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风险


重要性据报道，患有精神疾病的个体的炎症生物标志物水平升高，关于炎症生物标志物与后续精神疾病风险之间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，之前没有精神病诊断并且测量了至少 1 种炎症生物标志物。使用来自英国生物样本库的数据进行验证。在诊断 AMORIS 队列的精神疾病之前，通过嵌套病例对照研究可视化了所研究生物标志物的纵向轨迹。此外，还进行了遗传相关性和孟德尔随机化 （MR） 分析，以使用公开可用的 GWAS 汇总统计数据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、结合珠蛋白、免疫球蛋白 G （IgG）、C 反应蛋白 （CRP）、血小板或白蛋白。主要结局和措施任何精神疾病或特定精神疾病（即抑郁、焦虑和压力相关障碍）都是通过国际疾病统计分类第八、第九和第十修订代码确定的。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水平 （风险比 [HR] ，1.11;95% CI，1.09-1.14）、结合珠蛋白 （HR，1.13;95% CI，1.12-1.14） 或 CRP （HR，1.02;95% CI，1.00-1.04） 有任何精神疾病的相关风险升高。相比之下，我们发现 IgG 水平呈负相关 （HR， 0.92;95% CI， 0.89-0.94）。具体来说，抑郁症、焦虑症和压力相关疾病的估计值具有可比性，这些结果在英国生物样本库中得到了很大程度上的验证 （n = 485 620）。轨迹分析显示，在诊断前 30 年，患有精神疾病的个体比对照组的白细胞和结合珠蛋白水平更高，IgG 水平更低。MR 分析表明白细胞与抑郁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、结合珠蛋白、 CRP 和 IgG 在内的炎症生物标志物与随后的精神疾病风险相关，因此可用于高危人群识别。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。