Cerebrospinal fluid erythropoietin, oxidative stress, and cognitive functions in patients with bipolar disorder and healthy control participants: A longitudinal case-control study
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Cerebrospinal fluid erythropoietin, oxidative stress, and cognitive functions in patients with bipolar disorder and healthy control participants : A longitudinal case-control study. / Miskowiak, Kamilla W.; Simonsen, Anja H.; Meyer, Morten; Poulsen, Henrik Enghusen; Wilkan, Mira; Forman, Julie; Hasselbalch, Steen G.; Kessing, Lars V.; Knorr, Ulla.
I: Journal of Psychiatric Research, Bind 163, 2023, s. 240-246.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Cerebrospinal fluid erythropoietin, oxidative stress, and cognitive functions in patients with bipolar disorder and healthy control participants
T2 - A longitudinal case-control study
AU - Miskowiak, Kamilla W.
AU - Simonsen, Anja H.
AU - Meyer, Morten
AU - Poulsen, Henrik Enghusen
AU - Wilkan, Mira
AU - Forman, Julie
AU - Hasselbalch, Steen G.
AU - Kessing, Lars V.
AU - Knorr, Ulla
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Bipolar disorder
KW - Cerebrospinal fluid
KW - Cognitive impairment
KW - Erythropoietin
KW - Oxidative stress
U2 - 10.1016/j.jpsychires.2023.05.045
DO - 10.1016/j.jpsychires.2023.05.045
M3 - Journal article
C2 - 37244061
AN - SCOPUS:85162235818
VL - 163
SP - 240
EP - 246
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
SN - 0022-3956
ER -
ID: 358230704