Simon Maria S, Burger Bianka, Weidinger Elif, Arteaga-Henríquez Gara, Zill Peter, Musil Richard, Drexhage Hemmo A, Müller Norbert
Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
Marion von Tessin Memory-Center, Munich, Germany.
Front Psychiatry. 2021 Sep 27;12:615261. doi: 10.3389/fpsyt.2021.615261. eCollection 2021.
Previous research delivers strong indications that inflammatory activation leads to treatment resistance in a subgroup of patients with Major Depressive Disorder (MDD). Thus, tailored interventions are needed. The present study aimed to find potential biomarkers that may enable patients to be stratified according to immune activation. A phase IIa randomized placebo-controlled trial was performed to assess levels of inflammatory compounds in responders/remitters and non-responders/non-remitters to sertraline plus celecoxib ( = 20) and sertraline plus placebo ( = 23). Levels of macrophage migration inhibitory factor, neopterin, and tumor necrosis factor alpha were determined by enzyme-linked immunosorbent assay; response and remission were measured by reduction of the Montgomery Åsberg Depression Rating Scale score. Both treatment groups showed a significant decline in depression symptoms, but no difference was found between groups. A clear pattern emerged only for macrophage migration inhibitory factor: placebo remitters showed significantly lower baseline levels than non-remitters (a similar trend was seen in responders and non-responders) while celecoxib responders showed a trend for higher baseline levels than non-responders. Small subsample sizes are a notable limitation, wherefore results are preliminary. However, the present study provides novel insights by suggesting macrophage migration inhibitory factor as a promising biomarker for treatment choice. The trial was registered in EU Clinical Trials Register (EU-CTR): https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011990-34/DE, EudraCT-No.: 2009-011990-34.
先前的研究有力地表明，炎症激活会导致一部分重度抑郁症（MDD）患者产生治疗抵抗。因此，需要针对性的干预措施。本研究旨在寻找潜在的生物标志物，以便能够根据免疫激活情况对患者进行分层。开展了一项IIa期随机安慰剂对照试验，以评估接受舍曲林加塞来昔布（n = 20）和舍曲林加安慰剂（n = 23）治疗的反应者/缓解者与无反应者/未缓解者体内炎症化合物的水平。通过酶联免疫吸附测定法测定巨噬细胞迁移抑制因子、新蝶呤和肿瘤坏死因子α的水平；通过蒙哥马利-阿斯伯格抑郁评定量表评分的降低来衡量反应和缓解情况。两个治疗组的抑郁症状均有显著下降，但两组之间未发现差异。仅巨噬细胞迁移抑制因子呈现出一种明显的模式：安慰剂缓解者的基线水平显著低于未缓解者（反应者和无反应者中也观察到类似趋势），而塞来昔布反应者的基线水平有高于无反应者的趋势。样本量较小是一个显著的局限性，因此结果是初步的。然而，本研究通过提出巨噬细胞迁移抑制因子作为治疗选择的一个有前景的生物标志物，提供了新的见解。该试验已在欧盟临床试验注册库（EU-CTR）注册：https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011990-34/DE，欧盟临床试验编号（EudraCT-No.）：2009-011990-34。
