Oxytocin, Trauma Disclosure and Intrusions

Effects of a Prolonged Oxytocin Treatment on Intrusions and Amygdala Reactivity in an Analogue Trauma Model

Severe traumatic experiences such as falling victim to assault, torture, or rape have deleterious effects. Clinical manifestations include intrusions, avoidance behavior, and hyperarousal, which are associated, at a circuit level, with hyperfunction of the amygdala and hypofunction of prefrontal cortex (PFC) subregions. In up to 50 % of the cases, resilience is not sufficient and trauma-exposed individuals develop posttraumatic stress disorder (PTSD). Oxytocin (OXT) is a hypothalamic peptide hormone that exerts anxiolytic effects. Recent clinical trials provide preliminary evidence that post-trauma administration of OXT could be effective as a preventive intervention for PTSD in a subsample of individuals exhibiting early PTSD symptoms prior to the onset of the disorder. However, the underlying neurobiological mechanisms are unclear. Therefore, the rationale of the present project is to expose a sample of healthy participants to experimental trauma in order to explore the circuit mechanisms by which OXT influences, and interferes with, traumatic experience. Functional magnetic resonance imaging (fMRI) will be employed in order to elucidate the long-term effects of intranasal OXT on trauma-induced intrusions, amygdala and PFC responses during an emotional face matching task and resting state functional connectivity.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Oxytocin

Detailed Description

Participants will be exposed to an experimental trauma (i.e. a highly aversive movie) at days 1 and 4 of the study. After the first experimental trauma and after the first functional magnetic resonance imaging (fMRI) measurement, the participants will receive intranasal OXT or placebo in three different groups (1. OXT for six days, 2. OXT for three days and then placebo for three days, 3. placebo for six days). The same fMRI tasks will be used after the first and second trauma exposure (i.e. one measurement before the treatment and one measurement after three days of treatment).

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bonn, Germany, 53105
    • Department of Psychiatry, University of Bonn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy female volunteers
• Right-handed

Exclusion Criteria:

• Current or past psychiatric disease
• Current or past physical illness
• Psychoactive medication
• Hormonal contraception
• MRI contraindication (e.g. metal in body, claustrophobia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oxytocin (6 days); Intranasal administration, 24 international units (IU) oxytocin for three days after the first trauma movie exposure and three days after the second trauma movie exposure (24 IU per day)	Drug: Oxytocin; Intranasal administration, 24 international units (IU) oxytocin.; Other Names: syntocinon
Active Comparator: Oxytocin (3 days); Intranasal administration, 24 international units (IU) oxytocin for three days after the first trauma movie exposure (24 IU per day) and placebo nasal spray for three days after the second trauma movie exposure	Drug: Oxytocin; Intranasal administration, 24 international units (IU) oxytocin.; Other Names: syntocinon
Placebo Comparator: Placebo; Placebo nasal spray for six days	Drug: Placebo; The placebo nasal sprays contain identical ingredients except for the peptide itself.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total number of intrusions following the first trauma movie exposure.	The participants will be asked to complete intrusion diaries at home in the evening of the days 1 to 3. Intrusions will be defined as involuntary recollections relating to film events that appear, apparently spontaneously, in consciousness.	Three days following the first trauma movie exposure.
Total number of intrusions following the second trauma movie exposure.	The participants will be asked to complete intrusion diaries at home in the evening of the days 4 to 6. Intrusions will be defined as involuntary recollections relating to film events that appear, apparently spontaneously, in consciousness.	Three days following the second trauma movie exposure.
Neural responses to emotional faces in the amygdala.	Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal in response to emotional face stimuli. The investigators specifically plan to investigate amygdala responses to emotional faces, because pilot data indicate that neural responses to emotional faces in these regions are associated with the total number of intrusions.	Neural activations will be measured with fMRI in an emotional face matching task that lasts 20 min.
Neural responses to emotional faces in the prefrontal cortex.	Functional magnetic resonance imaging (fMRI) will be performed to measure blood-oxygen-level dependent signal in response to emotional face stimuli. The investigators specifically plan to investigate prefrontal cortex responses to emotional faces, because pilot data indicate that neural responses to emotional faces in these regions are associated with the total number of intrusions.	Neural activations will be measured with fMRI in an emotional face matching task that lasts 20 min.
fMRI resting state data	Participants will be instructed to lie still with open eyes during the resting state measurement and not think of anything in particular.	Functional data will be acquired for 6 min.
Trauma disclosure (time spend discussing the movie)	The intrusion diaries will contain a question for how long participants discussed the trauma movie.	Six days following the first trauma movie exposure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in pupil diameter in response to the trauma movie	Changes in pupil diameter will be measured.	2 min baseline before the trauma movie and during 15 min of the trauma movie.
Changes in skin conductance level in response to the trauma movie	Changes in skin conductance level will be measured.	2 min baseline before the trauma movie and during 15 min of the trauma movie.
Changes in respiration rate in response to the trauma movie	Changes in respiration rate will be measured.	2 min baseline before the trauma movie and during 15 min of the trauma movie.
Salivary oxytocin concentrations	Saliva samples will be collected before and after the trauma movie to assess changes in oxytocin concentrations.	Immediately before the trauma movie, immediately after the trauma movie and 40 min after the trauma movie.
Salivary cortisol concentrations	Saliva samples will be collected before and after the trauma movie to assess changes in cortisol concentrations.	Immediately before the trauma movie, immediately after the trauma movie and 40 min after the trauma movie.
Questionnaire measurement of mood (PANAS)	Positive and negative affect will be assessed via self-rating questionnaire 'The Positive and Negative Affect Schedule' using a categorical 5 point scale.	10 min before and 10 min after the trauma movie.

Collaborators and Investigators

• Sponsor: University Hospital, Bonn
• Investigators: Principal Investigator: René Hurlemann, MD, PhD, University of Bonn

Publications and helpful links

Helpful Links

• Neuromodulation of Emotion (NEMO) research group

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): March 18, 2017
• Study Completion (Actual): March 18, 2017

Study Registration Dates

• First Submitted: January 28, 2018
• First Submitted That Met QC Criteria: February 1, 2018
• First Posted (Actual): February 8, 2018

Study Record Updates

• Last Update Posted (Actual): February 8, 2018
• Last Update Submitted That Met QC Criteria: February 1, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: amygdala, fear, intrusion, oxytocin, trauma disclosure
• Additional Relevant MeSH Terms: Wounds and Injuries; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: PROXY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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