Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders: A randomized, double-blinded, placebo-controlled trial
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Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders : A randomized, double-blinded, placebo-controlled trial. / Macoveanu, Julian; Petersen, Jeff Zarp; Mariegaard, Johanna; Jespersen, Andreas Elleby; Cramer, Katrine; Bruun, Caroline Fussing; Madsen, Helle Østergaard; Jørgensen, Martin Balslev; Vinberg, Maj; Fisher, Patrick M.; Knudsen, Gitte Moos; Hageman, Ida; Ehrenreich, Hannelore; Kessing, Lars Vedel; Miskowiak, Kamilla Woznica.
In: Journal of Psychopharmacology, Vol. 38, No. 4, 2024, p. 362-374.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders
T2 - A randomized, double-blinded, placebo-controlled trial
AU - Macoveanu, Julian
AU - Petersen, Jeff Zarp
AU - Mariegaard, Johanna
AU - Jespersen, Andreas Elleby
AU - Cramer, Katrine
AU - Bruun, Caroline Fussing
AU - Madsen, Helle Østergaard
AU - Jørgensen, Martin Balslev
AU - Vinberg, Maj
AU - Fisher, Patrick M.
AU - Knudsen, Gitte Moos
AU - Hageman, Ida
AU - Ehrenreich, Hannelore
AU - Kessing, Lars Vedel
AU - Miskowiak, Kamilla Woznica
N1 - Publisher Copyright: © The Author(s) 2024.
PY - 2024
Y1 - 2024
N2 - Background: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments. Aim: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders. Methods: In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period. Assessments were conducted at baseline, after 2 weeks of treatment (week 3), immediately after treatment (week 13) and at 6-months follow-up. Participants underwent functional MRI during performance on a n-back working memory (WM) task at baseline and week 3, and for a subgroup 6 weeks post-treatment (week 18). The primary outcome was a cognitive composite score at week 13, whereas secondary outcomes comprised sustained attention and functioning. WM-related dPFC activity was a tertiary outcome. Results: Data were analysed for 101 of the 103 included patients (EPO, n = 58; saline, n = 43). There were no effects of EPO over saline on any cognitive or functional outcomes or on WM-related dPFC activity. Conclusions: The absence of treatment-related changes in cognition and neural activity was unexpected and contrasts with multiple previous preclinical and clinical studies. It is possible that the lack of effects resulted from a recent change in the manufacturing process for EPO. Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity. Trial registrations: EudraCT no.: 2016–004023-24; ClinicalTrials.gov identifier: NCT03315897.
AB - Background: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments. Aim: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders. Methods: In this randomized, double-blinded, placebo-controlled trial, cognitively impaired patients with remitted BD or MDD received 1 weekly recombinant human EPO (40,000 IU/mL) or saline infusion for a 12-week period. Assessments were conducted at baseline, after 2 weeks of treatment (week 3), immediately after treatment (week 13) and at 6-months follow-up. Participants underwent functional MRI during performance on a n-back working memory (WM) task at baseline and week 3, and for a subgroup 6 weeks post-treatment (week 18). The primary outcome was a cognitive composite score at week 13, whereas secondary outcomes comprised sustained attention and functioning. WM-related dPFC activity was a tertiary outcome. Results: Data were analysed for 101 of the 103 included patients (EPO, n = 58; saline, n = 43). There were no effects of EPO over saline on any cognitive or functional outcomes or on WM-related dPFC activity. Conclusions: The absence of treatment-related changes in cognition and neural activity was unexpected and contrasts with multiple previous preclinical and clinical studies. It is possible that the lack of effects resulted from a recent change in the manufacturing process for EPO. Nevertheless, the findings support the validity of dPFC target engagement as a biomarker model for pro-cognitive effects, according to which treatments that do not improve cognition should not modulate dPFC activity. Trial registrations: EudraCT no.: 2016–004023-24; ClinicalTrials.gov identifier: NCT03315897.
KW - Cognition
KW - cognitive impairment
KW - erythropoietin
KW - fMRI
KW - randomized controlled trial
U2 - 10.1177/02698811241237869
DO - 10.1177/02698811241237869
M3 - Journal article
C2 - 38519416
AN - SCOPUS:85188295647
VL - 38
SP - 362
EP - 374
JO - Journal of Psychopharmacology
JF - Journal of Psychopharmacology
SN - 0269-8811
IS - 4
ER -
ID: 387691979