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Children with autism and comorbid sleep disorder exhibit neuroclearance dysfunction linked to systemic iron deficiency

In a study of 230 children with ASD (114 with sleep disorder, 116 without) and 110 typically developing controls, those with ASD and sleep disorder showed significantly reduced ALPS indices and elevated free water fraction, indicating impaired perivascular clearance. Serum iron was markedly lower in the ASD-sleep disorder group, and mediation analysis supported a pathway from iron deficiency to cerebral edema to impaired neuroclearance.

Last updated: Jul 7, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score34/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Neuroclearance dysfunction in autism with sleep disorder: MRI evidence and mediation by systemic iron deficiency.

observational

Yin BY, Deng YY, Chen X, Zhao JY, Ni YX, Zhong SS, Zou FY, Shen LS, Luo XW, Zhou X, Zhang JL, Zhou WY, Deng HZ, Guo RM · Journal of affective disorders (2026)

Participants: N/A
Duration: N/A (cross-sectional)
Intervention: None (observational study comparing groups with and without sleep disorder)
Outcome: Neuroclearance function (DKI-ALPS index, free water fraction, perivascular space volume fraction) and serum iron levels
Effect Size: AUC up to 0.94 for combined ALPS and serum Fe distinguishing ASD-SD from ASD-nSD and controls
Population: Children with autism spectrum disorder (ASD) aged 2-17 years, with and without comorbid sleep disorder, plus typically developing controls

Result:

PubMed: 42208817DOI: 10.1016/j.jad.2026.122035

Mechanism Graph

Systemic iron deficiency
↓
Increased free water fraction (cerebral edema)
↓
Impaired perivascular neuroclearance
↓
Sleep disruption exacerbates neurodevelopmental impairments

Limitations

  • ⚠Observational design cannot establish causality
  • ⚠Single-center study may limit generalizability
  • ⚠Potential confounding by other trace element imbalances not fully assessed

Frequently Asked Questions

What is the DKI-ALPS index?▼

It is a diffusion kurtosis imaging measure along the perivascular space used to quantify neuroclearance function.

How many children were in the study?▼

The study included 230 children with ASD (114 with sleep disorder, 116 without) and 110 typically developing controls, totaling 340 participants.

What was the main finding regarding iron?▼

Serum iron was markedly lower in children with ASD and sleep disorder compared to those without sleep disorder and controls, and iron levels strongly correlated with neuroclearance indices (r=0.75-0.95).

Could this lead to a biomarker for sleep disorder in autism?▼

Yes, the combination of DKI-ALPS and serum iron showed high accuracy (AUC up to 0.94) in distinguishing ASD with sleep disorder from other groups, suggesting potential as a candidate biomarker.

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References

  1. 1.Yin BY, Deng YY, Chen X, Zhao JY, Ni YX, Zhong SS, Zou FY, Shen LS, Luo XW, Zhou X, Zhang JL, Zhou WY, Deng HZ, Guo RM. "Neuroclearance dysfunction in autism with sleep disorder: MRI evidence and mediation by systemic iron deficiency.." Journal of affective disorders, 2026. PMID: 42208817 DOI: 10.1016/j.jad.2026.122035
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