Levels of acylated and deacylated ghrelin are elevated in unmedicated patients with major depressive disorder and obesity: a cross-sectional study

Major depressive disorder (MDD) frequently co-occurs with obesity, suggesting shared neuroendocrine mechanisms. Ghrelin, a hormone involved in appetite regulation, stress response, and reward processing, has been proposed as a biological link between metabolic and mood disorders. However, previous studies have reported inconsistent findings, and most assessed only total ghrelin rather than its biologically distinct fractions. This cross-sectional study examined circulating concentrations of acylated and deacylated ghrelin in unmedicated (≥ 12 months) patients with MDD and comorbid obesity compared with non-depressed controls with obesity, matched by sex, age, and BMI. Sixty-two adults were included (31 with MDD and 31 controls), and MDD diagnosis was confirmed using the MINI-International Neuropsychiatric Interview. Fasting plasma ghrelin fractions were measured using ELISA under standardised preanalytical conditions. Participants with MDD exhibited significantly higher acylated (p < 0.001) and deacylated (p = 0.007) ghrelin concentrations than controls. In multivariable general linear models adjusted for sex, age, and BMI, MDD remained an independent predictor of both acylated (F(1,56) = 17.17, p < 0.001) and deacylated (F(1,56) = 6.93, p = 0.011) ghrelin, with a stronger effect observed for the biologically active, acylated form. The acyl-to-deacyl ghrelin ratio did not differ significantly between groups, suggesting increased overall ghrelin secretion rather than a selective shift in acylation. The persistence of ghrelin elevation within a metabolic state physiologically associated with ghrelin suppression supports the involvement of the ghrelin system in MDD pathophysiology.