Effects of escitalopram on resting-state functional connectivity in comorbid depressive and anxious adolescents

Given that anxiety is highly comorbid in depressive adolescents, understanding the neural pathways underlying concurrent depression and anxiety could provide potential targets for treatment. We aimed to investigate treatment trajectories for depression and anxiety, and their relationships with neural circuits in the amygdala and hippocampus.

Major depressive disorder (MDD) adolescents and healthy controls were recruited. MDD participants administered escitalopram for eight weeks. Pre- and post-treatment resting-state functional magnetic resonance imaging scans were performed. We investigated treatment trajectories of MDD adolescents (n = 59) considering both depression and anxiety assessed by the Children's Depression Inventory and Screen for Child Anxiety Related Emotional Disorders, respectively. We examined the treatment effect on resting-state functional connectivity (RSFC) of the amygdala and hippocampus across trajectory groups compared these with RSFC patterns in controls (n = 43).

We identified three treatment trajectory groups: fast-decreasing (FDG, n = 21), no change (NCG, n = 15), and slow-decreasing group (SDG, n = 23). The longitudinal treatment effects on RSFC were pronounced in the FDG. FDG presented decreasing patterns of amygdala RSFC with the post- and precentral gyri, supplementary motor area, and calcarine gyrus. Conversely, the amygdala RSFCs in the middle frontal gyrus and inferior parietal lobule exhibited increasing trends in FDG after treatment. Compared to FDG, SDG showed different patterns of amygdala RSFC, and the amygdala RSFCs of the NCG and healthy controls did not change after treatment.

Longitudinal amygdala RSFC changes following treatment may vary among depressive and anxious adolescents. Neural biomarkers may underlie diverse treatment trajectories, offering potential avenues for targeted interventions.