Diurnal dynamic range as index of dysregulation of system dynamics. A cortisol examplar using data from the Study of Midlife in the United States

Abstract

We discuss the importance of including measures of dysregulated system dynamics in the operationalization of allostatic load. The concept of allostatic load, as originally proposed by McEwen and Stellar, included dysregulation not only in the resting state of physiological systems, but also in system dynamics. We describe previous work on cortisol diurnal dynamic range (peak to nadir spread) as an index of the health of the hypothalamic-pituitary-adrenal axis, with compression of dynamic range being a marker of dysregulation. In particular, we review the evidence for a) diurnal dynamic range compression in people from disadvantaged backgrounds, b) cross-sectional association of cortisol diurnal dynamic range compression with dysregulation in other systems' resting states, and c) cross-sectional association of cortisol diurnal dynamic range compression with lower scores on cognitive testing. Then, we present new data from the Study of Midlife in the United States (MIDUS) on longitudinal associations of cortisol dynamic range compression with subsequent cognitive decline and all-cause mortality. Briefly, each standard deviation decrement in cortisol diurnal dynamic range is associated with adjusted mortality hazard ratio of 1.35 (95% confidence interval: 1.19, 1.54). Among those who scored at median or lower in executive functioning at baseline and survive, each standard deviation decrement in cortisol dynamic range is associated with 1% greater decline in executive functioning over a decade (95% confidence interval: 0.4%, 2.0%). We conclude that including measures of system dynamics like diurnal dynamic range in the next generation of allostatic load measurement will likely advance understanding of the cumulative physiological burden of chronic stress and life experiences, and improve the prediction of future health consequences.

Keywords: All-cause mortality; Allostatic load; Cognitive decline; Cortisol area under the curve; Cortisol diurnal peak and nadir; HPA axis dysregulation.