Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry & Psychology and Neuroscience, King's College of London, UK.
Department of Psychosis Studies, Institute of Psychiatry, Psychology &Neuroscience, King's College London, London, UK; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, UK.
Eur Neuropsychopharmacol. 2023 Dec;77:93-102. doi: 10.1016/j.euroneuro.2023.08.500. Epub 2023 Sep 23.
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.
下丘脑-垂体-肾上腺 (HPA) 轴在心境障碍的病理生理学中起着重要作用，初步数据表明，糖皮质激素受体 (GR) 拮抗剂可能是一种重要的治疗机制。调节 HPA 轴功能对情绪处理相关大脑活动的影响在抑郁情绪中可能异常，但目前对此知之甚少。本研究使用药理学功能磁共振成像 (fMRI) 设计，以确定 GR 和孕激素受体拮抗剂米非司酮对 19 名右利手健康男性参与者在进行情绪面孔处理任务时相关大脑活动的影响。每位参与者在两天的单独成像日接受 600mg 米非司酮或安慰剂，然后在四个小时后进行情绪处理 fMRI 任务。使用感兴趣区 (ROI) 分析和探索性全脑体素分析来确定米非司酮对任务相关大脑活动的影响。在定义的 ROI（杏仁核、前扣带回皮层、脑岛）或与米非司酮给药相关的探索性全脑分析中，未观察到与愤怒与快乐面孔或愤怒和快乐面孔与隐含基线对比相关的显著变化。在米非司酮和安慰剂条件下，任务反应时间和准确性相似（均 p>0.05）。我们的研究未能显示出与急性米非司酮给药相关的情绪处理相关大脑活动调节的显著证据。未来的研究应使用 fMRI 来研究米非司酮在健康参与者和情绪障碍患者中的长期给药对情绪的影响，以更深入地了解对抑郁症状的潜在影响。
