Anhedonia is a core multidimensional feature of major depressive disorder (MDD) characterized by reduced motivation and enjoyment. Anhedonia is a common residual symptom of MDD, particularly in populations with comorbid MDD and obesity (Treadway et al., 2012; Moreira et al., 2019; Nirenberg and Waters, 2006). Results from cross-sectional and longitudinal studies provide replicated evidence of the clinical overlap of obesity and MDD (Armbrecht et al., 2020). Notwithstanding the phenotypic overlap, the underlying biological substrates are not sufficiently characterized (Mulugeta et al., 2018; Mannan et al., 2016; Jung et al., 2017; Luppino et al., 2010). Notably, a point of neurological convergence observed in populations with MDD and obesity are structural and functional abnormalities in brain structures subserving reward and cognitive control, characterized by structural and functional impairments in these same brain regions (Treadway et al., 2012; Mansur et al., 2019; Sherdell et al., 2012; Yang et al., 2014; Hidese et al., 2018; Singh et al., 2019).

In populations with obesity, motivational deficits are a replicated observation, where individuals demonstrate reduced effort expenditure for reward, and diminished responsivity in motivational contexts, such as reward valuation and learning (Mansur et al., 2019; Nusslock and Alloy, 2017; Davis et al., 2007). Similarly, reduced responsiveness to motivation, positive valence, and effort for reward is present in individuals with MDD (Meehl, 2001). Results from meta-analytic studies suggest genetic similarities underlying anhedonia and reward dysfunction in obese and MDD populations (Amare et al., 2017). There are converging units of analysis that putatively subserve obesity and MDD. For example, alterations in neuroanatomy subserving reward and cognition are observed in both populations, suggesting a neurobiological nexus (Bruce et al., 2010; Reyes et al., 2020; Restivo et al., 2016). The foregoing evidence underscores the shared pathophysiological abnormalities in MDD and obesity that moderate deficits in reward circuitry, further demonstrating the impetus to investigate the role of reward processing in these patient populations.

Extant literature consists of original studies that have evaluated reward dysfunction in the context of food-related rewards, and findings suggest abnormalities in reward circuitry in individuals with obesity (Jurdak et al., 2008; Johnson and Kenny, 2010; Kube et al., 2018). However, neuroimaging studies demonstrate overlapping but differential responses to food and monetary stimuli. In particular, literature suggests differential activation in the prefrontal cortex (PFC) and the lateral orbitofrontal cortex in response to food-related stimuli compared to monetary reward (Simon et al., 2015).

Available literature suggests that disturbances in reward circuitry in populations with MDD and anhedonia are similar to deficits induced by obesity. Moreover, individuals with comorbid MDD and obesity display reduced reward salience and willingness to expend effort for a reward (Kozak and Cuthbert, 2016). However, there remains a paucity of literature investigating the patterns of response to monetary rewards in the context of reward learning, valuation, and anticipation. Furthermore, whether reward disturbances in mood and metabolic disorders are a result of a shared biosignature remains unclear (Pizzagalli et al., 2008).

There is a need to parse the specific subcomponents of reward dysfunction in individuals with obesity. As such, additional trials evaluating deficits in reward processing in individuals with obesity using validated monetary reward paradigms are needed to deepen our understanding of the association between mood disorders and obesity. Herein, we explore the neural correlates associated with reward dysfunction in populations with comorbid MDD and obesity using a validated task-based monetary reward measure (i.e., the Effort Expenditure for Rewards Task (EEfRT)) and functional magnetic resonance imaging (fMRI). Extant literature indicates reduced motivation and willingness to exert effort for monetary reward in individuals with obesity (Treadway et al., 2012; Mansur et al., 2019; Yang et al., 2014; Gill et al., 2021). The clinical trial herein aimed to explore the effects of obesity on the underlying neural mechanisms of effort-based decision-making in individuals with MDD.