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通过急性静脉注射激发后脑功能连接变化预测抗抑郁药西酞普兰的治疗反应

Predicting Antidepressant Citalopram Treatment Response via Changes in Brain Functional Connectivity After Acute Intravenous Challenge.

作者信息

Klöbl Manfred, Gryglewski Gregor, Rischka Lucas, Godbersen Godber Mathis, Unterholzner Jakob, Reed Murray Bruce, Michenthaler Paul, Vanicek Thomas, Winkler-Pjrek Edda, Hahn Andreas, Kasper Siegfried, Lanzenberger Rupert

机构信息

Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.

出版信息

Front Comput Neurosci. 2020 Oct 6;14:554186. doi: 10.3389/fncom.2020.554186. eCollection 2020.

Abstract

The early and therapy-specific prediction of treatment success in major depressive disorder is of paramount importance due to high lifetime prevalence, and heterogeneity of response to standard medication and symptom expression. Hence, this study assessed the predictability of long-term antidepressant effects of escitalopram based on the short-term influence of citalopram on functional connectivity. Twenty nine subjects suffering from major depression were scanned twice with resting-state functional magnetic resonance imaging under the influence of intravenous citalopram and placebo in a randomized, double-blinded cross-over fashion. Symptom factors were identified for the Hamilton depression rating scale (HAM-D) and Beck's depression inventory (BDI) taken before and after a median of seven weeks of escitalopram therapy. Predictors were calculated from whole-brain functional connectivity, fed into robust regression models, and cross-validated. Significant predictive power could be demonstrated for one HAM-D factor describing insomnia and the total score ( = 0.45-0.55). Remission and response could furthermore be predicted with an area under the receiver operating characteristic curve of 0.73 and 0.68, respectively. Functional regions with high influence on the predictor were located especially in the ventral attention, fronto-parietal, and default mode networks. It was shown that medication-specific antidepressant symptom improvements can be predicted using functional connectivity measured during acute pharmacological challenge as an easily assessable imaging marker. The regions with high influence have previously been related to major depression as well as the response to selective serotonin reuptake inhibitors, corroborating the advantages of the current approach of focusing on treatment-specific symptom improvements.

摘要

由于重度抑郁症的终生患病率高,且对标准药物治疗的反应和症状表现存在异质性,因此对其治疗成功进行早期和特定治疗的预测至关重要。因此,本研究基于西酞普兰对功能连接的短期影响,评估了艾司西酞普兰长期抗抑郁作用的可预测性。29名重度抑郁症患者在静脉注射西酞普兰和安慰剂的影响下,以随机、双盲交叉方式接受了两次静息态功能磁共振成像扫描。在艾司西酞普兰治疗中位数七周前后,对汉密尔顿抑郁量表(HAM-D)和贝克抑郁量表(BDI)确定症状因素。从全脑功能连接计算预测指标,输入稳健回归模型并进行交叉验证。对于一个描述失眠的HAM-D因子和总分(=0.45-0.55),可证明具有显著的预测能力。此外,缓解和反应的预测分别采用受试者操作特征曲线下面积为0.73和0.68。对预测指标有高度影响的功能区域尤其位于腹侧注意、额顶叶和默认模式网络。结果表明,使用急性药理学激发期间测量的功能连接作为易于评估的成像标记,可以预测特定药物的抗抑郁症状改善。具有高度影响的区域此前已与重度抑郁症以及对选择性5-羟色胺再摄取抑制剂的反应相关,证实了当前专注于特定治疗症状改善方法的优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/030a/7573155/b91f76316556/fncom-14-554186-g0001.jpg

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