Francisco, USA.
⁵ Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, USA; F.M. Kirby Center for Functional MRI, Kennedy Krieger Institute, USA.
⁶ Institute on Human Development and Disability (IHDD), University of Washington, USA; Department of Speech and Hearing Sciences, University of Washington, USA; University of Washington Autism Center, USA.
⁷ University of Washington Autism Center, USA; Department of Medicine, University of California, San Francisco, USA.
⁸ Department of Radiology, University of Washington, USA; Institute on Human Development and Disability (IHDD), University of Washington, USA; Department of Biomedical Engineering, University of Washington, USA.
⁹ Department of Radiology, University of Washington, USA; Integrated Brain Imaging Center (IBIC), University of Washington, Box 357115, 1959 NE Pacific St, Seattle, WA 98195, USA; Institute on Human Development and Disability (IHDD), University of Washington, USA. Electronic address: nkleinha@uw.edu.

PMID: 37956467
PMCID: PMC10841920 (available on 2024-12-01)
DOI: 10.1016/j.pscychresns.2023.111745

Abstract

Theories of altered inhibitory/excitatory signaling in autism spectrum disorder (ASD) suggest that gamma amino butyric acid (GABA) and glutamate (Glu) abnormalities may underlie social and sensory challenges in ASD. Magnetic resonance spectroscopy was used to measure Glu and GABA+ levels in the amygdala-hippocampus region and cerebellum in autistic children (n = 30), a clinical control group with sensory abnormalities (SA) but not ASD (n = 30), and children with typical development (n = 37). All participants were clinically assessed using the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Scale-2, and the Child Sensory Profile-2. The Social Responsiveness Scale-2, Sniffin Sticks Threshold Test, and the University of Pennsylvania Smell Identification Test were administered to assess social impairment and olfactory processing. Overall, autistic children showed increased cerebellar Glu levels compared to TYP children. Evidence for altered excitatory/inhibitory signaling in the cerebellum was more clear-cut when analyses were restricted to male participants. Further, lower cerebellar GABA+/Glu ratios were correlated to more severe social impairment in both autistic and SA males, suggesting that the cerebellum may play a transdiagnostic role in social impairment. Future studies of inhibitory/excitatory neural markers, powered to investigate the role of sex, may aid in parsing out disorder-specific neurochemical profiles.

Keywords: Amygdala; Cerebellum; Sensory processing disorder; Sex-differences.

MeSH terms

Autism Spectrum Disorder* / diagnostic imaging
Child
Glutamic Acid*
Humans
Magnetic Resonance Spectroscopy / methods
Male
Smell
gamma-Aminobutyric Acid

Substances

Glutamic Acid
gamma-Aminobutyric Acid

Abstract

MeSH terms

Substances

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