Early Adverse Events, HPA Activity and Anterior Cingulate Volume in Major Depressive Disorder

Abstract

Recent findings confirm an association between major depressive disorder (MDD) and altered hypothalamic-pituitary-adrenal (HPA) axis activity, with elevated plasma cortisol concentrations. Prolonged exposure to glucocorticoids may damage brain regions that underlie negative feedback regulation of the HPA axis. While prior research relating this hypothesis to structural abnormalities in MDD has focused on the hippocampus, the anterior cingulate cortex (ACC) is also involved in HPA regulation, and has been shown to exhibit functional and structural abnormalities in MDD. The present study sought to evaluate the role of ACC morphology in relationship to early adverse events and HPA activity in MDD. Grey matter volume of the ACC, amygdala and hippocampus of 17 patients with MDD and 15 healthy controls were compared using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire, and salivary cortisol samples were acquired to evaluate HPA axis activity. Depressed patients showed structural decreases in grey-matter volume in the rostral ACC as compared to controls. Furthermore, rostral ACC volume was inversely correlated with both cortisol and early adverse events. Structural differences in the hippocampus and amygdala were not found. These findings suggest a key relationship between cingulate morphology, a history of early adverse events and current elevation of cortisol.