Anxiety disorders are the most common mental disorders in adolescents. However, only 50% of pediatric patients with anxiety disorders respond to the first-line pharmacologic treatments—selective serotonin reuptake inhibitors (SSRIs). Thus, identifying the neurofunctional targets of SSRIs and finding pretreatment or early-treatment neurofunctional markers of SSRI treatment response in this population is clinically important. We acquired pretreatment and early-treatment (2 weeks into treatment) functional magnetic resonance imaging during a continuous processing task with emotional and neutral distractors in adolescents with generalized anxiety disorder (GAD, N = 36) randomized to 8 weeks of double-blind escitalopram or placebo. Generalized psychophysiological interaction analysis was conducted to examine the functional connectivity of the amygdala while patients viewed emotional pictures. Full-factorial analysis was used to investigate the treatment effect of escitalopram on amygdala connectivity. Correlation analyses were performed to explore whether pretreatment and early (week 2) treatment-related connectivity were associated with treatment response (improvement in anxiety) at week 8. Compared to placebo, escitalopram enhanced emotional processing speed and enhanced negative right amygdala-bilateral ventromedial prefrontal cortex (vmPFC) and positive left amygdala-right angular gyrus connectivity during emotion processing. Baseline amygdala-vmPFC connectivity and escitalopram-induced increased amygdala-angular gyrus connectivity at week 2 predicted the magnitude of subsequent improvement in anxiety symptoms. These findings suggest that amygdala connectivity to hubs of the default mode network represents a target of acute SSRI treatment. Furthermore, pretreatment and early-treatment amygdala connectivity could serve as biomarkers of SSRI treatment response in adolescents with GAD. The trial registration for the study is ClinicalTrials.gov Identifier: NCT02818751.

焦虑症是青少年最常见的精神障碍。然而，只有 50% 的儿童焦虑症患者对一线药物治疗——选择性 5-羟色胺再摄取抑制剂 (SSRIs) 有反应。因此，确定 SSRI 的神经功能靶标并在该人群中寻找 SSRI 治疗反应的治疗前或早期治疗神经功能标志物具有临床意义。我们在患有广泛性焦虑症 (GAD, N = 36) 随机接受为期 8 周的双盲艾司西酞普兰或安慰剂治疗。进行了广义心理生理学相互作用分析，以检查患者观看情感图片时杏仁核的功能连接性。全因子分析用于研究艾司西酞普兰对杏仁核连通性的治疗效果。进行相关性分析以探讨治疗前和早期（第 2 周）治疗相关连接是否与第 8 周的治疗反应（焦虑改善）相关。与安慰剂相比，艾司西酞普兰增强了情绪处理速度并增强了右杏仁核负性-双侧腹内侧前额叶皮层 (vmPFC) 和情绪处理过程中左杏仁核-右角回的正连通性。第 2 周基线杏仁核-vmPFC 连通性和艾司西酞普兰诱导的杏仁核-角回连通性增加预测了焦虑症状随后改善的程度。这些发现表明，杏仁核与默认模式网络中枢的连接代表了急性 SSRI 治疗的目标。此外，治疗前和早期治疗的杏仁核连接性可以作为 GAD 青少年 SSRI 治疗反应的生物标志物。该研究的试验注册是 ClinicalTrials.gov 标识符：NCT02818751。治疗前和早期治疗的杏仁核连通性可以作为 GAD 青少年 SSRI 治疗反应的生物标志物。该研究的试验注册是 ClinicalTrials.gov 标识符：NCT02818751。治疗前和早期治疗的杏仁核连通性可以作为 GAD 青少年 SSRI 治疗反应的生物标志物。该研究的试验注册是 ClinicalTrials.gov 标识符：NCT02818751。