An experimental medicine investigation of the effects of potential novel antidepressant interventions on emotion and reward related information proces

最近试图调和抑郁症的神经药理学和认知帐户，导致抗抑郁治疗作用的认知神经心理学模型的发展。这个模型表明，抗抑郁药物发挥其临床效果，急性诱导积极的偏见，在“热”（即情绪相关）的认知过程，可以抵消负面偏见的情感信息处理是抑郁症固有的。这个模型的有效性得到了大量实证研究的支持，这些研究调查了不同的抗抑郁药物的作用，这些研究表明，诱导正偏差是抗抑郁作用的一个常见和关键的因果机制。我的哲学博士项目的目的是调查潜在的新型抗抑郁治疗是否可以产生类似的效果。采用实验医学方法，在健康志愿者中研究了三种不同的干预措施：明亮的光治疗，积极心理学练习和多巴胺D2/D3受体偏好激动剂普拉克索的管理。除了对热认知过程的影响外，对于这些干预措施中的每一种，还测试了对主观状态的潜在影响，以及在感兴趣的情况下，对其他相关测量的影响（例如，用于实践积极心理学的HPA轴活动，用于普拉克索治疗的味觉处理）。这项工作的结果将使我们能够更好地了解这三种干预措施的潜在认知效应，并显示其临床效应是否可以在抗抑郁治疗作用的认知神经心理学模型的理论框架内解释。

Recent attempts to reconcile neuropharmacological and cognitive accounts of depression have led to the development of a cognitive neuropsychological model of antidepressant treatment action. This model suggests that antidepressant drugs exert their clinical effects by acutely inducing positive biases in "hot" (i.e. emotion-related) cognitive processes which can counteract the negative biases in affective information processing that are inherent to depression. The validity of this model is well supported by a multitude of empirical studies investigating the effects of different established antidepressant drugs which, taken together, suggest that the induction of positive biases is a common and crucial causal mechanism of antidepressant action.The aim of my DPhil project is to investigate whether potential novel antidepressant treatments could have similar effects. Taking an experimental medicine approach, three different interventions are studied in healthy volunteers: bright light treatment, practising positive psychology, and administration of the dopamine D2/D3 receptor-preferring agonist pramipexole. In addition to their effects on hot cognitive processes, for each of these interventions, potential effects on subjective state and, where of interest, also effects on other relevant measures (e.g. HPA axis activity for practising positive psychology, gustatory processing for pramipexole treatment) are tested. The results of this work will allow us to better understand potential cognitive effects of the three interventions and will show whether their clinical effects could be explained within the theoretical framework of the cognitive neuropsychological model of antidepressant treatment action.