19 researchers and clinicians from Essen, Marburg and Hamburg are working in close cooperation on 16 projects. © SFB Treatment Expectation
The transregional DFG (German Research Foundation) collaborative research centre (CRC/Transregio 289) entitled "Treatment Expectation" is an interdisciplinary team investigating the impact of patient expectation on the efficacy of medical treatments.
Video: Patient perspectives
No placebo effect without expectation
Researchers have known for a long time that expectations can influence physical symptoms, the course of an illness and the efficacy of treatments. Patients experience what are known as placebo effects. It has been shown that a capsule with no active ingredient or specific information from the doctor can have powerful effects. Patient expectation of treatment is the key to these effects.
This has great therapeutic potential. Where do expectations come from and how can we influence them? Can treatment providers use this knowledge to improve the efficacy and tolerability of medications and treatments? What happens in the brain, and what are the psychological and neurobiological mechanisms underlying the effect?
Scientific basis for personalised medicine
The "Treatment Expectation" research network provides a unique opportunity for an interdisciplinary team led by the University of Duisberg-Essen to examine these questions from different perspectives in clinical and experimental studies. The first stage of its research focuses on two common conditions: chronic pain and depression. Autoimmune and cardiovascular diseases will be studied later.
Its research is highly interdisciplinary and translational in nature. The overall objective is to apply the knowledge gained from basic research to the systematic use of expectation effects in everyday clinical practice for targeted optimisation of treatment efficacy and tolerability.
Collaborative research centres are long-term, university-based research institutions in which scientists work together in an interdisciplinary research programme for up to 12 years.
They enable innovative, ambitious, complex and long-term research projects to be undertaken through the coordination and concentration of individuals and resources at the universities that apply, thereby facilitating institutional specialisation and structural development. Cooperation with non-university research institutions is actively encouraged. Collaborative research centres consist of many different projects, which are led either by individuals or by a team of scientists.
Collaborative Research Centre CRC/TRR 289 has received DFG funding of around 12 million euros to cover – as is usual – the first four years of the project.
Interdisciplinary and translational approach
The role of the collaborative research centre "Treatment Expectation" is to find valid answers to the following questions through clear hypotheses and highly standardised experimental set-ups – from animal models to clinical studies – in two suitable model systems: Where do expectations come from? What role do positive or negative expectations play in the treatment of patients? Do they help or hinder the treatment outcome? And which mechanisms in the brain and body underlie these effects?
Researchers in fields ranging from neurobiology to computer science, psychologists and medics from a variety of disciplines conduct research together in three locations. It is a structure that is unique and exemplary in Europe. The individual projects are orchestrated in such a way that ultimately they come together to answer the big question: How can medicine use patient expectations to improve treatment?
An example to illustrate this special translational approach to research.
From dopamine to expectation
The brain is constantly making decisions that are influenced by experience. It is a rule-seeking machine made of around 100 billion nerve cells with an estimated 15 trillion connections, which changes permanently as we observe, learn, think and remember. The dorsolateral prefrontal cortex (DLPFC) – a small area on the side of the upper frontal lobes – has the most diverse connections to other areas of the brain. It controls our motivation, memory, decisions and expectations, our feelings in social relationships, whether we are sceptical, whether we reject or desire something and our sense of well-being. The DLPFC is therefore the hub of the reward system.
This neural network is where we develop our own very personal self over the course of our lives, and it is subject to constant change. Stress and depression, for example, have an effect on this system. One of the most important neurotransmitters, which relays all of this information between neurons, is the messenger dopamine.
One of the CRC's central research questions is therefore: How important are dopamine and the entire dopaminergic reward system for treatment expectation and what are the resulting effects on the efficacy of medication?
From animal models to clinical studies
Project A09 uses an animal model to explore how the dopaminergic signalling system interacts with antidepressants and influences their efficacy. It investigates effects on the behaviour of rats at molecular and neural level.
How previous negative experiences influence brain function and promote the development of side effects in rats is the focus of A10.
A01 shows how the brains of healthy participants respond to mild pain evoked by heat with varying modulation of dopamine and the dopaminergic system. Using functional magnetic resonance imaging, this study design shows variations in treatment expectation and the sensation of pain.
The importance of the dopaminergic system for expectation effects in healthy participants with depressive mood is at the core of project A07. The dopaminergic system is modulated in the same way as in A01 and activity in the prefrontal cortex is studied using EEG (electroencephalography).
Project A08 explores how individual patient expectations affect the efficacy of an antidepressant during an acute depressive episode. How do the symptoms and activity in the prefrontal cortex and reward system of these patients change?
Projects Z02 and Z03 combine the results of the individual projects and look for general markers to help predict which treatment effects will be seen in which patients as a result of positive or negative expectations of a disease.
Patient expectation of treatment is a key determinant of its success. Expectations can influence the onset of physical symptoms, the development and course of diseases and the efficacy and tolerability of treatments. The overall objective of the collaborative research centre "Treatment Expectation" (CRC/TRR 289) is to obtain the information required for systematic use of expectation effects during medical treatments. To achieve this, the psychological and neurobiological mechanisms of positive and negative treatment expectations and their effects on pharmacological treatments will be studied in two clinically relevant conditions – pain and affective disorders – using appropriate experimental models. This highly interdisciplinary and translational research focuses on general hypotheses, which will be tested together in animal, human and proof-of-concept clinical studies of the mechanisms and effects of treatment expectations, both alone and particularly in combination with so-called gold-standard treatments.
CRC/TRR 289 is a long-term project in which the focus will shift from characterisation of the underlying mechanisms to systematic use of expectation effects in medical treatment situations. In the first funding period, priority will be given to experimental studies of the mechanisms of expectation effects on physical and psychological symptoms during medical treatments, with special focus on the identification of predictors for interindividual differences. At the same time, initial proof-of-concept clinical studies will explore opportunities for clinical use of expectation effects in patients with chronic pain or depression. The overall objective of the second funding period will be to investigate the dynamic nature of expectations. How expectations change and how these changes are influenced by individual previous experiences and by other contextual and personal variables will be studied in this phase. We further plan to extend the model systems so that treatment expectation mechanisms and effects can also be studied for disorders with primarily objective outcomes (e.g. autoimmune or cardiovascular diseases).
In a third and final period of funding, this basic research from the first and second phase will be used systematically to influence patient expectations and thereby optimise the efficacy and tolerability of medical treatments in the form of personalised medicine. The knowledge gained promises to have significant implications for the planning and analysis of clinical studies as well as treatment planning.