Interoception in Patients With Medically Unexplained Symptoms

The goal of this observational study is to learn about interoception in patients with stress related syndromes (overstrain, burnout; SRS) and functional disorder (fibromyalgia/ chronic fatigue syndrome; FD). The main questions it aims to answer are:

* Is there a significant difference in interoception between patients with SRS and healthy controls?
* Is there a significant difference in interoception between patients with FD and healthy controls?
* Is there a significant difference in interoception between patients with SRS and FD?

The participants will perform the respiratory occlusion discrimination task and have to fill out some questionnaires.

Researchers will compare healthy controls to see if there is a significant difference.

About 40-49% of primary care patients report somatic symptoms that cannot be explained by any well-known organic disease. Typical examples are headache, dizziness, shortness of breath, fatigue, muscle aches, nausea, and gastrointestinal symptoms. These bodily symptoms can occur in the context of SRS such as overstrain and burnout, but also as clusters in a more chronic form, often referred to as FD, such as fibromyalgia or chronic fatigue syndrome.

Fibromyalgia is a chronic widespread pain condition characterized by point tenderness, fatigue, sleep disturbance, cognitive complaints, and increasing somatic complaints. In addition, chronic fatigue syndrome is a chronic condition characterized by severe fatigue, impairments in concentration and short-term memory, sleep disturbance, and musculoskeletal pain. Both are multi-faceted and challenging chronic conditions with considerable overlap in symptoms, causes and treatments. According to multidisciplinary guidelines, overstrain is characterized by the following symptoms: disturbed or restless sleep, irritability, not being able to stand commotion/ noise, emotional lability, feeling stressed or rushed, not being able to relax, difficulty concentrating and/or forgetfulness with a duration of 3 months. Burnout occurs when symptoms of overstrain persist for more than 6 months, and feelings of fatigue and exhaustion become prominent. The patient experiences significant limitations in professional and/or social functioning.

Interoception has been described in the literature as "the overall process of how the nervous system senses, integrates, stores and displays information about the state of the internal body". Theory suggests that interoception should be divided into three measurable constructs: interoceptive accuracy (objective accuracy in detecting internal bodily sensations), interoceptive sensitivity (the self-perceived tendency to be internally self-focused), and interoceptive awareness (metacognition about his/her own interoceptive accuracy).

The measurement will take place in the TRACE labs of Ziekenhuis Oost Limburg (ZOL). The informed consent will be signed before any data collection takes place. The experiment will take approximately 30 minutes. Participants will start with the interoceptive accuracy task using the Respiratory Occlusion Discrimination Task (ROD task). The ROD task measures how good subjects are at distinguishing the lengths of short (max 620 ms) inspiratory occlusions (or respiratory interruptions). Occlusions of these lengths are not aversive or unpleasant. One trial consists of two occlusions within one inspiration (inter-occlusion interval = 300 milliseconds), one occlusion being the reference occlusion (always 440 milliseconds) and one occlusion being the test occlusion (longer or shorter than 440 milliseconds), administered in random order. The participant is asked to indicate which of the two occlusions was longest. An adaptive staircase paradigm is used to determine the just noticeable difference in lengths of inspiratory occlusions. The length of the task depends on the performance of the subject, but is on average 56 trials (= 15 minutes). After the experiment, another short side experiment of 16 trials will be conducted in which the participant should indicate how confident they were in their response on a Visual Analogue scale (VAS), in order to estimate interoceptive awareness. In the meantime, participants will be also asked to complete a questionnaire bundle at home (online), which takes approximately 45 minutes to complete.

The power calculations resulted in a total of 28 persons per group. Therefore the investigators plan to recruit a total of 84 people.

Primary outcomes are interoceptive accuracy, interoceptive sensibility, and interoceptive awareness. Secondary outcome measures are psychological variables measured using questionnaires.

Descriptive statistics will be used to display baseline group characteristics. To evaluate between-group differences (i.e. the difference between patients with FD,SRS and healthy controls regarding interoception and psychological variables) one-way ANOVA's will be used.

Eligibility Criteria:
Eligibility Criteria patients with FD (fibromyalgia and/or chronic fatigue syndrome)

Inclusion Criteria:

* patients with fibromyalgia should be diagnosed by using the ACR criteria (American College of Rheumatology, Wolfe et al., 2010; Wolfe et al., 2016). patients with chronic fatigue syndrome should be diagnosed by using the CDC criteria (Centers for Disease Control and Prevention; Fukuda et al., 1994).

Exclusion Criteria:

* Younger than 18 or older than 65
* Pregnancy
* Primary depressive episode, anxiety disorder, eating disorder, substance abuse, neurocognitive, or psychotic episode diagnosed with DSM-V (Diagnostic and Statistical Manual of Mental Disorders; MINI-s; Overbeek et al., 1999).
* Presence of a chronic organic disorder (One speaks of a chronic organic disorder if it is present for a period of at least 3 months. Examples include: Epilepsy, Heart Disease, Rheumatism, Asthma, Diabetes, etc.) or acute organic condition (fever, flu, etc.)
* BMI \> 30

Eligibility Criteria patients with SRS (overstrain or burnout)

Inclusion Criteria:

- patients with overstrain or burnout should be diagnosed according to the multidisciplinary guidelines for overstrain and burnout for first-line professionals from the Dutch Society of Occupational Medicine (NVAB, 2011)

Exclusion Criteria:

* Younger than 18 or older than 65
* Pregnancy
* Primary depressive episode, anxiety disorder, eating disorder, substance abuse, neurocognitive, or psychotic episode diagnosed with DSM-V (MINI-s; Overbeek et al., 1999).
* Presence of a chronic organic disorder (One speaks of a chronic organic disorder if it is present for a period of at least 3 months. Examples include: Epilepsy, Heart Disease, Rheumatism, Asthma, Diabetes, etc.) or acute organic condition (fever, flu, etc.)
* BMI \> 30

Eligibility Criteria healthy controls

Inclusion Criteria:

Healthy controls will be selected so that there is an equal ratio between patients and healthy controls for

* Age group (per 5 years)
* Gender (including X)
* Educational attainment
* BMI

all participants need a score \< 75 on the CSD (Walentynowicz, et al., 2018)

Exclusion Criteria:

* Younger than 18 or older than 65
* Pregnancy
* Presence of a depressive episode, anxiety disorder, eating disorder, substance abuse, neurocognitive, or psychotic disorder diagnosed with DSM-V (MINI-s; Overbeek et al., 1999).
* Presence of a chronic organic disorder (One speaks of a chronic organic disorder if it is present for a period of at least 3 months. Examples are: epilepsy, heart disease, rheumatism, asthma, diabetes, etc.) or acute organic disorder (fever, flu, etc.)
* BMI \> 30
* Persistent physical symptoms (e.g., hyperventilation symptoms, prolonged COVID, chronic pain or fatigue, chronic tinnitus, etc.)