Cited by 99Treatment of Major DepressionErythropoietin and Anemia TreatmentBipolar Disorder and Treatment

Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

Miskowiak, Kamilla W., Vinberg, Maj, Macoveanu, Julian, Ehrenreich, Hannelore, Køster, Nicolai, Inkster, Becky, Paulson, Olaf B., Kessing, Lars V. +2 more·2015·Biological Psychiatry

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.

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Crossref · 10.1016/j.biopsych.2014.12.013

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  • The erythropoietin effects on verbal learning and memory were accompanied by and correlated with reversal of subfield hippocampal volume loss.

    “Notably, these effects were accompanied by (and correlated with) reversal of subfield hippocampal volume loss [98].”

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Authors
Miskowiak, K. W., Vinberg, M., Macoveanu, J., Ehrenreich, H., Køster, N., Inkster, B., Paulson, O. B., Kessing, L. V., Skimminge, A., & Siebner, H. R.
Affiliations
  • Copenhagen University Hospital (DK)
  • Hvidovre Hospital (DK)
  • Max Planck Institute of Experimental Medicine (DE)
  • University of Cambridge (GB)
  • Bispebjerg Hospital (DK)
Corresponding author
Miskowiak, Kamilla W.
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2015-08
Volume
78
Issue
4
Pages
270-277
ISSN
0006-3223 (ISSN-L)
OpenAlex
W2037656344
Cited by
99
References
46
Citations by year
2026: 4 · 2025: 5 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 14 · 2020: 11 · 2019: 7 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 7
FWCI
5.81
Type
journal article
Language
en
Open access
closed
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • GRO (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
Lundbeckfonden (R59-2010-5399)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
erythropoietin, hippocampal volume, memory, treatment-resistant depression, bipolar disorder, cognitive impairment, hippocampal subfields, neuroplasticity, brain atrophy, subiculum, neuroanatomy
MeSH terms
Adult, Bipolar Disorder, Depressive Disorder, Erythropoietin, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Psychiatric Status Rating Scales, Mood Disorders, Depressive Disorder, Treatment-Resistant

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