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Adolescent brain-age differences between profiles based on suicidal ideation, distress and wellbeing

Crethar, M.; Han, L. K.; Prince, T.; Mills, L.; Silk, T.; Vijayakumar, N. K.; Hermens, D. F.; Boyes, A.

2026-08-05 neuroscience
10.64898/2026.07.31.741956 bioRxiv
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BackgroundPredicted brain-age derived from structural neuroimaging is being increasingly explored as a marker of brain maturation and biological age, with mental ill-health linked to advanced biological ageing in adults. Longitudinal evidence in adolescents remains limited, and the relationship between suicidality, psychological distress, wellbeing and brain-age gap (BrainAGE; predicted brain-age minus chronological age) is poorly understood. MethodsData were drawn from 135 adolescents (54.8% female; 12-16.9 years; n=688 observations) from the Longitudinal Adolescent Brain Study. Latent profile analysis (LPA) used person-level means and standard deviations of distress (K10), wellbeing (COMPAS-W) and suicidal ideation (SIDAS). BrainAGE was estimated using the CentileBrain Global-BrainAGE pipeline from FreeSurfer-derived morphometric features. Associations between cluster membership and BrainAGE were examined using linear regression and linear mixed-effects models, adjusted for chronological age and sex. ResultsThree profiles emerged: low distress (N=110; 50% female), moderate distress with greater suicidal ideation (N=14; 64% female) and moderate distress with lower suicidal ideation (N=11; 91% female). The moderate distress with lower suicidal ideation cluster showed significantly higher BrainAGE relative to the low distress cluster (B=1.87, SE=0.76, p=.015). Whereas, the moderate distress with greater suicidal ideation cluster did not differ to the low distress cluster. Chronological age was positively associated with BrainAGE (B=0.67, SE=0.07, p<.001). ConclusionsDistinct adolescent mental health profiles may be associated with BrainAGE, depending on the levels and stability of distress and suicidality. However, the longitudinal associations were less robust across small extensions of the developmental range studied, warranting some cautious interpretation and need for replication.

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