Background

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.

Methods

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.

Results

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).

Conclusions

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.

中文翻译：

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脑脊液检测结果以及与随后的精神障碍、神经系统疾病和中枢神经系统感染的关联：一项基于人群的队列研究

背景

脑脊液 (CSF) 免疫改变与精神障碍、神经系统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脑脊液研究。

方法

通过使用丹麦中部地区（1994-2012 年）的临床实验室信息系统 (LABKA) 研究数据库，我们纳入了 15,030 名接受 CSF WBC、CSF/血清白蛋白比率、IgG 指数、总蛋白、白蛋白或 IgG 测试的个体，并遵循以下要求- 通过 Cox 回归估计的精神障碍、精神药物处方、神经系统疾病或 CNS 感染的风险。

结果

在脑脊液检测后接受精神障碍诊断的个体 (N = 1,147) 中，30 · 0% 的人脑脊液检测结果异常，而对于神经系统疾病患者 (N = 3,201)，39 · 9% 的人检测结果异常，在中枢神经系统感染的个体中（N = 1,276），73 · 0% 的检测结果异常。CSF 检测结果异常的个体患精神障碍（HR = 3 · 20；95%CI = 2 · 86-3 · 59）、神经系统疾病（HR = 12 · 40；95%CI = 11 · 65-）的风险增加13 · 20) 和 CNS 感染（HR = 338 · 59；95%CI = 299 · 06-383 ·35) 与未注册 CSF 测试的个人相比。然而，脑脊液检查结果在正常范围内（HR = 4 · 45；95%CI = 4 · 08-4 · 86）后，精神障碍的风险较高（P < 0 · 001 ），而神经系统疾病（HR = 9 · 72; 95%CI = 9 · 19-10 · 29）和 CNS 感染（HR = 55 · 17; 95%CI = 47 · 12-64 · 60），CSF 检测结果异常后风险最高（所有 P < 0 ·001）。脑脊液检查结果异常的个体患器质性精神障碍的风险往往最高（HR = 19·30；95%CI = 13·44-27·71），尽管与患有脑脊液检查结果异常的人群的风险没有显着差异CSF检测结果在正常范围内（HR=13·55；95%CI=9·36-19·60）（P≥0 · 05）。CSF 检测结果异常与精神药物处方风险升高相关（HR = 3 · 91；95%CI = 3 · 66-4 · 18），CSF 检测结果在正常范围内（HR = 4 · 26；95 %CI = 4 · 03–4 · 51) (P < 0 · 05)。

结论

免疫学 CSF 异常与精神障碍、神经系统疾病，尤其是中枢神经系统感染的风险增加有关；然而，所包含的 CSF 参数并非针对精神障碍，并且尚未发现精神病学中的相关 CSF 生物标志物。