Universiteit Leiden

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Research project

Psychophysiological responses to stress and stress management

The major aim is to determine the psychophysiological responses to stress and stress-management interventions and to examine the role of stress and stress-related psychophysiological mechanisms (e.g., cognitions, behaviors, and physiological stress responses) in both healthy and medical populations.

Andrea Evers
NWO Research Talent
ERC Consolidator Grant

STRESS-NL consortium


Background/Scientific relevance:

Stress is a broad concept for a complex process including the exposure to psychological or physical triggers (i.e., stress exposure), the  evaluation or perception of these stimuli as being stressful (i.e., stress evaluation), and the subsequent activation of a psychophysiological cascade (i.e., the stress response) in the organism in order to re-establish homeostasis. Because this cascade acts upon the autonomic nervous system (ANS), including the sympathetic adrenal  medullary (SAM) axis, and the neuroendocrine system, including the hypothalamus-pituitary-adrenal (HPA) axis,  this cascade also acts upon the immune system and consequently possibly stress is able to influence disease processes. In patients with (persistent) physical symptoms, such as pain or fatigue, and chronic conditions, such as rheumatoid arthritis or psoriasis, physical disability, uncertainty about the future, long-term medication use with side effects, and social dependence all contribute to a higher stress level. Consequently, stress may be contributing to the etiology or maintenance of persistent physical symptoms and chronic conditions.

There is a growing body of evidence, including research of our research group (see publications of De Brouwer et al.), that suggests that psychological interventions are able to change various psychophysiological parameters of stress and/or disease, which indicates that it may be possible to counteract the harmful effects of stress on health with an intervention aimed at reducing the psychophysiological response to stress. 


Aims for current research:

This research program aims to provide greater insight into the nature and reactivity of the psychophysiological stress response system in both healthy participants and patients with different persistent physical symptoms or chronic diseases, and to develop and investigate the effectiveness of stress management interventions to alter the psychophysiological stress response. Several research projects are currently ongoing or have recently finished with regard to this Stress and Stress management program:

The underlying physiological and psychological mechanisms of nocebo effects remain largely unclear. One potential factor that may trigger nocebo effects is stress. As such, one of our projects focuses on whether social stress is a facilitator of nocebo effects and whether people who were recently exposed to social stress demonstrate larger nocebo effects, compared with people who were not exposed to stress. This project also relates to the topic ‘Placebo Effects'  (Postdocs Aleksandrina Skvortsova and Stefanie Meeuwis).

Another project examines the effect of sleep quality on the relationship between stress and cortisol. The goal of this study is to examine the influence of non-manipulated poor

sleep quality in healthy young adults on the cortisol response to two different types of experimental stressors, psychosocial and physical stress (PhD student Fabian Wolters).

A different project investigates whether verbal suggestions on a person’s psychophysiological stress profile (being stress-resistant or stress-sensitive), aimed to change one’s stress mindset, influences the psychophysiological response to stress. In this study, affective, autonomous, and HPA-axis parameters are assessed, as well as implicit cognitive processes. Knowledge on the potential effects of verbal suggestions on subjective and physiological stress responses is not only of conceptual relevance in investigating placebo and nocebo effects, but also of clinical relevance as they provide insight in the development and treatment of stress-related disorders. This project is also related to the topic Placebo Effects'.


Another project examines the conditioning of a stress management training to a distinctive scent. In this project, we aim to investigate whether the administration of a distinctive scent after conditioning of the scent to a stress management training can result in positive psychological and physiological stress response effects after acute stress in a population of healthy adults (PhD student Meriem Manaï). This project is also related to the topic Placebo Effects’.

A large national project in which our research group participates is the STRESS-NL consortium (https://stress-nl.nl/). The Stress-NL consortium aims to change the current way of performing stress studies, by combining knowledge, efforts, and sharing data, but also joining efforts to emphasize the importance of fundamental and applied stress research to funding agencies, the government and the general public. Several of our previous studies in which an acute stressor has been applied in either healthy participants or patients with chronic inflammatory conditions have been included into a large database, building a platform for exchange and integration of data to enable larger (meta) analyses of data acquired across multiple sites and research groups.

De Brouwer, S.J.M., Van Middendorp, H., Kraaimaat, F.W., Radstake, R.D.J., Joosten, I., Donders, A.R.T., Eijsbouts, E., Spillekom-van Koulil, S., Van Riel, P.L.C.M., & Evers, A.W.M. (2013). Immune responses to stress after stress management training in patients with rheumatoid arthritis. Arthritis Research and Therapy, 15, R200.

De Brouwer, S.J.M., Van Middendorp, H., Stormink, C., Kraaimaat, F.W., Joosten, I., Radstake, T.R.D.J., De Jong, E.M.G.J., Schalkwijk, J., Donders, A.R.T., Eijsbouts, A., Van de Kerkhof, P.C.M., Van Riel, P.L.C.M., & Evers, A.W.M. (2014). Immune responses to stress in rheumatoid arthritis and psoriasis. Rheumatology, 53, 1844-1848.

De Brouwer, S.J.M., Van Middendorp, H., Stormink, C., Kraaimaat, F.W., Sweep, F.C.G.J., De Jong, E.M.G.J., Schalkwijk, J., Eijsbouts, E., Donders, A.R.T., Van de Kerkhof, P.C.M., Van Riel, P.L.C.M., & Evers, A.W.M. (2014). The psychophysiological stress response in psoriasis and rheumatoid arthritis. British Journal of Dermatology, 170, 824-831.

Evers, A.W.M., Verhoeven, E.W.M., Van Middendorp, H., Sweep, F.C.G.J., Kraaimaat, F.W., Donders, A.R.T., Eijsbouts, A.E., Van Laarhoven, A.I.M., De Brouwer, S.J.M., Wirken, L., Radstake, T.R.D.J., & Van Riel, P.L.C.M. (2014). Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis. Annals of the Rheumatic Diseases, 73, 1683-1688.

Geenen, R., Van Middendorp, H., & Bijlsma, J.W.J. (2006). The impact of stressors on health status and hypothalamic-pituitary-adrenal axis and autonomic nervous system responsiveness in rheumatoid arthritis. Annals of the New York Academy of Sciences, 1069, 77-97.

Overman, C.L., Bossema, E.R., Van Middendorp, H., Wijngaards-de Meij, L., Verstappen, S.M.M., Bulder, M., Jacobs, J.W.G., Bijlsma, J.W.J., & Geenen, R. (2012). The prospective association between psychological distress and disease activity in rheumatoid arthritis: A multilevel regression analysis. Annals of the Rheumatic Diseases, 71, 192-197.

Schakel, L., Veldhuijzen, D.S., Crompvoets, P.I., Bosch, J.A., Cohen, S, Van Middendorp, H., Joosten, S.A., Ottenhoff, T.H.M., Visser, L.G., & Evers, A.W.M. (2019). Effectiveness of stress-reducing interventions on the response to challenges to the immune system: A meta-analytic review. Psychotherapy and Psychosomatics, 88, 274-286. doi: 10.1159/000501645.

Schakel, L., Veldhuijzen, D.S., Van Middendorp, H., Manaï, M., Meeuwis, S.H., Van Dessel, P., & Evers, A.W.M. (2019). Can verbal suggestions strengthen the effects of a relaxation intervention? PLoS One, 14, e0220112.

Van Middendorp, H., & Evers, A.W.M. (2016). The role of psychological factors in inflammatory rheumatic diseases: From burden to tailored treatment. Best Practice & Research in Clinical Rheumatology, 30, 932-945. doi:10.1016/j.berh.2016.10.012

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