Clinical trial NCT01566539: Biological Basis of Individual Variation in Social Cooperation
Official title: The Biological Basis of Individual Variation in Social Cooperation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Social cooperation
Oxytocin
Vasopressin
Prisoner's Dilemma game
Empathy
fMRI
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: John Templeton Foundation
First posted: 2012-03-29
Enrollment: 707
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Men
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Healthy Volunteers-OT, Placebo: Mean Percent Signal Change in Right Caudate Nucleus in Women
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Men
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Healthy Volunteers-AVP, Placebo: Mean Percent Signal Change in Left Insula in Women
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Within Subject Group: Mean Percent Signal Change in Left Caudate Nucleus in Men and Women
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)
Secondary outcomes:
measure: Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Men During the Prisoners Dilemma Game
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Healthy Volunteer Groups: Total Number of Cooperate Choices Made by Women During the Prisoners Dilemma Game
timeFrame: Visit 1 (40-100 Minutes Post-Intervention)
measure: Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Male During the Prisoners Dilemma Game
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)
measure: Within Subject Group: Mean Difference in Number of Cooperate Choices Made by Female During the Prisoners Dilemma Game
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 2 Weeks)
measure: Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Men
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Faces Task Groups: Mean Percent Signal Change in Nucleus Accumbens to Faces in Women
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Faces Task Groups: Mean Approachability Rating of Faces in Men
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Faces Task Group: Mean Approachability Rating of Faces in Women
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Faces Task Groups: Mean Attractiveness Rating of Faces in Men
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Faces Task Groups: Mean Attractiveness Rating of Faces in Women
timeFrame: Visit 1 (30-75 Minutes Post-Intervention), Visit 2 (Up to 7 Days)
measure: Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Women
timeFrame: Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)
measure: Empathy Task Groups: Mean Percent Signal Change in Early Visual Cortex in Response to Animation in Men
timeFrame: Visit 1 (40-75 Minutes Post-Intervention), Visit 2 (Up to 1 Month)
Other outcomes:
measure: Healthy Volunteers Groups: Mean Vasopressin (AVP) Plasma Level
timeFrame: Visit 1 (Up to 3 Hours)
measure: Healthy Volunteers Groups: Mean Oxytocin (OT) Plasma Level
timeFrame: Visit 1 (Up to 3 Hours)
measure: Healthy Volunteers Groups: Mean Testosterone Plasma Level
timeFrame: Visit 1 (Up to 3 Hours)
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University 1462 Clifton Rd
state: Georgia
Study officials:
affiliation: Emory University
name: James K Rilling, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature. 2005 Jun 2;435(7042):673-6. doi: 10.1038/nature03701.
citation: 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. doi: 10.1002/cne.20772.
citation: 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. doi: 10.1073/pnas.0600406103. Epub 2006 May 8.
citation: 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.
citation: 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. doi: 10.1016/s0896-6273(04)00014-5.
citation: Guroglu B, Haselager GJ, van Lieshout CF, Takashima A, Rijpkema M, Fernandez 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. doi: 10.1016/j.neuroimage.2007.09.007. Epub 2007 Sep 15.