Assessing salivary cortisol in large-scale, epidemiological research
Introduction
The addition of biological measures (“biomarkers”) to large-scale social science and epidemiological studies has recently been advocated by a number of funding bodies (Finch et al., 2001). In this interdisciplinary approach, extensive information on social and behavioural processes, health behaviours and self-reported health in existing large-scale, representative samples, is complemented by the addition of objective biological markers of physiological processes and pre-disease states.
Measures of the hypothalamic pituitary adrenal axis (HPA), and in particular levels of salivary cortisol are obvious candidates for inclusion in these studies, given the important role that the HPA axis plays in ‘transducing’ subjective social–environmental experience into physiological changes relevant to health. While salivary cortisol has been successfully gathered in a number of large-scale, population-based studies, the design, collection and interpretation of salivary cortisol data in naturalistic settings presents numerous challenges. Here we discuss these challenges, and related solutions, and review some existing results that have emerged from this new wave of research.
Section snippets
Background
The HPA axis serves as an important pathway by which social and psychological factors influence biology and health. Stressful stimuli serve to activate HPA function to cause an increase in peripheral cortisol. Cortisol can effect physiological changes that encompass most of the main organ systems, helping to provide the energetic resources needed to face the stressor at hand, and also helping to modulate and contain other components of the physiological stress response (Sapolsky et al., 2000).
Epidemiological research: strengths and challenges
Epidemiological research is characterized by: (1) representative sampling, in which the sample is carefully selected and retained to ensure that participants precisely reflect the characteristics of the larger population of interest; (2) large sample sizes (in the order of hundreds to tens of thousands), typically of a broader socioeconomic and racial/ethnic range than in samples of convenience; and (3) extensive measurement of and statistical control for potentially confounding variables.
As a
Methodological priorities in epidemiological research: design implications
These defining features of epidemiological research, and their relative advantages, also require a shift in several priorities regarding the design of cortisol data collection protocols for large-scale research.
Existing epidemiological cortisol research
While many salivary cortisol protocols have been implemented in convenience samples, we focus here on studies in which participants were purposefully sampled to accurately reflect the characteristics of a particular population of interest, such as samples chosen to be representative of a particular occupational status or age group (Ranjit et al., 2005, Rosmalen et al., 2005, Cohen et al., 2006, Badrick et al., 2007). The sample sizes, basic demographic characteristics, ages, data collection
Data analytic approaches and controversies
Approximately 1% of cortisol measures are found to be 3 standard deviations above the mean cortisol value (Whitehall II and Rotterdam Studies). It is unclear what these high cortisol values represent. In large-scale studies, the absolute numbers with these very high values can be substantial; it is not yet resolved whether it is best to remove these values altogether from analyses, or windsorize them in order to reduce their influence on the analysis. Even with such outliers removed, cortisol
Some findings from epidemiological cortisol research
The investment that researchers have made thus far in gathering salivary cortisol in population-based research studies is beginning to pay off. Studies are now appearing in the published literature, examining problems and processes that would have been difficult to capture with cortisol research utilizing smaller sample sizes. One area of research that these studies are uniquely suited to examine is association between race/ethnicity and/or socioeconomic position and cortisol levels. In
Research guiding design choices
The addition of salivary cortisol protocols to large-scale studies heralds a new and exciting period for HPA axis research, that should lead to a better understanding of the role of daytime cortisol secretion, its behavioural and biological correlates and how it relates to the development of disease. More research is however needed to quantify the extent of unreliability introduced by minimal protocols, and the extent to which that unreliability compromises investigators’ abilities to detect
Role of funding source
Whitehall II study has been supported by grants from the Medical Research Council; Economic and Social Research Council; British Heart Foundation; Health and Safety Executive; Department of Health; National Heart Lung and Blood Institute (HL36310), US, NIH: National Institute on Aging (AG13196), US, NIH; Agency for Health Care Policy Research (HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health.
Conflict of interest
The authors have no conflicts of interests to declare.
Acknowledgements
We would like to thank Martin Shipley for providing the power calculations. We would like to thank all the principal investigators that provided information on the studies in which salivary samples have been incorporated.
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The authors made equal contributions to this paper.