Köhler O, Petersen L, Mors O, Mortensen P B, Yolken R H, Gasse C, Benros M E
Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
Acta Psychiatr Scand. 2017 Feb;135(2):97-105. doi: 10.1111/acps.12671. Epub 2016 Nov 21.
Severe infections are associated with increased risks of mental disorders; however, this is the first large-scale study investigating whether infections treated with anti-infective agents in the primary care setting increase the risks of schizophrenia and affective disorders.
We identified all individuals born in Denmark 1985-2002 (N = 1 015 447) and studied the association between infections treated with anti-infective agents and the subsequent risk of schizophrenia and affective disorders during 1995-2013. Cox regression analyses were adjusted for important confounders.
Infections treated with anti-infective agents were associated with increased risks of schizophrenia by a hazard rate ratio (HRR) of 1.37 (95%-CI = 1.20-1.57) and affective disorders by a HRR of 1.64 (95%-CI = 1.48-1.82), fitting a dose-response and temporal relationship (P < 0.001). The excess risk was primarily driven by infections treated with antibiotics, whereas infections treated with antivirals, antimycotics, and antiparasitic agents were not significant after mutual adjustment. Individuals with infections requiring hospitalization had the highest risks for schizophrenia (HRR = 2.05; 95%-CI = 1.77-2.38) and affective disorders (HRR = 2.59; 95%-CI = 2.31-2.89).
Infections treated with anti-infective agents and particularly infections requiring hospitalizations were associated with increased risks of schizophrenia and affective disorders, which may be mediated by effects of infections/inflammation on the brain, alterations of the microbiome, genetics, or other environmental factors.
严重感染与精神障碍风险增加相关；然而，这是第一项大规模研究，旨在调查在初级保健环境中接受抗感染药物治疗的感染是否会增加精神分裂症和情感障碍的风险。
我们确定了1985年至2002年在丹麦出生的所有个体（N = 1015447），并研究了1995年至2013年期间接受抗感染药物治疗的感染与随后患精神分裂症和情感障碍风险之间的关联。Cox回归分析对重要的混杂因素进行了校正。
接受抗感染药物治疗的感染与精神分裂症风险增加相关，风险比（HRR）为1.37（95%置信区间 = 1.20 - 1.57），与情感障碍风险增加相关，HRR为1.64（95%置信区间 = 1.48 - 1.82），符合剂量反应和时间关系（P < 0.001）。额外风险主要由抗生素治疗的感染驱动，而在相互调整后，抗病毒药物、抗真菌药物和抗寄生虫药物治疗的感染则不显著。需要住院治疗的感染个体患精神分裂症的风险最高（HRR = 2.05；95%置信区间 = 1.77 - 2.38）和情感障碍（HRR = 2.59；95%置信区间 = 2.31 - 2.89）。
接受抗感染药物治疗的感染，尤其是需要住院治疗的感染，与精神分裂症和情感障碍风险增加相关，这可能是由感染/炎症对大脑的影响、微生物群的改变、遗传因素或其他环境因素介导的。
