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Cerebrospinal fluid test results and associations with subsequent mental disorders, neurological diseases, and CNS infections: A population-based cohort study

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  • Sonja Orlovska-Waast
  • Liselotte Vogdrup Petersen
  • Christiane Gasse
  • Merete Nordentoft
  • Preben Bo Mortensen
  • Daniel Kondziella
  • Michael Eriksen Benros
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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.

TidsskriftBrain, Behavior, and Immunity
Sider (fra-til)210-218
Antal sider9
StatusUdgivet - nov. 2021

Bibliografisk note

Funding Information:
The study was partly funded by the Independent Research Fund Denmark (grant number 7025-00078B ) and by an unrestricted grant from The Lundbeck Foundation (grant number R268-2016-3925 and R278-2018-1411 ). The funding sources had no role in the collection, analysis or interpretation of the data, in writing of the manuscript or the decision to publish the findings.

Publisher Copyright:
© 2021 The Author(s)

Copyright 2021 Elsevier B.V., All rights reserved.

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