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.

Study Overview

• Status: Recruiting
• Conditions: Burnout, Psychological; Fibromyalgia
• Intervention / Treatment: Other: Interoceptive accuracy measurement; Other: Interoceptive awareness measurement; Other: Interoceptive sensibility measurement

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 84

Contacts and Locations

• Study Contact: Name: Marleen Missotten; Phone Number: +32(0)11268502; Email: CME@uhasselt.be
• Study Contact Backup: Name: Indra Ramakers, Dra; Phone Number: +32483082723; Email: indra.ramakers@uhasselt.be

Study Locations

• Belgium
  • Lanaken, Belgium, 3620
    • Recruiting
    • TRACE labs Ziekenhuis Oost-Limburg (ZOL)
    • Contact: Indra Ramakers; Phone Number: +32483082723; Email: indra.ramakers@uhasselt.be
  • Limburg
    • Diepenbeek, Limburg, Belgium, 3590
      • Recruiting
      • Hasselt University
      • Contact: Indra Ramakers; Phone Number: +32483082723; Email: indra.ramakers@uhasselt.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

All patients with fibromyalgia diagnosed according to the ACR criteria (Wolfe et al., 2010; 2016) are eligible to participate, all patients with chronic fatigue syndrome diagnosed according to the CDC criteria (Fukuda et al., 1994), and all patients with overstrain or burnout diagnosed according to the multidisciplinary guidelines for overstrain and burnout for first-line professionals from the Dutch Society of Occupational Medicine (NVAB, 2011) are eligible to participate

Description

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.)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with functional disorder (FD); Patients with fibromyalgia diagnosed using the ACR criteria (American College of Rheumatology, Wolfe et al., 2010; 2016) Patients with chronic fatigue syndrome diagnosed using the CDC criteria (Centers for Disease Control and Prevention; Fukuda et al., 1994)	Other: Interoceptive accuracy measurement; Interoceptive accuracy will be measured using the Respiratory Occlusion Discrimination Task (ROD task; Van Den Houte et al., 2021). The ROD task measures how good subjects are at distinguishing the lengths of short (max 620 milliseconds) inspiratory occlusions (or respiratory interruptions).; Other: Interoceptive awareness measurement; Interoceptive awareness will be measures using a visual analogue scale (VAS); Other: Interoceptive sensibility measurement; Interoceptive sensibility will be measured using two self-report questionnaires, the The Interoceptive Sensitivity and Attention Questionnaire (ISAQ; Bogaerts et al., 2022) and the the Three-domain Interoceptive Sensations Questionnaire (THISQ; Vlemincx et al., 2021)
Patients with stress related syndromes (SRS); Patients with overstrain and burnout according to the multidisciplinary guidelines for overstrain and burnout in primary care from the Dutch Society of Occupational Medicine (NVAB, 2011)	Other: Interoceptive accuracy measurement; Interoceptive accuracy will be measured using the Respiratory Occlusion Discrimination Task (ROD task; Van Den Houte et al., 2021). The ROD task measures how good subjects are at distinguishing the lengths of short (max 620 milliseconds) inspiratory occlusions (or respiratory interruptions).; Other: Interoceptive awareness measurement; Interoceptive awareness will be measures using a visual analogue scale (VAS); Other: Interoceptive sensibility measurement; Interoceptive sensibility will be measured using two self-report questionnaires, the The Interoceptive Sensitivity and Attention Questionnaire (ISAQ; Bogaerts et al., 2022) and the the Three-domain Interoceptive Sensations Questionnaire (THISQ; Vlemincx et al., 2021)
Healthy controls; Healthy controls will consist of people who experience few physical complaints in daily life. The healthy controls will thus be screened for inclusion using the CSD (Checklist for Symptoms in Daily life; Walentynowicz, et al., 2018). Only volunteers with a score of 75 or lower on this questionnaire will be included	Other: Interoceptive accuracy measurement; Interoceptive accuracy will be measured using the Respiratory Occlusion Discrimination Task (ROD task; Van Den Houte et al., 2021). The ROD task measures how good subjects are at distinguishing the lengths of short (max 620 milliseconds) inspiratory occlusions (or respiratory interruptions).; Other: Interoceptive awareness measurement; Interoceptive awareness will be measures using a visual analogue scale (VAS); Other: Interoceptive sensibility measurement; Interoceptive sensibility will be measured using two self-report questionnaires, the The Interoceptive Sensitivity and Attention Questionnaire (ISAQ; Bogaerts et al., 2022) and the the Three-domain Interoceptive Sensations Questionnaire (THISQ; Vlemincx et al., 2021)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interoceptive accuracy	Respiratory occlusion discrimination task (ROD task; Van Den Houte et al., 2021)	20 minutes
Interoceptive sensibility	Interoceptive Sensitivity and Attention Questionnaire (ISAQ; Bogaerts et al., 2022)	5 minutes
Interoceptive sensibility	THree-domain Interoceptive Sensations Questionnaire (THISQ; Vlemincx et al., 2021)	5 minutes
Interoceptive awareness	Visual analogue scale (0-100). A score of 0 indicates that participants are not certain at all of their answer, a score of 100 indicates that participants are entirely certain of their answer	5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological variables	Positive and Negative Affect Scale (PANAS; Watson et al., 1988)	5 minutes
Psychological variables	Tellegen Absorption Scale (TAS; Tellegen & Atkinson, 1974)	5 minutes
Psychological variables	Traumatic Experiences Checklist (TEC; Nijenhuis et al., 2002)	10 minutes
Psychological variables	Toronto Alexithymia Scale (TAS-20; Bagby et al., 1994)	5 minutes
Psychological variables	Need for Controllability and Predictability Questionnaire (NCP-q; Ramakers et al., manuscript in preparation)	5 minutes
Psychological variables	Frost Multidimensional Perfectionism Scale (FMPS; Frost et al., 1990)	5 minutes
Psychological variables	Acceptance and Action Questionnaire-II (AAQ-II; Bond et al., 2011)	5 minutes
Psychological variables	Checklist for Symptoms in Daily Life (CSD; Walentynowicz et al., 2018)	5 minutes

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: TRACE labs Ziekenhuis Oost-Limburg (ZOL)
• Investigators: Principal Investigator: Katleen Bogaerts, PhD, Hasselt University

Publications and helpful links

General Publications

• Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988 Jun;54(6):1063-70. doi: 10.1037//0022-3514.54.6.1063.
• Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Hauser W, Katz RL, Mease PJ, Russell AS, Russell IJ, Walitt B. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016 Dec;46(3):319-329. doi: 10.1016/j.semarthrit.2016.08.012. Epub 2016 Aug 30.
• Bagby RM, Parker JD, Taylor GJ. The twenty-item Toronto Alexithymia Scale--I. Item selection and cross-validation of the factor structure. J Psychosom Res. 1994 Jan;38(1):23-32. doi: 10.1016/0022-3999(94)90005-1.
• Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken). 2010 May;62(5):600-10. doi: 10.1002/acr.20140.
• Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15;121(12):953-9. doi: 10.7326/0003-4819-121-12-199412150-00009.
• Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, Waltz T, Zettle RD. Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 2011 Dec;42(4):676-88. doi: 10.1016/j.beth.2011.03.007. Epub 2011 May 25.
• Khalsa SS, Adolphs R, Cameron OG, Critchley HD, Davenport PW, Feinstein JS, Feusner JD, Garfinkel SN, Lane RD, Mehling WE, Meuret AE, Nemeroff CB, Oppenheimer S, Petzschner FH, Pollatos O, Rhudy JL, Schramm LP, Simmons WK, Stein MB, Stephan KE, Van den Bergh O, Van Diest I, von Leupoldt A, Paulus MP; Interoception Summit 2016 participants. Interoception and Mental Health: A Roadmap. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Jun;3(6):501-513. doi: 10.1016/j.bpsc.2017.12.004. Epub 2017 Dec 28.
• Garfinkel SN, Seth AK, Barrett AB, Suzuki K, Critchley HD. Knowing your own heart: distinguishing interoceptive accuracy from interoceptive awareness. Biol Psychol. 2015 Jan;104:65-74. doi: 10.1016/j.biopsycho.2014.11.004. Epub 2014 Nov 20.
• Walentynowicz, M., Witthöft, M., Raes, F., Van Diest, I., & Van den Bergh, O. (2018). Sensory and affective components of symptom perception: a psychometric approach. Journal of Experimental Psychopathology, 9(2), 1-13. Doi: 10.5127/jep.059716
• Van Den Houte M, Vlemincx E, Franssen M, Van Diest I, Van Oudenhove L, Luminet O. The respiratory occlusion discrimination task: A new paradigm to measure respiratory interoceptive accuracy. Psychophysiology. 2021 Apr;58(4):e13760. doi: 10.1111/psyp.13760. Epub 2021 Jan 12.
• Bogaerts K, Walentynowicz M, Van Den Houte M, Constantinou E, Van den Bergh O. The Interoceptive Sensitivity and Attention Questionnaire: Evaluating Aspects of Self-Reported Interoception in Patients With Persistent Somatic Symptoms, Stress-Related Syndromes, and Healthy Controls. Psychosom Med. 2022 Feb-Mar 01;84(2):251-260. doi: 10.1097/PSY.0000000000001038.
• Vlemincx E, Walentynowicz M, Zamariola G, Van Oudenhove L, Luminet O. A novel self-report scale of interoception: the three-domain interoceptive sensations questionnaire (THISQ). Psychol Health. 2021 Dec 7:1-20. doi: 10.1080/08870446.2021.2009479. Online ahead of print.
• Nijenhuis, E. R. S., van der Hart, O., & Kruger, K. (2002). The psychometric characteristics of the Traumatic Experiernce Checklist (TEC): First findings among psychiatric outpatients. Clinical Psychology & Psychotherapy, 9(3). 200-210. DOI: 10.1002/cpp.332
• Ramakers, I., Fonteyne, R., Walentynowicz, M., Van Oudenhove, L., Van Den Houte, M., & Bogaerts, K. (2023). The need for controllability and predictability questionnaire (NCP-q): Psychometric properties and first findings in a clinical sample. (Manuscript in preparation).
• Frost, R. O., Marten, P., Lahart, C., & Rosenblate, R. (1990). The dimensions of perfectionism. Cognitive Therapy and Research, 14(5), 449-468. https://doi.org/10.1007/BF01172967
• Tellegen A, Atkinson G. Openness to absorbing and self-altering experiences ("absorption"), a trait related to hypnotic susceptibility. J Abnorm Psychol. 1974 Jun;83(3):268-77. doi: 10.1037/h0036681. No abstract available.
• Overbeek, T., Schrueurs, K., & Griez, E. (1999). MINI-the international neuropsychiatric interview. Dutch version 5.0.0 DSM-IV. Maastricht (Netherlands): University of Maastricht.
• Haller H, Cramer H, Lauche R, Dobos G. Somatoform disorders and medically unexplained symptoms in primary care. Dtsch Arztebl Int. 2015 Apr 17;112(16):279-87. doi: 10.3238/arztebl.2015.0279.
• Barsky AJ, Borus JF. Functional somatic syndromes. Ann Intern Med. 1999 Jun 1;130(11):910-21. doi: 10.7326/0003-4819-130-11-199906010-00016.
• Courtois I, Cools F, Calsius J. Effectiveness of body awareness interventions in fibromyalgia and chronic fatigue syndrome: a systematic review and meta-analysis. J Bodyw Mov Ther. 2015 Jan;19(1):35-56. doi: 10.1016/j.jbmt.2014.04.003. Epub 2014 Apr 18.
• NVAB. (2011). Eén lijn in de eerste lijn bij overspanning en burnout: Multidisciplinaire richtlijn overspanning en burnout voor eerstelijns professionals. Geraadpleegd van https://nvab-online.nl/sites/default/files/bestanden-webpaginas/MDRL_Overspanning-Burnout.pdf
• Terluin, B., Van der Klink, J., Schaufeli, W. (2005). Stressgerelateerde klachten: spanningsklachten, overspanning en burnout. In J. Van der Klink, B. Terluin B (Reds), Psychische problemen en werk. Handboek voor een activerende begeleiding door huisarts en bedrijfsarts (p. 259-290). Houten: Bohn Stafleu Van Loghum.
• van der Klink JJ, van Dijk FJ. Dutch practice guidelines for managing adjustment disorders in occupational and primary health care. Scand J Work Environ Health. 2003 Dec;29(6):478-87. doi: 10.5271/sjweh.756.

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Estimated): June 16, 2023

Study Record Updates

• Last Update Posted (Estimated): June 16, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Fibromyalgia; Burnout; Interoception
• Additional Relevant MeSH Terms: Behavioral Symptoms; Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Stress, Psychological; Burnout, Psychological; Fibromyalgia; Myofascial Pain Syndromes; Medically Unexplained Symptoms
• Other Study ID Numbers: B1152021000014

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No