Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance
Abstract
Autism spectrum disorders (ASD) and epilepsy are common neurological diseases of childhood, with an estimated incidence of approximately 0.5-1% of the worldwide population. Several genetic, neuroimaging and neuropathological studies clearly showed that both ASD and epilepsy have developmental origins and a substantial degree of heritability. Most importantly, ASD and epilepsy frequently coexist in the same individual, suggesting a common neurodevelopmental basis for these disorders. Genome-wide association studies recently allowed for the identification of a substantial number of genes involved in ASD and epilepsy, some of which are mutated in syndromes presenting both ASD and epilepsy clinical features. At the cellular level, both preclinical and clinical studies indicate that the different genetic causes of ASD and epilepsy may converge to perturb the excitation/inhibition (E/I) balance, due to the dysfunction of excitatory and inhibitory circuits in various brain regions. Metabolic and immune dysfunctions, as well as environmental causes also contribute to ASD pathogenesis. Thus, an E/I imbalance resulting from neurodevelopmental deficits of multiple origins might represent a common pathogenic mechanism for both diseases. Here, we will review the most significant studies supporting these hypotheses. A deeper understanding of the molecular and cellular determinants of autism-epilepsy comorbidity will pave the way to the development of novel therapeutic strategies.
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Deregulation of AMPA and/or NMDA receptors in inhibitory interneurons and dysregulation of E/I balance could be responsible for the cognitive and behavioural abnormalities characteristic of a range of neurodegenerative and psychiatric disorders.
“In particular, the deregulation of AMPA and/or NMDA receptors in inhibitory interneurons and the dysregulation of E/I balance could be responsible for the cognitive and behavioural abnormalities characteristic of a range of neurodegenerative and psychiatric disorders (Belforte et al. 2010; Bozzi et al. 2018; Caputi et al. 2012; Foss-Feig et al. 2017; Fuchs et al. 2007; Korotkova et al. 2010; Lewis”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Bozzi et al. 2018
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- Authors
- Bozzi, Y., Provenzano, G., & Casarosa, S.
- Affiliations
- University of Trento (IT)
- Corresponding author
- Bozzi, Yuri
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2017-05-17
- Volume
- 47
- Issue
- 6
- Pages
- 534-548
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2608216424
- Cited by
- 250
- References
- 24
- Citations by year
- 2026: 25 · 2025: 25 · 2024: 24 · 2023: 33 · 2022: 34 · 2021: 35 · 2020: 36 · 2019: 18 · 2018: 16 · 2017: 4
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Iris (University of Trento) (submittedVersion)
- Funders
- Università degli Studi di Trento
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- autism spectrum disorder, epilepsy, excitatory-inhibitory imbalance, neurodevelopmental disorders, genetic susceptibility, immune dysfunction, metabolic dysfunction, environmental risk factors, treatment options
- MeSH terms
- Autism Spectrum Disorder, Cortical Excitability, Animals, Epilepsy, gamma-Aminobutyric Acid, Humans, Neural Inhibition, Comorbidity, Glutamic Acid
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