Universiteit Leiden

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Research project

The power of expectations: Unraveling the role of placebo and nocebo effects in somatic symptoms

Somatic symptoms are highly prevalent and have a major impact on patients and society. This project studies the role of placebo and nocebo effects in the onset, experience, course, and recovery of such somatic symptoms by means of innovative psychological and neurobiological methods and treatments.

Andrea Evers
NWO Vici grant
CSC grant
NWO talent grant

Somatic symptoms have a high prevalence and impact on patients and society. A substantial proportion of these symptoms sensitize (i.e. progressively amplify and generalize) and develop into chronic complaints such as chronic pain, itch, or fatigue. Placebo and nocebo effects contribute substantially to somatic symptoms and might partially explain sensitization and desensitization of somatic symptoms.

We use a comprehensive psychoneurobiological approach to 1) study the mechanisms of placebo and nocebo effects in the sensitization and desensitization of somatic symptoms; 2) identify patients at risk for symptom sensitization; and 3) develop innovative treatments for desensitization of somatic symptoms.

For this purpose, we use a unique set of psychoneurobiological methods, particularly focused on psychological (counter)conditioning, in experimental, prospective, and treatment studies, both in healthy participants and in patients with chronic somatic symptoms.

This interdisciplinary, translational project progresses key theoretical knowledge of the main psychoneurobiological nocebo mechanisms of various somatic symptoms. Findings open up new horizons for prevention and treatment, by identifying patients at risk for symptom sensitization and generating targeted treatments for symptom desensitization and recovery.

This project is divided into six PhD projects, conducted by: Mia Thomaïdou, Joe Blythe, Fabian Wolters, Merve Karacaoglu, Simone Meijer, LingLing Weng. The projects are supervised by Prof. dr. Andrea Evers, Dr. Judy Veldhuijzen, Dr. Henriët van Middendorp, Dr. Kaya Peerdeman, & Dr. Antoinette van Laarhoven

1. Mechanisms: Unraveling mechanisms of placebo and nocebo effects

We aim to contribute to unraveling the psychoneurobiological mechanisms of nocebo effects on physical symptoms, specifically pain, itch, and fatigue. We study the induction of nocebo effects by  classical conditioning procedures as well as counterconditioning procedures in healthy participants. Pharmacological inductions (i.e., modulating NMDA receptors) and resting-state fMRl scans will aid in the study of the psychological and neurophysiological correlates involved in (counter) conditioned nocebo effects on pain and itch. Moreover, we investigate the transferability of placebo and nocebo effects, specifically whether the effects generalize from pain to itch and from itch to pain. Furthermore, we study the conditioning of circadian rhythms in humans, specifically the cortisol awakening response.

2. Prediction: Identifying patients at risk for the sensitization of somatic symptoms

To identify patients at risk for sensitization of their somatic symptoms, we use an integrated multimethod approach that makes use of nocebo (counter)conditioning methods in experimental laboratory studies in combination with a prospective design. Patients with somatic symptoms will be followed during the ongoing process of the sensitization or desensitization of their somatic symptoms.

3. Treatment: Developing innovative treatments for the desensitization of somatic symptoms

A novel treatment for patients with chronic somatic symptoms is developed to desensitize somatic symptoms by psychological counterconditioning of nocebo effects. If found to be effective, this treatment could open up new horizons for the application of fundamental knowledge about psychoneurobiological mechanisms of change, and, more importantly, for possible recovery for patients with chronic somatic symptoms.

 This research program is part of the Research Group Psychoneurobiology of Health and Disease (www.andreaevers.nl) and is conducted in collaboration with the Leiden University Medical Center among other centers. 

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