National Institutes of Health, National Institute of Mental Health, Bethesda, MD, USA.
Int J Neuropsychopharmacol. 2013 Nov;16(10):2195-208. doi: 10.1017/S146114571300062X. Epub 2013 Jul 1.
An emerging hypothesis regarding the mechanisms underlying antidepressant pharmacotherapy suggests that these agents benefit depressed patients by reversing negative emotional processing biases (Harmer, 2008). Neuropsychological indices and functional neuroimaging measures of the amygdala response show that antidepressant drugs shift implicit and explicit processing biases away from the negative valence and toward the positive valence. However, few studies have explored such biases in regions extensively connected with the amygdala, such as the pregenual anterior cingulate cortex (pgACC) area, where pre-treatment activity consistently has predicted clinical outcome during antidepressant treatment. We used functional magnetic resonance imaging (fMRI) to investigate changes in haemodynamic response patterns to positive vs. negative stimuli in patients with major depressive disorder (MDD) under antidepressant treatment. Participants with MDD (n = 10) underwent fMRI before and after 8 wk sertraline treatment; healthy controls (n = 10) were imaged across an equivalent interval. A backward masking task was used to elicit non-conscious neural responses to sad, happy and neutral face expressions. Haemodynamic responses to emotional face stimuli were compared between conditions and groups in the pgACC. The response to masked-sad vs. masked-happy faces (SN-HN) in pgACC in the depressed subjects was higher in the pre-treatment condition than in the post-treatment condition and this difference was significantly greater than the corresponding change across time in the controls. The treatment-associated difference was attributable to an attenuated response to sad faces and an enhanced response to happy faces. Pre-treatment pgACC responses to SN-HN correlated positively with clinical improvement during treatment. The pgACC participates with the amygdala in processing the salience of emotional stimuli. Treatment-associated functional changes in this limbic network may influence the non-conscious processing of such stimuli by reversing the negative processing bias extant in MDD.
一种关于抗抑郁药治疗机制的新兴假说表明，这些药物通过逆转负面情绪处理偏差使抑郁患者受益（Harmer，2008）。神经心理学指标和杏仁核反应的功能神经影像学测量表明，抗抑郁药物将内隐和外显处理偏差从负性偏向转移到正性偏向。然而，很少有研究探索过与杏仁核广泛连接的区域中的这种偏差，例如前扣带回皮质（pgACC）区域，在抗抑郁治疗中，治疗前的活动一直预测着临床结果。我们使用功能磁共振成像（fMRI）来研究接受抗抑郁治疗的重度抑郁症（MDD）患者的前扣带回皮质（pgACC）区域的正性与负性刺激的血液动力学反应模式的变化。MDD 患者（n=10）在接受 8 周舍曲林治疗前后接受 fMRI 检查；健康对照组（n=10）在相同的时间间隔内进行成像。使用后向掩蔽任务诱发对悲伤、快乐和中性面部表情的非意识神经反应。在 pgACC 中比较了情绪面孔刺激条件和组之间的血液动力学反应。在治疗前条件下，与治疗后条件相比，pgACC 中对掩蔽悲伤面孔与掩蔽快乐面孔（SN-HN）的反应在抑郁患者中更高，这种差异明显大于对照组中随时间的相应变化。与治疗相关的差异归因于对悲伤面孔的反应减弱和对快乐面孔的反应增强。治疗前 pgACC 对 SN-HN 的反应与治疗期间的临床改善呈正相关。pgACC 与杏仁核一起处理情绪刺激的显著性。该边缘网络中的治疗相关功能变化可能通过逆转 MDD 中存在的负性处理偏差来影响对这些刺激的非意识处理。
