Tore Erdmann, Isabel M. Berwian, Klaas Enno Stephan, Erich Seifritz, Henrik Walter, Quentin J. M. Huys
{"title":"杏仁核反应性、抗抑郁药停药和复发","authors":"Tore Erdmann, Isabel M. Berwian, Klaas Enno Stephan, Erich Seifritz, Henrik Walter, Quentin J. M. Huys","doi":"10.1001/jamapsychiatry.2024.2136","DOIUrl":null,"url":null,"abstract":"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 (<jats:italic>t</jats:italic><jats:sub>125.136</jats:sub> = 0.33; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .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; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; <jats:italic>P</jats:italic> = .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.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":null,"pages":null},"PeriodicalIF":22.5000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Amygdala Reactivity, Antidepressant Discontinuation, and Relapse\",\"authors\":\"Tore Erdmann, Isabel M. Berwian, Klaas Enno Stephan, Erich Seifritz, Henrik Walter, Quentin J. M. Huys\",\"doi\":\"10.1001/jamapsychiatry.2024.2136\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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 (<jats:italic>t</jats:italic><jats:sub>125.136</jats:sub> = 0.33; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .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; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .04). Amygdala reactivity change was associated with shorter times to relapse (hazard ratio, 1.05; 95% CI, 1.01-1.09; <jats:italic>P</jats:italic> <jats:italic>=</jats:italic> .01) and predictive of relapse (leave-one-out cross-validation balanced accuracy, 67%; 95% posterior predictive interval, 53-80; <jats:italic>P</jats:italic> = .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.\",\"PeriodicalId\":14800,\"journal\":{\"name\":\"JAMA Psychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":22.5000,\"publicationDate\":\"2024-09-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAMA Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamapsychiatry.2024.2136\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamapsychiatry.2024.2136","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Amygdala Reactivity, Antidepressant Discontinuation, and Relapse
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.
期刊介绍:
JAMA Psychiatry is a global, peer-reviewed journal catering to clinicians, scholars, and research scientists in psychiatry, mental health, behavioral science, and related fields. The Archives of Neurology & Psychiatry originated in 1919, splitting into two journals in 1959: Archives of Neurology and Archives of General Psychiatry. In 2013, these evolved into JAMA Neurology and JAMA Psychiatry, respectively. JAMA Psychiatry is affiliated with the JAMA Network, a group of peer-reviewed medical and specialty publications.