Godlewska B R, Browning M, Norbury R, Cowen P J, Harmer C J
Psychopharmacology Research Unit, University Department of Psychiatry, University of Oxford, Oxford, UK.
Psychopharmacology and Emotion Research Laboratory, University Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
Transl Psychiatry. 2016 Nov 22;6(11):e957. doi: 10.1038/tp.2016.130.
Antidepressant treatment reduces behavioural and neural markers of negative emotional bias early in treatment and has been proposed as a mechanism of antidepressant drug action. Here, we provide a critical test of this hypothesis by assessing whether neural markers of early emotional processing changes predict later clinical response in depression. Thirty-five unmedicated patients with major depression took the selective serotonin re-uptake inhibitor (SSRI), escitalopram (10 mg), over 6 weeks, and were classified as responders (22 patients) versus non-responders (13 patients), based on at least a 50% reduction in symptoms by the end of treatment. The neural response to fearful and happy emotional facial expressions was assessed before and after 7 days of treatment using functional magnetic resonance imaging. Changes in the neural response to these facial cues after 7 days of escitalopram were compared in patients as a function of later clinical response. A sample of healthy controls was also assessed. At baseline, depressed patients showed greater activation to fear versus happy faces than controls in the insula and dorsal anterior cingulate. Depressed patients who went on to respond to the SSRI had a greater reduction in neural activity to fearful versus happy facial expressions after just 7 days of escitalopram across a network of regions including the anterior cingulate, insula, amygdala and thalamus. Mediation analysis confirmed that the direct effect of neural change on symptom response was not mediated by initial changes in depressive symptoms. These results support the hypothesis that early changes in emotional processing with antidepressant treatment are the basis of later clinical improvement. As such, early correction of negative bias may be a key mechanism of antidepressant drug action and a potentially useful predictor of therapeutic response.
抗抑郁治疗在治疗早期可减少负面情绪偏向的行为和神经标志物，这一作用机制已被提出。在此，我们通过评估早期情绪加工变化的神经标志物是否能预测抑郁症患者后期的临床反应，对这一假设进行了关键检验。35名未接受过药物治疗的重度抑郁症患者服用选择性5-羟色胺再摄取抑制剂（SSRI）艾司西酞普兰（10毫克），疗程为6周，并根据治疗结束时症状至少减轻50%，分为反应者（22例患者）和无反应者（13例患者）。在治疗7天前后，使用功能磁共振成像评估对恐惧和快乐情绪面部表情的神经反应。将接受艾司西酞普兰治疗7天后，患者对这些面部线索的神经反应变化，作为后期临床反应的函数进行比较。同时也评估了一组健康对照者。在基线时，抑郁症患者与对照组相比，在脑岛和背侧前扣带回对恐惧面孔的激活程度高于快乐面孔。在接受SSRI治疗后有反应的抑郁症患者，在服用艾司西酞普兰仅7天后，在包括前扣带回、脑岛、杏仁核和丘脑在内的多个脑区网络中，对恐惧面部表情的神经活动比对快乐面部表情的神经活动有更大程度的降低。中介分析证实，神经变化对症状反应的直接影响并非由抑郁症状的初始变化所介导。这些结果支持了以下假设：抗抑郁治疗引起的情绪加工早期变化是后期临床改善的基础。因此，早期纠正负面偏向可能是抗抑郁药物作用的关键机制，也是治疗反应的潜在有用预测指标。
