Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol
Predicting Treatment Outcome in Major Depressive Disorder Using Serotonin 4 Receptor PET Brain Imaging, Functional MRI, Cognitive-, EEG-Based, and Peripheral Biomarkers: A NeuroPharm Open Label Clinical Trial Protocol
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DOI：
10.3389/fpsyt.2020.00641
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发表时间：
2020-07-23
影响因子：
4.7
通讯作者：
Frokjaer, Vibe Gedsoe
中科院分区：
文献类型：
--
作者：
Kohler-Forsberg, Kristin;Jorgensen, Anders;Frokjaer, Vibe Gedsoe
背景：30 - 50%的重度抑郁症（MDD）患者对抗抑郁药治疗方案反应不充分。传统的药物治疗主要靶向多巴胺能脑信号，但需要更好的工具来预测治疗反应和识别MDD的相关亚组，以支持个体化和机械靶向治疗策略。本研究的目的是通过神经影像学、电生理学、分子学、认知和临床检查来调查无抗抑郁药的MDD患者，并评估他们作为单独或联合预测因子预测SSRI治疗临床反应的能力。我们将纳入100名未经治疗的中度至重度抑郁症患者（汉密尔顿抑郁量表17> 17）。我们将收集标准抗抑郁药治疗前（基线）、期间和12周后5-羟色胺4受体正电子发射断层扫描（PET）脑扫描、功能性磁共振成像（fMRI）、脑电图（EEG）、认知测试、心理测量和外周生物标志物的数据。患者将接受艾司西酞普兰治疗，如果在第4周时无应答或出现不可耐受的副作用，则可转为度洛沙坦二线治疗。我们的主要结果（治疗反应）是使用汉密尔顿抑郁评定子量表6项评分在第8周进行评估，与基线相比。在一个患者亚组（n = 40）中，我们将在开始药物抗抑郁治疗后8周重新评估神经生物学反应（使用PET、fMRI和EEG），以绘制治疗反应的神经生物学特征。来自匹配对照的数据将被收集或已经从其他队列中获得。在这个大型参与者队列中进行随访的广泛研究项目提供了一种独特的可能性，以（a）发现抗抑郁治疗反应的潜在生物标志物，（B）将研究结果应用于未来的MDD分层，（c）促进对MDD病理生理学基础的理解，和（d）揭示推定的生物标志物如何响应于8周的药理学抗抑郁治疗而改变。我们的数据可以为MDD的优化治疗的精准医学方法铺平道路，也为未来的研究和数据共享提供了资源。
Background: Between 30 and 50% of patients with major depressive disorder (MDD) do not respond sufficiently to antidepressant regimens. The conventional pharmacological treatments predominantly target serotonergic brain signaling but better tools to predict treatment response and identify relevant subgroups of MDD are needed to support individualized and mechanistically targeted treatment strategies. The aim of this study is to investigate antidepressant-free patients with MDD using neuroimaging, electrophysiological, molecular, cognitive, and clinical examinations and evaluate their ability to predict clinical response to SSRI treatment as individual or combined predictors.Methods: We will include 100 untreated patients with moderate to severe depression (>17 on the Hamilton Depression Rating Scale 17) in a non-randomized open clinical trial. We will collect data from serotonin 4 receptor positron emission tomography (PET) brain scans, functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), cognitive tests, psychometry, and peripheral biomarkers, before (at baseline), during, and after 12 weeks of standard antidepressant treatment. Patients will be treated with escitalopram, and in case of non-response at week 4 or intolerable side effects, offered to switch to a second line treatment with duloxetine. Our primary outcome (treatment response) is assessed using the Hamilton depression rating subscale 6-item scores at week 8, compared to baseline. In a subset of the patients (n = similar to 40), we will re-assess the neurobiological response (using PET, fMRI, and EEG) 8 weeks after initiated pharmacological antidepressant treatment, to map neurobiological signatures of treatment responses. Data from matched controls will either be collected or is already available from other cohorts.Discussion: The extensive investigational program with follow-up in this large cohort of participants provides a unique possibility to (a) uncover potential biomarkers for antidepressant treatment response, (b) apply the findings for future stratification of MDD, (c) advance the understanding of pathophysiological underpinnings of MDD, and (d) uncover how putative biomarkers change in response to 8 weeks of pharmacological antidepressant treatment. Our data can pave the way for a precision medicine approach for optimized treatment of MDD and also provides a resource for future research and data sharing.