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，但在包括严重抑郁障碍(MDD)在内的许多精神障碍中都会受到干扰。负性加工偏差在抑郁症中存在，并预测缓解期患者的复发，这表明偏见在抑郁症的发生和维持中起着因果作用。最近的一项大型试验(STAR*D)表明，药物治疗在三分之一到一半的患者中无效。此外，越来越多的证据表明，抗抑郁药物(如选择性5-羟色胺再摄取抑制剂，SSRI)不足以改善患者单独缺乏积极影响的情况，它们与心理疗法结合使用效果最好。虽然最近抑郁症心理治疗的进展集中在促进积极偏见上，但在治疗快感缺乏症方面仍然存在困难，这与较差的结果有关。除了药物治疗之外，几乎没有工作来确定最低限度的有效心理干预是什么，也缺乏类似的研究来检验这种辅助治疗的作用机制。我们将调查远程提供的心理干预是否可以提供足够的机会重新学习情绪，以提高SSRI的治疗效果，以对情绪面孔的神经反应为指标。功能磁共振研究已经提供了很好的证据，SSRI降低了神经反应，特别是在杏仁核，对负面情绪面孔的反应。对情绪刺激做出反应的行为和神经变化都与后来的情绪改善有关。我们的简短、自动化、情绪认知偏差修正(CBM)技术导致情绪表达感知的强大和普遍变化，对情绪低落的成年人的fMRI结果表明，它还增加了杏仁核对快乐表达的反应。值得注意的是，与主要影响负面情绪处理的SSRI诱导效应相比，它对负面情绪的反应影响较小。这表明，CBM和SSRI联合治疗可能特别有效。我们的目标是调查一种改善我们看待他人情绪的方式的心理疗法是否可以提高抗抑郁药物的疗效。具体地说，我们将在新的抑郁症发作患者中提供CBM培训和SSRI药物治疗，以研究这是否增强了对消极情绪(通常是由SSRI治疗产生的)反应的杏仁核活动减少，以及对积极表达的反应增加杏仁核活动(这是我们早期工作的一个关键结果，在SSRI研究中很少见)。从机制上讲，我们对这种效应将如何在神经对情绪刺激的反应中具体化有明确的预测。在治疗上，这种预防措施的组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.