ArticlebioRxiv : the preprint server for biology2026
Nonlinear associations between body mass index and brain microstructure across adolescence in the ABCD Study.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Introduction: Body mass index (BMI) is widely used to screen for weight-related health risks during adolescence. Prior neuroimaging studies have assumed a linear relationship between BMI and brain microstructure, potentially obscuring how this association varies across the BMI distribution. Using restriction spectrum imaging (RSI) in the Adolescent Brain Cognitive Development (ABCD) Study, previous work has identified positive linear associations between BMI and weight-related metrics and the restricted normalized isotropic (RNI) signal fraction in subcortical structures, but it remains unclear whether these associations are uniform across the full BMI spectrum or driven by particular portions of the distribution. Methods: We examined the relationship between BMI percentile and voxelwise RNI in subcortical gray matter and white matter structures using data from the ABCD Study 6.1 release, which includes four imaging timepoints spanning ages 9-18 years (22,011 observations from 10,465 unique participants). Sex-stratified generalized additive mixed-effects models with smooth terms for BMI percentile, age, and pubertal development were used to model the shape of the BMI-microstructure association across the full percentile range, controlling for genetic principal components, household income, parental education, and MRI scanner/software version. Results: The association between BMI percentile and RNI was nonlinear in the bilateral nucleus accumbens, caudate, pallidum, putamen, thalamus, and forceps minor. A modest, positive association was present across most of the BMI range, but the rate of change accelerated markedly above the 80 Discussion: The relationship between BMI and subcortical brain microstructure during adolescence is not uniform but instead accelerates at the upper end of the BMI distribution, suggesting that prior linear estimates may reflect a blended average of a modest slope across most of the range and a steep slope above the 80
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