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Individuals with autism spectrum disorder (ASD) and co-occurring global developmental delay or intellectual disability (GDD-ID) are highly vulnerable to stress, but a very small amount of research is being conducted at the physiological level. This review aims to identify and synthesize studies examining autonomic nervous system (ANS) and hypothalamic–pituitary–adrenal (HPA) axis biomarkers in such populations.

The review followed PRISMA 2020 guidelines (Pages et al., 2021) and the inclusion criteria encompassed peer-reviewed studies published in English that reported direct physiological biomarker measurements (e.g., heart rate variability, electrodermal activity, cortisol) in individuals with ASD and documented GDD-ID (IQ < 75 and/or developmental delay). Exclusion criteria included studies involving animals, pharmacological interventions, or solely behavioural outcomes. The literature search was conducted across four databases: PubMed, Scopus, Web of Science, and OpenAlex (last search: April 2025). Two reviewers independently screened publications, assessed bias (JBI) and evaluated the certainty (GRADE). No meta-analysis was performed due to high heterogeneity. The protocol was registered on PROSPERO (CRD420251025329).

Thirty-four studies (n ≈ 1160 individuals with ASD; mean age: 10.7 years) were included. ANS studies reported that ASD individuals had a sympathetic hyperactivation, a reduced parasympathetic tone (low respiratory sinus arrhythmia), and a delayed recovery after stress. HPA findings were mixed, showing both hypoactivation (low cortisol) and feedback dysfunction (e.g., Dexamethasone non-suppression) in those individuals. Respiratory sinus arrhythmia (RSA) was positively associated with social adaptation. Age-related physiological maturation appeared atypical. ASD’s symptom severity was more consistently positively associated with physiological profiles than IQ.

Clear evidence was limited since most studies had low certainty due to small sample sizes, variability and heterogeneity in methods, populations, and task relevance. Only few recent studies targeted ASD-GDD-ID profiles.

Individuals with ASD and GDD-ID exhibit autonomic hyperarousal and altered HPA regulation, suggesting reduced physiological flexibility. However, strong discrepancies exist among studies, and hereby, more inclusive and adapted protocols are needed to better characterise this physiological profile.