Biological Basis of Individual Variation in Social Cooperation

Study Overview
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Brief Summary
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The project has three overall objectives. The first is to determine whether and how administration of intranasal oxytocin (OT) and intranasal vasopressin (AVP) influence cooperative decision-making and neural responses to cooperative and un-cooperative social interactions. The second is to determine whether and how intranasal vasopressin influences subjective evaluations of and neural responses to same and opposite-sex face stimuli and to determine if any of these effects persist beyond the period of AVP exposure. The third objective is to determine if intranasal OT influences empathy-related behavior and associated brain activity.

Detailed Description
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There are several objective to the study. Objective 1: In this double-blind, placebo-controlled, pharmaco- fMRI study, men and women will be randomized to treatment with either 24 IU intranasal OT, 20 IU intranasal AVP, or placebo (PL). Approximately 40 minutes later, brain function will be imaged with fMRI as participants play an iterated Prisoner's Dilemma game with same-sex partners. The resulting data will be analyzed to investigate OT and AVP effects on cooperative behavior and the neural response to cooperative social interactions. In addition to this cross-sectional design, a subset of participants will return on a second day for a within-subject study. Objective 2: Men and healthy women will be randomized to treatment with either 40 IU intranasal AVP or a saline placebo approximately 30 minutes before their brain function is measured with fMRI as they view same and other-sex faces. All subjects will be scanned a second time several days later with no treatment to evaluate the persistence of AVP effects over time. The resulting data will be analyzed to investigate AVP effects on subjective evaluations and neural responses to viewing same and opposite sex faces. Objective 3: Healthy men and healthy women will receive either 24IU intranasal OT or PL approximately 40 minutes before their brain function is measured with fMRI as they view animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, fighting. All participants will receive PL on scan 1 and will be randomized to either 24IU intranasal OT or PL on scan 2. The resulting data will be analyzed to investigate OT effects on subjective evaluations and neural responses to the animations.

Official Title
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The Biological Basis of Individual Variation in Social Cooperation

Conditions
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Healthy

Intervention / Treatment
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* Drug: Intranasal Oxytocin (OT) 24 IU
* Drug: Intranasal Vasopressin (AVP)
* Drug: Intranasal Placebo
* Drug: Intranasal Vasopressin (AVP) 40 IU
* Drug: Lorazepam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-30 years of age 21-30 for Faces component Normal or corrected-to-normal vision of 20/40 Unmedicated depressed or anxious men between 18-22 years of age for Anxious and Depressed component Exclusion Criteria: Pregnancy, recent birth, or breastfeeding History of seizures Neurological Disorder Current psychiatric disorder Previous psychiatric disorder (can be included as discretion of PI) Current use of psychoactive drugs Previous use of psychoactive drugs (can be included as discretion of PI) Previous head trauma (can be included at discretion of PI) Alcoholism or substance abuse Hypertension Cardiovascular Disease Nephritis Diabetes Endocrine disease or malignancy Asthma (can be included as discretion of PI, if episodes are infrequent, nonmedicated, and no active problems at time of study) Migraines (can be included as discretion of PI, if episodes are infrequent, nonmedicated, and no active problems at time of study) Claustrophobia (at discretion of PI) Additional exclusion criteria for Lorazepam arm Acute narrow-angle glaucoma Compromised respiratory function (e.g. sleep apnea and chronic obstructive pulmonary disease) Impaired renal and hepatic function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

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: Factorial Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers - Intranasal Vasopressin (AVP)<br>The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. | Drug: Intranasal Vasopressin (AVP)<br>* Participants will self-administer a 1 ml solution containing 20 units of AVP. Five puffs per nostril, each with 2 International Units (IU) AVP. Ten puffs total).<br>|
| Experimental: Healthy Volunteers - Intranasal Oxytocin (OT)<br>The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. | Drug: Intranasal Oxytocin (OT) 24 IU<br>* Participants will self-administer a single dose of 24 international units (IU) oxytocin. Five puffs per nostril, each with 2.4 IU oxytocin. Ten puffs total.<br>* Other names: Oxytocin: Syntocinon Nasal Spray;|
| Placebo Comparator: Healthy Volunteers - Intranasal Placebo<br>The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. | Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Experimental: Within Subject Group<br>Some healthy volunteer participants who received drug in their first session will receive placebo in their second session and vice-versa prior to completing the PD task. For each gender, half will receive AVP in one session and placebo in the other session, and half will receive OT in one session and placebo in the second session. In each group, half of the subjects will receive drug first and half will receive placebo first. Additionally, a group of subjects who receive placebo the first time will receive placebo the second time. | Drug: Intranasal Oxytocin (OT) 24 IU<br>* Participants will self-administer a single dose of 24 international units (IU) oxytocin. Five puffs per nostril, each with 2.4 IU oxytocin. Ten puffs total.<br>* Other names: Oxytocin: Syntocinon Nasal Spray;Drug: Intranasal Vasopressin (AVP)<br>* Participants will self-administer a 1 ml solution containing 20 units of AVP. Five puffs per nostril, each with 2 International Units (IU) AVP. Ten puffs total).<br>Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Experimental: Faces Task - Vasopressin (AVP)<br>Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. | Drug: Intranasal Vasopressin (AVP) 40 IU<br>* Participants will self-administer a 0.5 ml solution containing 40 international units (IU) of AVP. 5 puffs in total, each with 4 International Units (IU) AVP.<br>|
| Placebo Comparator: Faces Task - Placebo<br>Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. | Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Experimental: Empathy Task - Oxytocin (OT)<br>Healthy volunteers between the ages of 18-30 years will receive placebo at scan 1 and OT at scan 2 prior to completing an empathy task. | Drug: Intranasal Oxytocin (OT) 24 IU<br>* Participants will self-administer a single dose of 24 international units (IU) oxytocin. Five puffs per nostril, each with 2.4 IU oxytocin. Ten puffs total.<br>* Other names: Oxytocin: Syntocinon Nasal Spray;Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Placebo Comparator: Empathy Task - Placebo<br>Healthy volunteers between the ages of 18-30 years will receive placebo at scan 1 and placebo at scan 2 prior to completing an empathy task. | Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Experimental: Anxious and Depressed Subjects - OT<br>Depressed or anxious men between the ages of 18 and 22 will receive intranasal OT prior to completing the Prisoner's Dilemma game task and MRI scan. | Drug: Intranasal Oxytocin (OT) 24 IU<br>* Participants will self-administer a single dose of 24 international units (IU) oxytocin. Five puffs per nostril, each with 2.4 IU oxytocin. Ten puffs total.<br>* Other names: Oxytocin: Syntocinon Nasal Spray;|
| Placebo Comparator: Anxious and Depressed Subjects - Placebo<br>Depressed or anxious men between the ages of 18 and 22 will receive intranasal placebo prior to completing the Prisoner's Dilemma game task and MRI scan. | Drug: Intranasal Placebo<br>* Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.<br>|
| Experimental: Healthy Volunteers - Lorazepam<br>Healthy normal men between the ages of 18 and 22 will receive lorazepam prior to completing the Prisoner's Dilemma game task and MRI scan. | Drug: Lorazepam<br>* Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men | The effect of the drug treatment will be assessed by determining differences in brain activation between OT and placebo groups in the right caudate nucleus region during reciprocated cooperation in Prisoner Dilemma game while undergoing an fMRI scan. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women | The effect of the drug treatment will be assessed by determining differences in brain activation between OT and placebo groups in the right caudate nucleus region during reciprocated cooperation in Prisoner Dilemma game while undergoing an fMRI scan. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men | The effect of the drug treatment will be assessed by determining differences in brain activation between AVP and placebo groups in the left insula region during reciprocated cooperation in Prisoner Dilemma game while undergoing an fMRI scan. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women | The effect of the drug treatment will be assessed by determining differences in brain activation between AVP and placebo groups in the left insula during reciprocated cooperation in Prisoner Dilemma game while undergoing an fMRI scan. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women | The effect of the drug will be assessed by determining changes in brain activation between the visit where the participant received drug and the visit where the participant received PL in the right caudate during reciprocated cooperation in Prisoner Dilemma game while undergoing an fMRI scan. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Men During the Prisoners Dilemma Game | The effect of the drug treatments will be assessed by determining the number of cooperative choices made during the prisoner's dilemma game. Participants may make two choices that are considered cooperative. The higher the total number, the more cooperative choices made. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Women During the Prisoners Dilemma Game | The effect of the drug treatments will be assessed by determining the number of cooperative choices made during the prisoner's dilemma game. Participants may make two choices that are considered cooperative. The higher the total number, the more cooperative choices made. | Visit 1 (40-100 Minutes Post-Intervention) | 
| Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Male During the Prisoners Dilemma Game | The effect of the drug treatments will be assessed by determining the number of cooperative choices made during the prisoner's dilemma game. Participants may make two choices that are considered cooperative. The higher the total number, the more cooperative choices made. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks) | 
| Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Female During the Prisoners Dilemma Game | The effect of the drug treatments will be assessed by determining the number of cooperative choices made during the prisoner's dilemma game. Participants may make two choices that are considered cooperative. The higher the total number, the more cooperative choices made. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks) | 
| Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Men | The effect of the drug treatment will be assessed by determining differences in brain activation between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Women | The effect of the drug treatment will be assessed by determining differences in brain activation between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Faces Task Groups: Mean Approachability Rating of Faces in Men | Approachability is rated by a study specific seven point scale where -3 indicates threatening and unapproachable and +3 indicates friendly and approachable. Participants will rate same-sex and other-sex faces. The effect of the drug treatment will be assessed by determining differences in approachability ratings between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Faces Task Group: Mean Approachability Rating of Faces in Women | Approachability is rated by a study specific seven point scale where -3 indicates threatening and unapproachable and +3 indicates friendly and approachable. Participants will rate same-sex and other-sex faces. The effect of the drug treatment will be assessed by determining differences in approachability ratings between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Faces Task Groups: Mean Attractiveness Rating of Faces in Men | Attractiveness is rated by a study specific seven point scale where -3 indicates least attractive and +3 indicates most attractive. Participants will rate same-sex and other-sex faces. The effect of the drug treatment will be assessed by determining differences in attractiveness ratings between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Faces Task Groups: Mean Attractiveness Rating of Faces in Women | Attractiveness is rated by a study specific seven point scale where -3 indicates least attractive and +3 indicates most attractive. Participants will rate same-sex and other-sex faces. The effect of the drug treatment will be assessed by determining differences in attractiveness ratings between AVP and PL group when participants are viewing same-sex faces, and when participants are viewing other-sex faces. | Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days) | 
| Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women | The effect of the drug treatment will be assessed by determining differences in brain activation between OT and PL group when participants are viewing animations. | Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month) | 
| Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men | The effect of the drug treatment will be assessed by determining differences in brain activation between OT and PL group when participants are viewing animations. | Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Empathy, Social cooperation, Oxytocin, Vasopressin, Prisoner's Dilemma game, fMRI