TY - JOUR
T1 - Acute effects of mifepristone on emotional processing related brain activity
T2 - a functional MRI study
AU - Yalin, Nefize
AU - Kempton, Matthew
AU - Mazibuko, Ndaba
AU - Mehta, Mitul
AU - Young, Allan
AU - Stokes, Paul
N1 - Funding Information:
We thank Dr Dilveer Sually for his help in scoring the National Adult Reading Test. This paper represents independent research [part] funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Neuroimaging for this study was provided by support from the NIHR Maudsley BRC. Corcept Therapeutics provided investigator-initiated research grant funding to provide study medications and for participant expenses.
Publisher Copyright:
© 2023 Elsevier B.V. and ECNP
PY - 2023/12
Y1 - 2023/12
N2 - The Hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of mood disorders, and preliminary data suggests that glucocorticoid receptor (GR) antagonism may be an important therapeutic mechanism. The effects of modulating HPA axis function on emotional processing related brain activity, which may be abnormal in depressed mood, is poorly understood. This study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine the effects of the GR and progesterone receptor antagonist mifepristone on emotional faces processing task related brain activations in 19 right-handed healthy male participants. Each participant received 600 mg mifepristone or placebo on two separate imaging days and then performed an emotional processing fMRI task four hours later. The effect of mifepristone on task related brain activations was determined using Region-of-Interest (ROI) analyses and an exploratory whole brain voxel-wise analyses. No significant changes were observed in the defined ROIs (amygdala, anterior cingulate cortex, insula) or in the exploratory whole brain analyses that was associated with mifepristone administration in either the angry vs happy faces or angry and happy faces vs implicit baseline contrasts. Task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our study failed to show significant evidence of modulation of emotional processing related brain activity associated with acute mifepristone administration. Future research should use fMRI to investigate the longer-term administration effects of mifepristone on mood in healthy participants and people with mood disorders to provide a deeper understanding of the potential effects on depressive symptoms.
AB - The Hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of mood disorders, and preliminary data suggests that glucocorticoid receptor (GR) antagonism may be an important therapeutic mechanism. The effects of modulating HPA axis function on emotional processing related brain activity, which may be abnormal in depressed mood, is poorly understood. This study used a pharmacological functional magnetic resonance imaging (fMRI) design to determine the effects of the GR and progesterone receptor antagonist mifepristone on emotional faces processing task related brain activations in 19 right-handed healthy male participants. Each participant received 600 mg mifepristone or placebo on two separate imaging days and then performed an emotional processing fMRI task four hours later. The effect of mifepristone on task related brain activations was determined using Region-of-Interest (ROI) analyses and an exploratory whole brain voxel-wise analyses. No significant changes were observed in the defined ROIs (amygdala, anterior cingulate cortex, insula) or in the exploratory whole brain analyses that was associated with mifepristone administration in either the angry vs happy faces or angry and happy faces vs implicit baseline contrasts. Task reaction times and accuracy were similar in both mifepristone and placebo conditions (all p > 0.05). Our study failed to show significant evidence of modulation of emotional processing related brain activity associated with acute mifepristone administration. Future research should use fMRI to investigate the longer-term administration effects of mifepristone on mood in healthy participants and people with mood disorders to provide a deeper understanding of the potential effects on depressive symptoms.
UR - http://www.scopus.com/inward/record.url?scp=85172885978&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2023.08.500
DO - 10.1016/j.euroneuro.2023.08.500
M3 - Article
SN - 0924-977X
VL - 77
SP - 93
EP - 102
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -