Non-invasive vagus nerve stimulation conditions increased invigoration and wanting in depression

Ferstl, Magdalena; Kühnel, Anne; Klaus, Johannes; Lin, Wy Ming; Kroemer, Nils B.

doi:10.1101/2023.09.28.23296284

Cited by 1 publication

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References 92 publications

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“…Such mechanisms may contribute to the anti-depressive effects of fasting interventions (Berthelot et al, 2021; Murta et al, 2023). Taken together, capitalizing on metabolic signals might provide better treatments for motivational deficits in depression (Ferstl et al, 2022, 2023).…”

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confidence: 99%

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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