Effects of Oxytocin Dose Frequency on Behavioral and Neural Responses

Study Overview
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Brief Summary
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The main aim of the study is to examine effects of different dose frequencies of repeated oxytocin administration on neural and behavioral markers of oxytocin in healthy male subjects. In addition modulatory effects of autism traits and oxytocin receptor genotype (OXTR) will be explored.

Detailed Description
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In the present study, healthy male subjects will be screened according to the study inclusion criteria. After enrollment buccal swaps will be collected for genotyping and subjects will be randomly assigned to three experimental groups that will receive treatment for 5 subsequent days: (1) placebo for five days, (2) oxytocin on days 1, 3 and 5, or (3) oxytocin for five days. Behavioral measures, task-based and resting fMRI will be assessed after the first treatment (acute effects) and the last treatment (chronic effects). The task-based fMRI will employ an implicit emotional face processing paradigm and ratings of the facial emotions will be collected after the fMRI. Moreover, to control for potential confounding effects of relevant traits all participants will complete the following questionnaires: Interpersonal Reactivity Index (IRI),Beck depression inventory (BDI), State-Trait Anxiety Inventory (STAI). To explore potential modulatory effects of trait autism, all subjects will be administered the Autism Spectrum Quotient (ASQ) scale to assess pre-treatment autism traits.

Official Title
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Effects of Oxytocin Dose Frequency on Behavioral and Neural Responses, and Modulation by Trait Autism and Genotype

Conditions
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Healthy

Intervention / Treatment
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* Drug: Nasal Sprays


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: healthy adult males Exclusion Criteria: past or current psychiatric or neurological disorder head trauma substance abuse medication fMRI contraindications (e.g. metal implants)

Ages Eligible for Study
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Minimum Age: 17 Years
Maximum Age: 30 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin nasal spray(5 doses)<br>Oxytocin nasal spray for 5 days, 24 IU per day | Drug: Nasal Sprays<br>* Intranasal administration of 24 international units per dose.<br>|
| Experimental: Oxytocin nasal spray(3 doses)<br>Oxytocin nasal spray or placebo nasal spray interleaved during the 5 days( on the 1st,3rd and 5th day),24 IU per day. | Drug: Nasal Sprays<br>* Intranasal administration of 24 international units per dose.<br>|
| Placebo Comparator: Placebo nasal spray(control group)<br>Placebo nasal spray for 5 days,24 IU per day. | Drug: Nasal Sprays<br>* Intranasal administration of 24 international units per dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between group differences in the changes between acute and chronic administration effects of oxytocin on amygdala reactivity towards fearful faces as assessed by fMRI. | Differences between the treatment groups will be determined by examining differential changes of acute treatment (day 1) vs chronic treatment (day 5) on amygdala activity towards fearful faces. Amygdala activity will be assessed using task-based BOLD fMRI analyses. | 45 minutes after treatment (day 1 vs day 5) | 
| Between group differences in the changes between acute and chronic administration effects of oxytocin on amygdala resting state connectivity as assessed by fMRI. | Differences between the treatment groups will be determined by examining differential changes of acute treatment (day 1) vs chronic treatment (day 5) on amygdala resting state fMRI connectivity. Amygdala functional connectivity will be examined using a seed to whole brain approach. | 45 minutes after treatment (day 1 vs day 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between trait autism with acute and chronic treatment effects on amygdala activity in response to fearful faces | Associations between autism traits and amygdala response to fearful faces during acute effects (single dose, day 1) and chronic effects (over the course of 5 days) will be examined by means of correlation analyses. Pre-treatment autism trait scores will be assessed using the Autism Spectrum Quotient (ASQ) | 45 minutes after treatment (day 1 vs day 5) | 
| Association between trait autism with acute and chronic treatment effects on amygdala resting state connectivity | Associations between autism traits and amygdala resting state connectivity during acute effects (single dose, day 1) and chronic effects (over the course of 5 days) will be examined by means of correlation analyses. Pre-treatment autism trait scores will be assessed using the Autism Spectrum Quotient (ASQ) | 45 minutes after treatment (day 1 vs day 5) | 
| Interaction of acute and chronic treatment effects on amygdala activity with oxytocin receptor genotype. | Participants will be divided in sub-groups according to their oxytocin receptor (OXTR) genetic profile. Modulatory effects of the OXTR on acute and chronic effects will be explored by comparing effects of treatment on amygdala activity in response to fearful faces as assessed by fMRI between the genotype groups. | 45 minutes after treatment (day 1 vs day 5) | 
| Interaction of acute and chronic treatment effects on amygdala connectivity with oxytocin receptor genotype. | Participants will be divided in sub-groups according to their oxytocin receptor (OXTR) genetic profile. Modulatory effects of the OXTR on acute and chronic effects will be explored by comparing effects of treatment on amygdala resting state connectivity as assessed by fMRI between the genotype groups. | 45 minutes after treatment (day 1 vs day 5) | 
| Treatment effects on arousal will be assessed by subjects rating their arousal on a 9-point Likert scale in response to the face pictures presented again after their fMRI scans on day 1 and day 5 | After assessment of the implicit fMRI emotional face paradigm participants will rate the emotional arousal of the stimuli using Likert scales (9 point). Acute and chronic effects will be assessed using repeated measures ANOVAs (day 1 vs day 5) to compare differential changes between the groups. | 45 minutes after treatment (day 1 vs day 5) | 
| Treatment effects on valence will be assessed by subjects rating their valence on a 9 point Likert scale in response to the face pictures presented again after their fMRI scans on day 1 and day 5 | After assessment of the implicit fMRI emotional face paradigm participants will rate the emotional valence of the stimuli using Likert scales (9 point). Acute and chronic effects will be assessed using repeated measures ANOVAs (day 1 vs day 5) to compare differential changes between the groups. | 45 minutes after treatment (day 1 vs day 5) | 
| Treatment effects on intensity will be assessed by subjects rating their intensity on a 9 point Likert scale in response to the face pictures presented again after their fMRI scans on day 1 and day 5 | After assessment of the implicit fMRI emotional face paradigm participants will rate the emotional intensity of the stimuli using Likert scales (9 point). Acute and chronic effects will be assessed using repeated measures ANOVAs (day 1 vs day 5) to compare differential changes between the groups. | 45 minutes after treatment (day 1 vs day 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple doses, oxytocin, genotype, autism trait