Neuroimaging subtypes of adolescent sleep insufficiency stratify natural short sleepers from comorbidity or environment driven insufficiency

Insufficient sleep (less than 8 hours for adolescents) has heterogeneous neurobiological underpinnings. Using the SuStaIn model on brain MRI from ABCD Study, we identified three distinct subtypes with reduced cortical thickness, starting from the postcentral, pericalcarine, and entorhinal cortices. The subtypes diverged in sleep-related determinants. The postcentral subtype mirrored the controls of sufficient sleep in sleep behavior and sleep environment and showed no psychiatric comorbidities, which aligned with natural short sleepers (phenotypically normal despite short sleep). Notably, this subtype displayed significantly advanced brain age, and polygenetic score analysis revealed a genetic predisposition for short sleep. The pericalcarine subtype was linked to environmental factors (e.g., light/noise pollution), with sleep duration mediating environmental effects on cortical thinning. The entorhinal subtype showed elevated psychiatric risk, younger brain age, and larger spatial correlations with psychosis-related neurotransmitter systems. This work deciphers the heterogeneous neurobiology of insufficient sleep and offers a framework for stratified interventions.