Serotonin, Anxiety and Visceral Sensation

General and Anxiety-Linked Influence of Acute Serotonin Reuptake Inhibition on Neural Responses Associated With Attended Visceral Sensation

The goal of this crossover study was to learn about the potential regulatory role of serotonin in interoceptive processing and its relationship to levels of state anxiety. This experiment directly compared the impact of a selective serotonin reuptake inhibitor (SSRI) (20mg CITALOPRAM) to that of a PLACEBO on the neural processing of ordinary interoceptive sensations and the relationship of these influences to anxious states.

Healthy young volunteers completed the visceral interoceptive attention task with each treatment condition (citalopram and placebo). The task involves focusing attention on heart, stomach, or visual sensation control while scanned with functional magnetic resonance imaging (fMRI). The difference in haemodynamic response between interoceptive sensation(s) and visual sensation (i.e. the relative interoceptive response) is compared between treatment conditions. State anxiety is measured at each test period. It is used to test for a moderating effect of state anxiety on the influence of serotonin in interoceptive processing and used post-hoc to explore associations between changes in state anxiety and changes of interoceptive relative interoceptive response due to the SSRI.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Citalopram 20mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • East Sussex
    • Falmer, East Sussex, United Kingdom, BN1 9QH
      • School of Psychology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

- healthy volunteer

Exclusion criteria included:

• the presence of significant ongoing medical condition;
• pregnancy or breastfeeding;
• currently taking any medication (excluding contraceptive pill);
• first-degree family history of bipolar disorder;
• an indication of current or historical mental health disorder,
• MRI scanner contraindications (e.g. metallic implants)
• data that is unanalyzable due to movement
• excessive side effects of the drug (e.g. nausea)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: citalopram first, placebo second; Citalopram was taken first. Placebo was taken at least 7 days later.	Drug: Citalopram 20mg; Doses were delivered in gelatine capsules filled with microcrystalline cellulose.; Drug: Placebo; Doses were gelatine capsules filled with microcrystalline cellulose
Other: placebo first, citalopram second; Placebo was taken first. Citalopram was taken at least 7 days later.	Drug: Citalopram 20mg; Doses were delivered in gelatine capsules filled with microcrystalline cellulose.; Drug: Placebo; Doses were gelatine capsules filled with microcrystalline cellulose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relative neural interoceptive response - heart	Neural response, inferred via functional magnetic resonance imaging from focusing attention on the heart, minus the response during focus on a visual stimulus	15 minutes
relative neural interoceptive response - stomach	Neural response, inferred via functional magnetic resonance imaging from focusing attention on the stomach, minus the response during focus on a visual stimulus	15 minutes
State Anxiety	State Trait Anxiety Inventory	5 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metacognitive Interoceptive Insight	Ability of confidence to predict accuracy when making decisions about whether heartbeat is in sync with an auditory tone. This is an exploratory measure.	45 minutes
Physiological and Psychological state	Three scales (from 0-100) were given to assess three somatic side effects (nausea, headache and dizziness). Five anxiety-related effects (pairs of antonyms: alert-drowsy, stimulated-sedated, restless-peaceful, irritable-good-humoured, anxious-calm) were used to confirm other anxiety measures and alert the researchers to excessive side effects. Used to confirm anxiety measure detect side effects.	Measured twice, for 2 minutes, before and after scanning. Average taken to estimate state inside scanner.
Positive and Negative Affect Scale	Measures affective state, confirming anxiety measure	Measured twice, for 2 minutes, before and after scanning. Average taken to estimate state inside scanner.
Heartrate	Participants had their heartrate recorded with the participant relaxed and sitting.	Before scans of each session, 2 minutes
Cerebral Blood Flow Change	Perfusion imaging, to control for effects of citalopram on blood flow	2 minutes, at scan
Anatomical scan and fieldmaps	For coregistration of functional magnetic resonance images	6 minutes, at scan

Collaborators and Investigators

• Sponsor: University of Sussex
• Investigators: Principal Investigator: Daniel Campbell-Meiklejohn, DPhil, University of Sussex

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2018
• Primary Completion (Actual): November 13, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: January 8, 2024
• First Submitted That Met QC Criteria: January 8, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: anxiety; serotonin; interoception; ssri
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Selective Serotonin Reuptake Inhibitors; Citalopram
• Other Study ID Numbers: ER/JL332/9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized data will be shared on a publically accessible database with a link accessible through the official publication.
• IPD Sharing Time Frame: After publication
• IPD Sharing Access Criteria: Public Access

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No