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Is birth a critical period in the pathogenesis of autism spectrum disorders?

Abstract

Birth is associated with a neuroprotective, oxytocin-mediated abrupt excitatory-to-inhibitory GABA shift that is abolished in autism, and its restoration attenuates the disorder in offspring. In this Opinion article, I discuss the links between birth-related stressful mechanisms, persistent excitatory GABA actions, perturbed network oscillations and autism. I propose that birth (parturition) is a critical period that confirms, attenuates or aggravates the deleterious effects of intrauterine genetic or environmental insults.

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Figure 1: Synchronous calcium plateau assemblies are regulated by oxytocin.
Figure 2: The excitatory-to-inhibitory GABA developmental switch is abolished in animal models of autism and fragile X syndrome.
Figure 3: Bumetanide treatment improves recognition of facial expressions in adolescents with ASDs.
Figure 4: Effect of different birth conditions on catecholamine levels in newborns.

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Acknowledgements

The author is extremely grateful to his colleagues H. Lagercrantz, H. Bruining, N. Hadjikhani and D. Ferrari for their suggestions. He is also indebted to D. Ferrari for her help in preparing the figures. The author is thankful to his many colleagues who took part in the experiments summarized in this article. Financial support for the author's investigations is acknowledged from the French National Institute for Health and Medical Research (INSERM), the Institute of Neurobiology of the Mediterranean Sea (INMED), the National Agency for Research (ANR), The Bettencourt/Schuller foundation and the biotechnology company Neurochlore.

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Correspondence to Yehezkel Ben-Ari.

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The author is founder and CEO of Neurochlore, a company devoted to study autism and develop a treatment based on the regulation of intracellular chloride.

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Ben-Ari, Y. Is birth a critical period in the pathogenesis of autism spectrum disorders?. Nat Rev Neurosci 16, 498–505 (2015). https://doi.org/10.1038/nrn3956

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