fMRI investigation of the neural mechanisms of Emotional Cognitive Bias Modification as an adjunct therapy to SSRIs in depression.

情绪信息的处理对社会功能至关重要，但在许多精神疾病中被破坏，包括重度抑郁症（MDD）。负性加工偏倚在抑郁症中存在，并预测缓解患者的复发，表明偏倚在抑郁症的发病和维持中起因果作用。最近的一项大型试验（STAR*D）表明，药物治疗对三分之一至一半的患者无效。此外，越来越多的证据表明，抗抑郁药物（如选择性血清素再摄取抑制剂，SSRIs）不能充分改善患者单独缺乏积极影响的情况，它们与心理治疗相结合效果最好。虽然抑郁症心理治疗的最新进展侧重于促进积极偏见，但在治疗快感缺乏方面仍然存在困难，这与较差的结果有关。很少有研究确定除了药物治疗之外，最低限度的有效心理干预可能是什么，同样也缺乏对这种辅助疗法的作用机制的研究。我们将调查远程传递的心理干预是否可以提供足够的机会来重新学习情绪，以提高SSRI的治疗效果，如对情绪面孔的神经反应。功能磁共振成像（fMRI）研究已经提供了很好的证据，表明ssri类药物可以减少神经反应，尤其是杏仁核对消极情绪面孔的反应。对情绪刺激反应的行为和神经变化都与后来情绪的改善有关。我们的简单、自动化的情绪认知偏差修正（CBM）技术导致情绪表达感知的强大和可推广的变化，在成年人情绪低落的fMRI结果表明，它也增加了杏仁核活动，以回应快乐的表达。值得注意的是，与ssri诱导的主要影响负面情绪加工的效应相比，它对负面情绪反应的影响较小。这表明CBM和SSRI联合治疗可能特别有效。我们的目标是研究一种心理疗法，它能改善我们看待他人情绪的方式，是否能提高抗抑郁药物的疗效。具体来说，我们将对新发作的抑郁症患者进行CBM训练和SSRI药物治疗，以研究这是否会增强对负面情绪（通常是SSRI治疗的结果）反应的减少的杏仁核活动，并增加对积极表达的杏仁核活动（我们早期工作的关键结果，在SSRI研究中很少见到）。从机制上讲，我们已经清楚地预测了这种影响将如何在对情绪刺激的神经反应中实例化。在治疗上，这种干预措施的结合有可能解决目前难以治疗的抑郁症状。

Processing of emotional information is critical to social functioning but is disrupted in many psychiatric disorders, including Major Depressive Disorder (MDD). Negative processing biases are present in depression and predict relapse in remitted patients, suggesting that biases play a causal role in the onset and maintenance of depression. A recent large trial (STAR*D) indicates that pharmacotherapy is ineffective in one-third to a half of patients. Furthermore, mounting evidence suggests that antidepressant drugs (e.g., selective serotonin reuptake inhibitors, SSRIs) do not sufficiently improve the absence of positive affect in patients alone, and that they work best in combination with psychological therapies. While recent advances in psychological therapy for depression focus on promoting positive biases, there are still difficulties in treating anhedonia, which is associated with poorer outcomes. There is little work to determine what the minimum effective psychological intervention may be in addition to drug treatment, and a similar lack of studies examining mechanisms of action of such adjunct therapies. We will investigate whether a remotely delivered psychological intervention can provide sufficient opportunity for relearning about emotion to improve the therapeutic effectiveness of SSRI, as indexed by neural responses to emotional faces.fMRI studies have provided good evidence that SSRIs reduce neural responses, particularly in the amygdala, to negative emotional faces. Both behavioural and neural changes in response to emotional stimuli are associated with later improvement in mood. Our brief, automated, Emotional Cognitive Bias Modification (CBM) technique leads to robust and generalizable changes in emotional expression perception, with fMRI results in adults with low mood demonstrating it also increases amygdala activity in response to expressions of happiness. Notably, it has less effect on responses to negative emotions, in contrast to SSRI-induced effects which primarily impact the processing of negative emotions. This suggests that the combination of CBM and SSRI treatment might be particularly effective. We aim to investigate whether a psychological therapy that improves the way we see emotion in others could improve antidepressant drug efficacy. Specifically, we will deliver both CBM training and SSRI pharmacotherapy in patients with a new episode of depression, to investigate whether this enhances the reduced amygdala activity in response to negatively valenced emotions (that typically results from SSRI therapy) and increases amygdala activity in response to positive expressions (a key result from our earlier work that is rarely seen in SSRI studies). Mechanistically, we have clear predictions about how such effects will be instantiated in neural responses to emotional stimuli. Therapeutically, this combination of inetreventions has the potential to address depressive symptoms that are currently difficult to treat.