Biological Basis of Individual Variation in Social Cooperation

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
James K. Rilling, PhD, Emory University
ClinicalTrials.gov Identifier:
NCT01566539
First received: March 26, 2012
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

The overall objective of this project is to explore the biological bases of individual variation in cooperative social behavior among normal subjects, with the goal of developing hypotheses to explain more extreme variation that manifests as mental illness. Cooperative behavior will be measured in an interactive social task known as the Prisoner's Dilemma (PD) Game. There are eight specific aims. Aim 1 is to examine the relationship between individual variation in cooperative behavior and individual variation in brain function during the PD game. This will be accomplished by imaging subjects' brains with functional Magnetic Resonance Imaging (fMRI) as they play many rounds of the PD Game with two assumed human partners. Aim 2 is to examine the relationship between individual variation in cooperative behavior and individual variation in prefrontal cortex anatomy. This aim will involve acquiring a structural Magnetic Resonance Imaging (MRI) scan from each subject to measure morphometric variation, as well as a diffusion tensor imaging (DTI) brain scan to measure white matter integrity. Aim 3 is to investigate the impact of intranasal oxytocin (OT) and vasopressin (AVP), neuropeptides associated with social bonding, on cooperative behavior and associated brain activity. In this placebo-controlled, double-blind experiment, subjects will be randomized to one of three conditions: intranasal oxytocin (OT) administration, intranasal vasopressin (AVP) administration, or intranasal placebo administration. Functional brain activity and behavior will be compared across treatment groups. Aim 4 is to examine the effect of oxytocin (OT) and vasopressin (AVP) on cortisol levels. Aim 5 is to examine the relationship between individual variation in cooperative behavior and individual genetic variation. Saliva samples will be collected from each subject for analysis of genes hypothesized to have an influence on cooperative social behavior. Aim 6 is to examine the relationship between individual variation in cooperative behavior and individual variation in personality, as assessed by personality tests. Aim 7 is to examine the relationship between individual variation in social intelligence and individual variation in brain anatomy. Aim 8 is to use functional Magnetic Resonance Imaging (fMRI) to test the effect of vasopressin (AVP) on neural responses to faces, which are powerful social signals important for emotional communication. Aim 9 is to use fMRI to investigate the brain regions active during an empathy and perspective-taking task. Aim 10 involves testing the effect of OT on both empathy-related behavior and functional brain activation, using a within-subjects placebo-controlled design. Aim 11 investigates the role of early life experience, spirituality, self-reported prosocial activities, and general cognition on empathic and cooperative behavior. Aim 12 is to examine the neural and behavioral effect of Lorazepam used as a challenge agent in the context of iterated PD game in healthy controls. Aim 13 is to examine the effect of OT on behavior and brain activity of unmedicated depressed or anxious men in the context of the iterated PD game.


Condition Intervention
Healthy
Drug: Intranasal Oxytocin
Drug: Intranasal Vasopressin 40 or 20 units
Drug: Intranasal Vasopressin
Drug: Intranasal Placebo OT Vehicle
Drug: Intranasal Placebo Saline
Drug: Intranasal Placebo AVP Vehicle
Drug: Lorazepam

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: The Biological Basis of Individual Variation in Social Cooperation

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Functional Magnetic Resonance Imaging (fMRI) Data [ Time Frame: January 2015 thru June 2015 the final analyses will be done on all subjects' brain imaging fMRI data. Also, periodic monthly single subject analyses will be done through the last 6 months of 2013. Data will be collected during 3 hour subject visit. ] [ Designated as safety issue: No ]
    The effect of the drug treatments will be assessed by determining changes in brain activation between treatment and placebo groups.


Secondary Outcome Measures:
  • Plasma levels of Vasopressin (AVP) [ Time Frame: All subjects assayed Dec 2014, Blood will be collected and centrifuged during 3 hour subject visit ] [ Designated as safety issue: No ]
    Peripheral levels of AVP will be assessed via assay of plasma collected.

  • Behavioral data [ Time Frame: Starting January 2015 thru June 2015 the final analyses will be done on all subjects' behavioral data. Data will be collected during 3 hour subject visits. ] [ Designated as safety issue: No ]
    The effect of the drug treatments will be assessed by determining changes in behavior in an economic game between treatment and placebo groups .

  • Plasma levels of Oxytocin (OT) [ Time Frame: All subjects assayed December 2014, Blood will be collected and centrifuged during 3 hour subject visit ] [ Designated as safety issue: No ]
    Peripheral levels of OT will be assessed via assay of plasma collected.

  • Plasma levels of Testosterone [ Time Frame: All subjects assayed Dec 2014; Blood will be collected and centrifuged during 3 hour subject visit ] [ Designated as safety issue: No ]
    Peripherals levels of testosterone will be assessed via assay of plasma collected.


Estimated Enrollment: 750
Study Start Date: April 2008
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intranasal Vasopressin
IND#101480, Serial #001 Following Thompson et al (Thompson et al., 2006), the AVP group will self-administer a 1 ml solution containing 20 units of AVP (American Reagent Laboratories, Shirley, NY; 5 puffs per nostril, each with 2 International Units (IU) AVP, 10 puffs total).
Drug: Intranasal Vasopressin
Dosage and details described in arm.
Experimental: Intranasal Oxytocin
IND#100959, Serial #001 Following Kosfeld et al (Kosfeld et al., 2005), the OT group will self-administer a single dose of 24 IU oxytocin (Syntocinin-Spray, Novartis; 5 puffs per nostril, each with 2.4 IU oxytocin, 10 puffs total).
Drug: Intranasal Oxytocin
Dosage and details described in arm.
Other Name: Oxytocin: Syntocinon Nasal Spray
Placebo Comparator: Intranasal Placebo

Intranasal AVP placebo: The AVP placebo will consist of the vasopressin vehicle only, and will be prepared by adding 125 mg of 0.5% chlorobutanol to 50 ml saline, followed by acetic acid until the pH fell within the range of 2.5—4.5 as measured with a pH meter. The solution will then be sterilized using a 0.22 m filter. 6 ml will be transferred to a plastic bottle with nasal applicator.

Intranasal OT placebo: The OT placebo will consist of the Syntocinon vehicle only. Each 5 ml of OT placebo consists of: chlorobutanol hemihydrate 12.5 mg, methyl-4-hydroxy-benzoate 2.0 mg, propyl-4-hydroxybenzoate 1.0 mg, 85% ethanol 125 ml, sodium acetate 14.0 mg, purified water 4.8455 g. 6 ml will be transferred to a plastic bottle with nasal applicator.

Drug: Intranasal Placebo OT Vehicle
Dosage and details described in arm.
Drug: Intranasal Placebo AVP Vehicle
Dosage and details described in arm.
Experimental: Intranasal Vasopressin 40 or 20 units

IND# 113332, Serial #001. For hypotheses 8A-8D.

Following Thompson et al (Thompson et al 2006), the AVP group will self-administer a 0.5 ml solution containing a to be determined dose of AVP.

Briefly, prior to the experiment, lyophilized AVP purchased from Polypeptide Group (Hillerod, Denmark) will be diluted in sterile saline at concentration of 40 units/ml. The pH of the resulting solution should be between 5.5 and 6.0, well within the range of acceptable pH for human use, so no buffering is anticipated. However, if the pH is less than 5.0, we will adjust upward with sodium hydroxide. If the pH is greater than 7.0, we will adjust downward with hydrochloric acid. Thus, no subject will administer a solution with a pH less than 5 or greater than 7.

Drug: Intranasal Vasopressin 40 or 20 units
Dosage and details described in arm.
Placebo Comparator: Intranasal Placebo Saline
A placebo spray comprised of 0.5 mL sterile saline, pH adjusted and filtered in a similar manner as the Intranasal Vasopressin 40 ml or 20 ml, but not containing the neuropeptide, prepared ahead of time and stored at -80°C until use.
Drug: Intranasal Placebo Saline
Dosage and details described in arm.
Other Name: Saline
Experimental: Lorazepam

This arm of the study has been granted IND exempt status by Emory University IRB.

Lorazepam group (healthy controls) will receive 1.0 mg Lorazepam tablets as a challenge agent.

Drug: Lorazepam
Dosage and details described in arm
Other Name: Ativan

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18-22 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)

    • Date last episode (if > 1 year, include; if <1 year, at discretion of PI)
  • Current use of psychoactive drugs
  • Previous use of psychoactive drugs (can be included as discretion of PI)

    • Date last medicated _____Type of medication___________________________________
  • 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)

    • Medication
    • Frequency of episodes
    • Date of last episode
  • Migraines (can be included as discretion of PI, if episodes are infrequent, nonmedicated, and no active problems at time of study)

    • Medication
    • Frequency of migraines
    • Date of last migraine
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566539

Locations
United States, Georgia
Emory University 1462 Clifton Rd
Atlanta, Georgia, United States, 30322
Emory University Hospital
Atlanta, Georgia, United States, 30307
Sponsors and Collaborators
James K. Rilling, PhD
Investigators
Principal Investigator: James K Rilling, Ph.D. Emory University
  More Information

Additional Information:
Publications:
Responsible Party: James K. Rilling, PhD, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT01566539     History of Changes
Other Study ID Numbers: IRB00007905, 1R01MH084068-01A1, MH087721-01A1
Study First Received: March 26, 2012
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Emory University:
Social cooperation
Oxytocin
Vasopressin
Prisoner's Dilemma game
Empathy
fMRI

Additional relevant MeSH terms:
Arginine Vasopressin
Lorazepam
Oxytocin
Vasopressins
Anti-Anxiety Agents
Anticonvulsants
Antidiuretic Agents
Antiemetics
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Coagulants
GABA Agents
GABA Modulators
Gastrointestinal Agents
Hematologic Agents
Hemostatics
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Neurotransmitter Agents
Oxytocics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Reproductive Control Agents
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 22, 2014