Developmental regression and mitochondrial function in children with autism
Author
Singh, KanwaljitSingh, Indrapal N
Diggins, Eileen
Connors, Susan L
Karim, Mohammad A
Lee, David
Zimmerman, Andrew W
Frye, Richard E
Affiliation
Univ Arizona, Coll Med, Dept Child HlthIssue Date
2020-04-28
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WILEYCitation
Singh, K., Singh, I., Diggins, E., Connors, S., Karim, M., & Lee, D. et al. (2020). Developmental regression and mitochondrial function in children with autism. Annals Of Clinical And Translational Neurology, 7(5), 683-694. doi: 10.1002/acn3.51034Rights
Copyright © 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.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.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.Note
Open access journalISSN
2328-9503PubMed ID
32343046Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1002/acn3.51034
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