How to measure stress in a clinical study?

Maastricht, 30th August, 2024

Long exposure to stress can come with several clinical implications for one’s physical as well as mental health. Stress can be clinically measured at multiple levels. Self-assessment scales reflect a subjective way to measure stress while biomarkers reflect a more objective measure of stress. Both types of measures are important in order to understand the relationship between stress and health and how to properly intervene. In this article we will outline Perceived Stress Scale (PSS), the Life Events and Difficulties Schedule (LEDS) and physiological measures such as cortisol levels, heart rate, and cytokine levels.

 

clinical endpoints for stress

What is stress?

Stress refers to experiences in which the demands of a certain event surpass an individual’s ability to cope with the situation. An important distinction has to be made between so-called stressors and the following response to these. Stressors are certain stressful events that have the potential to disturb an individual’s ability to function optimally. Stressors lead to stress responses, which are the cognitive, emotional, and biological reactions that evoke after such event (1).

When measuring stress, clinical endpoints often focus on both psychological as well as physiological indicators.

 

Below are the top clinically validated measures for stress

 

Psychological Measures for Stress

Psychological measures often include self-report measures of stress in the form of scales and questionnaires.

 

The Perceived Stress Scale:

The Perceived Stress Scale (PSS) is the most common psychological scale to measure stress. It measures to what extent certain life situations are perceived as stressful over the past month. Scores are calculated through the use of the following five-point scale: 0 = never, 1 = almost never, 2 = once in a while, 3 = often, and 4 = very often. The total of this score represents the level of perceived stress. It captures stress over a shorter period of time (2).

 

Life Events and Difficulties Schedule:

The Life Events and Difficulties Schedule (LEDS) measures the exposure to severe acute events and chronic obstacles over the previous year. It involves an interview where the participant has to recall 95 possible life events. Additional context around each event is proved by the participant as well. Such events are grouped into one of the following 10 domains: education, work, reproduction, housing, money/possessions, crime/legal, health/treatment/accidents, marital/partner relationship, other relationships, and miscellaneous (2).

 

Physiological Measures for Stress

Physiological measures often include tracking the levels of several biomarkers in order to assess the HPA axis, autonomic nervous system, and immune system.

 

Cortisol – HPA axis:

The HPA axis is especially responsive to psychosocial stress. The main output of this axis is the hormone cortisol. Cortisol levels in the body can vary depending on environmental events and surrounding stressors. Cortisol can fluctuate acutely but can also be chronically high or low. Cortisol can be measured at multiple levels (2):

  • Saliva – representing acute cortisol changes
  • Blood – representing acute cortisol changes
  • Urine – representing daily cortisol secretion
  • Hair – representing long-term cortisol levels

 

Cardiac performance – Autonomic nervous system:

The autonomic nervous system (ANS) is one of the main influencers of cardiac performance. Heart rate and heart rate variability (HRV) can be used to assess variations within the ANS response to stressors. Heart rate refers to the number of beats per minute. HRV refers to the fluctuating time in between heart beats. When exposed to stress, heart rate as well as breathing patterns often speed up while HRV decreases (2).

 

Cytokines – Immune system:

Activation of the immune system is also a response to stress. Cytokines are a group of signalling molecules which regulate immune function. They can be measured from the blood. Interleukin (IL)-6, for example, plays an important role in the onset of fever and the acute inflammatory response. C-reactive protein (CRP) is released in response to inflammation and has been associated with stress in humans (2).

 

Grasping the relationship between stress and health

Stress can be measured at multiple levels. Self-assessment scales reflect a subjective way to measure stress while biomarkers reflect a more objective measure of stress. Both types of measures are important in order to understand the relationship between stress and health.