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White matter as a monitoring biomarker for neurodevelopmental disorder intervention studies
Meghan R Swanson1, Heather C Hazlett2
1School of Behavioral and Brain Sciences, University of Texas at Dallas, GR41, 800 W. Campbell Road, Richardson, TX, 75080-3021, USA. meghan.swanson@utdallas.edu.
Insights
White matter development can be a sensitive biomarker for early intervention in neurodevelopmental disorders like autism spectrum disorder (ASD) and Fragile X syndrome (FXS). This approach offers objective monitoring for infants, potentially improving treatment outcomes.
Area of Science:
- Neuroscience
- Developmental Biology
- Biomarker Research
Background:
- Early intervention is crucial for toddlers with neurodevelopmental disorders.
- Advances in early detection enable pre-symptomatic identification of autism spectrum disorder (ASD) in infancy.
- Biologically based outcome measures are needed to support early intervention strategies.
Purpose of the Study:
- To evaluate white matter neurodevelopment as a monitoring biomarker for early treatment of neurodevelopmental disorders.
- To examine the potential of white matter as a responsive target for intervention.
- To use Fragile X syndrome (FXS) and ASD as exemplars for this evaluation.
Main Methods:
- Review of existing literature on white matter neurobiology in neurodevelopmental disorders.
- Analysis of aberrant white matter development in ASD and FXS.
- Consideration of rodent histologic findings for pharmacological targets in FXS.
Main Results:
- White matter exhibits unique, prolonged developmental periods, suggesting responsiveness to treatment.
- Aberrant white matter development is observed in children with ASD and FXS.
- Previous pharmaceutical trials for FXS showed limited clinical success.
Conclusions:
- Neurobiological monitoring biomarkers, such as white matter development, offer objective and dimensional measures.
- These biomarkers are not susceptible to placebo effects, addressing limitations in clinical trials.
- The use of neurobiological features as monitoring biomarkers is encouraged for early intervention in neurodevelopmental disorders.
Background:
Early intervention is a valuable tool to support the development of toddlers with neurodevelopmental disorders. With recent research advances in early identification that allow for pre-symptomatic detection of autism in infancy, scientists are looking forward to intervention during infancy. These advances may be supported by the identification of biologically based treatment and outcome measures that are sensitive and dimensional. The purpose of this review is to evaluate white matter neurodevelopment as a monitoring biomarker for early treatment of neurodevelopmental disorders. Fragile X syndrome (FXS) and autism spectrum disorder (ASD) as used as exemplars. White matter has unique neurobiology, including a prolonged period of dynamic development. This developmental pattern may make white matter especially responsive to treatment. White matter develops aberrantly in children with ASD and FXS. Histologic studies in rodents have provided targets for FXS pharmacological intervention. However, pharmaceutical clinical trials in humans failed to garner positive clinical results. In this article, we argue that the use of neurobiological monitoring biomarkers may overcome some of these limitations, as they are objective, not susceptible to placebo effects, and are dimensional in nature.
Short Conclusion:
As the field moves towards earlier detection and early intervention for neurodevelopmental disorders, we encourage scientists to consider the advantages of using neurobiological features as monitoring biomarkers.
