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Neural correlates of improved executive function following erythropoietin treatment in mood disorders

Published online by Cambridge University Press:  21 March 2016

K. W. Miskowiak ,
M. Vinberg ,
L. Glerup ,
O. B. Paulson ,
G. M. Knudsen ,
H. Ehrenreich ,
C. J. Harmer ,
L. V. Kessing ,
H. R. Siebner  and
J. Macoveanu
K. W. Miskowiak*
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark
M. Vinberg
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
L. Glerup
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
O. B. Paulson
Affiliation:
Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
G. M. Knudsen
Affiliation:
Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
H. Ehrenreich
Affiliation:
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany
C. J. Harmer
Affiliation:
Department of Psychiatry, University of Oxford, Oxford, UK
L. V. Kessing
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
H. R. Siebner
Affiliation:
Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark
J. Macoveanu
Affiliation:
Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark Center for Integrated Molecular Brain Imaging, Rigshospitalet, Copenhagen, Denmark
*
*Address for correspondence: Dr K. W. Miskowiak, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark. (Email: [email protected])
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Abstract

Background

Cognitive dysfunction in depression and bipolar disorder (BD) is insufficiently targeted by available treatments. Erythropoietin (EPO) increases neuroplasticity and may improve cognition in mood disorders, but the neuronal mechanisms of these effects are unknown. This functional magnetic resonance imaging (fMRI) study investigated the effects of EPO on neural circuitry activity during working memory (WM) performance.

Method

Patients with treatment-resistant major depression, who were moderately depressed, or with BD in partial remission, were randomized to eight weekly infusions of EPO (40 000 IU) (N = 30) or saline (N = 26) in a double-blind, parallel-group design. Patients underwent fMRI, mood ratings and blood tests at baseline and week 14. During fMRI patients performed an n-back WM task.

Results

EPO improved WM accuracy compared with saline (p = 0.045). Whole-brain analyses revealed that EPO increased WM load-related activity in the right superior frontal gyrus (SFG) compared with saline (p = 0.01). There was also enhanced WM load-related deactivation of the left hippocampus in EPO-treated compared to saline-treated patients (p = 0.03). Across the entire sample, baseline to follow-up changes in WM performance correlated positively with changes in WM-related SFG activity and negatively with hippocampal response (r = 0.28–0.30, p < 0.05). The effects of EPO were not associated with changes in mood or red blood cells (p ⩾0.08).

Conclusions

The present findings associate changes in WM-load related activity in the right SFG and left hippocampus with improved executive function in EPO-treated patients. Clinical trial registration: clinicaltrials.gov: NCT00916552.

Keywords

Bipolar disordercognitiondorsolateral prefrontal cortexerythropoietinEPOexecutive functionfMRItreatment-resistant depression
Type
Original Articles
Information
Psychological Medicine , Volume 46 , Issue 8 , June 2016 , pp. 1679 - 1691
Copyright
Copyright © Cambridge University Press 2016 

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