Sweat equity?: (left to right) Julian Thayer, Ohio State University; Esther Sternberg, NIMH; Andrea Marques, NIMH; and Terry Phillips, NIBIB

At the NIH Research Festival symposium on a new noninvasive method for detecting stress and immune-related biomarkers in sweat, immunochemist Terry Phillips described his work as "pulling nothing out of nothing." However, the "nothing" he wrings from a tiny sponge soaked in sweat can reveal the emotional state of the sweat’s producer.

The motivation for this project, neuroendocrinologist Esther Sternberg recounted, was the request from some architects for a noninvasive way to measure the stress levels of employees in traditional and modern workplace environments.

The architects wanted to design better offices. Sternberg, director of the Integrative Neural Immune Program and chief of the Section on Neuroendocrine Immunology and Behavior, NIMH, envisioned a case study of the interdisciplinary development of an assay.

The first step was to develop a collection method. A small absorbent skin patch was already commercially available. The trick was in squeezing it dry.

Phillips, chief of the Nanoscale Immunodiagnostic Group at NIBIB, tried different centrifuge-and-squeeze approaches before settling on a solid-phase extractor that was gathering dust in his lab. After developing a protocol for cleaning the sweat sample of salt and recovering the integral proteins, he then created a microfluidic chamber for high-sensitivity recycling immunoaffinity chromatography.

The next step was to test this assay in a clinical setting, continued Andrea Marques, a postdoc in Sternberg’s section. A comparison of the levels of neuroimmune biomarkers in the sweat and plasma of depressed women and healthy volunteers enrolled in an ongoing study of osteoporosis in women with depression led by Giovanni Cizza, NIDDK, revealed an abundance of proinflammatory cytokines and stress-related neuropeptides in both the sweat and plasma of women with depression, even though they were medicated and in remission at the time of the study.

Psychophysiologist Julian Thayer, of Ohio State University in Columbus (and formerly of NIA), is now verifying these results against another measure of stress—heart-rate variability. A decrease in heart-rate variability, especially while sleeping, indicates an increased likelihood of heart disease. However, it may also signify an increase in stress.

In a previous study, when Thayer and his colleagues told healthy study subjects that they would have a test in the morning, they displayed decreased heart rate variability at night compared with other healthy subjects who were simply told to return to the lab in the morning. Interestingly—especially to the architects—when applying this method to office workers, the researchers found that working in a more modern workspace was associated with an increase in heart-rate variability.

Although Thayer’s group has not finished comparing the results of the two approaches in the office workers, they anticipate that the use of both sweat-patch biomarkers and heart-rate variability will be helpful in establishing the status of the subjects’ stress responses from two different perspectives.

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