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Type: Journal article
Title: Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia
Author: Ji, E.
Weickert, C.S.
Purves-Tyson, T.
White, C.
Handelsman, D.J.
Desai, R.
O'Donnell, M.
Liu, D.
Galletly, C.
Lenroot, R.
Weickert, T.W.
Citation: Psychoneuroendocrinology, 2020; 123:104916-104916
Publisher: Elsevier
Issue Date: 2020
ISSN: 0306-4530
Statement of
Ellen Ji, Cynthia Shannon Weickert, Tertia Purves-Tyson, Christopher White, David J Handelsman, Reena Desai ... et al.
Abstract: While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia.
Keywords: Schizophrenia; dehydroepiandrosterone; cortisol; hippocampus; dorsolateral prefrontal cortex; hypothalamic-pituitary-adrenal axis
Rights: © 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (
DOI: 10.1016/j.psyneuen.2020.104916
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