Autism Spectrum Disorder (ASD) is characterized by impairments in social and communicative function and repetitive behaviors. Recent work suggests that oxidative stress (arising from both genetic and environmental causes) is a contributing factor to the neuropathology of ASD. Emerging evidence suggests that increased oxidative stress may contribute to the neuronal and cognitive impairments seen in children with Autism Spectrum Disorder (ASD). Glutathione (GSH) is the main redox compound in the brain, and reduced GSH during development may lead to such increases in oxidative stress and may be a primary cause of secondary neurophysiological impairments in ASD. GSH can be measured using edited Magnetic Resonance Spectroscopy (MRS). Here, we propose using a highly novel MRS technique (HERMES) to measure GSH in the brain of children with ASD and investigate its relation to functional behavioral measures of autism, and peripheral markers of oxidative stress, work not previously performed. The novelty lies in the application in children, using a recently developed, more specific and valid MRS technique. Increased oxidative stress, and associated GSH dysfunction, may therefore be an important contributor to autism-associated alterations in brain development, contributing in turn to cognitive and social impairments common in ASD. Understanding the role of oxidative stress in ASD is important for understanding the emergence of ASD and offers a promising target for future early interventions to increase GSH concentration in the brain.

Public Health Relevance

Recent work suggests that oxidative stress (arising from both genetic and environmental causes) is a contributing factor to the neuropathology of ASD. Glutathione (GSH) is the main redox compound in the brain, and reduced GSH during development may lead to such increases in oxidative stress and may be a primary cause of secondary neurophysiological impairments in Autism. Here, we propose use a highly novel Magnetic Resonance Spectroscopy technique to measure GSH in the brain of children with ASD and investigate its relation to autism severity and peripheral markers of oxidative stress, work not previously performed.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HD100869-01A1
Application #
10055287
Study Section
Developmental Brain Disorders Study Section (DBD)
Program Officer
Kau, Alice S
Project Start
2020-07-24
Project End
2022-06-30
Budget Start
2020-07-24
Budget End
2021-06-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205