ImportanceAntidepressant discontinuation substantially increases the risk of a depression relapse, but the neurobiological mechanisms through which this happens are not known. Amygdala reactivity to negative information is a marker of negative affective processes in depression that is reduced by antidepressant medication, but it is unknown whether amygdala reactivity is sensitive to antidepressant discontinuation or whether any change is related to the risk of relapse after antidepressant discontinuation.ObjectiveTo investigate whether amygdala reactivity to negative facial emotions changes with antidepressant discontinuation and is associated with subsequent relapse.Design, Setting, and ParticipantsThe Antidepressiva Absetzstudie (AIDA) study was a longitudinal, observational study in which adult patients with remitted major depressive disorder (MDD) and currently taking antidepressants underwent 2 task-based functional magnetic resonance imaging (fMRI) measurements of amygdala reactivity. Patients were randomized to discontinuing antidepressants either before or after the second fMRI measurement. Relapse was monitored over a 6-month follow-up period. Study recruitment took place from June 2015 to January 2018. Data were collected between July 1, 2015, and January 31, 2019, and statistical analyses were conducted between June 2021 and December 2023. The study took place in a university setting in Zurich, Switzerland, and Berlin, Germany. Of 123 recruited patients, 83 were included in analyses. Of 66 recruited healthy control individuals matched for age, sex, and education, 53 were included in analyses.ExposureDiscontinuation of antidepressant medication.OutcomesTask-based fMRI measurement of amygdala reactivity and MDD relapse within 6 months after discontinuation.ResultsAmong patients with MDD, the mean (SD) age was 35.42 (11.41) years, and 62 (75%) were women. Among control individuals, the mean (SD) age was 33.57 (10.70) years, and 37 (70%) were women. Amygdala reactivity of patients with remitted MDD and taking medication did not initially differ from that of control individuals (t125.136 = 0.33; P = .74). An increase in amygdala reactivity after antidepressant discontinuation was associated with depression relapse (3-way interaction between group [12W (waited) vs 1W2 (discontinued)], time point [MA1 (first scan) vs MA2 (second scan)], and relapse: β, 18.9; 95% CI, 0.8-37.1; P = .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; P = .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; P = .02).Conclusions and RelevanceAn increase in amygdala reactivity was associated with risk of relapse after antidepressant discontinuation and may represent a functional neuroimaging marker that could inform clinical decisions around antidepressant discontinuation.

中文翻译：

---

杏仁核反应性、抗抑郁药停药和复发


重要性停用抗抑郁药会大大增加抑郁症复发的风险，但发生这种情况的神经生物学机制尚不清楚。杏仁核对负面信息的反应是抑郁症中消极情感过程的标志，抗抑郁药物会降低这种反应，但尚不清楚杏仁核反应性是否对抗抑郁药停药敏感，或者任何变化是否与抗抑郁药停药后复发的风险有关。目的探讨杏仁核对负面面部情绪的反应是否会随着抗抑郁药的停用而改变，并与随后的复发相关。设计、设置和参与者抗抑郁研究 （AIDA） 是一项纵向观察性研究，其中患有缓解型重度抑郁症 （MDD） 且目前正在服用抗抑郁药的成年患者接受了 2 次基于任务的功能性磁共振成像 （fMRI） 杏仁核反应性测量。患者被随机分配到在第二次 fMRI 测量之前或之后停用抗抑郁药。在 6 个月的随访期内监测复发情况。研究招募于 2015 年 6 月至 2018 年 1 月进行。数据是在 2015 年 7 月 1 日至 2019 年 1 月 31 日期间收集的，统计分析是在 2021 年 6 月至 2023 年 12 月期间进行的。该研究在瑞士苏黎世和德国柏林的一所大学环境中进行。在招募的 123 名患者中，83 名被纳入分析。在年龄、性别和教育程度匹配的 66 名招募的健康对照个体中，包括 53 名被纳入分析。暴露停用抗抑郁药物。结果停药后 6 个月内杏仁核反应性和 MDD 复发的基于任务的 fMRI 测量。结果MDD 患者的平均 （SD） 年龄为 35.42 （11.41） 岁，其中 62 例 （75%） 为女性。在对照个体中，平均 （SD） 年龄为 33.57 （10.70） 岁，其中 37 名 （70%） 为女性。缓解型 MDD 和服用药物的患者的杏仁核反应性最初与对照组个体没有差异 （t125.136 = 0.33;P= .74）。停用抗抑郁药后杏仁核反应性的增加与抑郁复发（组 [12W（等待）] vs 1W2（停药）]、时间点 [MA1（第一次扫描）vs MA2（第二次扫描）] 和复发相关：β，18.9;95% CI，0.8-37.1;P= .04）。杏仁核反应性变化与较短的复发时间相关（风险比，1.05;95% CI，1.01-1.09;P= .01） 和复发预测 （留一法交叉验证平衡准确性，67%;95% 后验预测区间，53-80;P = .02）。结论和相关性杏仁核反应性的增加与停用抗抑郁药后复发的风险相关，可能代表功能性神经影像学标志物，可以为停用抗抑郁药的临床决策提供信息。