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Title: Brain markers of cumulative stress response and allostatic load in the ageing Whitehall II cohort
Author: Zsoldos, Enikö
ISNI:       0000 0004 6494 0501
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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The Whitehall II (Stress and Health) study is a prospective study based on originally 10,308 British civil servants. Since 1985, rich socio-demographic, health and life-style measures have been acquired every 2-5 years. Eight hundred participants were randomly selected from the remaining 6,308 participants of Phase 11 for magnetic resonance imaging (MRI) and further examination in Oxford (2012-14). There is evidence of changes in brain anatomy and mental health following traumatic events, such as combat stress or sexual abuse, in patients with posttraumatic stress disorder, mood or personality disorders, but little is known about the association between everyday stress, brain structure and function, and mental health in the general population. The secondary stress markers, Allostatic Load (AL) index, Framingham Stroke Risk score (FSRS) and Metabolic Syndrome (MetS) were selected as potential predictors of brain changes at follow-up. This thesis focuses on measures of structural grey and white matter (GM, WM) integrity, collected with the Siemens 3T Verio scanner in the first 563 participants of the Oxford study. As hypothesised, stress markers measured as early as 20 years prior to the scan, predicted lower GM and WM integrity in older age. Unique linear relationships remained even after controlling for socio-demographic confounders between each stress marker and GM density but not with measures of WM integrity. This suggests that some, if not most variance is shared between the stress markers and the usual correlates of general health, such as age and employment class. The three markers did not have equal power to predict brain measures: AL added more unique predictive variance to GM density than MetS and FSRS. On the other hand, FSRS was the more powerful predictor of poor WM integrity compared with AL and MetS, and after removing confounding variable effects. This thesis thus provides some empirical support for the concept of allostatic load, linking 'everyday' stress and features of the ageing human brain.
Supervisor: Ebmeier, Klaus Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Epidemiology ; Neuroscience ; Psychiatry ; human brain ageing ; stress ; MRI