Biological Basis of Individual Variation in Social Cooperation

• Sponsor: Emory University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01566539
• Collaborator: National Institute of Mental Health (NIMH) (NIH), John Templeton Foundation (Other)
• Enrollment: 707
• Locations: 2
• Arms: 11
• Duration (Months): 103
• Patients Per Site: 353.5
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Intranasal Oxytocin (OT) 24 IU; Drug: Intranasal Vasopressin (AVP); Drug: Intranasal Placebo; Drug: Intranasal Vasopressin (AVP) 40 IU; Drug: Lorazepam	N/A

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 707 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: The Biological Basis of Individual Variation in Social Cooperation
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Healthy Volunteers - Intranasal Vasopressin (AVP) The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task.	Drug: Intranasal Vasopressin (AVP); 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).
Experimental: Healthy Volunteers - Intranasal Oxytocin (OT) The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task.	Drug: Intranasal Oxytocin (OT) 24 IU; 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.; Other Names: Oxytocin: Syntocinon Nasal Spray
Placebo Comparator: Healthy Volunteers - Intranasal Placebo The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task.	Drug: Intranasal Placebo; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Experimental: Within Subject Group 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; 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.; Other Names: Oxytocin: Syntocinon Nasal Spray ; Drug: Intranasal Vasopressin (AVP); 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).; Drug: Intranasal Placebo; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Experimental: Faces Task - Vasopressin (AVP) 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; 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.
Placebo Comparator: Faces Task - Placebo Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning.	Drug: Intranasal Placebo; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Experimental: Empathy Task - Oxytocin (OT) 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; 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.; Other Names: Oxytocin: Syntocinon Nasal Spray ; Drug: Intranasal Placebo; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Placebo Comparator: Empathy Task - Placebo 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; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Experimental: Anxious and Depressed Subjects - OT 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; 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.; Other Names: Oxytocin: Syntocinon Nasal Spray
Placebo Comparator: Anxious and Depressed Subjects - Placebo 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; Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Experimental: Healthy Volunteers - Lorazepam 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; Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.

Outcome Measures

Primary Outcome Measures

1. Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

2. Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

3. Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

4. Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

5. Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)]

   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.

Secondary Outcome Measures

1. Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Men During the Prisoners Dilemma Game [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

2. Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Women During the Prisoners Dilemma Game [Visit 1 (40-100 Minutes Post-Intervention)]

   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.

3. Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Male During the Prisoners Dilemma Game [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)]

   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.

4. Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Female During the Prisoners Dilemma Game [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)]

   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.

5. Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Men [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

   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.

6. Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Women [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

   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.

7. Faces Task Groups: Mean Approachability Rating of Faces in Men [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

   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.

8. Faces Task Group: Mean Approachability Rating of Faces in Women [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

   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.

9. Faces Task Groups: Mean Attractiveness Rating of Faces in Men [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

   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.

10. Faces Task Groups: Mean Attractiveness Rating of Faces in Women [Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)]

    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.

11. Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women [Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)]

    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.

12. Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men [Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)]

    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.

Other Outcome Measures

1. Healthy Volunteers Groups: Mean Vasopressin (AVP) Plasma Level [Visit 1 (Up to 3 Hours)]

   Peripheral levels of AVP will be assessed via assay of plasma collected.

2. Healthy Volunteers Groups: Mean Oxytocin (OT) Plasma Level [Visit 1 (Up to 3 Hours)]

   Peripheral levels of OT will be assessed via assay of plasma collected.

3. Healthy Volunteers Groups: Mean Testosterone Plasma Level [Visit 1 (Up to 3 Hours)]

   Peripherals levels of testosterone will be assessed via assay of plasma collected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Hospital	Atlanta	Georgia	United States	30307
2	Emory University 1462 Clifton Rd	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• National Institute of Mental Health (NIMH)
• John Templeton Foundation

Investigators

• Principal Investigator: James K Rilling, Ph.D., Emory University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

• Fisher H, Aron A, Brown LL. Romantic love: an fMRI study of a neural mechanism for mate choice. J Comp Neurol. 2005 Dec 5;493(1):58-62. Review.
• Güroğlu B, Haselager GJ, van Lieshout CF, Takashima A, Rijpkema M, Fernández G. Why are friends special? Implementing a social interaction simulation task to probe the neural correlates of friendship. Neuroimage. 2008 Jan 15;39(2):903-10. Epub 2007 Sep 15.
• Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005 Jun 2;435(7042):673-6.
• Singer T, Kiebel SJ, Winston JS, Dolan RJ, Frith CD. Brain responses to the acquired moral status of faces. Neuron. 2004 Feb 19;41(4):653-62.
• Thompson RR, George K, Walton JC, Orr SP, Benson J. Sex-specific influences of vasopressin on human social communication. Proc Natl Acad Sci U S A. 2006 May 16;103(20):7889-94. Epub 2006 May 8.
• Vrticka P, Andersson F, Sander D, Vuilleumier P. Memory for friends or foes: the social context of past encounters with faces modulates their subsequent neural traces in the brain. Soc Neurosci. 2009;4(5):384-401. doi: 10.1080/17470910902941793. Epub 2009 Jul 27.

• Responsible Party: James K. Rilling, PhD, Associate Professor, Emory University
• ClinicalTrials.gov Identifier: NCT01566539
• Other Study ID Numbers: IRB00007905; 1R01MH084068-01A1; MH087721-01A1
• First Posted: Mar 29, 2012
• Last Update Posted: Sep 25, 2017
• Last Verified: Sep 1, 2017

• Keywords provided by James K. Rilling, PhD, Associate Professor, Emory University: Social cooperation; Oxytocin; Vasopressin; Prisoner's Dilemma game; Empathy; fMRI
• Additional relevant MeSH terms: Vasopressins; Arginine Vasopressin; Lorazepam; Oxytocin

Study Results

Participant Flow

Recruitment Details	A total of 707 signed the consent form, 449 started the main study period.
Pre-assignment Detail	The study team did not recruit any participants for the "Anxious and Depressed Subjects - OT", or "Anxious and Depressed Subjects - Placebo" arms.Therefore, these arms have been removed from the record.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo	Within Subject Group	Faces Task - Vasopressin (AVP)	Faces Task - Placebo	Empathy Task - Oxytocin (OT)	Empathy Task - Placebo	Healthy Volunteers - Lorazepam
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Vasopressin (AVP): 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). Intranasal Placebo: Participants will receive placebo sprays that are pH	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Lorazepam: Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.
Period Title: Main Study Period
STARTED	101	100	104	0	40	43	30	30	1
COMPLETED	100	100	104	0	40	40	30	30	1
NOT COMPLETED	1	0	0	0	0	3	0	0	0
Period Title: Main Study Period
STARTED	0	0	0	156	0	0	0	0	0
COMPLETED	0	0	0	153	0	0	0	0	0
NOT COMPLETED	0	0	0	3	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo	Faces Task - Vasopressin (AVP)	Faces Task - Placebo	Empathy Task - Oxytocin (OT)	Empathy Task - Placebo	Healthy Volunteers - Lorazepam	Total
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Lorazepam: Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.	Total of all reporting groups
Overall Participants	101	100	104	40	43	30	30	1	449
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	101 100%	100 100%	104 100%	40 100%	43 100%	30 100%	30 100%	1 100%	449 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	52 51.5%	50 50%	50 48.1%	20 50%	21 48.8%	15 50%	15 50%	0 0%	223 49.7%
Male	49 48.5%	50 50%	54 51.9%	20 50%	22 51.2%	15 50%	15 50%	1 100%	226 50.3%
Region of Enrollment (participants) [Number]
United States	101 100%	100 100%	104 100%	40 100%	43 100%	30 100%	30 100%	1 100%	449 100%

Outcome Measures

1. Primary Outcome

Title	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Oxytocin (OT) and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with excessive motion, missing data, abnormal brain anatomy or partial data collection were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	43	48
Mean (Standard Error) [percent signal change]	0.21 (0.03)	0.07 (0.02)

2. Primary Outcome

Title	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Oxytocin (OT) and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with excessive motion, missing data, abnormal brain anatomy or partial data collection were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	47	46
Mean (Standard Error) [percent signal change]	0.04 (0.02)	0.15 (0.02)

3. Primary Outcome

Title	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Vasopressin (AVP) and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with excessive motion, missing data, abnormal brain anatomy or partial data collection were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	44	48
Mean (Standard Error) [percent signal change]	0.13 (0.02)	-0.02 (0.02)

4. Primary Outcome

Title	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Vasopressin (AVP) and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with excessive motion, missing data, abnormal brain anatomy or partial data collection were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	49	46
Mean (Standard Error) [percent signal change]	-0.05 (0.03)	0.10 (0.03)

5. Primary Outcome

Title	Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the within subject group per protocol. Subjects with excessive motion during scanning were excluded from the analysis.

Arm/Group Title	Within Subject Group
Arm/Group Description	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Vasopressin (AVP): 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). Intranasal Placebo: Participants will receive placebo sprays that are pH
Measure Participants	57
Oxytocin treatment in men	0.21 (0.19)
Placebo treatment in men	0.19 (0.29)
Oxytocin treatment in women	0.06 (0.21)
Placebo treatment in women	0.10 (0.18)

6. Secondary Outcome

Title	Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Men During the Prisoners Dilemma Game
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Healthy Volunteers - Intranasal Vasopressin (AVP), Healthy Volunteers - Intranasal Oxytocin (OT), and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with missing data were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	49	50	53
Mean (Standard Error) [number of choices]	15.71 (0.98)	16.18 (1.01)	17.68 (0.93)

7. Secondary Outcome

Title	Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Women During the Prisoners Dilemma Game
Description	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.
Time Frame	Visit 1 (40-100 Minutes Post-Intervention)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Healthy Volunteers - Intranasal Vasopressin (AVP), Healthy Volunteers - Intranasal Oxytocin (OT), and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with missing data were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	51	50	50
Mean (Standard Error) [number of choices]	15.84 (0.76)	18.14 (1.03)	16.92 (0.98)

8. Secondary Outcome

Title	Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Male During the Prisoners Dilemma Game
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Within Subject Group per protocol. Subjects with missing data were excluded from the analysis. The difference between OT and PL visits is reported here (OT-PL).

Arm/Group Title	Within Subject Group
Arm/Group Description	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.
Measure Participants	29
Mean (Standard Deviation) [number of choices]	-1.10 (5.21)

9. Secondary Outcome

Title	Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Female During the Prisoners Dilemma Game
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Within Subject Group per protocol. Subjects with missing data were excluded from the analysis.

Arm/Group Title	Within Subject Group
Arm/Group Description	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.
Measure Participants	30
Oxytocin treatment	16.13 (6.87)
Placebo treatment	15.53 (6.70)

10. Secondary Outcome

Title	Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Men
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Faces Task - Vasopressin (AVP) and Faces Task - Placebo groups per protocol. Subjects with missing data were excluded from the analysis.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	20
viewing same-sex faces	0.03 (0.30)	-0.14 (0.22)
viewing other-sex faces	0.14 (0.33)	-0.13 (0.30)

11. Secondary Outcome

Title	Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Women
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Analysis was completed for the Faces Task - Vasopressin (AVP) and Faces Task - Placebo groups per protocol. Subjects with missing data were excluded from the analysis.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	19
viewing same-sex faces	-0.08 (0.31)	0.12 (0.22)
viewing other-sex faces	0.003 (0.16)	0.13 (0.22)

12. Secondary Outcome

Title	Faces Task Groups: Mean Approachability Rating of Faces in Men
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the AVP and placebo faces groups.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	20
viewing same-sex faces scan 1	0.31 (0.96)	-0.06 (0.96)
viewing other-sex faces scan 1	1.00 (1.09)	0.81 (0.92)
viewing same-sex faces scan 2	0.78 (0.88)	0.25 (0.99)
viewing other-sex faces scan 2	1.19 (1.04)	0.89 (0.98)

13. Secondary Outcome

Title	Faces Task Group: Mean Approachability Rating of Faces in Women
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the AVP and placebo faces groups.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	20
viewing same-sex faces scan 1	0.37 (0.57)	0.21 (0.86)
viewing other-sex faces scan 1	-0.04 (0.83)	0.28 (0.61)
viewing same-sex faces scan 2	0.37 (0.57)	0.23 (0.88)
viewing other-sex faces scan 2	0.12 (0.66)	0.22 (0.63)

14. Secondary Outcome

Title	Faces Task Groups: Mean Attractiveness Rating of Faces in Men
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the AVP and placebo faces groups.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	20
viewing same-sex faces scan 1	0.35 (0.78)	-0.06 (0.77)
viewing other-sex faces scan 1	1.79 (0.58)	1.60 (0.46)
viewing same-sex faces scan 2	0.52 (0.86)	-0.08 (0.79)
viewing other-sex faces scan 2	1.70 (0.69)	1.43 (0.64)

15. Secondary Outcome

Title	Faces Task Groups: Mean Attractiveness Rating of Faces in Women
Description	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.
Time Frame	Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the AVP and placebo faces groups.

Arm/Group Title	Faces Task - Vasopressin (AVP)	Faces Task - Placebo
Arm/Group Description	Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.	Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	20	20
viewing same-sex faces scan 1	1.56 (0.54)	1.02 (0.80)
viewing other-sex faces scan 1	0.55 (1.16)	0.61 (0.62)
viewing same-sex faces scan 2	1.29 (0.68)	0.82 (0.92)
viewing other-sex faces scan 2	0.53 (1.04)	0.28 (0.51)

16. Secondary Outcome

Title	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women
Description	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.
Time Frame	Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the OT and placebo empathy task groups.

Arm/Group Title	Empathy Task - Oxytocin (OT)	Empathy Task - Placebo
Arm/Group Description	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	15	15
Mean (Standard Deviation) [percent signal change]	-.910 (.417)	-.377 (.656)

17. Secondary Outcome

Title	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men
Description	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.
Time Frame	Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)

Outcome Measure Data

Analysis Population Description

Data was collected per protocol in the OT and placebo empathy task groups.

Arm/Group Title	Empathy Task - Oxytocin (OT)	Empathy Task - Placebo
Arm/Group Description	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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.	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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	15	15
Mean (Standard Deviation) [percent signal change]	-.429 (.711)	-.382 (1.012)

18. Other Pre-specified Outcome

Title	Healthy Volunteers Groups: Mean Vasopressin (AVP) Plasma Level
Description	Peripheral levels of AVP will be assessed via assay of plasma collected.
Time Frame	Visit 1 (Up to 3 Hours)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Vasopressin (AVP), Healthy Volunteers - Intranasal Oxytocin (OT), and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with unreliable or missing data were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	27	27	36
Mean (Standard Error) [pg/ml]	4.5 (0.49)	3.5 (0.34)	3.1 (0.40)

19. Other Pre-specified Outcome

Title	Healthy Volunteers Groups: Mean Oxytocin (OT) Plasma Level
Description	Peripheral levels of OT will be assessed via assay of plasma collected.
Time Frame	Visit 1 (Up to 3 Hours)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the Healthy Volunteers - Intranasal Vasopressin (AVP), Healthy Volunteers - Intranasal Oxytocin (OT), and Healthy Volunteers - Intranasal Placebo groups per protocol. Subjects with unreliable or missing data were excluded from the analysis.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	27	27	36
Mean (Standard Error) [pg/ml]	120.6 (7.3)	134.7 (10.2)	129.4 (12.2)

20. Other Pre-specified Outcome

Title	Healthy Volunteers Groups: Mean Testosterone Plasma Level
Description	Peripherals levels of testosterone will be assessed via assay of plasma collected.
Time Frame	Visit 1 (Up to 3 Hours)

Outcome Measure Data

Analysis Population Description

Analysis was completed in the first batch of data collection from Healthy Volunteers - Intranasal Vasopressin (AVP), Healthy Volunteers - Intranasal Oxytocin (OT), and Healthy Volunteers - Intranasal Placebo groups per protocol. Due to the lack of funds, no subsequent analysis has been done on the samples collected.

Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)	Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers - Intranasal Placebo
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).	The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.	The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.
Measure Participants	25	30	31
Mean (Standard Deviation) [ng/dl]	214.92 (125.42)	475.82 (134.76)	437.99 (160.36)

Adverse Events

Time Frame	Adverse event were collected throughout the duration of the study.
Arm/Group Title	Healthy Volunteers - Intranasal Vasopressin (AVP)		Healthy Volunteers - Intranasal Oxytocin (OT)		Healthy Volunteers - Intranasal Placebo		Within Subject Group		Faces Task - Vasopressin (AVP)		Faces Task - Placebo		Empathy Task - Oxytocin (OT)		Empathy Task - Placebo		Healthy Volunteers - Lorazepam
Arm/Group Description	The AVP group of healthy volunteers will self-administer vasopressin solution prior to completing the PD task. Intranasal Vasopressin (AVP): 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).		The OT group of healthy volunteers will self-administer oxytocin solution prior to completing the PD task. Intranasal Oxytocin (OT) 24 IU: 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.		The placebo group of healthy volunteers will self-administer a placebo spray prior to completing the PD task. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.		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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Vasopressin (AVP): 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). Intranasal Placebo: Participants will receive placebo sprays that are pH		Healthy volunteers between the ages of 21-30 years will receive Faces Intranasal Vasopressin (AVP) prior to completing the Faces task during fMRI scanning. Intranasal Vasopressin (AVP) 40 IU: 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.		Healthy volunteers between the ages of 21-30 years will receive placebo prior to completing the Faces task during fMRI scanning. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.		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. Intranasal Oxytocin (OT) 24 IU: 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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.		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. Intranasal Placebo: Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.		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. Lorazepam: Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.
All Cause Mortality
	Healthy Volunteers - Intranasal Vasopressin (AVP)		Healthy Volunteers - Intranasal Oxytocin (OT)		Healthy Volunteers - Intranasal Placebo		Within Subject Group		Faces Task - Vasopressin (AVP)		Faces Task - Placebo		Empathy Task - Oxytocin (OT)		Empathy Task - Placebo		Healthy Volunteers - Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/100 (0%)		0/104 (0%)		0/156 (0%)		0/40 (0%)		0/43 (0%)		0/30 (0%)		0/30 (0%)		0/1 (0%)
Serious Adverse Events
	Healthy Volunteers - Intranasal Vasopressin (AVP)		Healthy Volunteers - Intranasal Oxytocin (OT)		Healthy Volunteers - Intranasal Placebo		Within Subject Group		Faces Task - Vasopressin (AVP)		Faces Task - Placebo		Empathy Task - Oxytocin (OT)		Empathy Task - Placebo		Healthy Volunteers - Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/100 (0%)		0/104 (0%)		0/156 (0%)		0/40 (0%)		0/43 (0%)		0/30 (0%)		0/30 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Volunteers - Intranasal Vasopressin (AVP)		Healthy Volunteers - Intranasal Oxytocin (OT)		Healthy Volunteers - Intranasal Placebo		Within Subject Group		Faces Task - Vasopressin (AVP)		Faces Task - Placebo		Empathy Task - Oxytocin (OT)		Empathy Task - Placebo		Healthy Volunteers - Lorazepam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/101 (3%)		4/100 (4%)		12/104 (11.5%)		0/156 (0%)		0/40 (0%)		1/43 (2.3%)		0/30 (0%)		0/30 (0%)		0/1 (0%)
General disorders
fever	0/101 (0%)	0	0/100 (0%)	0	1/104 (1%)	1	0/156 (0%)	0	0/40 (0%)	0	0/43 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0
felt faint after blood draw	0/101 (0%)	0	1/100 (1%)	1	0/104 (0%)	0	0/156 (0%)	0	0/40 (0%)	0	0/43 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0
nose bleed	1/101 (1%)	1	0/100 (0%)	0	0/104 (0%)	0	0/156 (0%)	0	0/40 (0%)	0	0/43 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0
nausea	0/101 (0%)	0	0/100 (0%)	0	1/104 (1%)	1	0/156 (0%)	0	0/40 (0%)	0	0/43 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0
Psychiatric disorders
claustrophobia	0/101 (0%)	0	0/100 (0%)	0	1/104 (1%)	1	0/156 (0%)	0	0/40 (0%)	0	0/43 (0%)	0	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0
Vascular disorders
high blood pressure or heart rate post-drug administration	3/101 (3%)	3	3/100 (3%)	3	9/104 (8.7%)	9	0/156 (0%)	0	0/40 (0%)	0	1/43 (2.3%)	1	0/30 (0%)	0	0/30 (0%)	0	0/1 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.