Discussion
MDD, depression
PATHOPHYSIOLOGY
To the best of our knowledge, this cohort study is one of the first to investigate neurobiological treatment markers after SSRI treatment that are associated with clinical symptom improvement in adolescents with MDD. We also examined the associations between neurobiological treatment markers, such as DLPFC volume and DLPFC rsFC. First, we found significant longitudinal associations of SSRI treatment with DLPFC volume and rsFC. Compared with nonresponders, responders showed increases in the gray matter volume of the right DLPFC, decreases in DLPFC rsFC with the prefrontal regions involved in cognitive control (eg, the left SFG and MFG), and decreases in rsFC between the left DLPFC and prefrontal regions involved in self-referential processing (eg, the VMPFC). Furthermore, increased right DLPFC volume after treatment was associated with decreased rsFC between the right DLPFC and left SFG.As hypothesized, the longitudinal associations of SSRI treatment with both DLPFC volume and rsFC were more pronounced in responders than nonresponders. First, the right DLPFC volume increased after SSRI treatment in responders, but not in nonresponders. This result is in line with a previous longitudinal studySecond, compared with nonresponders, responders showed significantly reduced rsFC between the right DLPFC and left prefrontal regions (ie, the left SFG and MFG) and between the left DLPFC and right prefrontal regions (ie, the right SFG) over the course of treatment. Elevated rsFCs within the prefrontal regions of cognitive control have been found in adults with MDD.Responders also showed greater reductions in rsFC between the left DLPFC and VMPFC, and between the left DLPFC and anterior temporal regions, compared with nonresponders over time. The VMPFC and anterior temporal regions are known to be responsible for self-referential processing. Therefore, reduced rsFC in the left DLPFC with the VMPFC and anterior temporal regions after SSRI treatment may indicate decreased communications between these regions in responders. Hyperconnectivity between the cognitive control regions and self-referential regions of the brain has been shown in depressionWe found some novel results. There was a significant negative correlation between right DLPFC volume change and right DLPFC–left SFG rsFC change after SSRI treatment. Although structural and functional alterations are known to be associated with the pathophysiology and recovery of depression, the association of structural with functional changes in depression remains largely unknown. Structural alterations could lead to altered functional connectivity or vice versa in depression.