Neural correlates of improved recognition of happy faces after erythropoietin treatment in bipolar disorder

Acta Psychiatr Scand. 2018 Oct;138(4):336-347. doi: 10.1111/acps.12915. Epub 2018 Jun 7.


Objective: Bipolar disorder is associated with impairments in social cognition including the recognition of happy faces. This is accompanied by imbalanced cortico-limbic response to emotional faces. We found that EPO improved the recognition of happy faces in patients with bipolar disorder. This randomized, controlled, longitudinal fMRI study explores the neuronal underpinnings of this effect.

Method: Forty-four patients with bipolar disorder in full or partial remission were randomized to eight weekly erythropoietin (EPO; 40 000 IU) or saline (NaCl 0.9%) 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 viewed happy and fearful faces and performed a gender discrimination task.

Results: Thirty-four patients had complete pre- and post-treatment fMRI data (EPO: N = 18, saline: N = 16). Erythropoietin vs. saline increased right superior frontal response to happy vs. fearful faces. This correlated with improved happiness recognition in the EPO group. Erythropoietin also enhanced gender discrimination accuracy for happy faces. These effects were not influenced by medication, mood, red blood cells or blood pressure.

Conclusions: Together with previous findings, the present observation suggests that increased dorsal prefrontal attention control is a common mechanism of EPO-associated improvements across several cognitive domains.

Keywords: bipolar disorder; neurocognition; neuroimaging; randomized controlled trial.

Publication types

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

MeSH terms

  • Adult
  • Bipolar Disorder* / complications
  • Bipolar Disorder* / diagnostic imaging
  • Bipolar Disorder* / drug therapy
  • Bipolar Disorder* / physiopathology
  • Cognitive Dysfunction* / diagnostic imaging
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / etiology
  • Cognitive Dysfunction* / physiopathology
  • Double-Blind Method
  • Erythropoietin / administration & dosage
  • Erythropoietin / pharmacology*
  • Facial Expression*
  • Facial Recognition / drug effects*
  • Female
  • Happiness*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prefrontal Cortex* / diagnostic imaging
  • Prefrontal Cortex* / drug effects
  • Prefrontal Cortex* / physiopathology
  • Social Perception*
  • Treatment Outcome


  • Erythropoietin