Resting-state functional connectivity in Autoimmune Addison's Disease

Abstract

Patients with autoimmune Addison’s disease (AAD) are unable to produce glucocorticoids (GCs), mineralocorticoids (MCs) and androgens from the adrenal cortex and therefore require life-long treatment with GCs and MCs. Due to the sensitivity of the brain to cortisol and androgens, brain function might be affected in patients, as the replacement regime cannot mimic the natural rhythmicity of hormonal secretion. Alterations in brain function might predispose to cognitive or mood disturbances. The present study investigated resting-state functional connectivity (rs-fc) in patients with AAD. Resting-state fMRI data was collected from 57 (33 females) patients with AAD and 69 (39 females) control participants, aged 19-43 years. Resting-state brain networks were identified with independent component analysis (FSL MELODIC). Dual-regression analysis was applied to test for group differences in rs-fc in these networks. Within the patient group we tested the association between rs-fc and glucocorticoid replacement dose in mg/m2/day. Significant clusters were identified with threshold free cluster enhancement and considered to be significant at p<0.05. Patients with AAD had increased fc in the bilateral medial orbitofrontal cortex compared to controls. A higher glucocorticoid replacement dose was associated with stronger functional connectivity in several networks in the prefrontal cortex in patients. AAD seems to be associated with stronger fc at rest in an area known to contain a high density of GC receptors. Further research is needed to investigate if this increased activity is part of an adaptive mechanism or if it predisposes to disturbances in mood and executive functioning.