Excitatory and inhibitory imbalance and atypical sensory sensitivity in autism

Autism spectrum disorder (ASD) represents a cluster of neurodevelopmental conditions characterized by challenges in social interactions, communication, and repetitive behaviors. Most research already conducted has focused on social interactions, treating atypical sensory processing as secondary. However, it is crucial to highlight that sensory sensitivities, experienced by up to 90% of autistic individuals, may hold significant promise as diagnostic biomarkers for this condition. In this comprehensive review, the excitatory/inhibitory (E/I) imbalance hypothesis for sensory sensitivities in autism has been examined by analysis of existing literature. The hypothesis posits that an imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms could cause a reduction in signal-to-noise in key neural circuits and underlie the behavioral characteristics of autism. Evidence was found for disrupted E/I ratios in ASD that correlate with impaired sensory processing and multisensory integration. Here, findings from a range of sources, including studies on GABAergic, glutamatergic, dopaminergic, and serotonergic systems, were synthesized to provide a thorough exploration of the neurobiological underpinnings of autism hypo-and hypersensitivities.

Abbreviations: ADOS - Autism Diagnostic Observation Schedule; AI - anterior insula; ASD - Autism spectrum disorder; DA - dopamine; DAT - dopamine transporter; E/I - excitatory/inhibitory; GABA - γ-Aminobutyrate; MAO-A - monoamine oxidase A; MMN - mismatch negativity; OCD - obsessive-compulsive disorder; PE - Prediction error; SERT - serotonin transporter; SNR - signal-to-noise ratio; SOR - sensory overresponsiveness; SIFI - Sound Induced-Flash-Illusions; TD - typical developing; TBW - temporal binding window; VPA - valproic acid; WCC - weak central coherence; 5-HT - serotonin

Keywords: ASD; sensory processing; sensory sensitivity; neurotransmitter; prediction error, priors; attention

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