Longitudinal development of resting-state functional connectivity in adolescents with and without internalizing...

Longitudinal studies using resting-state functional magnetic resonance imaging (rs-fMRI) focused on adolescent internalizing psychopathology are scarce and have mostly investigated standardized treatment effects on functional connectivity (FC) of the full amygdala. The role of amygdala subregions and large resting-state networks had yet to be elucidated, and treatment is in practice often personalized. Here, longitudinal FC development of amygdala subregions and whole-brain networks are investigated in a clinically representative sample. Treatment-naïve adolescents with clinical depression and comorbid anxiety who started care-as-usual (n = 23; INT) and healthy controls (n = 24; HC) participated in rs-fMRI scans and questionnaires at baseline (before treatment) and after three months. Changes between and within groups over time in FC of the laterobasal amygdala (LBA), centromedial amygdala (CMA) and whole-brain networks derived from independent component analysis (ICA) were investigated. Groups differed significantly in FC development of the right LBA to the postcentral gyrus and the left LBA to the frontal pole. Within INT, FC to the frontal pole and postcentral gyrus changed over time while changes in FC of the right LBA were also linked to symptom change. No significant interactions were observed when considering FC from CMA bilateral seeds or within ICA-derived networks. Results in this cohort suggest divergent longitudinal development of FC from bilateral LBA subregions in adolescents with internalizing disorders compared to healthy peers, possibly reflecting nonspecific treatment effects. Moreover, associations were found with symptom change. These results highlight the importance of differentiation of amygdala subregions in neuroimaging research in adolescents.