The impact of endogenous cortisol exposure on hippocampal stepwise functional connectivity in Cushing's disease

SHANG Guosong; ZHANG Yanyang; XU Junpeng; LIU Bin; FENG Zhebin; HE Kunyu; YU Xinguang

doi:10.13276/j.issn.2097-1656.2025.03.010

Abstract：Objective To explore the effects of endogenous cortisol exposure on hippocampal stepwise functional connectivity(SFC),and analyze its associations with emotional and cognitive functions based on a model of Cushing's disease(CD).Methods From May 2017 to May 2024,a total of 86 CD patients and 83 healthy controls(HC)were recruited at the First Medical Center of the Chinese PLA General Hospital.Demographic data,neuroendocrine indicators,neuropsychiatric scale scores,quality of life scores,and T1-weighted MRI and resting-state functional MRI data were collected from all subjects.With hippocampus as the seed point,SFC method was used to analyze the differences of degree centrality(DC)values in functional connectivity architectures of cerebral cortex between the two groups and assess their correlations with clinical indicators.Results At the brain region level,the initial differences between the CD group and the HC group(Step 2)primarily involved the bilateral inferior frontal gyrus,left temporal lobe,right parahippocampal gyrus,and insula.As the step length increased(Steps 3-5),these abnormalities gradually extended to brain regions associated with the default mode network(DMN)and the visual network.At the brain network level,CD patients exhibited significant abnormalities in the DC values of hippocampus and limbic system network as well as DMN at specific step lengths(Steps 2-5),which showed a positive correlation with scores on emotional state assessment scales(P＜0.05).Conclusion This study reveals that abnormalities in hippocampal SFC in CD patients under endogenous cortisol exposure are associated with emotional dysfunction.This provides new insights into neuropsychiatric disorders related to cortisol exposure and offers a basis for potential intervention strategies.