Blunted anticipation but not consummation of food rewards in depression

BackgroundAnhedonia is a core symptom of major depressive disorder (MDD). While its narrow definition as a hedonic or consummatory deficit evolved to encompass anticipatory and motivational reward facets, it remains unclear where reward deficits manifest. As evidence accumulates for metabolic hormones affecting reward processing, studying their role in mitigating reward deficits could yield crucial insights. Here, we compare food reward ratings between patients with MDD and healthy control participants (HCPs) from anticipation to consummation and evaluate associations with anhedonia and metabolic parameters. MethodsWe conducted a cross-sectional study with 103 participants, including 52 patients with MDD and 51 HCPs. After overnight fasting, blood samples were collected to determine levels of ghrelin, glucose, insulin, and triglycerides. Participants completed a taste test, providing repeated ratings of wanting and liking, gradually moving from reward anticipation to consummation. FindingsPatients with MDD showed decreased wanting (p = .046) but not liking for food rewards during visual anticipation. However, once food was inspected and tasted, patients increased wanting relative to HCPs (p = .004), providing strong evidence against a consummatory deficit (Bayes Factors > 9). In contrast to a narrow definition of anhedonia, higher scores on the Snaith-Hamilton Pleasure Scale were associated with reduced anticipatory food wanting (p = .010) and more pronounced increases in wanting with reward proximity (p = .037). Acyl ghrelin was associated with higher food reward ratings, while poor glycemic control was linked to symptoms of anhedonia. InterpretationOur study demonstrates that MDD and anhedonia are associated with reduced anticipation of rewards rather than consummatory pleasure deficits. Notably, ghrelins association with elevated reward ratings implicates the gut-brain axis as a potential target for treating reward deficits in MDD. FundingDFG KR 4555/7-1, KR 4555/9-1, KR 4555/10-1, and & WA 2673/15-1 Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/24304849v2_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@1320760org.highwire.dtl.DTLVardef@18244c1org.highwire.dtl.DTLVardef@16fe4e8org.highwire.dtl.DTLVardef@11d630f_HPS_FORMAT_FIGEXP M_FIG C_FIG Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAnhedonia, a core symptom of depression, has traditionally been conceptualised as a deficit in consummatory pleasure. However, recent definitions have expanded to include anticipatory and motivational aspects of reward processing. Despite this evolution, experimental studies that systematically investigate these facets are lacking, with most animal models of anhedonia focusing on consummatory deficits. Added value of this studyThis study contributes novel insights by demonstrating that patients with Major Depressive Disorder (MDD) and anhedonia exhibit reduced anticipatory wanting but not consummatory liking for food rewards. Bayesian hypothesis testing indicates strong evidence against the hypothesis of a consummatory deficit, suggesting instead a primary impairment in reward anticipation in anhedonia. Additionally, the study highlights the association between peripheral metabolic hormones and specific aspects of reward function, shedding light on the underlying mechanisms of anhedonia. Notably, lower insulin sensitivity and higher glucose levels were linked to symptoms of anhedonia, while elevated fasting acyl ghrelin levels were associated with increased food reward ratings. Implications of all the available evidenceThe findings suggest that deficits in anticipatory wanting, rather than consummatory pleasure, may underlie anhedonia in MDD. This distinction has important implications for treatment strategies, as targeting incentive motivation and reward anticipation could be more effective in alleviating anhedonia symptoms. The observation that wanting improves with the proximity of the reward indicates a potential therapeutic approach focusing on enhancing reward proximity. Furthermore, the association between ghrelin and reward ratings suggests a role for gut-brain signalling in motivational symptoms, particularly in cases of depression involving loss of appetite and weight.