Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.
Department of Psychiatry & Behavioral Neuroscience, College of Medicine, University of Cincinnati, Cincinnati, OH, USA.
Neuropsychopharmacology. 2022 Apr;47(5):1081-1087. doi: 10.1038/s41386-021-01186-0. Epub 2021 Sep 27.
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.
焦虑障碍是青少年中最常见的精神障碍。然而，只有 50%的焦虑障碍儿科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 SSRIs 的神经功能靶点，并在该人群中找到治疗反应的预处理或早期神经功能标志物，具有重要的临床意义。我们在广泛性焦虑障碍（GAD，N=36）青少年中获得了预处理和早期（治疗 2 周）的功能磁共振成像，他们在进行连续处理任务时接受了情绪和中性分心物的刺激，并随机分配到 8 周的艾司西酞普兰或安慰剂治疗中。我们进行了广义心理生理相互作用分析，以检查患者观看情绪图片时杏仁核的功能连接。我们使用全因子分析来研究艾司西酞普兰对杏仁核连接的治疗效果。相关性分析用于探讨预处理和早期（第 2 周）与治疗相关的连接是否与第 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，并增强了负性右杏仁核-双侧腹内侧前额叶皮质（vmPFC）和正性左杏仁核-右角回的连接。在情绪处理过程中，基线杏仁核-腹内侧前额叶皮质的连接和第 2 周艾司西酞普兰诱导的杏仁核-角回的连接增加，预测了随后焦虑症状改善的程度。这些发现表明，杏仁核对默认模式网络中枢的连接代表了急性 SSRIs 治疗的靶点。此外，预处理和早期治疗的杏仁核连接可以作为青少年 GAD 患者 SSRIs 治疗反应的生物标志物。该研究的临床试验注册号为：NCT02818751。
