Developmental regression and mitochondrial function in children with autism

Ann Clin Transl Neurol. 2020 May;7(5):683-694. doi: 10.1002/acn3.51034. Epub 2020 Apr 28.


Background: Developmental regression (DR) occurs in about one-third of children with Autism Spectrum Disorder (ASD) yet it is poorly understood. Current evidence suggests that mitochondrial function in not normal in many children with ASD. However, the relationship between mitochondrial function and DR has not been well-studied in ASD.

Methods: This cross-sectional study of 32 children, 2 to 8 years old with ASD, with (n = 11) and without (n = 12) DR, and non-ASD controls (n = 9) compared mitochondrial respiration and mtDNA damage and copy number between groups and their relation to standardized measures of ASD severity.

Results: Individuals with ASD demonstrated lower ND1, ND4, and CYTB copy number (Ps < 0.01) as compared to controls. Children with ASD and DR had higher maximal oxygen consumption rate (Ps < 0.02), maximal respiratory capacity (P < 0.05), and reserve capacity (P = 0.01) than those with ASD without DR. Coupling Efficiency and Maximal Respiratory Capacity were associated with disruptive behaviors but these relationships were different for those with and without DR. Higher ND1 copy number was associated with better behavior.

Conclusions: This study suggests that individuals with ASD and DR may represent a unique metabolic endophenotype with distinct abnormalities in respiratory function that may put their mitochondria in a state of vulnerability. This may allow physiological stress to trigger mitochondrial decompensation as is seen clinically as DR. Since mitochondrial function was found to be related to ASD symptoms, the mitochondria could be a potential target for novel therapeutics. Additionally, identifying those with vulnerable mitochondrial before DR could result in prevention of ASD.

MeSH terms

  • Autism Spectrum Disorder / metabolism*
  • Autism Spectrum Disorder / physiopathology*
  • Child
  • Child Behavior / physiology*
  • Child, Preschool
  • Cross-Sectional Studies
  • DNA Copy Number Variations
  • DNA, Mitochondrial
  • Endophenotypes
  • Female
  • Humans
  • Male
  • Mitochondria / metabolism*
  • NADH Dehydrogenase
  • Oxygen Consumption / physiology*
  • Problem Behavior*
  • Stress, Physiological / physiology


  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • NADH dehydrogenase subunit 1, human