Leveraging distributed brain signal at rest to predict internalizing symptoms in youth.

Abstract

Background: The prevalence of internalizing psychopathology rises precipitously from early to mid-adolescence, yet the underlying neural phenotypes that give rise to depression and anxiety during this developmental period remain unclear.

Methods: Youth from the Adolescent Brain and Cognitive Development^SM Study (ages 9-10 years at baseline) with a resting-state fMRI scan and mental health data were eligible for inclusion. Internalizing subscale scores from the Brief Problem Monitor - Youth Form were combined across two years of follow-up to generate a cumulative measure of internalizing symptoms. The total sample (n = 6521) was split into a large discovery dataset and a smaller validation dataset. Brain-behavior associations of resting-state functional connectivity (RSFC) with internalizing symptoms were estimated in the discovery dataset. The weighted contributions of each functional connection were aggregated using multivariate statistics to generate a polyneuro risk score (PNRS). The predictive power of the PNRS was evaluated in the validation dataset.

Results: The PNRS explained 10.73% of the observed variance in internalizing symptom scores in the validation dataset. Model performance peaked when the top 2% functional connections identified in the discovery dataset (ranked by absolute β-weight) were retained. The RSFC networks that were implicated most prominently were the default mode, dorsal attention, and cingulo-parietal networks. These findings were significant (p < 1*10^-6) as accounted for by permutation testing (n = 7000).

Conclusions: These results suggest that the neural phenotype associated with internalizing symptoms during adolescence is functionally distributed. The PNRS approach is a novel method for capturing relationships between RSFC and behavior.