Effects of erythropoietin on memory-relevant neurocircuitry activity and recall in mood disorders

Acta Psychiatr Scand. 2016 Sep;134(3):249-59. doi: 10.1111/acps.12597. Epub 2016 Jun 3.


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.

Trial registration: ClinicalTrials.gov NCT00916552.

Keywords: bipolar disorder; cognition disorders; functional neuroimaging; randomized controlled trial.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depressive Disorder / diagnostic imaging
  • Depressive Disorder / drug therapy*
  • Depressive Disorder, Treatment-Resistant / diagnostic imaging
  • Depressive Disorder, Treatment-Resistant / drug therapy*
  • Double-Blind Method
  • Erythropoietin / adverse effects*
  • Erythropoietin / pharmacology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Recall / drug effects*
  • Middle Aged
  • Prefrontal Cortex / diagnostic imaging
  • Psychiatric Status Rating Scales
  • Treatment Outcome


  • Erythropoietin

Associated data

  • ClinicalTrials.gov/NCT00916552