Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

Kamilla Woznica Miskowiak; Maj Vinberg; Julian Macoveanu; Hannelore Ehrenreich; Nicolai Køster; Becky Inkster; Olaf B. Paulson; Lars V. Kessing; Arnold Skimminge; Hartwig R. Siebner

doi:10.1016/j.biopsych.2014.12.013

Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

Kamilla Woznica Miskowiak, Maj Vinberg, Julian Macoveanu, Hannelore Ehrenreich, Nicolai Køster, Becky Inkster, Olaf B. Paulson, Lars V. Kessing, Arnold Skimminge, Hartwig R. Siebner

55 Citations (Scopus)

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.

Original language	English
Journal	Biological Psychiatry
Volume	78
Issue number	4
Pages (from-to)	270-277
Number of pages	8
ISSN	0006-3223
DOIs	https://doi.org/10.1016/j.biopsych.2014.12.013
Publication status	Published - 15 Aug 2015

Keywords

Adult
Bipolar Disorder
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Erythropoietin
Female
Hippocampus
Humans
Magnetic Resonance Imaging
Male
Memory
Middle Aged
Mood Disorders
Psychiatric Status Rating Scales

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10.1016/j.biopsych.2014.12.013

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@article{375b752fc8594c7abe3e1bc0338b7dfd,

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.",

keywords = "Adult, Bipolar Disorder, Depressive Disorder, Depressive Disorder, Treatment-Resistant, Erythropoietin, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory, Middle Aged, Mood Disorders, Psychiatric Status Rating Scales",

author = "Miskowiak, {Kamilla Woznica} and Maj Vinberg and Julian Macoveanu and Hannelore Ehrenreich and Nicolai K{\o}ster and Becky Inkster and Paulson, {Olaf B.} and Kessing, {Lars V.} and Arnold Skimminge and Siebner, {Hartwig R.}",

year = "2015",

month = aug,

day = "15",

doi = "10.1016/j.biopsych.2014.12.013",

language = "English",

volume = "78",

pages = "270--277",

journal = "Biological Psychiatry",

issn = "0006-3223",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

AU - Miskowiak, Kamilla Woznica

AU - Vinberg, Maj

AU - Macoveanu, Julian

AU - Ehrenreich, Hannelore

AU - Køster, Nicolai

AU - Inkster, Becky

AU - Paulson, Olaf B.

AU - Kessing, Lars V.

AU - Skimminge, Arnold

AU - Siebner, Hartwig R.

PY - 2015/8/15

Y1 - 2015/8/15

N2 - 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.

AB - 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.

KW - Adult

KW - Bipolar Disorder

KW - Depressive Disorder

KW - Depressive Disorder, Treatment-Resistant

KW - Erythropoietin

KW - Female

KW - Hippocampus

KW - Humans

KW - Magnetic Resonance Imaging

KW - Male

KW - Memory

KW - Middle Aged

KW - Mood Disorders

KW - Psychiatric Status Rating Scales

U2 - 10.1016/j.biopsych.2014.12.013

DO - 10.1016/j.biopsych.2014.12.013

M3 - Journal article

C2 - 25641635

SN - 0006-3223

VL - 78

SP - 270

EP - 277

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 4

ER -

Effects of Erythropoietin on Hippocampal Volume and Memory in Mood Disorders

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