UMMS Affiliation

Department of Pediatrics

Publication Date

2020-04-28

Document Type

Article

Disciplines

Biochemical Phenomena, Metabolism, and Nutrition | Endocrinology, Diabetes, and Metabolism | Mental Disorders | Nervous System Diseases | Neurology | Nutritional and Metabolic Diseases | Pediatrics

Abstract

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.

Keywords

developmental regression, mitochondrial function, autism

Rights and Permissions

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

DOI of Published Version

10.1002/acn3.51034

Source

Singh K, Singh IN, Diggins E, Connors SL, Karim MA, Lee D, Zimmerman AW, Frye RE. Developmental regression and mitochondrial function in children with autism. Ann Clin Transl Neurol. 2020 Apr 28. doi: 10.1002/acn3.51034. Epub ahead of print. PMID: 32343046. Link to article on publisher's site

Journal/Book/Conference Title

Annals of clinical and translational neurology

Related Resources

Link to Article in PubMed

PubMed ID

32343046

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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