Brain-Predicted Age Associates With Psychopathology Dimensions in Youths

This study aimed to investigate whether dimensional constructs of psychopathology relate to variation in patterns of brain development and to determine whether these constructs share common neurodevelopmental profiles.

Psychiatric symptom ratings from 9312 youths (8-21 years old) from the Philadelphia Neurodevelopmental Cohort were parsed into 7 independent dimensions of clinical psychopathology representing conduct, anxiety, obsessive-compulsive, attention, depression, bipolar, and psychosis symptoms. Using a subset of this cohort with structural magnetic resonance imaging (n = 1313), a normative model of brain morphology was established and the model was then applied to predict the age of youths with clinical symptoms. We investigated whether the deviation of brain-predicted age from true chronological age, called the brain age gap, explained individual variation in each psychopathology dimension.

Individual variation in the brain age gap significantly associated with clinical dimensions representing psychosis (t = 3.16, p = .0016), obsessive-compulsive symptoms (t = 2.5, p = .01), and general psychopathology (t = 4.08, p < .0001). Greater symptom severity along these dimensions was associated with brain morphology that appeared older than expected for typically developing youths of the same age. Psychopathology dimensions clustered into 2 modules based on shared brain loci where putative accelerated neurodevelopment was most prominent. Patterns of morphological development were accelerated in frontal cortices for depression, psychosis, and conduct symptoms (module 1), whereas acceleration was most evident in subcortex and insula for the remaining dimensions (module 2).

Our findings suggest that increased brain age, particularly in frontal cortex and subcortical nuclei, underpins clinical psychosis and obsessive-compulsive symptoms in youths. Psychopathology dimensions share common neural substrates, despite representing clinically independent symptom profiles.