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.
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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].”
From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [98]
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Self-citation
- 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.
- ORCID
- 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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