Mediation on the association between HPA axis hyperactivity and cognitive impairment by abnormal hippocampal function...

People who have lost their only child (PLOCs) in China exhibit chronic hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and a range of abnormal symptoms. The hippocampus may serve as a potential mediator between HPA axis dysregulation and the symptoms. However, the mechanisms underlying these developments remain unclear.

Functional magnetic resonance imaging data were collected from 51 PLOCs and 29 healthy individuals. A linear regression model was utilized to explore the interrelationships between blood cortisol levels, hippocampal structure and function, and abnormal symptoms. Additionally, a mediation effect model was employed to examine the influence of the hippocampus on the relationship between blood cortisol levels and abnormal symptoms.

Compared with the healthy controls, the PLOCs had significantly reduced gray matter volume in the hippocampus, and increased degree centrality (DC) values in the right hippocampus. Additionally, the PLOCs exhibited more severe cognitive impairment and poorer immediate memory ability, which were significantly negatively correlated with blood cortisol levels. The mediation effect model revealed specific effects of DC values in the right hippocampus on the association between blood cortisol levels and MMSE scores and immediate memory scores.

Cross-sectional design of this study could not demonstrate the causality.

The alterations in DC in the right hippocampus substantially mediated the relationship between HPA axis dysregulation and cognitive impairment in the sampled Chinese PLOCs. High blood cortisol levels led to cognitive impairment by causing changes in right hippocampal function.