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Title: An experimental medicine investigation of the effects of potential novel antidepressant interventions on emotion and reward related information processing
Author: Kaltenboeck, Alexander
ISNI:       0000 0004 9355 5063
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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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. emotionrelated) 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 this thesis is to investigate whether potential novel antidepressant treatments could have similar effects. Taking an experimental medicine approach, three different interventions were 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) were tested. Contrary to our predictions, we did not find conclusive evidence for an antidepressant-like effect on emotional information processing for any of the three treatments we studied. However, several interesting patterns in other measures were observed: First, an early memory practice that has previously been used as a supposedly inert control intervention in positive psychology studies showed a blunting effect on cortisol awakening responses and potentially also a general improvement of hot cognitive processes. Second, subacute pramipexole treatment showed a potential effect on exploration-exploitation strategies in an information bias learning task, maintaining random exploration after repeated-testing as compared to placebo. Furthermore, pramipexole also showed a potential effect on gustatory processing, enhancing taste recognition but blunting subjective evaluation of appetitive and aversive taste samples. In conclusion, previously reported antidepressant effects of the putative novel treatments that were studied in this thesis seem not to be explainable by the induction of positive biases in emotion-related information processing. Further studies on the mechanisms behind their efficacy are warranted. The observed effects of the mental practice and of subacute pramipexole treatment deserve further attention and should be interrogated in closer detail in future research.
Supervisor: Harmer, Catherine ; Cowen, Philip ; Browning, Michael Sponsor: University of Oxford ; MRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available