Circadian disruption in autism: Adding fuel to the fire?

There was a fantastic review of circadian rhythms in autism spectrum disorder early last month.  In it, they put forth the model that people with autism frequently have disturbances in sleep and circadian rhythms.  Some of this is likely due to genetics, but along with the genetics component comes the environmental component, as well as the interaction between the 2.

In this model, genetic polymorphisms in people with autism may predispose them to sleep problems, and when these sleep problems occur in the developmental period, brain development is impacted and symptoms of autism present themselves.  Furthermore, changes in brain development may predispose to circadian rhythms and sleep disorders.  A graphical representation of this model:

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This is a growing area in autism research and something people should really be paying attention to, both to limit developmental delays AND reduce symptomology in those who have already reached adulthood.  A couple of quotes from another review titled, Are circadian rhythms new pathways to understanding autism spectrum disorder:

“Sleep and circadian disorders are frequent in ASD. Consequence of sleep-circadian disorders can first worsen the autistic symptoms and can, according to a developmental hypothesis, put a spoke in the wheel of the child neurodevelopement. They prevent the child to learn from social interaction and from the environment. While early developmental and behavioral intervention is the cornerstone of management of ASD, according to the last review, the success of such intervention hinges, at least partially, on the quality of sleep.

Circadian and sleep rhythms can be impaired very early in pre-natal or post-natal periods. Even a slight impairment in circadian or sleep rhythms may cascade and increase individual’s vulnerability to ASD. It is difficult to assign a ‘‘cause and effect” relation to any circadian-sleep disorder, however, they prove to be useful in the identification of risk factors and markers of vulnerability during infants development for early ASD screening and diagnosis.”

 

“Only a few days of circadian rhythm impairments may impact the maturation and specialization of some brain functions at specific times of development. Circadian rhythm impairments can impact the temporal organization of brain maturation and have a cascade effect on several brain functions. Negative environmental conditions (sleep deprivation, stress, nutrients, etc…) may deregulate the circadian rhythms and thus redox homeostasis, transcriptional and splicing regulation of PV genes or other genes implicated in synapse formation and maturation of brain functions

Another interesting observation in autism related to circadian rhythms is the elevation of the short-chain fatty acid propionic acid.  This SCFA follows a natural circadian rhythm where it is elevated during the late fasting period.  However, now being an additive in processed foods, this circadian rhythm may be lost and can cause problems.

A recent study showed that chronic exposure to propionic acid can alter neural stem cells in to a more inflammatory pattern.  This could be set in utero if the mother consumes a diet high in processed foods that contain propionic acid, and continued if the same diet is passed on to the child.  This study was in a petri dish, so further and more rigorous study is needed to see if this translates in to real world situations.

Finally, circadian disruption may explain 2 other phenomena seen in children with autism: A leaky gut and a leaky blood brain barrierCircadian disruption has been shown to cause leaky gut in mice and humans with circadian disruption due to shiftwork are more susceptible to alcohol-induced leaky gut that people who work a normal schedule.

As for the blood brain barrier, there are no studies in mammals on the topic, but a study published last year showed that permeability of the blood-brain barrier follows a circadian rhythm in fruit fliesImpaired blood brain barrier function is also a common feature of Alzheimer’s and Parkinson’s disease, both of which are also highly associated with severe circadian disruption.

While we are far from a solid answer on the topic, addressing circadian rhythms and sleep disturbances seems to be a blossoming area of autism research.  This is definitely a low-risk, high-benefit approach to addressing autism that’s worth watching.

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