City Research Online

Abstract

Clinical depression and major depressive disorder are considered one of the primary global burdens of disease, impacting society and health economies with monumental prevalence, as of recent years. A primary factor which facilitates the development of such mental illnesses is the prevalence of psychological stress, which has been rising globally, notably since the Covid-19 pandemic. The trajectory of psychological stress towards the development of depressions has been vastly studied from a predominantly qualitative perspective, which has given rise to a plethora of subjective measures for psychological stress evaluation, including interview-based tools. Alternatively, research within physiological stress has principally focused on the physiological biomarkers of stress, including heart rate variability (HRV), electrodermal activity (EDA) and electroencephalography (EEG), enabling the collection of quantitative data regarding the manifestations of stress in the human body. The measurement of the stress hormones in the body, such as cortisol, facilitates the understanding of the biochemical pathways and bio-signals which arise during stress elicitation, that hold vastly informative cues regarding the stress response and how it is managed and controlled via the central and peripheral nervous systems. Although previous research has shown great promise for the measurement and analysis of stress hormones with regards to psychological and physiological stress, this has seldom led to the development of point-of-care technologies for the betterment of the public. One of the leading concerns throughout the Covid-19 pandemic was the practicalities of face-to-face therapeutic interventions, which are commonly practiced for mental health management. Due to the nature of the pandemic, such interventions soon became impractical and led to the rise in virtual therapy sessions, further isolating patients suffering from mental illnesses and perpetuating the stigmatisation that surrounds mental health management. Therefore, the development of point-of-care technologies for the management of markers of mental health, such as psychological stress levels, is a vital necessity to facilitate patient empowerment and assist in creating impactful strategies that consider the objective and quantitative measures of stress in the human body.

The research outlined in this thesis showcases the novel development of a colorimetric method for the determination of cortisol in human saliva. Notably, cortisol governs the stress response through release in a ‘hormonal cascade’ that leads to mobilisation of energy, increased awareness, and alertness, as reactions to restore the body to its homeostatic nature. Thereby, cortisol is a key logical indicator that can be used to determine stress levels, which can be monitored to facilitate stress management for mental health wellbeing. The research question underpinning this body of work is the prospect of fingerprinting cortisol in human saliva through optical techniques, such as infrared, ultraviolet, and visible light (UV-Vis) spectroscopy, towards a non-invasive, point-of-care application. Firstly, the existing state-of-the-art technologies for stress monitoring were evaluated, from which it was determined that cortisol is the fundamental biomarker to enable stress monitoring. Experimental studies were designed to critically evaluate the optical characteristics of cortisol using infrared and UV-Vis spectroscopy, towards fingerprinting the stress hormone in salivary samples. Further experimentation involved the development of a protocol for the fingerprinting of cortisol in the UV-Vis spectral range, with the aid of chromogenic reagents (tetrazolium blue and tetramethylammonium hydroxide), as well as comparison with the gold-standard salivary cortisol measurement technique, enzyme-linked immunoassays (ELISAs), showcasing promising results. After development of calibration curves through regression modelling, the novel method for colorimetric determination of cortisol was utilised for cortisol measurement in an in-vivo pilot study of 20 participants undergoing a standardised stress elicitation protocol. The Maastricht Acute Stress Test (MAST) protocol was implemented for stress elicitation in 20 healthy individuals from whom saliva samples were collected for rapid cortisol determination via the novel method and ELISA validation. Results from the in-vivo study demonstrated a coefficient of determination of 0.997, suggesting that the novel colorimetric method could determine cortisol levels from human saliva samples with great accuracy, comparable to the gold-standard technique. Finally, a preliminary sensor development stage was conducted in which a prototype colorimeter sensor was developed for the evaluation of cortisol in human saliva, towards point-of-care applications. The novel technological advancements presented in this research contribute towards the development of point-of-care devices which take a new and innovative approach to stress monitoring. Thus, deviating from dated practices that are limited by subjective and qualitative evaluations, towards transformative technology for the optical determination of stress hormones for improved mental health wellbeing. The work encompassed in this project showcases the development of a novel colorimetric method for the determination of salivary cortisol for the first time with the use of the blue tetrazolium dye and tetramethylammonium hydroxide catalyst, towards the development of a simple prototype colorimetric sensor to evaluate salivary cortisol levels in line with the current gold standard, ELISAs, within in vitro and in vivo scenarios with great accuracy, showing great promise for the future of stress monitoring.

Publication Type:	Thesis (Doctoral)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry T Technology > TA Engineering (General). Civil engineering (General)
Departments:	School of Science & Technology > Engineering School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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