Perinatal Factors and Neuroimaging Changes for Brain Maturation Among Adolescents

Brain maturation varies between individuals, particularly during dynamic developmental periods such as adolescence. Directly assessing the differences in longitudinal trajectories can reveal deviations from normative patterns.

To ascertain the association of longitudinal change in brain volumes with birth weight, gestational age, and longitudinal changes in psychopathology.

In this cohort study, cross-sectional and longitudinal normative models were developed for brain volumes from the first 2 neuroimaging data collection time points (baseline: 2016-2018; follow-up: 2019-2021) of the Adolescent Brain Cognitive Development (ABCD) Study, an ongoing community-based longitudinal cohort study at 21 US sites. Longitudinal models indexed an individual's expected brain volume at follow-up, conditioned on their baseline measurement, and thus were conditional-longitudinal models. Split-half subsets on demographically matched samples were used to fit the models. ABCD Study participants were recruited through the US school systems. Exclusion criteria included severe medical conditions that interfered with the study protocols. The present analysis further excluded the sample based on imaging quality flags and missing data. Data analysis was performed between May 2024 and August 2025.

Birth weight and gestational age derived from parent-reported questionnaires. General psychopathology and subfactor scores were calculated using a bifactor model.

Brain volumes and change in volume between time points 1 (baseline) and 2 (follow-up). Cross-sectional and longitudinal centiles were used to quantify deviations in volumes.

The sample included 10 830 ABCD Study participants with neuroimaging data collected at baseline (mean [SD] age, 9.9 [0.62] years; 5609 males [51.8%]) and 7262 with data collected at follow-up (mean [SD] age, 12.0 [0.65] years; 3875 males [53.4%]). Longitudinal centiles were sensitive to individual-specific changes in brain volumes. Lower birth weight was associated with lower longitudinal centiles, suggesting larger decreases in brain volumes over time (n = 27 regions, β range = 0.030-0.083). Lower longitudinal centiles were associated with greater increases in psychopathology, suggesting decreasing brain volumes with increasing psychopathology scores (n = 37 regions, β range = -0.061 to -0.031). Changes in psychopathology were not associated with brain volumes at either time point when indexed by cross-sectional centiles.

In this cohort study, conditional-longitudinal models captured individual-level deviations from expected growth trajectories, providing information beyond static positions on a growth curve to assess differences in maturation. Robust associations were observed between individual trajectory deviations, birth weight, and longitudinally assessed mental health symptoms. Conditional-longitudinal models hold promise for applications across psychiatric neuroscience, from development to aging.