Real-time salivary cortisol enhances the match of an individual's stressor with their stress reactivity

Abstract

Within the mismatch hypothesis, and specifically the Adaptive Calibration Model (Del Guidice, Ellis, Shirtcliff, 2011), individuals vary both in their environmental stressors and biological sensitivity to those experiences. Functioning of the Hypothalamic-Pituitary-Adrenal (HPA) axis via salivary cortisol reactivity provides one measure of biological sensitivity to context. The ACM includes two profiles of individuals who express a low biological sensitivity to context. The 'buffered' profile includes individuals with moderate stress exposure, who appear physiologically well-equipped to cope with stressors and typical challenges. Neurobiologically, such individuals appraise stressors and elicit limbic activation, but also express strong prefrontal cortical inhibition which helps them cope with a stressor (Taylor et al, 2010). In the face of more extreme challenges, these individuals should be capable of mounting a stress response as the prefrontal cortex no longer actively inhibits cortisol reactivity (Pruessner et al, 2010). The 'unemotional' profile appears physiological similar, but the implications of this low physiological arousal and concomitant extreme stress exposure is different. Even in the face of extreme stressors or social challenges, such individuals remain unperturbed and continue to express blunted limbic and paralimbic activity to achieve this hypoarousal (Teicher et al, 2003), even in situations which call for stress reactivity. One empirical challenge with these two profiles is that researchers are limited in their ability to manipulate the context for observing stress reactivity in such a manner that these two profiles become distinguished. It is not possible to alter the salience of a laboratory stressor to encourage the buffered individual to cross their personal reactivity threshold by lifting the prefrontal brake on the stress response and thereby appear distinct from the unemotional profile. The present study focuses on one cause for this limited information, i.e. that salivary cortisol results are not obtained for days to months later, rendering it impossible to alter – or match – the laboratory context to the participant's personal stress threshold. Both buffered and unemotional individuals are consequently classified as " nonresponders, " grouping the best and worst stress profiles into a single heterogenous group. To address this limitation, we have developed an innovative technology which quantitatively measures salivary cortisol in real-time called the VerOFy® device. Twenty-three participants provided saliva with the VerOFy® device and via passive drool. Figure 1 illustrates that the two methods were highly correlated, r(18)=.91, p<.0001, although a subset of 5 participants returned high lateral flow cortisol with the VerOFy® device, r(5)=.95, p=.01. This technology allows for a confirmation sample to be assayed via traditional assays as these methods remain the gold-standard. Preliminary work on integrating this research to individualize efficacy of a laboratory stressor with this time-sensitive information will be described, including an investigation of 68 participants completing a modified Trier Social Stress Test. The ultimate goal is to use this technology to better understand an individual's biological sensitivity to context, and potentially change the context to better match the individual's ability to cope with stress. Substantial information can be gained about an individual's context, and how their body calibrates functioning to that context, with this real-time biomarker information.

Full text

Real-time salivary cortisol enhances the match of an individual’s stressor with their stress reactivity
Shirtcliff, Elizabeth A.; Slowey, Paul D.; Hart, Tom; Buck, Robert
Within the mismatch hypothesis, and specifically the Adaptive Calibration Model (Del Guidice, Ellis,
Shirtcliff, 2011), individuals vary both in their environmental stressors and biological sensitivity to those
experiences. Functioning of the Hypothalamic-Pituitary-Adrenal (HPA) axis via salivary cortisol reactivity
provides one measure of biological sensitivity to context. The ACM includes two profiles of individuals
who express a low biological sensitivity to context. The ‘buffered’ profile includes individuals with
moderate stress exposure, who appear physiologically well-equipped to cope with stressors and typical
challenges. Neurobiologically, such individuals appraise stressors and elicit limbic activation, but also
express strong prefrontal cortical inhibition which helps them cope with a stressor (Taylor et al, 2010). In
the face of more extreme challenges, these individuals should be capable of mounting a stress response
as the prefrontal cortex no longer actively inhibits cortisol reactivity (Pruessner et al, 2010). The
‘unemotional’ profile appears physiological similar, but the implications of this low physiological arousal
and concomitant extreme stress exposure is different. Even in the face of extreme stressors or social
challenges, such individuals remain unperturbed and continue to express blunted limbic and paralimbic
activity to achieve this hypoarousal (Teicher et al, 2003), even in situations which call for stress
reactivity.
One empirical challenge with these two profiles is that researchers are limited in their ability to
manipulate the context for observing stress reactivity in such a manner that these two profiles become
distinguished. It is not possible to alter the salience of a laboratory stressor to encourage the buffered
individual to cross their personal reactivity threshold by lifting the prefrontal brake on the stress
response and thereby appear distinct from the unemotional profile. The present study focuses on one
cause for this limited information, i.e. that salivary cortisol results are not obtained for days to months
later, rendering it impossible to alter – or match – the laboratory context to the participant’s personal
stress threshold. Both buffered and unemotional individuals are consequently classified as
“nonresponders,” grouping the best and worst stress profiles into a single heterogenous group.
To address this limitation, we have developed an innovative technology which quantitatively measures
salivary cortisol in real-time called the VerOFy® device. Twenty-three participants provided saliva with
the VerOFy® device and via passive drool. Figure 1 illustrates that the two methods were highly
correlated, r(18)=.91, p<.0001, although a subset of 5 participants returned high lateral flow cortisol
with the VerOFy® device, r(5)=.95, p=.01. This technology allows for a confirmation sample to be
assayed via traditional assays as these methods remain the gold-standard. Preliminary work on
integrating this research to individualize efficacy of a laboratory stressor with this time-sensitive
information will be described, including an investigation of 68 participants completing a modified Trier
Social Stress Test. The ultimate goal is to use this technology to better understand an individual’s
biological sensitivity to context, and potentially change the context to better match the individual’s
ability to cope with stress. Substantial information can be gained about an individual’s context, and how
their body calibrates functioning to that context, with this real-time biomarker information.

Figure 1. The VerOFy® device measured cortisol via lateral flow (x-
axis) in real-time. Values are highly correlated with salivary cortisol
levels measured using a commercially available EIA kit (Salimetrics,
LLC) (y-axis)., Although the technology must be refined to account for
outliers, cortisol concentrations from laboratory standards are reliably
measured with the VerOFy® lateral flow system.