Stress is blamed for virtually anything these days— acne, digestive problems, fatigue, headaches, irritability, low mood, and the list goes on. While stress may be the culprit of many of these problems, our vague everyday understanding of “stress” clearly fails to encapsulate its true essence. Let us thus take a deep dive into the world of stress: what it is, what it can do, and how it can be detected.
by Jasmine Gowidjaja
Regardless of one’s age, status, or occupation, there is no escaping stress. A recent global study by Gallup in 2021 revealed that the world is more stressed out than ever, with 4 in 10 adults reporting overwhelming feelings of stress.1 The statistics are even more alarming in Singapore. Despite being widely regarded as one of the happiest countries to live in,2 approximately 9 in 10 Singaporeans declared feeling stressed.3
Stress can be generally defined as “a state of worry or mental tension caused by a difficult situation”.4 These stressors may be biological (e.g., starvation), physical (e.g., physical injury or temperature fluctuations), or social (e.g., isolation) in nature.5 While it is tempting to think of stress as an extreme feeling or experience, the right amount of stress is actually essential for survival, as stress is a natural response that helps and encourages the body to deal with challenges and threats.4 However, as with everything else, a divergence from moderate or tolerable levels of stress may affect one’s well-being.
A Biological Explanation for Stress
Everyone experiences stress to a certain degree in their life. Under stressful situations, the body kicks into “fight or flight” mode to increase the individual’s chance of survival.6 On a molecular level, this response can be attributed to the enhanced secretion of a number of hormones, including cortisol, which increases the mobilisation of energy sources and adapts the individual to new circumstances. 6,7
Aside from its role in the “fight or flight” response, cortisol also plays a more general role in maintaining the body’s metabolism and the functioning of the immune, cardiovascular, skeletal, and nervous systems.8,9 Under normal, stress-free conditions, a healthy adult secretes between 10 and 20 milligrams of cortisol per day.9 Similar to other hormones that are regulated by the circadian rhythm, cortisol levels fluctuate throughout the day, with peak concentration found between 8 am to 10 am.9
As noted above, having a moderate amount of stress can be good, even necessary. However, long-term stress may have detrimental effects on the body.8,9 According to Tanaka et al., stress is the leading cause of up to 95% of diseases, ranging from cardiovascular and metabolic diseases to mental health disorders.5 While the role of stress in mental health disorders may be intuitive, stress-induced physical diseases may be more difficult to grasp. Nonetheless, they both involve the dysfunction of cortisol regulation.
The Consequence of Too Much Stress
Prolonged exposure to stressful stimuli results in an elevated secretion of cortisol in the body.9 In the brain specifically, high concentrations of cortisol may affect behaviour and cognitive functioning.9 Initially, excessive levels of cortisol in the brain may cause feelings of euphoria.9 However, prolonged exposure may induce psychological symptoms such as irritability, emotional liability, and depression.9 Studies have observed that an increase in cortisol secretion is accompanied by many mental disorders, such as clinical depression, bipolar disorders, and schizophrenia.9 In more extreme cases, abnormally high levels of cortisol may lead to neurodegeneration.9
Stress-induced physical diseases are rarer, with two of the most well-understood being Cushing’s disease and Addison’s disease. Cushing’s disease occurs due to the overproduction of cortisol in the body and has a myriad of symptoms, including weight gain, a ruddy face, purple stretch marks, and high blood pressure.10 Meanwhile, Addison’s disease occurs due to an insufficient amount of cortisol in the body. Somewhat antithesis to the symptoms of Cushing’s disease, patients with Addison’s disease suffer from weight loss, skin hyperpigmentation, nausea, and lightheadedness.11
Methods of Cortisol Detection
Given the importance of cortisol in the body and the damaging effects arising from cortisol dysregulation, it is incredibly crucial to have a way of monitoring cortisol levels. Typically, cortisol levels are measured in the blood, where they exist in high concentrations.5 However, the invasiveness of the procedure could be stress-inducing for some, thus leading to inaccurate readings or overestimations of cortisol levels.12 Fortunately, the ubiquitous presence of cortisol allows it to be measured in other parts of the body, including saliva, hair, and urine.5
Conventional laboratory methods to detect cortisol levels include immunoassays and chromatography methods.5 However, these approaches are usually time-consuming, require the skills and expertise of trained personnel, or are environmentally harmful.5 As such, the development and use of non-invasive biosensors in detecting cortisol levels are starting to gain traction.5 While this article summarises the current landscape of non-invasive cortisol detection methods, a more comprehensive and detailed report can be found in the recently published review article written by Tanaka et al. in the World Scientific Annual Review of Functional Materials.
The simplest biosensor for detecting cortisol levels is a chromogenic sensor. Chromogenic sensors work by producing visible colour changes or fluorescent signals when exposed to a certain concentration of cortisol.5 Currently, four general chromogenic assays have been developed, each relying on a different chemical reagent to produce the colour change.5,12 Given their simplicity, chromogenic sensors hold promise for applications in point-of-care devices that allow for on-the-spot rapid testing and fast diagnosis.5 Although chromogenic sensors may be useful for qualitative analysis (i.e. Yes/No tests), they are not recommended for quantitative analysis of cortisol levels due to their low sensitivity towards cortisol; they are especially ineffective in detecting cortisol levels in the presence of other substances.5 Hence, the results from chromogenic sensors may not be very accurate and reliable.
Advancing further from simple detection, nanoparticle-based colourimetric sensors are useful tools to measure precise cortisol concentrations for use in clinical practice and drug studies.5 Similar to chromogenic sensors, nanoparticle-based colourimetric sensors reveal cortisol levels through visual colour change.5 However, unlike chromogenic sensors, the different intensities of colour change correspond to different cortisol levels.5 For example, a device developed by Dalirirad et al. was able to reveal the concentration of cortisol based on the intensity of a red line on the test zone of the device.12 For healthcare professionals, having precise measurements of cortisol levels is beneficial for disease monitoring and diagnostic accuracy, especially for stress-induced physical diseases.13 Furthermore, precise measurements of cortisol levels are useful for pharmaceutical researchers when drawing statistical conclusions about potential interventions or medications.13
Perhaps the most promising and all-rounded analytical method for ultrasensitive, rapid, and continuous detection of cortisol concentration is by electrochemical sensors.5 In the case of cortisol detection, certain molecules in the sensor may react with cortisol and release chemical energy.5 The device then converts this chemical energy into electrical signals that can be more easily measured and analysed.5 The strength of the electrical signals usually corresponds to the concentration of cortisol in the sample.5 Due to their high sensitivity to cortisol, electrochemical sensors can be used in a variety of samples, ranging from environmental to biomedical samples.5 In addition, their small size and portability have allowed them to be incorporated into wearable technologies, such as contact lenses and patches.5 Hence, electrochemical sensors can also be used by patients to monitor their cortisol levels during treatment.
Cortisol is a stress hormone that plays a critical role in regulating bodily functions. However, problems in cortisol production may have negative consequences for an individual’s physical and mental health. Hence, it is essential to develop selective, sensitive, rapid, and accurate sensors for timely detection and monitoring of cortisol levels. Aside from biomedical usage, cortisol monitoring is also essential for other applications, including aquaculture and farming. For example, in the case of poultry farming, studies have shown that heat-induced stress may lead to fewer egg-laying and lower-quality meat.14 This suggests that cortisol monitoring can be utilised to improve the living conditions of animals and, consequently, farming yield. Given the importance of cortisol monitoring, more theoretical and experimental research is needed to develop bioreceptors that have greater selectivity and sensitivity. [APBN]
This article was first published in the September & December 2023 print version of Asia-Pacific Biotech News.
About the Author
Jasmine Gowidjaja is an editorial intern at World Scientific Publishing and is currently pursuing an undergraduate degree in Life Sciences at Yale-NUS College. Evident in her diverse research background, from insect biodiversity to disease pathology, Jasmine is interested in just about anything.