超越症状：重度抑郁症抗抑郁治疗结局的早期预测生物标志物
Beyond Symptoms: Early Predictive Biomarkers of Antidepressant Outcomes in Major Depressive Disorder.
摘要(中文译文)
重性抑郁障碍的治疗疗效受其显著的病因学和表型异质性以及部分已知的神经生物学机制所限。尽管药物治疗是一线治疗手段，但约30%的抑郁患者对选择性5-羟色胺再摄取抑制剂获益不足。本叙述性综述总结了据报告可预测抗抑郁药治疗结局的候选生物标志物，涵盖不同诊疗阶段，包括症状应答/缓解、复发/再燃以及功能恢复和生活质量。本文重点阐述了不同抗抑郁药之间的异同，构建了功能性分类框架，并评估了其在治疗过程中的时效性。基于抑郁症的病理生理学假设，我们将生物标志物分为八种功能类型：神经营养因子（如外周BDNF和BDNF DNA甲基化）、神经内分泌标志物（HPA轴活性、皮质醇）、免疫炎症调节因子（如IL-6、IL-1β、TNF-α）、神经递质相关组分（如HTR2A变异）、非编码RNA（如miR-1202、miR-4707-3p、tiRNA-Gly-GCC-001）、肠道微生物群特征、神经影像学标志物（如海马体积、前扣带回厚度、5-羟色胺能靶点的PET标志物）以及其他分子指标（如CYP450多态性、S100B、CREB/pCREB）。证据提示，部分生物标志物在治疗早期即与治疗结局相关，尤其是外周BDNF相关指标、炎症细胞因子、海马结构、特定miRNA、CREB/pCREB和S100B。然而，现有证据并不一致，所观察到的关联通常较弱，且大多数生物标志物仍处于研究阶段，尚不适合常规临床应用。因此，统一的实验室方法、大型多民族队列、严格的外部验证以及整合性多模态预测模型对于实现生物标志物指导的精准精神病学至关重要，从而将现有研究结果转化为临床实践。
Abstract
The treatment efficacy of major depressive disorder is limited by its pronounced etiological and phenotypic heterogeneity and the partially understood neurobiology. Although pharmacotherapy is the first-line treatment, around 30% of depressive patients do not sufficiently benefit from selective serotonin reuptake inhibitors. This narrative review summarizes the candidate biomarkers that can reportedly predict antidepressant treatment outcomes across different care stages, including symptomatic response/remission, relapse/recurrence, and functional recovery and quality of life. It highlights the similarities and differences among antidepressants, constructs a functional division framework, and evaluates their temporal utility during treatment. Based on the pathophysiological assumptions of depression, we divide the biomarkers into eight functional types: neurotrophic factors (e.g., peripheral BDNF and BDNF DNA methylation), neuroendocrine markers (HPA-axis activity, cortisol), immune-inflammatory regulators (e.g., IL-6, IL-1β, TNF-α), neurotransmitter-related components (e.g., HTR2A variants), non-coding RNAs (e.g., miR-1202, miR-4707-3p, tiRNA-Gly-GCC-001), gut microbiota profiles, neuroimaging markers (e.g., hippocampal volume, ACC thickness, PET markers of serotonergic targets), and other molecular indices (e.g., CYP450 polymorphisms, S100B, CREB/pCREB). Evidence suggests that some biomarkers show early associations with treatment outcomes, particularly peripheral BDNF-related measures, inflammatory cytokines, hippocampal structure, selected miRNAs, CREB/pCREB, and S100B. However, the available evidence is mixed, the observed associations are generally weak, and most biomarkers remain investigational rather than suitable for routine clinical use. Thus, harmonized laboratory methods, large multi-ethnic cohorts, rigorous external validation, and integrative multimodal prediction models will be essential for achieving biomarker-guided precision psychiatry, so as to translate the existing findings into clinical practice.
如何引用
AMA
Xiaolan Liu, Changyu Fu, Qin Xie. Beyond Symptoms: Early Predictive Biomarkers of Antidepressant Outcomes in Major Depressive Disorder.. Current neuropharmacology. 2026; doi:10.2174/011570159X469939260607094252.
APA
Xiaolan Liu, Changyu Fu, Qin Xie (2026). Beyond Symptoms: Early Predictive Biomarkers of Antidepressant Outcomes in Major Depressive Disorder.. Current neuropharmacology. https://doi.org/10.2174/011570159X469939260607094252
GB/T 7714
Xiaolan Liu, Changyu Fu, Qin Xie. Beyond Symptoms: Early Predictive Biomarkers of Antidepressant Outcomes in Major Depressive Disorder.[J]. Current neuropharmacology, 2026 doi:10.2174/011570159X469939260607094252.
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