How gut hormones shape reward: A systematic review of the role of ghrelin and GLP-1 in human fMRI

Schulz, Corinna; Vezzani, Cecilia; Kroemer, Nils B.

doi:10.1016/j.physbeh.2023.114111

Cited by 10 publications

(10 citation statements)

References 139 publications

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“…According to a narrow definition of homeostatic function, one may speculate that surges in ghrelin appear in parallel to negative mood states which encourage food-seeking behavior to re-balance the energy budget of the organism (Yanagi et al, 2018, Keramati and Gutkin, 2014). In contrast, the alleged allostatic function is in line with a mood-enhancing effect that promotes food-seeking behavior and approach by tuning reward responsivity (Schulz et al, 2023b). Hence, it is conceivable that mood state shows stronger associations with fasting levels of ghrelin while associations with metabolic state might be larger when participants are neither hungry, nor full.…”

Section: Discussionmentioning

confidence: 99%

“…In line with this interpretation, the growth hormone secretagogue receptor type 1a receptor as the primary target of ghrelin is not only expressed in the hypothalamus. Instead, it is widely distributed across the brain, including the hippocampus, substantia nigra, ventral tegmental area, and raphe nuclei (Hattori et al, 2001), and involved in the regulation of a broad range of behavior and cognition, such as memory formation, reward processing, impulsivity, anxiety, and stress vulnerability (Schulz et al, 2023b). Overall, ghrelin plays an important role in promoting appetitive behavior according to metabolic needs through facilitating anticipatory behavior.…”

Section: Introductionmentioning

confidence: 99%

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Ghrelin is associated with an elevated mood after an overnight fast in depression

Fahed,

Schulz,

Klaus

et al. 2023

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BackgroundMajor depressive disorder (MDD) comprises subtypes with distinct symptom profiles. For example, patients with melancholic and atypical MDD differ in the direction of appetite and body weight changes as well as mood reactivity. Despite reported links to altered energy metabolism, the role of circulating neuropeptides from the gut in modulating such symptoms remains largely elusive.MethodsWe collected data from 103 participants, including 51 patients with MDD and 52 healthy control participants (HCP). After an overnight fast, we measured blood levels of (acyl and des-acyl) ghrelin and participants reported their current metabolic and mood states using visual analog scales (VAS). Furthermore, they completed symptom-related questionnaires (i.e., STAI-T).ResultsPatients with atypical versus melancholic MDD reported less negative affect (p= .025). Higher levels of acyl ghrelin (corrected for BMI) were associated with improved mood (p= .012), specifically in patients with MDD. These associations of ghrelin were not mood-item specific and exceeded correlations with trait markers of negative affectivity. In contrast to associations with mood state, higher levels of ghrelin were not associated with increased hunger per se or changes in appetite in patients with MDD.LimitationsThe study is limited by the cross-sectional design without an intervention.ConclusionsOur results reveal potentially mood-enhancing effects of ghrelin in fasting individuals that exceed associations with metabolic state ratings. These associations with circulating neuropeptides might help explain anti-depressive effects of fasting interventions and could complement conventional treatments in patients with melancholic MDD.Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ghrelin is associated with an elevated mood after an overnight fast in depression

Fahed,

Schulz,

Klaus

et al. 2023

Preprint

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“…An improved distinction between failing to seek pleasurable activities and not enjoying them holds actionable implications for treating anhedonia as a cardinal symptom of MDD (Husain & Roiser, 2018; Treadway & Zald, 2011). Here, we combined comprehensive clinical, behavioral, and metabolic assessments to localize reward dysfunction in MDD and gauge the potential for interventions targeting the gut-brain axis (Decarie-Spain & Kanoski, 2021; Geisler & Hayes, 2023; Schulz et al, 2023; Stouffer et al, 2015). First, we show that patients with MDD and anhedonia primarily experience reduced anticipatory wanting for food rewards.…”

Section: Discussionmentioning

confidence: 99%

“…By combining precision-oriented clinical and behavioral assessments with metabolic profiling, our study illustrates the potential of metabolic hormones to modulate reward responses (S. Liu & Borgland, 2015; Menzies et al, 2012; Schulz et al, 2023). In line with the comorbidity between MDD and type 2 diabetes (Kullmann et al, 2016), lower insulin sensitivity and higher fasting glucose levels were strongly associated with anhedonia.…”

Section: Discussionmentioning

confidence: 99%

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Blunted anticipation but not consummation of food rewards in depression

Schulz,

Klaus,

Peglow

et al. 2024

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Anhedonia is a core symptom of major depressive disorder (MDD) and is associated with worse treatment outcomes. 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. Since evidence that metabolic hormones influence reward processing accumulates, investigating their role in alleviating reward deficits may provide crucial insights. To address these gaps, we conducted a study with 103 participants, including 52 patients with MDD and 51 healthy control participants (HCPs). After overnight fasting, blood samples were collected to determine the concentration of ghrelin, glucose, insulin, and triglycerides in serum/plasma. Participants then completed a taste test with repeated ratings of wanting and liking for snacks before and after tasting, allowing to gradually move from reward anticipation to consummation. Patients with MDD showed decreased wanting (p = .046) but not liking for food rewards during visual anticipation. However, these group differences disappeared once patients inspected and tasted the food as patients increased wanting relative to HCPs (p = .004), providing strong evidence against the hypothesis of a consummatory deficit (Bayes Factors > 9). In contrast to a narrow definition of anhedonia, higher scores on the Snaith-Hamilton Pleasure Scale (SHAPS) were more strongly associated with reduced anticipatory food wanting (p = .010), not liking, and more pronounced increases in wanting with reward proximity (p = .037). Across groups and phases, acyl ghrelin was associated with higher wanting and liking ratings, while poor glycemic control was associated with anhedonia. Overall, our study demonstrates that MDD and its cardinal symptom, anhedonia, are associated with a reduced anticipation of rewards rather than an impaired ability to experience pleasure. Since ghrelin was associated with elevated reward ratings, targeting the gut-brain axis could be a promising avenue for treating reward deficits.

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