Symptom-specific links between internalizing problems and functional connectivity in adolescents: a network analysis

Previous fMRI studies have documented links between internalizing problems in youth and brain functional connectivity of the default (DN), frontoparietal (FP), and salience (SA) networks. Characterized by a large symptom heterogeneity and comorbidity, it remains elusive how individual internalizing symptoms relate to DN, FP, and SA connectivity. Leveraging a large population-based sample of adolescents (N = 2426; mean age = 14.1 years) and an integrated network modelling approach, we identified symptom-specific associations between internalizing problems and functional connectivity and explored sex and timing-specific differences in these links. Our findings revealed small negative associations between self-reported feelings of worthlessness and guilt and DN within-network connectivity and positive associations between fearfulness and FP within-network connectivity. Moreover, sadness and fearfulness were positively associated with DN-SA between-network connectivity. Exploratory analyses revealed no significant sex differences but indicated that DN within-network connectivity around age 10 was negatively associated with self-reported worthlessness at age 14. Our findings show symptom-specific associations between internalizing problems and brain functional circuitry in youth and highlight the complex interplay of symptoms and brain networks.