TY - JOUR
T1 - Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in Generation Scotland
AU - Green, Claire
AU - Stolicyn, Aleks
AU - Harris, Mathew A.
AU - Shen, Xueyi
AU - Romaniuk, Liana
AU - Barbu, Miruna C.
AU - Hawkins, Emma L.
AU - Wardlaw, Joanna M.
AU - Steele, J. Douglas
AU - Waiter, Gordon D.
AU - Sandu, Anca-Larisa
AU - Campbell, Archie
AU - Porteous, David J.
AU - Seckl, Jonathan R.
AU - Lawrie, Stephen M.
AU - Reynolds, Rebecca M.
AU - Cavanagh, Jonathan
AU - McIntosh, Andrew M.
AU - Whalley, Heather C.
N1 - 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.
PY - 2021/10/12
Y1 - 2021/10/12
N2 - 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 (β
range = −0.057 to −0.104, all P
FDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; β
range = 0.071 to 0.115, all P
FDR = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = −0.059, P = 0.043; nucleus accumbens: β = −0.075, P
FDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD.
AB - 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 (β
range = −0.057 to −0.104, all P
FDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; β
range = 0.071 to 0.115, all P
FDR = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = −0.059, P = 0.043; nucleus accumbens: β = −0.075, P
FDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD.
KW - Depression
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85117373160&partnerID=8YFLogxK
U2 - 10.1038/s41398-021-01644-9
DO - 10.1038/s41398-021-01644-9
M3 - Article
C2 - 34642301
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
M1 - 523
ER -
