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

Bo-Ya Yin1, Ya-Yin Deng1, Xi Chen1

  • 1Department of Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, No. 600 Tianhe Road, Guangzhou, 510630, China.

Journal of Affective Disorders
|May 28, 2026
PubMed

Insights

Children with autism spectrum disorder (ASD) and sleep issues show impaired brain fluid clearance, linked to low iron levels. This suggests iron deficiency may worsen neurodevelopmental problems in ASD.

Area of Science:

  • Neuroscience
  • Pediatrics
  • Biochemistry

Background:

  • Sleep disturbances are common in children with autism spectrum disorder (ASD), worsening neurodevelopmental issues.
  • The connection between sleep problems, brain fluid clearance, and trace elements in ASD is not well understood.

Purpose of the Study:

  • To investigate the relationship between sleep disturbances, neuroclearance, and systemic trace element status in children with ASD.
  • To explore the potential role of iron deficiency in impaired neuroclearance in ASD.

Main Methods:

  • 230 children with ASD (114 with sleep disorder, ASD-SD; 116 without, ASD-nSD) and 110 controls were studied.
  • Neuroclearance was assessed using diffusion kurtosis imaging along the perivascular space (DKI-ALPS), free water fraction (FW), and perivascular space volume fraction (PVSVF).
  • Serum iron (Fe), lead (Pb), and magnesium (Mg) levels were measured.

Main Results:

  • ASD-SD children had reduced ALPS indices and elevated FW, indicating impaired perivascular clearance.
  • Serum Fe was lower and Pb was higher in ASD-SD children.
  • Iron deficiency partially explained reduced ALPS via increased FW, suggesting a pathway from iron deficiency to cerebral edema and impaired neuroclearance.

Conclusions:

  • Children with ASD and sleep disorders exhibit significant neuroclearance dysfunction associated with systemic iron deficiency.
  • DKI-ALPS and serum Fe show promise as biomarkers for identifying ASD with sleep disorders.
  • Findings suggest interventions combining iron supplementation and sleep optimization for ASD.
Abstract

Keywords:
Autism spectrum disorderBiomarkerDKI-ALPSIron deficiencyNeuroclearanceSleep disorder

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