The Relationship Between Cumulative Exogenous Corticosteroid Exposure and Volumes of Hippocampal Subfields and Surrounding Structures

Duc M. Nguyen, Michael A. Yassa, Nicholas J. Tustison, Jared M. Roberts, Alexandra Kulikova, Alyson Nakamura, Elena I. Ivleva, Erin A Van Enkevort, E. Sherwood Brown

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Purpose/Background Glucocorticoids are a class of hormones that include naturally occurring cortisol and corticosterone, as well as prescription drugs commonly used to manage inflammatory, autoimmune, and allergic conditions. Adverse effects, including neuropsychiatric symptoms, are common. The hippocampus appears to be especially sensitive to the effects of glucocorticoids. However, to our knowledge, no studies to date have examined hippocampal subfields in humans receiving glucocorticoids. We examined patients on chronic glucocorticoid regimens to determine relationships between dose and duration of treatment, and hippocampal subfields, and related regions volumes. Methods/Procedures The study included adult men and women receiving at least 5 mg daily of prednisone equivalents for at least 6 months. Volumes of brain regions were measured via magnetic resonance imaging. A multivariate general linear model was used for analysis, with brain volumes as dependent variables and age, sex, and cumulative corticosteroid exposure, as predictors. Findings/Results The study population consisted of 81 adult outpatients (43 male) on corticosteroids (mean dose, 7.88 mg; mean duration, 76.75 months). Cumulative glucocorticoid exposure was negatively associated with left and right hippocampal dentate gyrus/CA3 volume. In subsequent subgroup analysis, this association held true for the age group older than the median age of 46 years but not for the younger age group. Implications/Conclusions This finding is consistent with previous studies showing detrimental effects of elevated glucocorticoids on the hippocampus but further suggests that the dentate gyrus and CA3 regions are particularly vulnerable to those effects, which is consistent with animal models of chronic stress but has not been previously demonstrated in humans.

Original languageEnglish (US)
Pages (from-to)653-657
Number of pages5
JournalJournal of clinical psychopharmacology
Issue number6
StatePublished - Nov 1 2019


  • corticosteroids
  • hippocampus
  • neuroimaging

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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