Abstract/Summary

Anhedonia, clinically referred to as the loss of interest and/or pleasure, is a core symptom of Major Depressive Disorder (MDD). Although this criterion acknowledges impairments in motivational and consummatory domains, it is unclear how each aspect contributes to MDD. Examining this may assist with the development of more effective treatments, which is essential given that selective serotonin reuptake inhibitors (SSRIs) are ineffective at treating anhedonia. Intriguingly, it has been proposed that catecholaminergic antidepressants might be more suitable treatments for anhedonia in MDD. However, few empirical studies have been conducted in humans to examine this notion. Three studies are included in this thesis. The first study investigated what aspects of reward processing are dysfunctional in individuals with high depression symptoms (HDS), using a novel progressive ratio task and explicit measures of wanting, anticipated pleasure, liking and intensity. We identified that individuals with HDS have deficits in accurately anticipating pleasure and a subset of HDS volunteers underestimate their performance. Interestingly, we did not observe impairments in experiencing pleasure to, or expending effort for, a pleasant taste. Our results not only contribute to the understanding of what reward-related aspects are impaired in individuals experiencing HDS, but they also have important methodological implications regarding how anhedonia is researched. Studies two and three were the first to examine how two catecholaminergic antidepressants, bupropion and agomelatine, affect reward and aversion anticipation, effort and consummation in the healthy human brain. We found that bupropion increased brain activity during both reward and aversion processing, and that agomelatine enhanced neural activity during aversion processing. Our findings may help explain why catecholaminergic antidepressants might be more effective treatments for anhedonia and emotional blunting, compared to SSRIs. Taken together, this body of work provides valuable insight into the prospect of developing more personalised treatments for MDD, based on symptoms as opposed to diagnosis alone.