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

Abstract

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

Blunted anticipation but not consummation of food rewards in depression

“…Notably, neither depression nor anhedonia was characterized by differences in perceived taste (SI2), further corroborating that depression and anhedonia are not associated with altered taste perception per se. As reported previously by our group, patients with MDD did not differ from HCPs in subjective ratings of metabolic state (i.e., hunger, fullness (Fahed et al, 2023)).…”

“…Adding depression severity to the model did not alter these associations (Pillai’s Trace V = .07, F (2, 89) = 3.47, p = .035). As reported previously by our group, ghrelin was not associated with subjective ratings of metabolic state (Fahed et al, 2023) and adding subjective state ratings to the models did not qualitatively alter the results. Notably, higher levels of acyl ghrelin reduced the correspondence between wanting and liking ratings ( b likingxGhrelin = -.23, p = .005), pointing to a potential shift in the integration of incentive salience and hedonics, such that with higher acyl ghrelin levels less liked food rewards are wanted more (Fig.…”

“…A stronger contribution of ghrelin to heightened reward function might be of high clinical relevance for melancholic MDD because this group showed the anticipatory deficit in food wanting. Melancholic MDD is associated with HPA hyperactivity (Lamers et al, 2013), and preclinical studies have shown that ghrelin regulates stress-induced anxious behavior via the HPA axis (Spencer, 2012), supporting a link between homeostatic signals and affective states (Fahed et al, 2023) . Such mechanisms may contribute to the anti-depressive effects of fasting interventions (Berthelot et al, 2021; Murta et al, 2023).…”

“…The sample consisted of 103 participants ( M Age = 29.3 ± 7.3 years, M BMI = 23.6 ± 3.3 kg/m 2 ; Table 1) from an ongoing study on the gut-brain axis in depression (https://clinicaltrials.gov/study/NCT05318924; Fahed et al, 2023), including 52 participants with MDD, and 51 healthy control participants (HCP), who had never experienced a depressive episode. All individuals interested in participating were screened for eligibility by telephone.…”

“…Blood samples for the determination of acyl and des-acyl ghrelin (EDTA plasma), glucose (fluoride EDTA plasma), insulin (serum), and triglycerides (lithium heparinized plasma) were taken upon arrival by using Monovettes (Sarstedt, Nümbrecht, Germany). Afterwards, information was recorded on the participant’s last meal and drink, on anthropometric data (e.g., body weight and height), and, in the case of female participants, on the menstrual cycle phase (Fahed et al, 2023). Then, participants started with a battery of reward-related tasks.…”