Life-time socio-economic position and cortisol patterns in mid-life
Introduction
It is now clear that socio-economic position in early life influences health status several decades later and that, for some outcomes, early life factors operate over and above any effect they have on adult position (Kuh et al., 2004). What is not well-established is how the socio-economic environment “gets under the skin” and translates into biological risk. Among the possible contributors is the hypothalamic–pituitary–adrenal (HPA) axis and its role in the regulation of secretion of cortisol. Cortisol secretion patterns vary among individuals and certain of these patterns are thought to represent dysregulation of the HPA axis. Effects of dysregulation have been investigated in humans in relation to several health outcomes, including blood pressure (Phillips et al., 1998, Phillips et al., 2000), glucose tolerance (Phillips et al., 1998), type 2 diabetes (Rosmond and Bjorntorp, 2000), stroke and cardiovascular disease risk (Rosmond and Bjorntorp, 2000; Reynolds et al., 2001), memory loss (Seeman et al., 1997) and breast cancer survival (Sephton et al., 2000).
Studies of several animal species suggest that cortisol levels are influenced by early nurturant experience (Suomi, 1997; Meaney, 2001). In children, differences in cortisol levels have been reported by socio-economic status (Lupien et al., 2000, Lupien et al., 2005), mother's depressive symptoms (Lupien et al., 2001; Essex et al., 2002), childhood adversity (Carlson and Earls, 1997; Gunnar et al., 2001) and stressful environments (Flinn and England, 1997; Gunnar and Vazquez, 2001). Elsewhere, it is reported that cortisol levels are associated with adult socio-economic status (Brandstadter, 1991; Steptoe et al., 2003; Kristenson et al., 2004; Kunz-Ebrecht et al., 2004; Cohen et al., 2006a, Cohen et al., 2006b) and chronic stress due to unemployment (Ockenfels et al., 1995). With few exceptions (Decker, 2000), studies of adult populations have lacked information on environment in early life. Hence, we do not know whether early socio-economic environment permanently alters cortisol metabolism, with effects of adversity persisting beyond childhood. More generally, we have a poor understanding of how a complex adaptive system, such as that regulating cortisol metabolism, might operate over the life course.
It has long been known that health and cognition risks are attendant on the pathophysiological states of both hyper-cortisolism (Cushing's disease) and hypo-cortisolism (Addison's disease). In sub-clinical settings, variations in cortisol secretion may be normative and adaptive in the short term, exposure to extremes of circulating cortisol over a prolonged period of the life-course may be detrimental to health. In experimental studies in animals, chronically elevated cortisol levels endanger memory and learning cells in the hippocampus and accelerate the ageing of a wide range of organ systems (Sapolsky, 2000). In humans higher cortisol levels are associated with greater cognitive decline in the elderly (Karlamangla et al., 2005). Chronic, repeated adversity may change the regulation of the HPA axis, (McEwen, 1998, McEwen, 2000) and may lead to either hyper or hypo secretory states, either of which may have adverse consequences, with the mid-range having the most favourable outcomes (Belanoff et al., 2001; Davis et al., 2002; Haley et al., 2006; Herbert et al., 2006). Some evidence exists suggesting that hypo-secretion is associated with health outcomes such as breast cancer survival (Sephton et al., 2000), and physiological risk factors for cardiovascular disease, diabetes and stroke (Rosmond and Bjorntorp, 2000).
In order to examine the role of chronic adversity on cortisol levels, we need to take account of cortisol secretion patterns. Largely on the basis of small study samples with multiple cortisol measures over the day(s), it has been established that cortisol typically follows a diurnal rhythm, with a peak soon after waking in the morning and a gradual decline throughout the day (Stone et al., 2001). However, in studies examining effects of environmental stimuli, other patterns have been observed, including an absence of the early morning peak or alternatively, prolongation of the high awakening level or rises later in the day (Gunnar and Vazquez, 2001). In sum, the literature suggests that an early morning peak followed by decline is a normative pattern but that alternate diurnal cortisol patterns are seen (Stone et al., 2001). These may include an absence of the morning peak in cortisol and its associated decline (Gunnar and Vazquez, 2001; Rohleder et al., 2004; Buchanan et al., 2004).
Our overall objective is to test whether chronic adversity contributes to cortisol levels, using lifetime socio-economic position (SEP) to indicate chronic adversity. For those with least advantaged SEP there is greater exposure to poor housing, poorer cognitive development, increased family disruption in childhood and, in adulthood, greater job insecurity, early parenthood and financial problems (Power and Matthews, 1997). We use data from a population followed at regular intervals from birth, the 1958 British birth cohort, with salivary cortisol samples at age 44–45 (Power and Elliott, 2006). These data provide a unique opportunity to understand the relationships between life-course SEP and cortisol in mid-life. This paper specifically addresses whether adult cortisol levels are associated with socio-economic position from birth to mid-adult life, and if so, whether the association is due primarily to SEP in childhood or in adulthood or both. We also examine the possible contribution of smoking and adult body mass index (BMI) to the associations between SEP and adult cortisol levels.
Section snippets
Study population
The 1958 birth cohort includes all children born in England, Scotland and Wales, in one week in March, 1958. A population of about 17,000 live births were followed-up at ages 7, 11, 16, 23, 33, 42 yr (Power and Elliott, 2006). More recently, at 44–45 yr, a target sample of 11,971 participants identified as still in contact with the study, and at age 42 had not required a proxy interview (due to learning disability) were invited to a clinical examination undertaken in their home by a trained
Results
Men had a lower time 1 cortisol level (median 18.8 nmol/l), but a higher time 2 level (median 7.1 nmol/l), compared to women (19.6 and 6.6 nmol/l, respectively). Some participants had a higher t2 measure than t1, but on average, cortisol levels declined, with women having a greater decline than men. Total 3 h ‘free’ cortisol (AUC) was similar for men and women; for both the range of AUC values is wide, indicating large differences. The majority showed a ‘normal’ decline (82.4% for men, 86.6% for
Discussion
In this large population-based study, in mid adult life, the majority (82.4% of men and 86.6% of women) showed a post-waking level of more than 7.5 nmol/l, and a decline of more than 20% from time 1 to time 2. The remaining 17.6% of men and 13.4% of women had abnormal patterns. Although there have been many previous studies on short-term influences on cortisol, there are far fewer studies, like ours, that examine long-term relationships. Our focus is on chronicity of adversity over decades, and
Role of the funding source
Data collection at age 45 years was funded by the Medical Research Council (MRC), Grant G0000934.
Analysis was funded by the MRC and the Human Early Learning Partnership (HELP), Vancouver, Canada.
Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive.
Conflict of interest
We confirm that there is no conflict of interest associated with any contribution to this paper.
Acknowledgements
Data collection at age 45 years was funded by the Medical Research Council, Grant G0000934. Analysis was funded by the MRC and the Human Early Learning Partnership (HELP), Vancouver, Canada. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R & D funding received from the NHS Executive. Data providers: Centre for Longitudinal Studies, Institute of Education and National Birthday Trust Fund, National Children's Bureau, City University
References (45)
- et al.
Corticosteroids and cognition
J. Psychiatr. Res.
(2001) - et al.
Developmental and personality correlates of adrenocortical activity as indexed by salivary cortisol, observations in the age range of 35–65 years
J. Psychosom. Res.
(1991) - et al.
Circadian regulation of cortisol after hippocampal damage in humans
Biol. Psych.
(2004) Salivary cortisol and social status among Dominican men
Horm. Behav.
(2000)- et al.
Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior
Biol. Psych.
(2002) - et al.
Cortisol, contingency learning, and memory in preterm and full-term infants
Psychoneuroendocrinology
(2006) - et al.
Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components
Psychoneuroendocrinology
(2007) - et al.
Estimating between- and within-individual variation in cortisol levels using multilevel models
Psychoneuroendocrinology
(2005) - et al.
Urinary cortisol excretion as a predictor of incident cognitive impairment
Neurobiol. Aging
(2005) - et al.
Salivary cortisol in psychoneuroendocrine research: recent developments and applications
Psychoneuroendocrinology
(1994)