| Summary: | <p>Anhedonia, the loss of pleasure or motivation for usually enjoyable activities and rewards, is an established cardinal symptom in Major Depressive Disorder (MDD) whose underlying pathophysiology is not well-understood, and which lacks specific efficacious treatments. This thesis investigates the effects that bupropion, a dual reuptake inhibitor of dopamine and noradrenaline, has on the neural substrates implicated in reward processing amongst clinically depressed individuals compared to unmedicated healthy controls. This investigation may help elucidate the role of aberrant dopaminergic activity on reward processing and the relevance of reward within anhedonia. First, examining baseline neural activation during completion of a monetary reward learning task revealed significantly different functional activity patterns at the whole brain level and for pre-specified anatomical regions of interest in MDD patients compared to healthy volunteers. These activation clusters largely pertained to brain regions implicated in the dopaminergic system, including the striatum, orbitofrontal cortex, and insular cortex. However, this was not found to correlate with symptomatic severity of anhedonia at baseline, which showed significant group differences in anhedonia and positive affect between depressed and healthy control participants.</p>
<p>Administering the NDRI-antidepressant drug bupropion was found to normalise initially aberrant neural activation during reward processing in MDD patients compared to their baseline measures and activation clusters obtained in healthy volunteers. Given the widely reported difficulty in the treatment of reward-related impairments with SSRIs, studying bupropion’s effects on neural activation during reward processing contributes to our understanding of alternative therapeutic options for alleviating maladaptive cognition associated with anhedonic MDD aside from those targeting the serotonin system. The gained insights may thus help inform the development and implementation of more precise and efficacious pharmacological interventions used for treating symptoms of anhedonia in clinical depression. Methodological strengths as well as possible limitations to the findings obtained in this study are discussed.</p>
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