Investigating functional connectivity differences during food vs. monetary reward processing across appetitive...

Reward processing deficits are prominent in major depressive disorder (MDD) and contribute to appetitive phenotypes: hyperphagic (HyperMDD) and hypophagic (HypoMDD). However, few studies have examined neurobiological processes underlying these phenotypes, and whether they stem from aberrant responsivity specific to food or rewards more broadly. This study probed group differences in functional connectivity during anticipation and outcome phases of food vs. monetary rewards across appetitive MDD phenotypes. 14 unmedicated HyperMDDs, 20 unmedicated HypoMDDs, and 36 healthy controls completed food and monetary incentive delay tasks while undergoing fMRI. Psychophysiological interaction analyses examined functional connectivity changes during relevant task conditions/reward processing components: anticipation, successful reward outcome, and failed reward outcomes. Findings revealed dissociable patterns of fronto-striatal and salience network connectivity during anticipatory reward processing among groups, reflecting differential top-down control of food versus monetary cues. HypoMDD was associated with heightened connectivity to food cues and negative connectivity to monetary cues, while HyperMDD exhibited the opposite patterns. MDD groups also differed in connectivity during reward outcome: HypoMDD demonstrated increased functional connectivity for successful food outcome and reduced functional connectivity for successful money outcome whereas HyperMDD demonstrated reduced connectivity during successful food outcome and increased connectivity during successful money reward outcome. For failed reward outcomes, only HyperMDD demonstrated reduced connectivity for failed food outcomes, and increased connectivity for failed money outcomes. These findings suggest that appetitive MDD phenotypes are distinguished by opposing circuitry profiles that bias responsivity toward food versus monetary rewards, patterns that may help guide the development of phenotype- and reward-specific interventions.