title: Hippocampal volume in healthy controls given 3-day stress doses of hydrocortisone.
abstract: In animal models, corticosterone elevations are associated with hippocampal changes that can be prevented with phenytoin. In humans, Cushing's syndrome and long-term prescription corticosteroid use are associated with a reduction in the hippocampal volume. However, little is known about the effects of short-term corticosteroid administration on the hippocampus. The current report examines changes in the hippocampal volume during a brief hydrocortisone exposure and whether volumetric changes can be blocked by phenytoin. A randomized, double-blind, placebo-controlled, within-subject crossover study was conducted in healthy adults (n=17). Participants received hydrocortisone (160 mg/day)/placebo, phenytoin/placebo, both medications together, or placebo/placebo, with 21-day washouts between the conditions. Structural MRI scans and cortisol levels were obtained following each medication condition. No significant difference in the total brain volume was observed with hydrocortisone. However, hydrocortisone was associated with a significant 1.69% reduction in the total hippocampal volume compared with placebo. Phenytoin blocked the volume reduction associated with hydrocortisone. Reduction in hippocampal volume correlated with the change in cortisol levels (r=-0.58, P=0.03). To our knowledge, this is the first report of structural hippocampal changes with brief corticosteroid exposure. The correlation between the change in hippocampal volume and cortisol level suggests that the volume changes are related to cortisol elevation. Although the findings from this pilot study need replication, they suggest that the reductions in hippocampal volume occur even during brief exposure to corticosteroids, and that hippocampal changes can, as in animal models, be blocked by phenytoin. The results may have implications both for understanding the response of the hippocampus to stress as well as for patients receiving prescription corticosteroids.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: E Sherwood
authors.initials: ES
authors.lastname: Brown
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Haekyung
authors.initials: H
authors.lastname: Jeon-Slaughter
authors.affiliation: The Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Rhoda
authors.initials: R
authors.lastname: Jamadar
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Sruthy
authors.initials: S
authors.lastname: Issac
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Mujeeb
authors.initials: M
authors.lastname: Shad
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Daren
authors.initials: D
authors.lastname: Denniston
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Tamminga
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Alyson
authors.initials: A
authors.lastname: Nakamura
authors.affiliation: The Advanced Imaging Research Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Binu P
authors.initials: BP
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D010672:Phenytoin / Q000008:administration & dosage; D010865:Pilot Projects; D013997:Time Factors; D055815:Young Adult
chemical_list: D002491:Central Nervous System Agents; D010672:Phenytoin; D006854:Hydrocortisone