Importance: Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression.
Objective: To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control.
Design, setting, and participants: This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022.
Main outcomes and measures: Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not.
Results: Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment.
Conclusions and relevance: The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.