AbstractAnhedonia – a diminished interest or pleasure in activities - is a core self-reported symptom of depression which is poorly understood and often resistant to conventional treatments. Advances in preclinical neuroscience suggest that anhedonia may be due to impairments in one or more sub-components of reward processing: motivation, sensitivity and/or learning. However, the precise deficits remain elusive. This thesis contributes to understanding the relationship between anhedonia and reward-related behaviour by (1) developing novel methods to assess sub-components of reward processing and (2) examining multiple aspects of reward processing using a battery of behavioural tasks in a non-clinical population with higher levels of anhedonia and in a depressed population.
We provide proof-of-concept for two new behavioural paradigms designed to assess: reward motivation (physical effort exerted for reward: Joystick-Operated Runway Task; JORT) and reward learning and memory (based on a procedurally similar rodent task). Using a battery of tasks based on rodent assays, we found evidence that different components of reward may also be dissociable in humans. In a non-clinical population, higher levels of anhedonia were associated with reduced sensitivity to detect reward (Sweet Taste Test) and aberrant effort-based decision-making (Effort Expenditure for Rewards Task). Interestingly, people who had reduced sensitivity did not also display aberrant effort-based decision-making lending support for the presence of sub-groups. We did not find evidence of reduced motivation on a simple effort-for-reward task (JORT). In the depressed population, we did not find clear evidence of dysfunctional reward processing on any paradigms. However, this study is a preliminary study (due to COVID-19) and requires further follow-up before strong conclusions can be drawn.
In summary, our findings support the hypothesis that anhedonia is a heterogeneous symptom. Going forward, there is a critical need for the development and validation of novel translational assays and for further probing of anhedonia in clinical populations.
|Date of Award||24 Jun 2021|
|Supervisor||Ian S Penton-Voak (Supervisor), Marcus R Munafo (Supervisor), Conor J Houghton (Supervisor) & Emma S J Robinson (Supervisor)|