Effect of Serotonergic Stimulation on the Gut-brain Axis

In this double-blinded, randomized, cross-over study, irritable bowel syndrome subjects (n = 40) and healthy controls (n = 20) will perform an emotional and the arithmetic task and receive visceral stimuli (by using a barostat) while placed in a functional magnetic resonance imaging scanner respectively during two different states, a) after oral administration of 10 mg Escitalopram, a well-known drug classified as Selective Serotonin Reuptake Inhibitor, packed in a coloured hydroxypropylmethylcellulose capsule, and b) during oral administration of a placebo, in a double-blinded randomized cross-over fashion. Background characteristics will be collected.

• serotonergic stimulation (Other): Increase of serotonergic activity by a single oral administration of 10 mg Escitalopram, a Selective Serotonin Reuptake Inhibitor (SSRI), packed in a coloured hydroxypropylmethylcellulose capsule.
• no serotonergic stimulation (Other): Oral administration of a placebo. The placebo will consist of a coloured hydroxypropylmethylcellulose capsule filled with microcrystalline cellulose.

Primary outcomes

• Differences in functional brain response pattern to the barostat in stimulated compared to unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging

Secondary outcomes

• Differences in functional brain response pattern to the Montreal Imaging Stress Task between stimulated and unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging
• Differences in functional brain response pattern to the Emotional Attention Task between stimulated and unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging
• Differences in functional brain response pattern to the barostat stimulus paradigm between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging
• Differences in functional brain response pattern to the Montreal imaging stress task (MIST) between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging
• Differences in functional brain response pattern to the emotional attention task (EAT) between irritable bowel syndrome patients and healthy controls for stimulated and unstimulated serotonergic activity [1 week]: functional magnetic resonance imaging

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion criteria for the irritable bowel syndrome group:

1. Subjects fulfill Rome IV diagnostic criteria for irritable bowel syndrome and pain frequency for at least 1 day per week in the last 12 weeks
2. Males or females aged 18-65 years
3. Signed informed consent

Exclusion criteria for the irritable bowel syndrome group:

1. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (< 12 weeks), antibiotics (< 12 weeks)
2. Concurrent or recent (< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics)
3. Diagnosis of major psychiatric or somatic disease other than part of irritable bowel syndrome
4. Suicidal tendencies according to Montgomery Åsberg Depression Ratings Scale and/or clinical judgment
5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
6. Recent (< 4 weeks) intake of proton pump inhibitors (e.g., omeprazole)
7. Epilepsy
8. Cerebral bleeding or history of cerebral bleeding
9. Pregnancy or breastfeeding (will be asked)
10. Claustrophobia
11. Smoking or using tobacco including snuff
12. Dominant left-hand
13. Medical implant (e.g., pacemaker)
14. Aneurysm clips in the head
15. Shunts in the head
16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
18. Comprehensive tooth-implants or prothesis
19. Operated in the head
20. Operated in the heart
21. Swallowed a video-capsule
22. Non-corrected astigmatism
23. Regular intake of antiinflammatory medication (including non-steroidal antiinflammatory drugs)
24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
25. Any other reason the investigator feels the subject is not suitable for participation in the study

Inclusion criteria for healthy group:

1. Males and females aged 18-65 years of age
2. Signed informed consent

Exclusion criteria for the healthy group:

1. Concurrent or recent history of gastrointestinal disorders or any somatic disorder
2. Concurrent or recent treatment with drugs affecting intestinal microbiota, function or mood, e.g., antidepressants (< 12 weeks), antibiotics (< 12 weeks)
3. Concurrent or recent (< 4 weeks) use of nutritional supplements or herb products affecting intestinal function or mood (e.g. aloe vera, St. John´s Wort and probiotics)
4. Concurrent psychiatric or psychological symptomatology defined as above cut-off on Montgomery Åsberg Depression Ratings Scale, above clinical cut-off on hospital anxiety and depression scale (equal to or above 8)
5. Abuse of alcohol or drugs according to Alcohol Use Disorders Identification Test, and/or clinical judgment
6. Recent (< 4 weeks) intake of proton pump inhibitors, (e.g., omeprazole)
7. Epilepsy
8. Cerebral bleeding or history of cerebral bleeding
9. Pregnancy or breastfeeding (will be asked)
10. Claustrophobia
11. Smoking or using tobacco including snuff
12. Dominant left-hand
13. Medical implant (e.g., pacemaker)
14. Aneurysm clips in the head
15. Shunts in the head
16. Grenade-splinter or metal-splinter in the body (e.g., eyes)
17. Metal or electrodes in the body (e.g., temp-catheter, aorta stent, cochlear implant)
18. Comprehensive tooth-implants or prothesis
19. Operated in the head
20. Operated in the heart
21. Swallowed a video-capsule
22. Non-corrected astigmatism
23. Intake of anti-inflammatory medication (including non-steroidal antiinflammatory drugs)
24. Visual defect without possibility to use lenses during functional magnetic resonance imaging scanning
25. Any other reason the investigator feels the subject is not suitable for participation in the study.

• Robert Brummer, Prof., Principal investigator, Örebro University, Region Örebro County