Limitations
MDD, trauma
This study has some limitations. First, this study was conducted with an open-label design, which made it difficult to disentangle the effects of SSRI treatment from the effects of nonspecific factors (eg, expectation of improvement or knowledge of treatment). Second, this study treated all adolescents with MDD with 1 SSRI, escitalopram, which further limited the generalizability of our findings across different classes of SSRIs. However, using 1 SSRI for treatment may also have some benefits by excluding possible confounding effects, which may be caused by different SSRIs. Third, given that several factors, including specific symptoms and abuse or trauma history, could alter the effects of SSRI treatment, we did not test the potential moderation because of the lack of available data. Fourth, given the significant baseline difference in right DLPFC–left SFG rsFC between responders and nonresponders, the significant change of this rsFC in responders may be associated with the baseline difference, indicating the potential role of baseline differences in examining longitudinal associations of treatment with rsFC. Fifth, for rsFC analysis, we applied a seed-based approach, which has some advantages, such as a straightforward interpretation of the findings. However, this approach has some limitations, and future research should use a large-scale network analysis approach.