Biological Basis of Individual Variation in Social Cooperation

The Biological Basis of Individual Variation in Social Cooperation

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01566539

Enrollment

707

Registered

2012-03-29

Start date

2008-04-30

Completion date

2016-11-30

Last updated

2017-09-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

Social cooperation, Oxytocin, Vasopressin, Prisoner's Dilemma game, Empathy, fMRI

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.

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.

Interventions

DRUGIntranasal 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.

DRUGIntranasal 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).

DRUGIntranasal Placebo

Participants will receive placebo sprays that are pH adjusted to comparable levels of the drugs given. Five puffs per nostril; ten puffs total.

DRUGIntranasal 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.

DRUGLorazepam

Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.

Study design

Allocation

RANDOMIZED

Intervention model

FACTORIAL

Primary purpose

BASIC_SCIENCE

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 30 Years

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

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
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.
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.
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.

Secondary

Measure	Time frame	Description
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Other

Measure	Time frame	Description
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.
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.
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.

Countries

United States

Participant flow

Recruitment details

A total of 707 signed the consent form, 449 started the main study period.

Pre-assignment details

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.

Participants by arm

Arm	Count
Healthy Volunteers - Intranasal Vasopressin (AVP) 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).	101
Healthy Volunteers - Intranasal Oxytocin (OT) 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.	100
Healthy Volunteers - Intranasal Placebo 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.	104
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. 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.	40
Faces Task - Placebo 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.	43
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. 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.	30
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. 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.	30
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. Lorazepam: Subjects will take 1.0 mg of lorazepam orally 60 minutes prior to fMRI scan.	1
Total	449

Baseline characteristics

Characteristic	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
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	101 Participants	100 Participants	104 Participants	40 Participants	43 Participants	30 Participants	30 Participants	1 Participants	449 Participants
Region of Enrollment United States	101 participants	100 participants	104 participants	40 participants	43 participants	30 participants	30 participants	1 participants	449 participants
Sex: Female, Male Female	52 Participants	50 Participants	50 Participants	20 Participants	21 Participants	15 Participants	15 Participants	0 Participants	223 Participants
Sex: Female, Male Male	49 Participants	50 Participants	54 Participants	20 Participants	22 Participants	15 Participants	15 Participants	1 Participants	226 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk
deaths Total, all-cause mortality	0 / 101	0 / 100	0 / 104	0 / 156	0 / 40	0 / 43	0 / 30	0 / 30	0 / 1
other Total, other adverse events	3 / 101	4 / 100	12 / 104	0 / 156	0 / 40	1 / 43	0 / 30	0 / 30	0 / 1
serious Total, serious adverse events	0 / 101	0 / 100	0 / 104	0 / 156	0 / 40	0 / 43	0 / 30	0 / 30	0 / 1

Outcome results

Primary

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.

Time frame: Visit 1 (40-100 Minutes Post-Intervention)

Population: 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	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men	0.13 percent signal change	Standard Error 0.02
Healthy Volunteers - Intranasal Placebo	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men	-0.02 percent signal change	Standard Error 0.02

Primary

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.

Time frame: Visit 1 (40-100 Minutes Post-Intervention)

Arm	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women	-0.05 percent signal change	Standard Error 0.03
Healthy Volunteers - Intranasal Placebo	Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women	0.10 percent signal change	Standard Error 0.03

Primary

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.

Time frame: Visit 1 (40-100 Minutes Post-Intervention)

Population: 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	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men	0.21 percent signal change	Standard Error 0.03
Healthy Volunteers - Intranasal Placebo	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men	0.07 percent signal change	Standard Error 0.02

Primary

Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women

Time frame: Visit 1 (40-100 Minutes Post-Intervention)

Arm	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women	0.04 percent signal change	Standard Error 0.02
Healthy Volunteers - Intranasal Placebo	Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women	0.15 percent signal change	Standard Error 0.02

Primary

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.

Time frame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women	Oxytocin treatment in men	0.21 percent signal change	Standard Deviation 0.19
Healthy Volunteers - Intranasal Oxytocin (OT)	Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women	Placebo treatment in men	0.19 percent signal change	Standard Deviation 0.29
Healthy Volunteers - Intranasal Oxytocin (OT)	Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women	Oxytocin treatment in women	0.06 percent signal change	Standard Deviation 0.21
Healthy Volunteers - Intranasal Oxytocin (OT)	Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women	Placebo treatment in women	0.10 percent signal change	Standard Deviation 0.18

Secondary

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.

Time frame: Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)

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

Arm	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men	-.429 percent signal change	Standard Deviation 0.711
Healthy Volunteers - Intranasal Placebo	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men	-.382 percent signal change	Standard Deviation 1.012

Secondary

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.

Time frame: Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)

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

Arm	Measure	Value (MEAN)	Dispersion
Healthy Volunteers - Intranasal Oxytocin (OT)	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women	-.910 percent signal change	Standard Deviation 0.417
Healthy Volunteers - Intranasal Placebo	Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women	-.377 percent signal change	Standard Deviation 0.656

Secondary

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.