Cortical thickness abnormalities in long-term remitted Cushing's disease

Long-term remitted Cushing's disease (LTRCD) patients commonly continue to present persistent psychological and cognitive deficits, and alterations in brain function and structure. Although previous studies have conducted gray matter volume analyses, assessing cortical thickness and surface area of LTRCD patients may offer further insight into the neuroanatomical substrates of Cushing's disease. Structural 3T magnetic resonance images were obtained from 25 LTRCD patients, and 25 age-, gender-, and education-matched healthy controls (HCs). T1-weighted images were segmented using FreeSurfer software to extract mean cortical thickness and surface area values of 68 cortical gray matter regions and two whole hemispheres. Paired sample t tests explored differences between the anterior cingulate cortex (ACC; region of interest), and the whole brain. Validated scales assessed psychiatric symptomatology, self-reported cognitive functioning, and disease severity. After correction for multiple comparisons, ROI analyses indicated that LTRCD-patients showed reduced cortical thickness of the left caudal ACC and the right rostral ACC compared to HCs. Whole-brain analyses indicated thinner cortices of the left caudal ACC, left cuneus, left posterior cingulate cortex, right rostral ACC, and bilateral precuneus compared to HCs. No cortical surface area differences were identified. Cortical thickness of the left caudal ACC and left cuneus were inversely associated with anxiety symptoms, depressive symptoms, and disease duration, although certain associations did not persist after correction for multiple testing. In six of 68 regions examined, LTRCD patients had reduced cortical thickness in comparison to HCs. Cortical thickness of the left caudal ACC was inversely associated with disease duration. This suggests that prolonged and excessive exposure to glucocorticoids may be related to cortical thinning of brain structures involved in emotional and cognitive processing.