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Title: Manipulating dopaminergic activity with bupropion : effects on reward and emotional processing biases implicated in depression
Author: Walsh, Annabel
ISNI:       0000 0004 6496 6672
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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Major depressive disorder is characterised by two core diagnostic symptoms, low mood and anhedonia, which have been suggested to be caused by negative biases in emotional processing and aberrant reward processing, respectively. Previous research using antidepressants predominantly affecting serotonin or noradrenaline activity suggests that antidepressants may act to reduce the negative biases in emotional processing, which then influences low mood; however, such antidepressants do not fully correct the anhedonia. This lack of efficacy underlines the need for further research to unravel the roles of various neurotransmitter systems in the modulation of processing biases implicated in major depressive disorder. For example, it is still unclear how the initial antidepressant effects on biases in emotional processing relate to effects on aberrant reward processing in major depressive disorder and whether they are also targeted by antidepressants affecting dopaminergic activity, such as bupropion. The current thesis aimed to delineate the role of the dopaminergic reward system in the cognitive neurobiological processes underlying the two symptom clusters of low mood and anhedonia in major depressive disorder. In order to do this, two experimental studies manipulating dopaminergic activity with the antidepressant bupropion were completed and the effects on reward and emotional processing biases implicated in major depressive disorder were assessed. The first study investigated the acute effects of bupropion on behavioural measures of reward and emotional processing in a non-clinical population. Compared to placebo, an acute dose of bupropion was found to reduce negative and increase positive emotional processing with little effect on reward processing. The second study investigated the early and longer-term effects of bupropion on behavioural and neural measures of reward and emotional processing in individuals suffering with major depressive disorder. Compared to untreated healthy controls, bupropion was again found to reduce negative and increase positive emotional processing but was found to worsen aberrant reward processing at 2 weeks prior to normalisation after the full 6 week treatment. Higher right lateral orbitofrontal cortex activity in response to happy faces and decreased right amygdala activity in response to sad faces at 2 weeks was associated with decreased HAM-D score at 6 weeks. This suggests a causal role for the early neural effects of bupropion in later change in subjective symptoms and has clinical implications providing further evidence for the potential to predict clinical outcome from the early effects of antidepressants.
Supervisor: Harmer, Catherine ; Browning, Michael Sponsor: Jansenn of Johnson & Johnson ; Medical Research Council ; Oxford Health Biomedical Research Center
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available