Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, Republic of Korea.
Integrative Care Hub, Seoul National University Children's Hospital, Seoul, Republic of Korea.
JAMA Netw Open. 2023 Aug 1;6(8):e2327331. doi: 10.1001/jamanetworkopen.2023.27331.
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.
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.
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.
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.
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.
选择性 5-羟色胺再摄取抑制剂（SSRIs）被认为是治疗中重度青少年抑郁症的一线药理学治疗方法。因此，了解抑郁症青少年在治疗过程中与 SSRIs 相关的神经生物学变化非常重要。
通过测量青少年重度抑郁症（MDD）患者背外侧前额叶皮质（DLPFC）的体积和静息态功能连接（rsFC）的纵向变化，来研究与 SSRIs 治疗相关的神经生物学变化，该区域是认知控制的核心区域。
设计、地点和参与者：这是一项队列研究，采用开放标签设计。MDD 青少年和健康对照者在首尔国立大学医院（韩国首尔）招募。MDD 青少年接受依地普仑治疗 8 周。数据分析于 2021 年 4 月至 2022 年 2 月进行。
使用儿童抑郁评定量表修订版（Children's Depression Rating Scale-Revised）评估抑郁症状。结局指标定义为从治疗前（第 0 周）到治疗后（第 8 周）或停药时儿童抑郁评定量表修订版评分的变化。参与者在接受 SSRIs 治疗前（第 0 周）和治疗后（第 8 周）完成结构和静息态功能磁共振成像（rsfMRI）评估。重复测量方差分析和线性混合模型分析用于检验 SSRI 治疗与反应者（抑郁症状至少降低 40%）和非反应者（无反应）之间 DLPFC 体积和 rsFC 的纵向关联。
最初招募了 95 名 MDD 青少年和 57 名健康对照者。体积的最终分析包括 36 名反应者（平均[SD]年龄，15.0[1.6]岁；25 名女孩[69.4%]）和 26 名非反应者（平均[SD]年龄，15.3[1.5]岁；19 名女孩[73.1%]）。rsFC 的分析包括 33 名反应者（平均[SD]年龄，15.2[1.5]岁；21 名女孩[63.6%]）和 26 名非反应者（平均[SD]年龄，15.3[1.5]岁；19 名女孩[73.1%]）。与非反应者相比，SSRIs 治疗的纵向关联在反应者中更为明显。与治疗前相比，治疗后反应者的右侧 DLPFC 体积增加，双侧 DLPFC 与额上回的 rsFC 减少，左侧 DLPFC 与腹内侧前额叶皮质的 rsFC 减少。此外，右侧 DLPFC 体积增加与 SSRI 治疗后右侧 DLPFC 与额上回之间的 rsFC 减少相关。
这项队列研究的初步结果表明，DLPFC 体积和 rsFC 的变化可能是潜在的神经生物学治疗标志物，与 MDD 青少年的症状改善相关。
