Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in Generation Scotland

Claire Green, Aleks Stolicyn, Mathew A. Harris, Xueyi Shen, Liana Romaniuk, Miruna C. Barbu, Emma L. Hawkins, Joanna M. Wardlaw, J. Douglas Steele, Gordon D. Waiter, Anca-Larisa Sandu, Archie Campbell, David J. Porteous, Jonathan R. Seckl, Stephen M. Lawrie, Rebecca M. Reynolds, Jonathan Cavanagh, Andrew M. McIntosh, Heather C. Whalley

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Hypothalamic–pituitary–adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (βrange = −0.057 to −0.104, all PFDR 
Original languageEnglish
Article number523
Number of pages9
JournalTranslational Psychiatry
Issue number1
Early online date12 Oct 2021
Publication statusPublished - 12 Oct 2021

Bibliographical note

We would like to thank all of the Generation Scotland participants for their contribution to this study. We also thank the research assistants, clinicians and technicians for their help in collecting the data. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award ‘Stratifying Resilience and Depression Longitudinally’ (STRADL) (Reference 104036/Z/14/Z). We acknowledge the support of the British Heart Foundation (RE/18/5/34216). CG is supported by the Medical Research Council and the University of Edinburgh through the Precision Medicine Doctoral Training Programme. MCB is supported by a Guarantors of Brain Non-Clinical Post-Doctoral Fellowship. JMW is funded by the UK Dementia Research Institute which is funded by the UK Medical Research Council, Alzheimer’s Research UK and Alzheimer’s Society


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