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Distinct Patterns of Weight Gain, Age, and Subcortical Microstructure in Early Adolescence
Shana Adise1, Zhaolong Adrian Li2, Jonatan Ottino-González1
1Division of Endocrinology, Diabetes and Metabolism, Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California.
JAMA Network Open
|July 23, 2025
Summary
Higher restricted normalized isotropic (RNI) values in adolescent females are linked to unhealthy weight gain, potentially indicating neuroinflammation. This suggests RNI may be an early indicator of obesity-related brain changes.
Area of Science:
- Neuroscience
- Pediatrics
- Radiology
Background:
- Childhood obesity is linked to brain microstructural differences.
- The role of sex-specific weight gain in these associations is unclear.
- Restriction spectrum imaging (RSI) measures brain microstructural health using water diffusion, with the restricted normalized isotropic (RNI) compartment reflecting cellularity.
Purpose of the Study:
- To investigate associations between RNI values, neurodevelopment, and weight gain in early adolescence.
- To explore potential sex differences in these relationships.
Main Methods:
- Longitudinal cohort study using data from the Adolescent Brain Cognitive Development (ABCD) Study.
- Linear mixed-effects models analyzed bidirectional associations between RNI, age, and BMI (body mass index) in 16 appetite-controlling brain regions.
- Analyses stratified by sex and weight-stable versus weight-varying status.
Main Results:
- Among weight-stable youth, RNI values correlated with age but not BMI.
- In youth with varying weight gain, RNI values showed bidirectional associations with BMI across subcortical regions, independent of age.
- Higher RNI values were robustly associated with increased BMI over time in females, but not males.
Conclusions:
- RNI values are associated with age and BMI, with higher values potentially indicating neuroinflammation.
- Elevated RNI may signal neuroinflammatory processes linked to unhealthy weight gain.
- The RNI scaling factor could serve as an early indicator of obesity-related neurodevelopmental changes in adolescents, particularly in females.
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