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

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.