Frequently, ME/CFS research compares patients with ME/CFS to healthy individuals. Sometimes differences in biomarkers are found. The challenge is that it can be difficult to know whether these differences are related to the causes of the disease. The differences might just as well be consequences of the illness. People with ME/CFS live very different lives than healthy people—they sleep differently and are much less active. That affects a wide range of biomarkers, such as certain hormones.

If you want to understand which mechanisms contribute to the development of the disease, you need to follow people while they are still healthy. Some of these people will develop ME/CFS in the years that follow. These individuals can then be compared to people who did not become ill. And if differences are found, researchers can investigate whether those differences were already present before illness onset. Lifelines is the first biobank in the world where such research is possible.

There is still no biomarker to diagnose ME/CFS. Four main diagnostic methods are used (the CDC, IOM, ICC, and CCC criteria). All of these rely on specific symptoms reported by patients.

In Lifelines, all these symptoms are included in an additional questionnaire (the DSQ 2) completed by all adult participants. However, the diagnostic methods for ME/CFS are based on symptoms—such as severe fatigue—that can also have other causes. That is why we use the medical examinations within Lifelines to assess whether other explanations might account for the symptoms.

Lifelines participants undergo a lung function test, an ECG, a psychiatric interview, and several blood and urine tests to check for conditions such as anemia or kidney disease. Medical specialists review the results to determine whether there are abnormalities requiring further investigation. Only when no alternative explanations are found do we conclude that the person has ME/CFS.

We have chosen a broad approach. Many studies focus on a single mechanism, but we also want to uncover new, yet unknown pathways. For this reason, we do not focus narrowly on specific abnormalities. Instead, we look broadly across many types of biological data. We examine genetic predisposition and measure more than 3,000 proteins in the blood, over 10,000 metabolic products, and antibodies against more than 100,000 bacterial and viral structures.

By measuring all these factors in individuals who developed ME/CFS, compared with those who did not, we gain clearer insight into the mechanisms underlying the illness. We also link these data together. For example, we can investigate how genetic predisposition contributes to ME/CFS and which proteins play a role. Or how antibodies against gut bacteria might influence energy metabolism.

Most participants in this study come from Lifelines, but not all. We are also recruiting 100 patients with severe ME/CFS who are not part of Lifelines. This is important because homebound patients are unable to participate in Lifelines. To ensure we include enough individuals with severe ME/CFS, we recruit these participants outside Lifelines. A single short home visit makes participation feasible even for the most severely ill patients. Participants outside Lifelines are also sought for the study on Post Exertional Malaise (PEM). In addition, there are several other studies within the ZonMw ME/CFS programme that patients can join. If you are not a Lifelines participant but may be interested in taking part in one of the studies in the ZonMw ME/CFS programme, you can express your interest via this website: mecvs.nl