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Characterizing the Interplay Between Autism Spectrum Disorder and Comorbid Medical Conditions: An Integrative Review


Characterizing the Interplay Between Autism Spectrum Disorder and Comorbid Medical Conditions: An Integrative Review

Charlotte Tye et al. Front Psychiatry.

Erratum in


Co-occurring medical disorders and associated physiological abnormalities in individuals with autism spectrum disorder (ASD) may provide insight into causal pathways or underlying biological mechanisms. Here, we review medical conditions that have been repeatedly highlighted as sharing the strongest associations with ASD-epilepsy, sleep, as well as gastrointestinal and immune functioning. We describe within each condition their prevalence, associations with behavior, and evidence for successful treatment. We additionally discuss research aiming to uncover potential aetiological mechanisms. We then consider the potential interaction between each group of conditions and ASD and, based on the available evidence, propose a model that integrates these medical comorbidities in relation to potential shared aetiological mechanisms. Future research should aim to systematically examine the interactions between these physiological systems, rather than considering these in isolation, using robust and sensitive biomarkers across an individual's development. A consideration of the overlap between medical conditions and ASD may aid in defining biological subtypes within ASD and in the development of specific targeted interventions.

Keywords: autism spectrum disorder; comorbidity; epilepsy; gastrointestinal disorders; immune function; sleep.


Figure 1
Figure 1
Possible models of the association between medical conditions and ASD: (A) Overlap between medical conditions and ASD arises from a common mechanism; (B) Overlap between medical conditions and ASD arises from the independent pathways or cumulative impact of impairments in two or more developmental pathways (possibly subgroups of individuals); (C) Overlap between medical conditions and ASD arises from the effect of medical abnormalities on underling mechanisms, or vice versa. These models are not mutually exclusive and more than one pathway may be involved.
Figure 2
Figure 2
Interdependent bidirectional associations between ASD and sleep problems. GI, gastrointestinal; RRBIs, restricted and repetitive behaviours and interest.
Figure 3
Figure 3
Bidirectional associations between alterations in central nervous system circuitry (epilepsy, sleep), immune system and gastrointestinal function and behaviors characteristic of ASD interacting with genetic and environmental risk.

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