The sex-specific relationship of ghrelin and cognition in Chinese han first-episode drug-naive major depressive disorder

Abstract

In major depressive disorder (MDD), alterations in ghrelin levels and cognitive impairment coexist, yet their association has remained largely elusive. This study aimed to investigate the association between ghrelin levels and cognition in both MDD patients and healthy controls (HCs) while also exploring sex-specific differences in this correlation. A total of 155 Chinese Han subjects, including 90 first-episode drug-naive MDD patients and 65 HCs, were enrolled. Ghrelin levels were measured using ELISA kits, and neurocognitive assessments were conducted using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). MDD patients exhibited significantly higher ghrelin levels and lower cognitive scores of RBANS compared to HCs. However, there was no significant correlation between ghrelin levels and cognitive function in both MDD patients and HCs. Exploratory analyses revealed sex-specific associations between ghrelin and cognitive function, particularly in MDD patients. Females with MDD showed distinct patterns of association between ghrelin levels and cognitive domains such as attention and language, which were not observed in healthy controls or male MDD patients. The relationship between ghrelin and cognition only existed in MDD patients, not in the HCs, and there was a sex-specific difference in this association. Further research on the mechanism of ghrelin in the cognitive function of MDD should focus on sex differences.

Keywords: Cognitive function; Ghrelin; Major depressive disorder.