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Licensed Unlicensed Requires Authentication Published by De Gruyter May 28, 2021

Disruption of circadian rhythm and risk of autism spectrum disorder: role of immune-inflammatory, oxidative stress, metabolic and neurotransmitter pathways

  • Fazal Abdul , Nikhitha Sreenivas , John Vijay Sagar Kommu , Moinak Banerjee , Michael Berk , Michael Maes , Marion Leboyer and Monojit Debnath EMAIL logo

Abstract

Circadian rhythms in most living organisms are regulated by light and synchronized to an endogenous biological clock. The circadian clock machinery is also critically involved in regulating and fine-tuning neurodevelopmental processes. Circadian disruption during embryonic development can impair crucial phases of neurodevelopment. This can contribute to neurodevelopmental disorders like autism spectrum disorder (ASD) in the offspring. Increasing evidence from studies showing abnormalities in sleep and melatonin as well as genetic and epigenetic changes in the core elements of the circadian pathway indicate a pivotal role of circadian disruption in ASD. However, the underlying mechanistic basis through which the circadian pathways influence the risk and progression of ASD are yet to be fully discerned. Well-recognized mechanistic pathways in ASD include altered immune-inflammatory, nitro oxidative stress, neurotransmission and synaptic plasticity, and metabolic pathways. Notably, all these pathways are under the control of the circadian clock. It is thus likely that a disrupted circadian clock will affect the functioning of these pathways. Herein, we highlight the possible mechanisms through which aberrations in the circadian clock might affect immune-inflammatory, nitro-oxidative, metabolic pathways, and neurotransmission, thereby driving the neurobiological sequelae leading to ASD.


Corresponding author: Monojit Debnath, Department of Human Genetics, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, 560029, Karnataka, India, E-mail:

Funding source: Vision Group of Science and Technology, Department of IT, BT and ST, Government of Karnataka

Award Identifier / Grant number: No. KSTePS/VGST-CESEM/2018-2019/GRD No. 744/315

Funding source: National Health and Medical Research Council

Award Identifier / Grant number: 1156072

Acknowledgements

MB is supported by an NHMRC Senior Principal Research Fellowship (1156072).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Works in the authors’ (MD and JVSK) laboratory are funded by a “Centre for Excellence” grant from Vision Group of Science and Technology (VGST), Government of Karnataka (No. KSTePS/VGST-CESEM/2018-2019/GRD No. 744/315) for the identification of immune based biomarkers in neurodevelopmental disorders including ASD. The authors gratefully acknowledge financial support provided by the VGST.

  3. Conflict of interest statement: The authors declare that they have no conflicts of interest to disclose.

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Received: 2021-02-09
Accepted: 2021-05-01
Published Online: 2021-05-28
Published in Print: 2022-01-27

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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