title: Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders.
abstract: BACKGROUND
  Persistent cognitive dysfunction in depression and bipolar disorder (BD) impedes patients' functional recovery. Erythropoietin (EPO) increases neuroplasticity and reduces cognitive difficulties in treatment-resistant depression (TRD) and remitted BD. This magnetic resonance imaging study assessed the neuroanatomical basis for these effects.
  
  
  METHODS
  Patients with TRD who were moderately depressed or BD in partial remission were randomized to 8 weekly EPO (40,000 IU) or saline infusions in a double-blind, parallel-group design. Patients underwent magnetic resonance imaging, memory assessment with the Rey Auditory Verbal Learning Test, and mood ratings with the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating Scale at baseline and week 14. Hippocampus segmentation and analysis of hippocampal volume, shape, and gray matter density were conducted with FMRIB Software Library tools. Memory change was analyzed with repeated-measures analysis of covariance adjusted for depression symptoms, diagnosis, age, and gender.
  
  
  RESULTS
  Eighty-four patients were randomized; 1 patient withdrew and data collection was incomplete for 14 patients; data were thus analyzed for 69 patients (EPO: n = 35, saline: n = 34). Compared with saline, EPO was associated with mood-independent memory improvement and reversal of brain matter loss in the left hippocampal cornu ammonis 1 to cornu ammonis 3 and subiculum. Using the entire sample, memory improvement was associated with subfield hippocampal volume increase independent of mood change.
  
  
  CONCLUSIONS
  EPO-associated memory improvement in TRD and BD may be mediated by reversal of brain matter loss in a subfield of the left hippocampus. EPO may provide a therapeutic option for patients with mood disorders who have impaired neuroplasticity and cognition.
authors: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: Kamilla@miskowiak.dk.
authors: Kamilla W
authors: KW
authors: Miskowiak
authors: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Maj
authors: M
authors: Vinberg
authors: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre.
authors: Julian
authors: J
authors: Macoveanu
authors: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors: Hannelore
authors: H
authors: Ehrenreich
authors: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Nicolai
authors: N
authors: Køster
authors: Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
authors: Becky
authors: B
authors: Inkster
authors: Neurobiological Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Olaf B
authors: OB
authors: Paulson
authors: Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Lars V
authors: LV
authors: Kessing
authors: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre.
authors: Arnold
authors: A
authors: Skimminge
authors: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Hvidovre; Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
authors: Hartwig R
authors: HR
authors: Siebner
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology*; D003866:Depressive Disorder / Q000188:drug therapy; D061218:Depressive Disorder, Treatment-Resistant; D004921:Erythropoietin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy / Q000473:pathology*; D011569:Psychiatric Status Rating Scales
chemical_list: D004921:Erythropoietin
keywords: Bipolar disorder; Cognition; Erythropoietin; Hippocampus; MRI; Treatment-resistant depression