Lower ghrelin in depression might be connected to the absence of psychotic-like experiences

Major depressive disorder (MDD) prevalence increases every year, with approximately 30% of patients remaining treatment-resistant. Ghrelin, a stomach-derived appetite-stimulating hormone, has been implicated in mood disorders, stress response, sleep-cycle regulation, reward behaviour, and neuroplasticity. However, findings in humans remain unconclusive, with reports of higher, unchanged, or lowered ghrelin concentration in patients with MDD. Psychotic-like experiences (PLEs), which are more common in the course of depression, might contribute to reported inconsistencies. This study aims to assess serum total ghrelin concentrations in individuals with depressive symptoms and investigate whether the presence of PLEs modulates the relationship. A cross-sectional study was conducted among 56 individuals screened for depressive symptoms (with patient health questionnaire-9 (PHQ-9)) and presence of PLEs in the past year (with prodromal questionnaire-16 (PQ-16)). Serum total ghrelin levels were determined by enzyme-linked immunosorbent assay (ELISA). The relationship between PHQ-9 scores and total ghrelin was analysed using linear regression and analysis of covariates (ANCOVA) when controlled for sex, age, and body mass index. Initially, depressive symptoms predicted lower ghrelin levels (P = 0.044). However, the model lost its significance when adjusted for covariates (P = 0.100). Pairwise comparisons revealed lower total ghrelin among patients with MDD but without PLEs when compared to controls (P = 0.037). No significant differences were observed within patients with a history of PLEs. This study provides preliminary evidence that PLEs modulate ghrelin secretion in patients with MDD symptoms. Further studies with larger samples are needed to clarify ghrelin's role in MDD pathophysiology.