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

TY - JOUR

T1 - Neural correlates of improved executive function following erythropoietin treatment in mood disorders

AU - Miskowiak, K. W.

AU - Vinberg, M.

AU - Glerup, L.

AU - Paulson, O. B.

AU - Knudsen, G. M.

AU - Ehrenreich, H.

AU - Harmer, Catherine J.

AU - Kessing, L. V.

AU - Siebner, H. R.

AU - Macoveanu, J.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1017/S0033291716000209

DO - 10.1017/S0033291716000209

M3 - Journal article

C2 - 26996196

SN - 0033-2917

VL - 46

SP - 1679

EP - 1691

JO - Psychological Medicine

JF - Psychological Medicine

IS - 8

ER -