Ghrelin hormone linked to better mood after fasting in depressed patients

A recent study has shed light on how short-term fasting might improve mood in individuals with major depressive disorder. The research focused on the role of ghrelin, a hormone produced in the stomach, in influencing mood and appetite. The findings, published in the Journal of Psychiatric Research, indicate that higher levels of ghrelin after fasting are associated with an improved mood, particularly in those with depression who are not on medication.

Major depressive disorder is a pervasive mental health condition characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in most activities. These symptoms significantly impair daily functioning and quality of life.

The study was motivated by the growing interest in how metabolic signals from the body, particularly from the gut, might influence mental health. Ghrelin, a hormone produced in the stomach, has been shown to play a role in regulating appetite and energy balance. However, recent research suggests that ghrelin may also affect mood and stress responses.

Previous studies on ghrelin’s role in depression have yielded mixed results, with some indicating that higher ghrelin levels could improve mood, while others found no significant effects. Given this inconsistency, the researchers aimed to explore whether ghrelin levels, influenced by short-term fasting, could have a mood-enhancing effect in individuals with major depressive disorder.

“We know that hunger exerts acute effects on motivation and mood,” said study author Nils B. Kroemer, a professor at the University of Bonn and group leader at the University of Tübingen. “Although we often associate hunger with a greater motivation to seek rewards and a negative mood (‘hangry’), fasting interventions have been shown to elicit antidepressive effects. Consequently, we were interested in the potential modulatory role of circulating levels of ghrelin, which is synthesized in the stomach, particularly when the stomach is empty.”

The study involved 103 participants, including 52 patients with depression and 51 healthy control participants. Participants were aged between 20 and 50 years and had a body mass index within the normal range. Those with severe mental disorders, eating disorders, or significant medical conditions were excluded.

Participants underwent two laboratory sessions. In the first session, they completed various questionnaires to assess their demographics, eating behavior, physical activity, and symptoms of depression. The severity of depression was measured using the Beck Depression Inventory, and negative affectivity was assessed using the State-Trait Anxiety Inventory.

For the second session, participants fasted overnight for 12 hours and then visited the laboratory, where blood samples were collected to measure ghrelin levels. They also reported their feelings of hunger, satiety, thirst, fatigue, and mood using visual analog scales. The blood samples were analyzed for acyl and des-acyl ghrelin levels.

The researchers found that higher levels of acyl ghrelin, the active form of the hormone, were associated with an improved mood. This effect was more pronounced in patients with depression compared to healthy control participants. Specifically, patients with higher levels of acyl ghrelin reported less negative affect and more positive affect.

“We show that higher levels of ghrelin after an overnight fast are associated with an improved mood in both healthy people and patients with depression,” Kroemer told PsyPost. “These results suggest that the mood-enhancing effects of hunger could be linked to its motivational effects. It is known that ghrelin also facilitates motivation by increasing dopamine release in the brain. A better understanding of how signals from the gut may improve mood may lead to more effective treatments for depression.”

The association between ghrelin and mood was stronger in patients with depression who were not taking antidepressant medication. This suggests that antidepressants might interfere with the mood-enhancing effects of ghrelin. The researchers also found that the mood improvement was not limited to specific mood items but was generally associated with an overall better mood state.

“It was interesting to see that higher levels of ghrelin were associated with an improved mood, even though participants did not feel more hungry,” Kroemer explained. “The best explanation for this discrepancy is that most participants were very hungry, masking medium-sized differences in subjective feelings of hunger while there was no such ceiling effect for mood.”

The research underscores the importance of considering gut-derived signals in the treatment of depression. But there are some caveats to consider. For instance, the study focused on short-term fasting, and longer fasting or weight loss interventions could yield different insights. Additionally, the researchers only measured endogenous levels of ghrelin and did not use experimental administration to confirm its effects on mood.

“Fasting leads to a cascade of hormonal changes,” Kroemer noted. “Although our focus on ghrelin was theory-driven, many other changes in circulating hormones could contribute to mood enhancements. Consequently, experimental designs with an administration of ghrelin are necessary to conclusively demonstrate its mood-enhancing effect. These studies are still ongoing.”

“Our long-term vision is to learn from the modulatory effects of bodily signals to improve the treatment of depression,” Kroemer said. “For example, we know that hunger can exert rapid and powerful effects on motivation and mood, but we do not fully understand how to capitalize on such bodily signals to achieve larger clinically relevant effects over long periods of treatment. In our opinion, targeting the gut-brain axis appears very promising to achieve meaningful improvements in the effectiveness of treatments.”

The study, “Ghrelin is associated with an elevated mood after an overnight fast in depression,” was authored by Rauda Fahed, Corinna Schulz, Johannes Klaus, Sabine Ellinger, Martin Walter, and Nils B. Kroemer.