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.
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
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
70
Department of Psychiatry, University of Bonn
Bonn, Germany
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Six days following the first trauma movie exposure.
Changes in pupil diameter in response to the trauma movie
Changes in pupil diameter will be measured.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 10 min before and 10 min after the trauma movie.
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