Cerebrospinal fluid erythropoietin, oxidative stress, and cognitive functions in patients with bipolar disorder and healthy control participants: A longitudinal case-control study

Kamilla W. Miskowiak*, Anja H. Simonsen, Morten Meyer, Henrik Enghusen Poulsen, Mira Wilkan, Julie Forman, Steen G. Hasselbalch, Lars V. Kessing, Ulla Knorr

*Corresponding author af dette arbejde

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Abstract

Persistent cognitive impairments occur in a large proportion of patients with bipolar disorder (BD) but their underlying pathological cellular processes are unclear. The aims of this longitudinal study of BD and healthy control (HC) participants were to investigate (i) the association of brain erythropoietin (EPO) and oxidative stress with cognitive functions and (ii) the changes in brain EPO during and after affective episodes. Participants underwent neurocognitive testing, lumbar punctures for cerebrospinal fluid (CSF) sampling and provided urine spot tests at baseline (all), after an affective episode (patients) and after one year (all). EPO was assayed in the CSF and oxidative stress metabolites related to RNA and DNA damage (8-dihydroguanosine [8-oxo-Guo], 8-hydroxy-2-deoxyguanosine [8-oxo-dG]) were assayed in the CSF and spot urine. Data was available for analyses for 60 BD and 37 HC participants. In unadjusted primary analyses, verbal memory decreased with increasing concentrations of CSF EPO and oxidative stress. In unadjusted explorative analyses, poorer verbal memory and psychomotor speed were associated with higher levels of oxidative stress. However, no associations between cognitive functions and CSF levels of EPO or oxidative stress were observed after adjustment for multiple testing. CSF EPO concentrations were unchanged during and after affective episodes. While CSF EPO correlated negatively with CSF DNA damage marker 8-oxo-dG, this association rendered non-significant after adjusting for multiple testing. In conclusion, EPO and oxidative stress do not seem to be robustly related to cognitive status in BD. Further insight into the cellular processes involved in cognitive impairments in BD is necessary to pave the way for novel therapeutic strategies to improve patients’ cognitive outcomes.
OriginalsprogEngelsk
TidsskriftJournal of Psychiatric Research
Vol/bind163
Sider (fra-til)240-246
Antal sider7
ISSN0022-3956
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
The current study of the relation between erythropoietin, oxidative stress and cognitive function was supported by the Jascha Foundation (J No. 2021–0098 ; recipient author KWM). The original study was supported by The Mental Health Services of Capital of Denmark Research Foundation , AP Møller Foundation for Promotion of Medical Science, The Beckett Foundation , The King Christian 10th Foundation and the Max and Oda Wørzner Foundation (recipient author UBK). The Danish Dementia Research Centre is supported by grants from the Danish Ministry of Health (J No. 2007- 12143-112 , project 59506/J No. 0901110 , project 34,501 ) and the Danish Health Foundation (J No. 2007B004 ). The funding sources of the study had no role in study design; in the collection, analysis and interpretation of data; in writing of the report; and in the decision to submit the paper for publication.

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© 2023 The Authors

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