Importance Depression has been associated with alterations in neurotransmitters, hormones, and inflammatory and neurodegenerative biomarkers, and biomarkers quantified in the cerebrospinal fluid (CSF) are more likely to reflect ongoing biochemical changes within the brain. However, a comprehensive overview of CSF biomarkers is lacking and could contribute to the pathophysiological understanding of depression. Objective To investigate differences in quantified CSF biomarkers in patients with unipolar depression compared with healthy control individuals. Data Sources PubMed, EMBASE, PsycINFO, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched for eligible trials from database inception to August 25, 2021. Study Selection All studies investigating CSF biomarkers in individuals 18 years and older with unipolar depression and healthy control individuals were included. One author screened titles and abstracts, and 2 independent reviewers examined full-text reports. Studies that did not include healthy control individuals or included control individuals with recent hospital contacts or admissions that might affect CSF biomarker concentrations were excluded. Data Extraction and Synthesis Data extraction and quality assessment were performed by 2 reviewers following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Meta-analyses were performed using standardized mean differences (SMDs) calculated with random-effects models. A third investigator was consulted if the 2 reviewers reached different decisions or when in doubt. Main Outcomes and Measures Quantifiable CSF biomarkers. Results A total of 167 studies met eligibility criteria, and 97 had available data and were included in the meta-analysis. These 97 studies comprised 165 biomarkers, 42 of which were quantified in 2 or more studies. CSF levels of interleukin 6 (7 studies; SMD, 0.35; 95% CI, 0.12 to 0.59; I2 = 16%), total protein (5 studies; SMD, 0.53; 95% CI, 0.35 to 0.72; I2 = 0%), and cortisol (2 studies; SMD, 1.23; 95% CI, 0.89 to 1.57; I2 = 0%) were higher in patients with unipolar depression compared with healthy control individuals, whereas homovanillic acid (17 studies; SMD, -0.26; 95% CI, -0.39 to -0.14; I2 = 11%), γ-aminobutyric acid (4 studies; SMD, -0.50; 95% CI, -0.92 to -0.08; I2 = 55%), somatostatin (5 studies; SMD, -1.49; 95% CI, -2.53 to -0.45; I2 = 91%), brain-derived neurotrophic factor (3 studies; SMD, -0.58; 95% CI, -0.97 to -0.19; I2 = 0%), amyloid-β 40 (3 studies; SMD, -0.80; 95% CI, -1.14 to -0.46; I2 = 0%), and transthyretin (2 studies; SMD, -0.82; 95% CI, -1.37 to -0.27; I2 = 0%) were lower. The remaining 33 biomarkers had nonsignificant results. Conclusions and Relevance The findings of this systematic review and meta-analysis point toward a dysregulated dopaminergic system, a compromised inhibitory system, hypothalamic-pituitary-adrenal axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology.

中文翻译：

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单相抑郁症患者的脑脊液生物标志物与健康对照个体的比较：系统评价和荟萃分析。


重要性抑郁症与神经递质、激素、炎症和神经退行性生物标志物的变化有关，脑脊液 (CSF) 中量化的生物标志物更有可能反映大脑内持续的生化变化。然而，缺乏对脑脊液生物标志物的全面概述，这可能有助于对抑郁症的病理生理学理解。目的 探讨单相抑郁症患者与健康对照个体相比量化脑脊液生物标志物的差异。数据源 检索了 PubMed、EMBASE、PsycINFO、Cochrane Library、Web of Science 和 ClinicalTrials.gov，以查找从数据库建立到 2021 年 8 月 25 日期间符合条件的试验。 研究选择 所有研究均调查 18 岁及以上患有单相抑郁症和包括健康对照个体。一位作者筛选了标题和摘要，两位独立审稿人审查了全文报告。不包括健康对照个体或最近与医院接触或入院可能影响脑脊液生物标志物浓度的对照个体的研究被排除在外。数据提取和综合 数据提取和质量评估由 2 名评价者按照系统评价和荟萃分析的首选报告项目 (PRISMA) 和流行病学观察研究荟萃分析 (MOOSE) 报告指南进行。使用随机效应模型计算的标准化平均差（SMD）进行荟萃分析。如果两位评审员做出不同的决定或有疑问，则会咨询第三位研究者。主要成果和措施 可量化的脑脊液生物标志物。 结果 共有 167 项研究符合资格标准，其中 97 项有可用数据并纳入荟萃分析。这 97 项研究包含 165 种生物标志物，其中 42 种在 2 项或更多研究中进行了量化。脑脊液中白细胞介素 6 水平（7 项研究；SMD，0.35；95% CI，0.12 至 0.59；I2 = 16%）、总蛋白水平（5 项研究；SMD，0.53；95% CI，0.35 至 0.72；I2 = 0%）和皮质醇（2 项研究；SMD，1.23；95% CI，0.89 至 1.57；I2 = 0%）在单相抑郁症患者中高于健康对照个体，而高香草酸（17 项研究；SMD，-0.26；95 % CI，-0.39 至 -0.14；I2 = 11%），γ-氨基丁酸（4 项研究；SMD，-0.50；95% CI，-0.92 至 -0.08；I2 = 55%），生长抑素（5 项研究；SMD） ，-1.49；95% CI，-2.53 至 -0.45；I2 = 91%），脑源性神经营养因子（3 项研究；SMD，-0.58；95% CI，-0.97 至 -0.19；I2 = 0%），淀粉样蛋白-β 40（3 项研究；SMD，-0.80；95% CI，-1.14 至 -0.46；I2 = 0%）和运甲状腺素蛋白（2 项研究；SMD，-0.82；95% CI，-1.37 至 -0.27； I2 = 0%) 较低。其余 33 个生物标志物的结果不显着。结论和相关性本次系统评价和荟萃分析的结果表明，多巴胺能系统失调、抑制系统受损、下丘脑-垂体-肾上腺轴过度活跃、神经炎症和血脑屏障通透性增加以及神经可塑性受损是抑郁症的重要因素病理生理学。