Kamilla W. Miskowiak1, Julie L. Forman1, Maj Vinberg1, Hartwig R. Siebner1, Lars V. Kessing1, Julian Macoveanu1. 1. From the Neurocognition and Emotion in Affective Disorder (NEAD) Group, Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital (Miskowiak, Macoveanu); the Department of Psychology, University of Copenhagen (Miskowiak); the Section of Biostatistics, Department of Public Health, University of Copenhagen (Forman); the Danish Research Centre for Magnetic Resonance (DRCMR), Centre for Functional and Diagnostic Imaging and Research, Hvidovre Hospital, University of Copenhagen (Siebner); the Department of Neurology, Copenhagen University Hospital Bispebjerg (Siebner); the Institute for Clinical Medicine, Faculty of Medical and Health Sciences, University of Copenhagen (Vinberg, Siebner); and the Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, Copenhagen University Hospital (Kessing), Copenhagen, Denmark.
Abstract
Background: Treatment development that targets cognitive impairment is hampered by a lack of biomarkers that can predict treatment efficacy. Erythropoietin (EPO) improves verbal learning and memory in mood disorders, and this scales with an increase in left hippocampal volume. This study investigated whether pretreatment left hippocampal volume, interhemisphere hippocampal asymmetry or both influenced EPO treatment response with respect to verbal learning. Methods: Data were available for 76 of 83 patients with mood disorders from our previous EPO trials (EPO = 37 patients; placebo = 39 patients). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. We conducted multiple linear regression and logistic regression to assess the influence of left hippocampal volume and hippocampal asymmetry on EPO-related memory improvement, as reflected by change in Rey Auditory Verbal Learning Test total recall from baseline to post-treatment. We set up a corresponding exploratory general linear model in FreeSurfer to assess the influence of prefrontal cortex volume on verbal learning improvement, controlling for age, sex and total intracranial volume. Results: At baseline, more rightward (left < right) hippocampal asymmetry — but not left hippocampal volume per se — was associated with greater effects of EPO versus placebo on verbal learning (p ≤ 0.05). Exploratory analysis indicated that a larger left precentral gyrus surface area was also associated with improvement of verbal learning in the EPO group compared to the placebo group (p = 0.002). Limitations: This was a secondary analysis of our original EPO trials. Conclusion: Rightward hippocampal asymmetry may convey a positive effect of EPO treatment efficacy on verbal learning. Clinical trial registration: Clinicaltrials.gov NCT00916552
RCT Entities:
Background: Treatment development that targets cognitive impairment is hampered by a lack of biomarkers that can predict treatment efficacy. Erythropoietin (EPO) improves verbal learning and memory in mood disorders, and this scales with an increase in left hippocampal volume. This study investigated whether pretreatment left hippocampal volume, interhemisphere hippocampal asymmetry or both influenced EPO treatment response with respect to verbal learning. Methods: Data were available for 76 of 83 patients with mood disorders from our previous EPO trials (EPO = 37 patients; placebo = 39 patients). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. We conducted multiple linear regression and logistic regression to assess the influence of left hippocampal volume and hippocampal asymmetry on EPO-related memory improvement, as reflected by change in Rey Auditory Verbal Learning Test total recall from baseline to post-treatment. We set up a corresponding exploratory general linear model in FreeSurfer to assess the influence of prefrontal cortex volume on verbal learning improvement, controlling for age, sex and total intracranial volume. Results: At baseline, more rightward (left < right) hippocampal asymmetry — but not left hippocampal volume per se — was associated with greater effects of EPO versus placebo on verbal learning (p ≤ 0.05). Exploratory analysis indicated that a larger left precentral gyrus surface area was also associated with improvement of verbal learning in the EPO group compared to the placebo group (p = 0.002). Limitations: This was a secondary analysis of our original EPO trials. Conclusion: Rightward hippocampal asymmetry may convey a positive effect of EPO treatment efficacy on verbal learning. Clinical trial registration: Clinicaltrials.gov NCT00916552
Authors: A John Rush; Madhukar H Trivedi; Stephen R Wisniewski; Andrew A Nierenberg; Jonathan W Stewart; Diane Warden; George Niederehe; Michael E Thase; Philip W Lavori; Barry D Lebowitz; Patrick J McGrath; Jerrold F Rosenbaum; Harold A Sackeim; David J Kupfer; James Luther; Maurizio Fava Journal: Am J Psychiatry Date: 2006-11 Impact factor: 18.112
Authors: Caroline Vintergaard Ott; Maj Vinberg; Lars V Kessing; Kamilla W Miskowiak Journal: Eur Neuropsychopharmacol Date: 2016-06-24 Impact factor: 4.600
Authors: K W Miskowiak; K E Burdick; A Martinez-Aran; C M Bonnin; C R Bowie; A F Carvalho; P Gallagher; B Lafer; C López-Jaramillo; T Sumiyoshi; R S McIntyre; A Schaffer; R J Porter; I J Torres; L N Yatham; A H Young; L V Kessing; E Vieta Journal: Bipolar Disord Date: 2017-09-12 Impact factor: 6.744