Reduced GABAergic Action in the Autistic Brain
Open accessAbstract
An imbalance between excitatory/inhibitory neurotransmission has been posited as a central characteristic of the neurobiology of autism [1], inspired in part by the striking prevalence of seizures among individuals with the disorder [2]. Evidence supporting this hypothesis has specifically implicated the signaling pathway of the inhibitory neurotransmitter, γ-aminobutyric acid (GABA), in this putative imbalance: GABA receptor genes have been associated with autism in linkage and copy number variation studies [3-7], fewer GABA receptor subunits have been observed in the post-mortem tissue of autistic individuals [8, 9], and GABAergic signaling is disrupted across heterogeneous mouse models of autism [10]. Yet, empirical evidence supporting this hypothesis in humans is lacking, leaving a gulf between animal and human studies of the condition. Here, we present a direct link between GABA signaling and autistic perceptual symptomatology. We first demonstrate a robust, replicated autistic deficit in binocular rivalry [11], a basic visual function that is thought to rely on the balance of excitation/inhibition in visual cortex [12-15]. Then, using magnetic resonance spectroscopy, we demonstrate a tight linkage between binocular rivalry dynamics in typical participants and both GABA and glutamate levels in the visual cortex. Finally, we show that the link between GABA and binocular rivalry dynamics is completely and specifically absent in autism. These results suggest a disruption in inhibitory signaling in the autistic brain and forge a translational path between animal and human models of the condition.
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In humans, a higher excitatory/inhibitory ratio is thought to contribute to the pathophysiology of various neurological and psychiatric disorders, including ASD.
“In humans, a higher excitatory/inhibitory ratio is thought to contribute to the pathophysiology of various neurological and psychiatric disorders, including ASD (Nelson & Valakh, 2015;Rubenstein & Merzenich, 2003;Robertson et al., 2016).”
From Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum (2025) · cites this paper as Robertson et al., 2016
The available copy contains the title and reference links, but no substantive passage about excitatory/inhibitory ratios or their role in ASD or other disorders. Searches for excitation–inhibition balance and psychiatric disorders returned no relevant text, so the claim cannot be checked against this copy. (LLM, conf=0.72)
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A computational perspective on autism
Rosenberg, A., Patterson, J. S., & Angelaki, D. E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510583112 · Cited by 156 · see citing works
Cortical variability in the sensory-evoked response in autism
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Robertson, C. E., & Baron-Cohen, S. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.112 · Cited by 1,157 · see citing works
Self-citationSohal, V. S., & Rubenstein, J. L. R. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0426-0 · Cited by 988 · see citing works
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Bumetanide for autism: more eye contact, less amygdala activation
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- Authors
- Robertson, C. E., Ratai, E.-M., & Kanwisher, N.
- Affiliations
- Harvard University (US)
- McGovern Institute for Brain Research (US)
- Corresponding author
- Robertson, Caroline E.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 26
- Issue
- 1
- Pages
- 80-85
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2197168351
- Cited by
- 327
- References
- 4
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 31 · 2023: 38 · 2022: 27 · 2021: 41 · 2020: 39 · 2019: 28 · 2018: 26 · 2017: 36 · 2016: 17
- FWCI
- 15.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, GABA signaling, excitatory-inhibitory imbalance, binocular rivalry, visual cortex, glutamate, GABAergic inhibition, magnetic resonance spectroscopy
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Brain, Female, gamma-Aminobutyric Acid, Humans, Magnetic Resonance Imaging, Male, Synaptic Transmission, Visual Cortex, Vision, Binocular, Biomarkers, Case-Control Studies, Glutamic Acid
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