TY - JOUR

T1 - Impact of pretreatment interhemispheric hippocampal asymmetry on improvement in verbal learning following erythropoietin treatment in mood disorders

T2 - a randomized controlled trial

AU - Miskowiak, Kamilla W.

AU - Forman, Julie L.

AU - Vinberg, Maj

AU - Siebner, Hartwig R.

AU - Kessing, Lars V.

AU - Macoveanu, Julian

N1 - 2019 Joule Inc. or its licensors

PY - 2020

Y1 - 2020

N2 - 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

AB - 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

U2 - 10.1503/jpn.180205

DO - 10.1503/jpn.180205

M3 - Journal article

C2 - 31804779

VL - 45

SP - 198

EP - 205

JO - Journal of Psychiatry and Neuroscience

JF - Journal of Psychiatry and Neuroscience

SN - 1180-4882

IS - 3

ER -