November 25, 2020

Brain-predicted age associates with psychopathology dimensions in youth

Background: This study aims to investigate whether dimensional constructs of psychopathology relate to advanced, attenuated or normal patterns of brain development, and to determine whether these constructs share common neurodevelopmental profiles.

Methods: Psychiatric symptom ratings from 9312 youths (8-21 years) 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 MRI (n=1313), a normative model of brain morphology was established and the model was then applied to predict the age of youth 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.

Results: Individual variation in the brain age gap significantly associated with clinical dimensions representing psychosis (t=3.16, p=0.0016), obsessive-compulsive symptoms (t=2.5, p=0.01), and general psychopathology (t=4.08, p<0.0001). Greater symptom severity along these dimensions was associated with brain morphology that appeared older than expected for typically developing youth of the same age. Psychopathology dimensions clustered into two 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 I), whereas acceleration was most evident in subcortex and insula for the remaining dimensions (Module II). Conclusions: Our findings suggest that advanced brain development, particularly in frontal cortex and subcortical nuclei, underpins clinical psychosis and obsessive-compulsive symptoms in youth. Psychopathology dimensions share common neural substrates, despite representing clinically independent symptom profiles.

 bioRxiv Subject Collection: Neuroscience

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