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Disaggregating physiological components of cortisol output: A novel approach to cortisol analysis in a clinical sample – a proof-of-principle study

Dobler, Veronika B., Neufield, Sharon A. S., Fletcher, Paul F., Perez, Jesus, Subramaniam, Naresh, Teufel, Christoph and Goodyer, Ian M. 2019. Disaggregating physiological components of cortisol output: A novel approach to cortisol analysis in a clinical sample – a proof-of-principle study. Neurobiology of Stress 10 , 100153. 10.1016/j.ynstr.2019.100153

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Although childhood adversity (CA) increases risk for subsequent mental illnesses, developmental mechanisms underpinning this association remain unclear. The hypothalamic-pituitary-adrenal axis (HPAA) is one candidate system potentially linking CA with psychopathology. However, determining developmental effects of CA on HPAA output and differentiating these from effects of current illness has proven difficult. Different aspects of HPAA output are governed by differentiable physiological mechanisms. Disaggregating HPAA output according to its biological components (baseline tonic cortisol, background diurnal variation, phasic stress response) may improve precision of associations with CA and/or psychopathology. In a novel proof-of-principle investigation we test whether different predictors, CA (distal risk factor) and current depressive symptoms, show distinct associations with dissociable HPAA components. A clinical group (aged 16–25) at high-risk for developing severe psychopathology (n = 20) were compared to age and sex matched healthy controls (n = 21). Cortisol was measured at waking (x4), following stress induction (x8), and during a time-environment-matched non-stress condition. Using piecewise multilevel modeling, stress responses were disaggregated into increase and decrease, while controlling for waking cortisol, background diurnal output and confounding variables. Elevated waking cortisol was specifically associated with higher CA scores. Higher non-stress cortisol was specifically associated with higher depressive scores. Following stress induction, depressive symptoms attenuated cortisol increase, whilst CA attenuated cortisol decrease. The results support a differential HPAA dysregulation hypothesis where physiologically dissociable components of HPAA output are differentially associated with distal (CA) or proximal (depressive symptoms) predictors. This proof-of-principle study demonstrates that future cortisol analyses need to disaggregate biologically independent mechanisms of HPAA output.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information: This is an open access article under the terms of the CC-BY license.
Publisher: Elsevier
ISSN: 2352-2895
Date of First Compliant Deposit: 12 March 2019
Date of Acceptance: 4 March 2019
Last Modified: 19 Oct 2020 09:00

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