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New Tool May Help Scientists Better Understand Stress

AU’s Professor of Chemistry Alexander Zestos’ new sensor rapidly measures cortisol levels and holds promise of advancing scientific understanding of stress and anxiety

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Alexander Zestos, a bioanalytical chemist and American University Professor of Chemistry, has developed a new carbon fiber microelectrode tool that can quickly and accurately measure cortisol, the body’s “stress hormone.”

Professor Alexander Zestos

The sensors hold vast implications for helping researchers better understand stress and anxiety and their effects on the human body. Zestos and student authors Michelle Hadad (BS public health ’22) and Nadine Hadad (BS public health ’23) have published the results in the open access journal Biosensors. 

“Cortisol is a vitally important neurohormone that has great importance in understanding stress, anxiety, and neuropsychiatric disorders," says Zestos. “Our work utilizes carbon fiber microelectrode sensors to measure cortisol with electrochemical detection. The sensors are minimally invasive, biocompatible, and fast responding. They will allow us to measure cortisol in a fraction of a second, which could have wide reaching impact and utility.”

“The Epidemic of the 21st Century”

Michelle Hadad

Being able to understand how cortisol functions in the body can help individuals achieve optimal brain health. More broadly, it can help improve health and economic outcomes across populations. The World Health Organization has declared stress “the epidemic of the 21st century,” and more than a quarter of all American adults say they experience so much stress in their lives that they cannot function well, according to the American Psychological Association. Stress can result in cancer and other diseases, cardiovascular events, accidents, diminished productivity, and increased insurance costs. All together, these problems cause untold personal anguish and cost the United States more than $300 billion every year.

So, what exactly is the cortisol-stress connection?

When a person experiences stress or a perceived threat, Zestos explains, cortisol is produced by the adrenal glands and released into the blood stream as controlled by the hypothalamus. In the short term, cortisol can enhance the ability to react quickly and cope with stress. During particularly stressful situations, cortisol levels rise to help prepare your body for a "fight-or-flight" response.

Nadine Hadad

However, chronically high levels of cortisol, often due to ongoing stress, can have negative impacts on the brain and lead to problems with memory and concentration, anxiety, and even depression. Elevated levels of cortisol are also associated with tumors on the pituitary or adrenal glands that contribute to Cushing syndrome, says Zestos. Low levels of cortisol may potentially cause Addison’s disease or primary adrenal insufficiency. Cortisol levels also affect mood, memory, immunity, glucose and protein homeostasis, blood sugar, metabolism, and inflammation.

Understanding how cortisol works is central to understanding brain health. This is where Zestos’ carbon fiber microelectrode tool comes into play. “It is simple, low cost, and effective way to detect cortisol in the body, due to its high sensitivity and selectivity of detection,” he says.  The sensors “capture” molecules such as cortisol on the electrode surface and use cyclic voltammetry to measure and detect cortisol. The sensors can be implantable in vivo and could also be tested in other biological fluids such as blood (plasma), urine, sweat, and saliva.

Professor Zestos (left) and lab team

Understanding the Physiological Role of Cortisol

Zestos’ next steps are to further develop the sensors for ex vivo or in vivo measurements in animals, and potentially in human samples as well. “We ultimately hope to measure fast, changing samples of cortisol during different times of the day or under different stimuli conditions such as the effect of different behaviors, disorders, or drug treatments on cortisol levels,” he says.

Ultimately, Zestos would like to see the sensors used as an analytical and diagnostic tool to help further understand the physiological role of cortisol on human health. They could be used by medical researchers and scientists in academia, government, hospitals, the pharmaceutical industry, and other research settings. These sensors could even potentially be used in doctor’s offices and other places as a screening test for diagnosing neuropsychiatric disorders and overall health and mood.

“We hope to measure cortisol from samples and patients undergoing specific behavioral and drug treatments," Zestos says. “If we can identify how the level of cortisol changes with (and how cortisol concentrations are changed by) certain diseases, behaviors, or those receiving drug treatment, then we can further understand the complex role that this hormone plays and its use as a means for treatment and potential therapies.”