Major depressive disorder (MDD) is characterized by changes in appetite and body weight as well as blunted reward sensitivity ('anhedonia'). However, it is not well understood which mechanisms are driving changes in reward sensitivity, specifically regarding food. Here, we used a sample of 117 participants (54 patients with MDD; 63 healthy control participants, HCP) who completed a food cue reactivity (FCR) task with ratings of wanting and liking for 60 food and 20 non-food items. To evaluate which components of the food may contribute to altered ratings in depression, we tested for associations with macronutrients of the depicted items. In line with previous studies, we found reduced ratings of food wanting (p = .003), but not liking (p = .23) in patients with MDD compared to matched HCPs. Adding macronutrient composition to the models of wanting and liking substantially improved their fit (ps < .001). Compared to carbohydrate-rich foods, patients with MDD reported lower liking and wanting ratings for high-fat and high-protein foods. Moreover, patients with MDD showed weaker correlations in their preferences for carbohydrate- versus fat- or protein-rich foods (ps < .001), pointing to potential disturbances in metabolic signaling. To conclude, our results suggest that depression-related alterations in food reward ratings are more specific to the macronutrient composition of the food than previously anticipated, hinting at disturbances in gut-brain signaling. These findings raise the intriguing question whether interventions targeting the gut could help normalize aberrant reward signals for foods rich in fat or protein.

JK works as a study therapist in a multicenter phase IIb study by Beckley Psychtech Ltd on 5-MeO-DMT in patients with MDD, unrelated to this investigation. JK did not receive any financial compensation from the company. MW is a member of the following advisory boards and gave presentations to the following companies: Bayer AG, Germany; Boehringer Ingelheim, Germany; Novartis, Perception Neuroscience, HMNC and Biologische Heilmittel Heel GmbH, Germany. MW has further conducted studies with institutional research support from HEEL and Janssen Pharmaceutical Research for a clinical trial (IIT) on ketamine in patients with MDD, unrelated to this investigation. MW did not receive any financial compensation from the companies mentioned above. All other authors report no biomedical financial interests or other potential conflicts of interest.

https://clinicaltrials.gov/study/NCT05318924

The study was supported by the German Research Foundation (DFG), KR 4555/7-1, KR 4555/9-1, KR 4555/10-1, and & WA 2673/15-1.

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Ethics committee/IRB of University of Tuebingen, Faculty of Medicine gave ethical approval for this work

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