Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

Ellen Ji; Cynthia Shannon Weickert; Tertia Purves-Tyson; Christopher White; David J Handelsman; Reena Desai; Maryanne O'Donnell; Dennis Liu; Cherrie Galletly; Rhoshel Lenroot; Thomas W Weickert

doi:10.1016/j.psyneuen.2020.104916

Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

Psychoneuroendocrinology. 2021 Jan:123:104916. doi: 10.1016/j.psyneuen.2020.104916. Epub 2020 Oct 14.

Authors

Affiliations

¹ University of Zurich Psychiatric Hospital, Zurich, Switzerland; Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: [email protected].
² Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia; Department of Neuroscience and Physiology, Upstate Medical University, Syracuse, 13210, New York, USA.
³ Schizophrenia Research Laboratory, Neuroscience Research Australia, Sydney, NSW 2031, Australia; School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Department of Endocrinology, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
⁵ ANZAC Research Institute, University of Sydney, Concord Hospital, NSW, Australia.
⁶ School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia.
⁷ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Northern Adelaide Local Health Network, Adelaide, South Australia, Australia.
⁸ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; Northern Adelaide Local Health Network, Adelaide, South Australia, Australia; Ramsay Health Care (SA) Mental Health Services, Adelaide, South Australia, Australia.

PMID: 33169678
DOI: 10.1016/j.psyneuen.2020.104916

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: Cortisol; Dehydroepiandrosterone; Dorsolateral prefrontal cortex, Hypothalamic-pituitary-adrenal axis; Hippocampus; Schizophrenia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Case-Control Studies
Dehydroepiandrosterone* / blood
Dorsolateral Prefrontal Cortex* / pathology
Hippocampus* / pathology
Humans
Hydrocortisone* / blood
Organ Size
Schizophrenia* / blood
Schizophrenia* / physiopathology

Substances

Dehydroepiandrosterone
Hydrocortisone