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

ElsevierVolume 163, July 2023, Pages 240-246Journal of Psychiatric ResearchAuthor links open overlay panel, , , , , , , , Highlights•

Pathological cellular processes underlying cognitive deficits in bipolar disorder are unclear.

Cerebrospinal fluid erythropoietin levels showed no correlation with cognitive functions.

Higher oxidative stress was associated with poorer cognition in unadjusted analyses.

Higher oxidative stress correlated with lower erythropoietin in unadjusted analyses.

The associations disappeared in adjusted analyses and must be regarded as preliminary.

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.

Keywords

Cerebrospinal fluid

Erythropoietin

Oxidative stress

Cognitive impairment

Bipolar disorder

© 2023 The Authors. Published by Elsevier Ltd.

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