Effects of behavioural activation with and without citalopram on emotional cognition and mood

大量的研究文献表明，抑郁症患者在他们的自动认知过程中倾向于对负面刺激有偏见。例如，抑郁与消极词汇和面部表情的注意力和记忆的相对增加（Roiser & Sahakian, 2013）以及健康样本中发现的对模糊刺激的积极偏见的减少（Milders等人，2010）有关。有证据表明，这些偏见不仅是一种附带现象，而且可能是抑郁症发病的一个风险因素（Joormann, Talbot, & Gotlib, 2007），也可能是复发的一个预测因素（Bouhuys, Geerts & Gordijn, 1999），从而发挥因果作用。重要的是，这些自动偏见的积极变化与抗抑郁药物治疗的早期阶段有关（Harmer et al., 2003）。Harmer， Goodwin和Cowen（2009）提出了一种抗抑郁药物机制的认知神经心理学模型，即情绪刺激自动加工的早期变化发生在情绪有意识变化之前。与此相一致，Tranter等人（2009）发现证据表明，在药物治疗两周时面部表情识别自动偏差的早期变化可能预示着治疗六周时的成功。然而，目前尚不清楚为什么这种情感偏见的早期变化并没有发生在每个人身上，而且许多人对他们的一线抗抑郁药物治疗没有反应。正如Harmer等人（2017）所提出的，药物治疗引起的情感偏见的早期认知变化有望与积极的环境强化相互作用，最终改善情绪。如果积极的环境强化是与药物诱导的积极偏倚相互作用的必要条件，从而增强药物疗效，这可以解释患者对抗抑郁药物反应的差异。事实上，一些证据表明环境强化在抗抑郁治疗中的重要性。例如，Shiroma等人（2014）发现，在社会支持水平较高的患者中，服用抗抑郁药后积极偏倚的增加幅度更大。这也与动物研究的证据相一致，在更好的环境中的动物对抗抑郁药物表现出更好的反应，以及更高的脑BDNF水平（Branchi et al., 2006）。据我们所知，抗抑郁药效果和环境强化之间的相互作用尚未在人类中进行实验测试。本博士的目的是研究环境强化对认知偏差的作用，使用行为激活（BA），在有无添加抗抑郁药物治疗的情况下。这是NICE推荐的一种抑郁症治疗方法（National Institute of Health and Care Excellence, [NICE], 2009），其目的是通过帮助患者在他们感到有动力之前重新开始放弃的活动，从而增加他们的活动和环境奖励。这是通过一个结构化的活动监测方案、逐步设定目标和教练式的支持来实现的。第一项研究的目的是测试BA干预对情绪认知和情绪的早期影响。我们的目标是招募90名参与者，并将他们随机分为1)4周的BA， 2) 4周的活动监测（主动对照组）或3)被动对照组，同时在干预的开始，中期和结束时收集数据。本博士的第二个实验将结合BA和抗抑郁药物治疗两周，以检查对认知偏差的早期影响。我们的目标是招募120名患有抑郁症的参与者，并将他们随机分为四组（BA联合抗抑郁药、BA联合安慰剂、BA单独服用抗抑郁药和安慰剂单独服用）。总的来说，这应该有助于我们理解不同抑郁症治疗类型的早期认知变化。

A body of research literature has shown that patients with depression tend to have a bias towards negative stimuli in their automatic cognitive processes. For example, depression is linked to a relative increase in attention to and memory for negative words and facial expressions (Roiser & Sahakian, 2013) as well as a decrease in the positive bias for ambiguous stimuli that is found in healthy samples (Milders et al., 2010). Rather than just being an epiphenomenon, evidence suggests that these biases might play a causal role by being a risk factor for depression onset (Joormann, Talbot, & Gotlib, 2007) as well as a possible predictor of relapse (Bouhuys, Geerts & Gordijn, 1999).Importantly, positive changes in these automatic biases have been linked to the early phase of antidepressant drug treatment (Harmer et al., 2003). Harmer, Goodwin and Cowen (2009) have proposed a cognitive neuropsychological model of antidepressant drug mechanism whereby early changes in automatic processing of emotional stimuli occur before conscious changes in mood. In line with this, Tranter et al. (2009) found evidence that early changes in the automatic bias for facial expression recognition at two weeks of drug treatment may be predictive of treatment success at six weeks. However, it is not clear why this early change in affective bias does not occur for everyone and many people don't respond to their first line antidepressant treatment.As suggested by Harmer et al. (2017), the early cognitive changes in affective bias induced by drug treatment are expected to interact with positive environmental reinforcement to eventually improve mood. If positive environmental reinforcement is necessary for interacting with the drug-induced positive bias and thus potentiating drug efficacy, this could explain variability in how patients respond to antidepressant drugs. Indeed, several lines of evidence suggest the importance of environmental reinforcement in antidepressant treatment. For instance, Shiroma et al. (2014) found that increase in positive bias after antidepressant administration was greater in patients with higher levels of social support. This is also consistent with evidence from animal research wherein animals in better environments show a better response to antidepressant drugs, as well as higher brain BDNF levels (Branchi et al., 2006). To our knowledge, the interaction between antidepressant effects and environmental reinforcement has not been experimentally tested in humans. The aim of this DPhil is to examine the role of environmental reinforcement on cognitive biases with and without added antidepressant treatment, using behavioural activation (BA). This is a NICE-recommended depression treatment (National Institute of Health and Care Excellence, [NICE], 2009), which aims to increase patients' activity and environmental reward by helping them get back to abandoned activities before they feel motivated for it. This is achieved through a structured programme of activity monitoring, gradual goal setting and coach-like support. The purpose of the first study is to test the early effects of a BA intervention on emotional cognition and mood. We aim to recruit 90 participants and randomise them into either 1) 4 weeks of BA, 2) 4 weeks of activity monitoring (active control group) or 3) passive control group, while collecting data at the beginning, middle and end of the intervention. The second experiment of this DPhil will combine BA with antidepressant drug treatment for 2 weeks to examine the early effects on cognitive biases. We aim to recruit 120 participants experiencing depression and randomise them into four groups (BA with antidepressants, BA with placebo, antidepressants alone and placebo alone). Overall, this should aid our understanding of the onset of early cognitive changes in different depression treatment types.