Fasting ghrelin as mediator between obesity and depressive symptoms: a pre-registered study

Ghrelin, a hunger-related gut hormone, may contribute to higher risk of depressive symptoms in obesity. Despite animal studies suggesting antidepressant effects of circulating ghrelin, human studies remain inconclusive. Therefore, we aimed to explore the association between obesity, ghrelin serum levels, and depressive symptoms in a large population-based cohort. Assessments of the LIFE-Adult cohort (n = 6037, 18-82 years) included questionnaires to evaluate depressive symptoms (CES-D and IDS-SR), anthropometric measurements for BMI, fasting ghrelin serum levels via radioimmunoassay (n = 1089), and 3 T MRI for hippocampal volume (n = 1080). Statistical analyses were pre-registered ( https://osf.io/y7sbx ). Higher BMI predicted more frequent depressive symptoms (β = 2.033, p < 0.001) and lower fasting serum ghrelin (β = -0.622, p < 0.001). Ghrelin did not correlate with depressive symptoms in obesity (n = 263, β = 0.123, p = 0.918). Exploratory analyses revealed links between ghrelin and eating-related depressive symptoms, and that higher BMI was more strongly associated with depressive symptoms in females than males. In this large, well-characterized sample, ghrelin was not associated with overall severity of depressive symptoms in participants with obesity. Future studies using more specific ghrelin assessments and clinical samples could help clarify this relationship.