Effects of Variations in Daily Cortisol Pattern and Long-Term Cortisol Output on Hippocampal Subfield Volumes in the Adult Human Brain

Abstract

Background

Animal models of adult chronic stress indicate that the cornu ammonis 1–3 (CA1–3) and dentate gyrus (DG) hippocampal subfields are most susceptible to cellular changes associated with prolonged psychogenic stressors and glucocorticoid overexposure. However, no study reported to date has examined associations between long-term cortisol output, chronic stress, and hippocampal subfield volumes in healthy adults experiencing different levels of chronic stress. The main goal of the current study was to test whether higher long-term cortisol output measured by hair cortisol concentration would be associated with atrophy of CA1–3 and DG hippocampal subfields.

Methods

We examined associations between short- and long-term cortisol output and hippocampal subfield volumes in healthy adults (N = 40). High-resolution structural magnetic resonance imaging datasets were acquired together with diurnal salivary cortisol and hair cortisol measures. Hair cortisol concentration was analyzed using the high-resolution liquid chromatography–mass spectrometry method.

Results

Higher hair cortisol concentration was associated with smaller volumes of all hippocampal subfields in the anterior hippocampus and smaller DG volumes in both the anterior and posterior hippocampus. We found that a larger increase in morning cortisol level after awakening was associated with smaller DG and CA1–3 volumes, while a smaller decrease in cortisol level in the afternoon from awakening was associated with smaller CA1–3 volume in the anterior hippocampus. The observed associations between cortisol and hippocampal subfield volumes were not predicted by individual chronic stress levels or history of childhood trauma.

Conclusions

Our results suggest that both increased hair cortisol concentration and daily cortisol fluctuations can have a negative impact on the CA1–3 and DG subfields.