Copenhagen Research Center for Mental Health (CORE), Mental Health Centre Copenhagen, Copenhagen University Hospital, Gentofte Hospitalsvej 15 4th Floor, 2900 Hellerup, Denmark.
Centre for Integrated Register-Based Research at Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
Brain Behav Immun. 2021 Nov;98:210-218. doi: 10.1016/j.bbi.2021.08.006. Epub 2021 Aug 12.
Cerebrospinal fluid (CSF) immune alterations have been associated with mental disorders, neurological disease, and CNS infections; however, comprehensive large-scale longitudinal CSF studies are lacking.
By using the Clinical Laboratory Information System (LABKA) Research Database in the Central Denmark Region (1994-2012), we included 15,030 individuals tested for CSF WBC, CSF/serum albumin ratio, IgG index, total protein, albumin, or IgG with follow-up for the risk of mental disorders, psychotropic prescriptions, neurological diseases, or CNS infections, estimated by Cox regression.
Among individuals receiving a mental disorder diagnosis (N = 1,147) after a CSF test, 30·0% had an abnormal CSF test result, while for those with a neurological disease (N = 3,201), 39·9% had abnormal test results, and among individuals with CNS infections (N = 1,276), 73·0% had abnormal test results. Individuals with abnormal CSF test results had an increased risk of mental disorders (HR = 3·20; 95%CI = 2·86-3·59), neurological diseases (HR = 12·40; 95%CI = 11·65-13·20), and CNS infections (HR = 338·59; 95%CI = 299·06-383·35) compared to individuals not registered with a CSF test. However, the risk of mental disorders was higher (P < 0·001) after CSF test results within the normal range (HR = 4·45; 95%CI = 4·08-4·86), whereas for neurological diseases (HR = 9·72; 95%CI = 9·19-10·29) and CNS infections (HR = 55·17; 95%CI = 47·12-64·60), the risk was highest after abnormal CSF test results (all P < 0·001). The risk of organic mental disorders tended to be highest in individuals with abnormal CSF test results (HR = 19·30; 95%CI = 13·44-27·71) even though not significantly different from the risk in the group of individuals with CSF test results in the normal range (HR = 13·55; 95%CI = 9·36-19·60) (P ≥ 0·05). Abnormal CSF test results were associated with an elevated risk of psychotropic prescriptions (HR = 3·91; 95%CI = 3·66-4·18), as were CSF test results within the normal range (HR = 4·26; 95%CI = 4·03-4·51) (P < 0·05).
Immunological CSF abnormalities are associated with an increased risk of mental disorders, neurological disease, and particularly CNS infections; however, the included CSF parameters were not specific for mental disorders and the relevant CSF biomarkers in psychiatry are yet to be discovered.
脑脊液（CSF）免疫改变与精神障碍、神经疾病和中枢神经系统感染有关；然而，缺乏全面的大规模纵向 CSF 研究。
通过使用丹麦中部地区的临床实验室信息系统（LABKA）研究数据库（1994-2012 年），我们纳入了 15030 名接受 CSF WBC、CSF/血清白蛋白比值、IgG 指数、总蛋白、白蛋白或 IgG 检测的个体，采用 Cox 回归估计随访期间发生精神障碍、精神药物处方、神经疾病或中枢神经系统感染的风险。
在接受 CSF 检测后被诊断为精神障碍的个体（N=1147）中，30.0%的 CSF 检测结果异常，而在患有神经疾病的个体（N=3201）中，39.9%的 CSF 检测结果异常，在患有中枢神经系统感染的个体（N=1276）中，73.0%的 CSF 检测结果异常。CSF 检测结果异常的个体发生精神障碍（HR=3.20；95%CI=2.86-3.59）、神经疾病（HR=12.40；95%CI=11.65-13.20）和中枢神经系统感染（HR=338.59；95%CI=299.06-383.35）的风险增加，与未进行 CSF 检测的个体相比。然而，CSF 检测结果在正常范围内时（HR=4.45；95%CI=4.08-4.86），发生精神障碍的风险更高（P<0.001），而对于神经疾病（HR=9.72；95%CI=9.19-10.29）和中枢神经系统感染（HR=55.17；95%CI=47.12-64.60），CSF 检测结果异常时风险最高（均 P<0.001）。即使与 CSF 检测结果正常范围内的个体（HR=13.55；95%CI=9.36-19.60）相比，CSF 检测结果异常的个体发生器质性精神障碍的风险也倾向于最高（HR=19.30；95%CI=13.44-27.71）（P≥0.05）。CSF 检测结果异常与精神药物处方风险增加相关（HR=3.91；95%CI=3.66-4.18），CSF 检测结果在正常范围内也与精神药物处方风险增加相关（HR=4.26；95%CI=4.03-4.51）（P<0.05）。
免疫性 CSF 异常与精神障碍、神经疾病、特别是中枢神经系统感染的风险增加有关；然而，纳入的 CSF 参数并不特异于精神障碍，精神病学中相关的 CSF 生物标志物仍有待发现。
