Psychological stress and its inevitable trajectory toward mental health deteriorations such as clinical and major depression has become an unprecedented global burden. The diagnostic procedures involved in the characterization of mental illnesses commonly follow qualitative and subjective measures of stress, often leading to greater socioeconomic burdens due to misdiagnosis and poor understanding of the severity of such illnesses, further fueled by the stigmatization surrounding mental health. In recent years, the application of cortisol and stress hormone measurements has given rise to an alternative, quantifiable approach for the psychological evaluation of stress and depression. This review comprehensively evaluates the current state-of-the-art technology for measuring cortisol and dehydroepiandrosterone (DHEA) and their applications within stress monitoring in humans. Recent advancements in these fields have shown the importance of measuring stress hormones for the characterization of stress manifestation within the human body, and its relevance in mental health decline. Preliminary results from studies considering multimodal approaches toward stress monitoring have showcased promising developments, emphasizing the need for further technological advancement in this field, which consider both neurochemical and physiological biomarkers of stress, for global benefit.

Traditional methods for management of mental illnesses in the post-pandemic setting can be inaccessible for many individuals due to a multitude of reasons, including financial stresses and anxieties surrounding face-to-face interventions. The use of a point-of-care tool for self-management of stress levels and mental health status is the natural trajectory towards creating solutions for one of the primary contributors to the global burden of disease. Notably, cortisol is the main stress hormone and a key logical indicator of hypothalamic-pituitary adrenal (HPA) axis activity that governs the activation of the human stress system. Therefore, the measurement of cortisol is imperative to lead the discussion of the relationship between psychological stress and mental health deterioration. The aim of the current study was to determine salivary cortisol concentrations of healthy individuals undergoing the MAST protocol for human stress activation, through optical-colorimetric techniques. The study demonstrates the use of the blue tetrazolium (BT) method as successful means of rapid measurement of cortisol in saliva, comparable to the gold-standard technique i.e., enzyme-linked immunoassays (ELISA) with a coefficient of determination (R²) of 0.997. The results support the future development of a point-of-care optical sensor-based device and mobile application for cortisol monitoring and stress profiling in adults.

Mental illnesses, such as clinical depression, have taken an unprecedented toll on society and the economy on a global scale. The relationship between stress management and mental health decline is of utmost significance, especially as most avenues of mental health management remain inaccessible for the majority of the general public, i.e., interview-based, and face-to-face interventions or costly drug-based therapies. Cortisol, the primary stress hormone, regulates the stress response in the human body and, through persistent activation, can lead to chronic stress and mental health deterioration. Thereby, the measurement and evaluation of cortisol within saliva could harness potential developments in management and diagnostic tools to monitor physiological and psychological stress in simple point-of-care applications. The current study aims to determine the concentration of salivary cortisol in spiked artificial saliva samples using blue tetrazolium (BT) dye as a colorimetric indicator. The proposed method showcases the use of the BT dye as an effective method for the rapid measurement of salivary cortisol, with accuracy comparable to the gold-standard method for salivary cortisol analysis, enzyme-linked immunoassays (ELISAs). Finally, a prototype colorimetric sensor has been developed for point-of-care applications of stress monitoring via salivary cortisol measurement.