Temporal Dynamics and Pharmacokinetics of Intranasally Administered Oxytocin

Study Overview
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Brief Summary
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The purpose of this study is to determine whether effects of intranasal oxytocin on amygdala response vary as a function of treatment dose and dose-test latency.

Detailed Description
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The objective of the present study is to determine whether intranasal oxytocin (IN-OXT) effects on blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) in the amygdala vary as a function of dose and latency. In particular, the investigators plan to compare effects of three different IN-OXT doses (12, 24, and 48 international units, IU) and three different dose-test latencies of IN-OXT administration (task starting at 15, 45 and 75min after administration) on established neural and behavioural correlates of emotion processing. As effects of OXT are particularly promising in autism, the investigators further want to investigate how autistic-like traits influence the OXT effects in exploratory post-hoc analyses

Conditions
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Healthy

Intervention / Treatment
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* Drug: Oxytocin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers Right-handed Exclusion Criteria: Current or past psychiatric disease Current or past physical illness Psychoactive medication Tobacco smokers MRI contraindication (e.g. metal in body, claustrophobia)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Oxytocin; 24IU, 15min<br>Intranasal administration, 24 international units (IU) oxytocin. Imaging starting 15min after nasal spray administration. | Drug: Oxytocin<br> <br> |
| Active Comparator: Oxytocin; 24IU, 45min<br>Intranasal administration, 24 IU oxytocin. Imaging starting 45min after nasal spray administration. | Drug: Oxytocin<br> <br> |
| Active Comparator: Oxytocin; 24IU, 75min<br>Intranasal administration, 24 IU oxytocin. Imaging starting 75min after nasal spray administration. | Drug: Oxytocin<br> <br> |
| Active Comparator: Oxytocin; 12IU, 45min<br>Intranasal administration, 12 IU oxytocin. Imaging starting 45min after nasal spray administration | Drug: Oxytocin<br> <br> |
| Active Comparator: Oxytocin; 48IU, 45min<br>Intranasal administration, 48 IU oxytocin. Imaging starting 45min after nasal spray administration | Drug: Oxytocin<br> <br> |
| Placebo Comparator: Placebo<br>Placebo nasal spray. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural substrates of emotion processing, measured via blood-oxygen-level dependent signal in the amygdala | Magnetic resonance imaging (MRI) will be performed to measure blood-oxygen-level dependent signal in response to emotional face stimuli of varying intensity. The investigators specifically plan to investigate amygdala response to fearful faces, as this subcortical region has repeatedly been reported to show activation changes after OXT treatment. Dose-test latency varies between the different treatment arms (i.e. imaging starts 15min [arm 1], 45min [arm 2,4 and 5] or 75min [arm 3] after nasal spray administration). | 45min after nasal spray administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratings of emotional faces | During each trial, subjects are asked to use a button response grip to indicate whether they perceived the depicted face as neutral, fearful or happy. Depending on the treatment arm, ratings are recorded 15min (arm 1), 45min (arm 2,4 and 5) or 75min (arm 3) after nasal spray administration. | 45min after nasal spray administration | 
| Questionnaire measurement of mood (PANAS) | Positive and negative affect is assessed via self-rating questionnaire 'The Positive and Negative Affect Schedule' using a categorical 5 point scale. | 10 min before and 105 min after nasal spray administration | 
| Questionnaire measurement of anxiety (STAI). | State anxiety is assessed via self-rating questionnaire 'and State Trait Anxiety Inventory' using a categorical 4 point scale. | 10 min before and 105 min after nasal spray administration | 
| Saliva oxytocin concentrations |  | immediately before the nasal spray administration and (on average) 15,40,80 and 105 min after administration | 
| Plasma oxytocin concentrations |  | immediately before the nasal spray administration and immediately after the fMRI experiment | 
| Modulatory effects of autistic like traits on neural and behavioral outcome measures | Autistic like traits are assessed via Autism Spectrum quotient in a screening session, preceding the testing sessions. The investigators expect pronounced OXT effects in subjects with high autistic-like traits. | screening session,  7days prior to imaging session |