ImportanceIndividuals with psychiatric disorders have been reported to have elevated levels of inflammatory biomarkers, and prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.ObjectiveTo assess the associations between inflammation biomarkers and subsequent psychiatric disorders risk.Design, Setting, and ParticipantsThis was a prospective cohort study including individuals from the Swedish Apolipoprotein Mortality Risk (AMORIS) cohort, with no prior psychiatric diagnoses and having a measurement of at least 1 inflammatory biomarker. Data from the UK Biobank were used for validation. Longitudinal trajectories of studied biomarkers were visualized before diagnosis of psychiatric disorders in the AMORIS cohort via a nested case-control study. In addition, genetic correlation and mendelian randomization (MR) analyses were conducted to determine the genetic overlap and causality of the studied associations using publicly available GWAS summary statistics.ExposuresInflammatory biomarkers, eg, leukocytes, haptoglobin, immunoglobulin G (IgG), C-reactive protein (CRP), platelets, or albumin.Main Outcomes and MeasuresAny psychiatric disorder or specific psychiatric disorder (ie, depression, anxiety, and stress-related disorders) was identified through the International Statistical Classification of Diseases, Eighth, Ninth, and Tenth Revision codes.ResultsAmong the 585 279 individuals (mean [SD] age, 45.5 [14.9] years; 306 784 male [52.4%]) in the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11; 95% CI, 1.09-1.14), haptoglobin (HR, 1.13; 95% CI, 1.12-1.14), or CRP (HR, 1.02; 95% CI, 1.00-1.04) had an elevated associated risk of any psychiatric disorders. In contrast, we found an inverse association for IgG level (HR, 0.92; 95% CI, 0.89-0.94). The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank (n = 485 620). Analyses of trajectories revealed that individuals with psychiatric disorders had higher levels of leukocytes and haptoglobin and a lower level of IgG than their controls up to 30 years before the diagnosis. The MR analysis suggested a possible causal relationship between leukocytes and depression.Conclusions and RelevanceIn this cohort study, inflammatory biomarkers including leukocytes, haptoglobin, CRP, and IgG were associated with a subsequent risk of psychiatric disorders, and thus might be used for high-risk population identification. The possible causal link between leukocytes and depression supports the crucial role of inflammation in the development of psychiatric disorders.

中文翻译：

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炎症生物标志物和精神疾病的风险


据报道，患有精神疾病的个体的炎症生物标志物水平升高，并且关于炎症生物标志物与随后的精神疾病风险之间的关联的前瞻性证据有限。目的评估炎症生物标志物与随后的精神疾病风险之间的关联。设计、设置和参与者这是一项前瞻性队列研究，包括来自瑞典载脂蛋白死亡风险 (AMORIS) 队列的个体，之前没有精神病学诊断，并且测量了至少 1 种炎症生物标志物。来自英国生物银行的数据用于验证。在 AMORIS 队列中诊断精神疾病之前，通过巢式病例对照研究对所研究的生物标志物的纵向轨迹进行可视化。此外，使用公开的 GWAS 摘要统计数据进行遗传相关性和孟德尔随机化 (MR) 分析，以确定所研究关联的遗传重叠和因果关系。暴露炎症生物标志物，例如白细胞、触珠蛋白、免疫球蛋白 G (IgG)、C 反应性蛋白质 (CRP)、血小板或白蛋白。 主要结果和测量任何精神疾病或特定精神疾病（即抑郁、焦虑和压力相关疾病）均通过《国际疾病统计分类》第八版、第九版和第十版修订版确定结果在 AMORIS 队列的 585 279 名个体（平均 [SD] 年龄，45.5 [14.9] 岁；306 784 名男性 [52.4%]）中，白细胞水平高于中位值的个体（风险比 [HR]，1.11） ；95% CI，1.09-1.14）、触珠蛋白（HR，1.13；95% CI，1.12-1.14）或 CRP（HR，1.02；95% CI，1.00-1）。04）任何精神疾病的相关风险都会升高。相反，我们发现 IgG 水平呈负相关（HR，0.92；95% CI，0.89-0.94）。特别是对于抑郁症、焦虑症和压力相关疾病，这些估计值具有可比性，并且这些结果在很大程度上在英国生物银行 (n = 485 620) 中得到了验证。轨迹分析显示，在诊断前 30 年内，精神疾病患者的白细胞和触珠蛋白水平高于对照组，而 IgG 水平较低。 MR 分析表明白细胞与抑郁症之间可能存在因果关系。结论和相关性在这项队列研究中，包括白细胞、触珠蛋白、CRP 和 IgG 在内的炎症生物标志物与随后发生精神疾病的风险相关，因此可用于高风险人群人口识别。白细胞与抑郁症之间可能存在的因果关系支持炎症在精神疾病发展中的关键作用。