K W Miskowiak1,2, J Macoveanu1,2,3, M Vinberg1, E Assentoft1, L Randers4, C J Harmer5, H Ehrenreich6, O B Paulson2,3,7, G M Knudsen3,7, H R Siebner2,3,8, L V Kessing1. 1. Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 2. Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. 3. Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark. 4. Psychiatric Centre Copenhagen, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. 5. Department of Psychiatry, University of Oxford, Oxford, UK. 6. Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. 7. Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 8. Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
Abstract
OBJECTIVE:Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. METHOD:Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS:Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. CONCLUSION: The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement.
RCT Entities:
OBJECTIVE:Erythropoietin (EPO) improves verbal memory and reverses subfield hippocampal volume loss across depression and bipolar disorder (BD). This study aimed to investigate with functional magnetic resonance imaging (fMRI) whether these effects were accompanied by functional changes in memory-relevant neuro-circuits in this cohort. METHOD: Eighty-four patients with treatment-resistant unipolar depression who were moderately depressed or BD in remission were randomized to eight weekly EPO (40 000 IU) or saline infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings, and blood tests at baseline and week 14. During fMRI, participants performed a picture encoding task followed by postscan recall. RESULTS: Sixty-two patients had complete data (EPO: N = 32, saline: N = 30). EPO improved picture recall and increased encoding-related activity in dorsolateral prefrontal cortex (dlPFC) and temporo-parietal regions, but not in hippocampus. Recall correlated with activity in the identified dlPFC and temporo-parietal regions at baseline, and change in recall correlated with activity change in these regions from baseline to follow-up across the entire cohort. The effects of EPO were not correlated with change in mood, red blood cells, blood pressure, or medication. CONCLUSION: The findings highlight enhanced encoding-related dlPFC and temporo-parietal activity as key neuronal underpinnings of EPO-associated memory improvement.
Authors: Lars Vedel Kessing; Klaus Munkholm; Maria Faurholt-Jepsen; Kamilla Woznica Miskowiak; Lars Bo Nielsen; Ruth Frikke-Schmidt; Claus Ekstrøm; Ole Winther; Bente Klarlund Pedersen; Henrik Enghusen Poulsen; Roger S McIntyre; Flavio Kapczinski; Wagner F Gattaz; Jakob Bardram; Mads Frost; Oscar Mayora; Gitte Moos Knudsen; Mary Phillips; Maj Vinberg Journal: BMJ Open Date: 2017-06-23 Impact factor: 2.692
Authors: Kasifa Khalid; Julia Frei; Mostafa A Aboouf; Christina Koester-Hegmann; Max Gassmann; Jean-Marc Fritschy; Edith M Schneider Gasser Journal: eNeuro Date: 2021-02-11
Authors: Caroline V Ott; Maj Vinberg; Christopher R Bowie; Ellen Margrethe Christensen; Gitte M Knudsen; Lars V Kessing; Kamilla W Miskowiak Journal: Trials Date: 2018-09-12 Impact factor: 2.279