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The relationship between cortisol reactivity and emotional brain function is differently moderated by childhood trauma, in bipolar disorder, schizophrenia and healthy individuals

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Abstract

Childhood trauma is a risk factor for psychotic and mood disorders that is associated with abnormal hypothalamic–pituitary–adrenal (HPA) axis function in response to stress and abnormal social brain function. Here, we aimed to determine whether childhood trauma exposure would differently moderate associations between cortisol reactivity and social brain function, among cases with schizophrenia (SZ), bipolar disorder (BD) and in healthy individuals (HC). Forty cases with SZ, 35 with BD and 34 HCs underwent functional magnetic resonance imaging while performing an emotional face-matching task. Participants completed the Childhood Trauma Questionnaire and cortisol reactivity (i.e. the slope indexing the within-subject difference between pre- and post-imaging salivary cortisol levels) was determined. The severity of childhood trauma moderated the relationship between cortisol reactivity and brain activation in the bilateral temporo-parieto-insular junctions, right middle cingulum, right pre/postcentral gyri, left cerebellum and right lingual gyrus, differently depending on the clinical group. When exposed to high levels of trauma, the cortisol slope was negatively associated with activation in these regions in HC, while the cortisol slope was positively associated with activation in these regions in SZ cases. Similarly, there were differences between the groups in how trauma severity moderated the relationship between cortisol reactivity and functional connectivity between the amygdala and dorsolateral prefrontal cortex. In addition to reflecting typical associations between cortisol reactivity and emotional brain function when not exposed to childhood trauma, these findings provide new evidence that trauma exposure disrupts these relationships in both healthy individuals and in cases with SZ or BD.

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Acknowledgements

We would like to thank the volunteers who participated in this study. We would like to acknowledge Meelah Hamilton (now deceased) Jesseca Rowland, Nicholas Vella Inika Gillis and Nicole O’Reilly for assistance with data collection and entry. We acknowledge recruitment assistance from the Australian Schizophrenia Research Bank (ASRB), which was supported by the National Health and Medical Research Council of Australia (NHMRC) Enabling Grant (No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute.

Funding

This study was funded by Project Grants from the NHMRC (APP630471 and APP1081603), and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (CE110001021). MJG was supported by the NMHRC’s R.D. Wright Biomedical Career Development Fellowship (APP1061875; 2014-17). OJW was supported by an Australian Government Research Training Program (RTP) Scholarship (administered by the University of New South Wales) and the Edward C Dunn Foundation Postgraduate Scholarship (administered by Neuroscience Research Australia; NeuRA). The funding bodies had no role in the decision to publish these results.

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  1. School of Psychiatry, University of New South Wales (UNSW), Sydney, NSW, 2052, Australia

    Yann Quidé, Leah Girshkin, Oliver J. Watkeys, Vaughan J. Carr & Melissa J. Green

  2. Neuroscience Research Australia, Randwick, NSW, Australia

    Yann Quidé, Leah Girshkin, Oliver J. Watkeys, Vaughan J. Carr & Melissa J. Green

  3. Department of Psychiatry, School of Clinical Sciences, Monash University, Clayton, VIC, Australia

    Vaughan J. Carr

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Human Research Ethics committees of the University of New South Wales (HC12384), the South East Sydney and Illawarra Area Health Service (HREC 09/081) and St Vincent’s Hospital (HREC/10/SVH/9).

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Quidé, Y., Girshkin, L., Watkeys, O.J. et al. The relationship between cortisol reactivity and emotional brain function is differently moderated by childhood trauma, in bipolar disorder, schizophrenia and healthy individuals. Eur Arch Psychiatry Clin Neurosci 271, 1089–1109 (2021). https://doi.org/10.1007/s00406-020-01190-3

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