Effects of cortisol on hippocampal subfields volumes and memory performance in healthy control subjects and patients with major depressive disorder

Abstract Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis in major depressive disorder (MDD) is among the most consistently replicated biological findings in psychiatry. Magnetic resonance imaging (MRI) studies have consistently demonstrated that hippocampal (HC) volume is decreased in patients with MDD. The improved spatial resolution of high field strength MRI has recently enabled measurements of HC subfield volumes in vivo. The main goal of the present study was to examine the relationship between cortisol concentrations over a day and HC subfield volumes in patients with MDD compared to healthy controls and to investigate whether diurnal cortisol measures are related to memory performance. Fourteen MDD patients with moderate or severe episodes were recruited, together with 14 healthy controls. Imaging was performed using a 4.7 T whole-body imaging system. HC subfields and subregions were segmented manually using previously defined protocol. Memory performance was assessed using the Wechsler Memory Scale IV. The salivary cortisol levels were measured over the course of one day. We found that cortisol awakening response to 8 h (CAR-8 h) was higher in MDD patients compared to controls and that this increase in CAR-8 h in MDD patients correlated negatively with left total Cornu Ammonis (CA)1–3 and left HC head volume. In healthy controls mean cortisol levels were negatively associated with right total CA1–3, right HC head, and right total HC volume. In addition, in healthy controls higher CAR-8 h was related to worse performance on the immediate content memory. These results provide the first in vivo evidence of the negative associations between cortisol level, CA1-3 HC subfield volume and memory performance in patients with MDD and healthy controls.