Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders : A randomized, double-blinded, placebo-controlled trial
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Journal of psychopharmacology (Oxford, England) - 38(2024), 4 vom: 22. Apr., Seite 362-374 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Macoveanu, Julian [VerfasserIn] |
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| Links: |
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| Themen: |
11096-26-7 |
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| Anmerkungen: |
Date Completed 12.04.2024 Date Revised 12.04.2024 published: Print-Electronic ClinicalTrials.gov: NCT03315897 Citation Status MEDLINE |
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| doi: |
10.1177/02698811241237869 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370089812 |
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| 100 | 1 | |a Macoveanu, Julian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of erythropoietin on cognitive impairment and prefrontal cortex activity across affective disorders |b A randomized, double-blinded, placebo-controlled trial |
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| 500 | |a Date Revised 12.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03315897 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Persistent cognitive impairment is frequent across bipolar disorder (BD) and major depressive disorder (MDD), highlighting an urgent need for pro-cognitive treatments | ||
| 520 | |a AIM: This study investigated effects of erythropoietin (EPO) on cognitive impairment and dorsal prefrontal cortex (dPFC) activity in affective disorders | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a TRIAL REGISTRATIONS: EudraCT no.: 2016-004023-24; ClinicalTrials.gov identifier: NCT03315897 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Cramer, Katrine |e verfasserin |4 aut | |
| 700 | 1 | |a Bruun, Caroline Fussing |e verfasserin |4 aut | |
| 700 | 1 | |a Madsen, Helle Østergaard |e verfasserin |4 aut | |
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| 700 | 1 | |a Kessing, Lars Vedel |e verfasserin |4 aut | |
| 700 | 1 | |a Miskowiak, Kamilla Woznica |e verfasserin |4 aut | |
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