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 pre-clinical 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. This article is protected by copyright. All rights reserved.

Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance / Bozzi, Yuri; Provenzano, Giovanni; Casarosa, Simona. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 47:6(2018), pp. 534-548. [10.1111/ejn.13595]

Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance

Bozzi, Yuri;Provenzano, Giovanni;Casarosa, Simona
2018

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 pre-clinical 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. This article is protected by copyright. All rights reserved.
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Bozzi, Yuri; Provenzano, Giovanni; Casarosa, Simona
Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance / Bozzi, Yuri; Provenzano, Giovanni; Casarosa, Simona. - In: EUROPEAN JOURNAL OF NEUROSCIENCE. - ISSN 0953-816X. - 47:6(2018), pp. 534-548. [10.1111/ejn.13595]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11572/175247
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