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治疗前 qEEG 生物标志物预测重度抑郁症药物治疗效果:NeuroPharm 研究的独立验证。

Pretreatment qEEG biomarkers for predicting pharmacological treatment outcome in major depressive disorder: Independent validation from the NeuroPharm study.

机构信息

Department of Clinical Pharmacology, H. Lundbeck A/S, Valby, Denmark; Neurobiology Research Unit, University Hospital Rigshospitalet, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Department of Psychiatry, Psychotherapy and Psychosomatic, University Zürich, Switzerland.

出版信息

Eur Neuropsychopharmacol. 2021 Aug;49:101-112. doi: 10.1016/j.euroneuro.2021.03.024. Epub 2021 Apr 25.

Abstract

Several electroencephalogram (EEG) biomarkers for prediction of drug response in major depressive disorder (MDD) have been proposed, but validations in larger independent datasets are missing. In the current study, we investigated the prognostic value of previously suggested EEG biomarkers. We gathered data that matched prior studies in terms of EEG methodology, clinical criteria for MDD, and statistical approach as closely as possible. The NeuroPharm study is a non-randomized and open label prospective clinical trial. One hundred antidepressant free patients with MDD were enrolled in the study and 79 (57 female) were included in the per-protocol analysis. The biomarkers candidates for cross-validation were derived from prior studies such as iSPOT-D and EMBARC and include frontal and occipital alpha power and asymmetry and delta and theta activity at anterior cingulate cortex (ACC). The alpha asymmetry, reported in two out of six prior studies, could be partially validated. We found that in female patients, larger right than left frontal alpha power prior to drug treatment was associated with better clinical outcome 8 weeks later. Moreover, female non-responder had higher central left alpha power relative to the right. In contrast to prior reports, we found that lower theta activity at ACC was present in remitters and was associated with greater improvement at week 8. We provide evidence that in women with MDD, alpha asymmetry seems to be the most promising EEG biomarker for prediction of treatment response. Registration number: NCT02869035.

摘要

已经提出了几种用于预测重度抑郁症 (MDD) 药物反应的脑电图 (EEG) 生物标志物,但在更大的独立数据集上进行验证的情况尚不清楚。在当前研究中,我们研究了先前提出的 EEG 生物标志物的预后价值。我们收集的数据在 EEG 方法、MDD 的临床标准和统计方法方面尽可能与之前的研究相匹配。NeuroPharm 研究是一项非随机和开放标签的前瞻性临床试验。100 名无抗抑郁药的 MDD 患者入组该研究,79 名(57 名女性)符合方案分析。用于交叉验证的候选生物标志物源自先前的研究,如 iSPOT-D 和 EMBARC,包括额区和枕区α功率和不对称性以及前扣带回皮层 (ACC) 的δ和θ活动。在六项先前研究中的两项中报告的α不对称性可以部分验证。我们发现,在女性患者中,药物治疗前右侧前额α功率大于左侧与 8 周后更好的临床结果相关。此外,女性无反应者的中央左α功率相对于右侧更高。与之前的报告相反,我们发现 REM 期的 ACC 处θ活动较低,并且与第 8 周的改善程度相关。我们提供的证据表明,在患有 MDD 的女性中,α不对称似乎是预测治疗反应的最有前途的 EEG 生物标志物。注册号:NCT02869035。

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