Clinical trial NCT06084325: The Role of Oxytocin and Interoception in Functional Neurological Disorder
Official title: The Role of Oxytocin and Interoception in Functional Neurological Disorder
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Functional Neurological Disorder
Lead sponsor: University of Fribourg
Sponsor class: OTHER
Collaborators: name: Insel Gruppe AG, University Hospital Bern
First posted: 2023-10-16
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: FND patients Participants who are patients will be recruited from the in- and out-patients pool of the Clinic for Neurology of the Hospital of Fribourg and the Inselspital. At both, the treating physician will identify suitable patients (i.e. patients who fulfil the clinical requirement for FND as described in the DSM-5). The treating physician will ask these patients whether they would like to be approached by the Investigator (or his/her designee) concerning a scientific study. In case of affirmative response, the Investigator will approach the patients, inform them about the study.

Healthy control Healthy controls will be recruited among students, collaborators, and visitors of the University of Fribourg and Bern, the Hospital of Fribourg and the Inselspital. They will be recruited by flyer, by word-of-mouth and through advertisements in public media.

Brief summary: The main goal of this project is to better understand the role of oxytocin and Interoception in FND. More specifically oxytocin's association with precision weighing, prediction errors and priors in the interoceptive domains will be investigated. To this end, several methods will be employed: analysis of interoceptive accuracy and sensibility (interoceptive tasks and questionnaires), biomarkers of oxytocin (peripheral, endogenous oxytocin), genetic oxytocin markers (such as allele-frequency in the oxytonergic receptor gene), epigenetics (methylation rates of genes related to oxytocin), neuroactivity (EEG).

Detailed description: The primary objective is to explore interoceptive processing during a behavioural (interoceptive) tasks and its association to the oxytocin (OT) system in patients affected by a functional neurological disorder (FND), in comparison to healthy controls (HC).

Concerning interoception, as primary outcome, it is hypothesized that:

A) FND patients are less interoceptive (judged by objectively measured accuracy) compared to HC in the interoceptive tasks.

Concerning OT, as primary outcome, it is hypothesized that:

B) The OT level is correlated with interoception tasks; specifically the adaption of precision weighting

The secondary objectives are to:

* Explore the validity and reliability of different interoceptive tasks (e.g. respiratory, cardiovascular, emotional tasks)
* Explore neuronal regions associated with interoceptive processing and interoceptive accuracy in FND compared to HC
* Investigate whether FND patients have a higher interoception trait-prediction error (discrepancy between subjective and objective interoception scores) and whether this correlates with their symptom severity
* Explore the association of the breathing cycle and the voluntary initiation of mental or motor actions, and its readiness potential
* Explore peripheral biomarkers (e.g. salivary OT) in FND patients, compared to HC
* Explore the differences in (epi)genetic profile associated with the OT-system in FND compared to HC
* Investigate the association of the OT-system and traumatic childhood experience, attachment styles and sexual functioning in patients of FND compared to HC

Eligibility criteria: Inclusion Criteria for Patients:

* A diagnosis of FND according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria
* Capable of judgement
* Willing to participate in the study (by signing the informed consent form)

Inclusion Criteria for Healthy controls:

* Capable of judgement
* Willing to participate in the study (by signing the informed consent form)

Exclusion Criteria for Patients:

* Presence of comorbid disorders such as psychosis or major depression with suicidal risk
* History of actual or suspected epilepsy
* Past surgery in the brain
* Cardio-vascular disease
* Implanted Investigational Medicinal Products (e.g. cochlear implants, neurostimulators, cardiac pacemakers)
* History of alcohol or drug abuse
* For female participants: breastfeeding, pregnancy (a standard urine pregnancy test will be provided)
* \<6h prior application prostaglandin
* Long QT-syndrome
* Inability to follow the procedures of the study, e.g. due to language problems

Exclusion Criteria for Healthy controls:

* History of actual or suspected epilepsy
* Past surgery in the brain
* Cardio-vascular disease
* Implanted Investigational Medicinal Products (e.g. cochlear implants, neurostimulators, cardiac pacemakers)
* History of alcohol or drug abuse
* For female participants: breastfeeding, pregnancy (a standard urine pregnancy test will be provided)
* \<6h prior application prostaglandin
* Long QT-syndrome
* Inability to follow the procedures of the study, e.g. due to language problems

Primary outcomes:
measure: Difference of interoception behavioural scores between FND patients and Healthy controls
timeFrame: 1 day
measure: Difference in brain electrophysiology during interoception processing between FND patients and Healthy controls
timeFrame: 1 day
measure: Association between oxytocin system and interoception and its difference between FND patients and Healthy controls
timeFrame: 1 day
Secondary outcomes:
measure: Oxytocin concentration (Saliva sampling)
timeFrame: 1 day
measure: Epigenetic profile
timeFrame: 1 day
measure: Respiratory Resistance Sensitivity
timeFrame: 1 day
measure: Behavioral measure: heartbeat counting
timeFrame: 1 day
measure: Electrophysiological measure (EEG): Heartbeat evoked potential (HEP) task1
timeFrame: 1 day
measure: Electrophysiological measure (EEG): Heartbeat evoked potential (HEP) task2
timeFrame: 1 day
measure: Neurophysiological measures: Correlation between agency task and respiration cycle (Libet)
timeFrame: 1 day
measure: Electrophysiological measure (EEG): the readiness potential (Libet)
timeFrame: 1 day
measure: The localization of neuronal activity derived from EEG during interoceptive tasks, and during resting state
timeFrame: 1 day
measure: Behavioral measure: Correlation between oxytocin and clinical questionaire
timeFrame: 1 day
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital
city: Fribourg
country: Switzerland
facility: University of Fribourg
Study officials:
References: