A longitudinal mediation study of peer victimization and resting-state functional connectivity as predictors of development of adolescent psychopathology.

Background: Peer victimization (PV) is associated with alterations in neural responses in regions subserving emotional regulatory processes and with increased risk of psychopathology during adolescence. The present study examined the longitudinal mediating effects of resting-state functional connectivity (rsFC) between adolescent PV and subsequent internalizing (depression and anxiety), and externalizing (conduct and hyperactivity/inattention) symptoms. Methods: 151 adolescents (baseline mean age 12-14; 54% males) were assessed and imaged three times during a five-year period. We focused on rsFC of a priori determined Regions-of-Interest (ROIs) guided by the literature (i.e., amygdala, anterior and posterior insula, anterior cingulate cortex, and medial prefrontal cortex). Multilevel mediation (MLM) analyses simultaneously examined the between-person, concurrent within-person, and lagged within-person associations between PV and internalizing/externalizing symptoms through changes in couplings of the amygdala with the other four ROIs. All models controlled for the effects of self-reported childhood maltreatment and sex differences. Results: An increased rsFC of the amygdala-posterior insula significantly mediated the lagged within-person association of PV and internalizing symptoms (ß = 0.144; 95% CI [0.018, 0.332]). This effect was significant regardless of childhood maltreatment, concurrent externalizing symptoms, and sex differences. The rsFC did not mediate the relationship between PV and externalizing symptoms. Conclusions: Results of this study suggest that adolescent PV may lead to long-lasting maladaptive neural communication between emotional response and sensory perception of pain (i.e., bottom-up emotion regulation) and that these neural responses may serve as unique markers for increased internalizing symptoms that appear in later adolescence in peer-victimized youth. These findings have implications for interventions targeting internalizing symptoms in victimized adolescents.