Brain Dynamics of Oxytocin

NCT01834261 | Completed Phase 1 Results DMC

• 2 other identifiers: 293408N000141210393
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 3

Brief Summary

Oxytocin is a neuropeptide that is well known for its role in social and affiliative behavior in humans. Oxytocin receptors are significantly lowered in autistic individuals and administration of oxytocin has shown benefits in enhancing social recognition and behavior in autistic children. However, more recent research has refined the behavioral effects of oxytocin, moving away from the notion that the neuropeptide blindly induces love and trust, towards the view that it actually increases social perception in assessing friend vs. foe: supporting cohesion with 'insiders' and distrust and aggression for 'outsiders.' Oxytocin is responsible for the selective aggression shown by lactating female mammals protecting their young, an effect demonstrated also in humans, and has been shown to strengthen feelings of ethnocentrism. However, no neuroimaging study to date has investigated this effect, with the consequence that its neurobiological basis is still unknown. The general aim of our study is to determine meso-circuit brain dynamics that underlie oxytocin's amplification of both trust and aggression; and specifically, using neuroimaging (fMRI, magnetoencephalography, and behavioral testing) whether oxytocin amplifies kinship bias by attenuating social reward learning.

Conditions

Brain Dynamics in Healthy Adults

Keywords

oxytocin; trust; kinship; kin selection

Outcome Measures

Primary Outcomes (2)

• Number of Benevolent Rounds

  This study recruited healthy adults. Subjects participated in an interactive neuroeconomic game, an iterative version of the classical "Trust Study." During this game, the subject ('investor') is first provided a sum of money (20 units). He then has the choice in terms of how much to invest in a fictional computer-generated trustee. The trustee then sends some percentage back to the subject ('investor'), and the game iterates over 20 trials (rounds). We computed the investment ratio as the ratio of the actual investment and the maximum allowed amount of 20 units, and analogously for the repayment ratio. Benevolent rounds were defined as those with increased investment ratios even after a decreased repayment ratio.

  Immediately after completion of the study, for each subject.

• Number of Malevolent Rounds

  This study recruited healthy adults. Subjects participated in an interactive neuroeconomic game, an iterative version of the classical "Trust Study." During this game, the subject ('investor') is first provided a sum of money (20 units). He then has the choice in terms of how much to invest in a fictional computer-generated trustee. The trustee then sends some percentage back to the subject ('investor'), and the game iterates over 20 trials (rounds). We computed the investment ratio as the ratio of the actual investment and the maximum allowed amount of 20 units, and analogously for the repayment ratio. Malevolent rounds were defined as those with decreased investment ratios even after an increased repayment ratio.

  Immediately after completion of the study, for each subject.

Secondary Outcomes (1)

• Functional Connectivity Between OFC and AMY

  Within two weeks of enrollment completion.

Study Arms (2)

Oxytocin

ACTIVE COMPARATOR

Healthy adult subjects will receive several puffs of Syntocinon Nasal Spray, 40IU, once, prior to MRI and/or MEG scanning.

Drug: Syntocinon Nasal Spray, 40IU; Drug: Syntocinon Placebo Formulation, 40IU

Placebo

PLACEBO COMPARATOR

Healthy adult subjects will receive several puffs of Syntocinon Placebo Formulation, 40IU, once, prior to MRI and/or MEG scanning.

Drug: Syntocinon Nasal Spray, 40IU; Drug: Syntocinon Placebo Formulation, 40IU

Interventions

Syntocinon Nasal Spray, 40IU DRUG

Subjects will be scanned twice. Prior to first brain scanning session, they will be randomly assigned to receive either Syntocinon or Placebo. Prior to second scanning session, they will receive what they have not received in the first session; i.e., same subjects will be receiving both Syntocinon and placebo on two different days.

Oxytocin; Placebo

Syntocinon Placebo Formulation, 40IU DRUG

Subjects will be scanned twice. Prior to first brain scanning session, they will be randomly assigned to receive either Syntocinon or Placebo. Prior to second scanning session, they will receive what they have not received in the first session; i.e., same subjects will be receiving both Syntocinon and placebo on two different days.

Oxytocin; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• years of age

You may not qualify if:

• any significant known medical condition, including mental disorders (confounds interpretation of brain activity)
• metal in the body or claustrophobia (contraindicated for fMRI)
• current use of any type of psychotropic medication (confounds interpretation of brain activity)
• body mass index of greater than 30 (to permit matched dosing across subjects)
• pregnancy (contraindicated for OT)
• breastfeeding (lactation endogenously triggers OT, which would not permit a placebo condition)
• smoking (affects use of nasal spray)
• use of drugs of abuse (confounds interpretation of brain activity)
• blood pressure above the normal range (140/90 mm Hg) or controlled with medication (may theoretically increase risk for OT side-effects)
• anosmia (affects use of nasal spray)

Sponsors & Collaborators

• Stony Brook University: lead
• Martinos Center for Biomedical Imaging: collaborator

Study Sites (3)

Martinos Imaging Center at the McGovern Institute for Brain Research at MIT

Cambridge, Massachusetts, 02139, United States

Location

Martinos Center for Biomedical Research, Building 149, 13th Street

Charlestown, Massachusetts, 02129, United States

Location

Bioengineering Building , Stony Brook University

Stony Brook, New York, 11794, United States

Location

Related Publications (25)

• Averbeck BB. Oxytocin and the salience of social cues. Proc Natl Acad Sci U S A. 2010 May 18;107(20):9033-4. doi: 10.1073/pnas.1004892107. Epub 2010 May 6. No abstract available.

  PMID: 20448196 BACKGROUND

• Insel TR. The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010 Mar 25;65(6):768-79. doi: 10.1016/j.neuron.2010.03.005.

  PMID: 20346754 BACKGROUND

• Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E. Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron. 2008 May 22;58(4):639-50. doi: 10.1016/j.neuron.2008.04.009.

  PMID: 18498743 BACKGROUND

• Delgado MR. Fool me once, shame on you; fool me twice, shame on oxytocin. Neuron. 2008 May 22;58(4):470-1. doi: 10.1016/j.neuron.2008.05.005.

  PMID: 18498730 BACKGROUND

• 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.

  PMID: 15931222 BACKGROUND

• Wermter AK, Kamp-Becker I, Hesse P, Schulte-Korne G, Strauch K, Remschmidt H. Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):629-639. doi: 10.1002/ajmg.b.31032.

  PMID: 19777562 BACKGROUND

• Park J, Willmott M, Vetuz G, Toye C, Kirley A, Hawi Z, Brookes KJ, Gill M, Kent L. Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30;34(4):697-702. doi: 10.1016/j.pnpbp.2010.03.029. Epub 2010 Mar 27.

  PMID: 20347913 BACKGROUND

• Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D, Markunas CA, Lintas C, Abramson RK, Wright HH, Ellis P, Langford CF, Worley G, Delong GR, Murphy SK, Cuccaro ML, Persico A, Pericak-Vance MA. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009 Oct 22;7:62. doi: 10.1186/1741-7015-7-62.

  PMID: 19845972 BACKGROUND

• Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94. doi: 10.1073/pnas.0910249107. Epub 2010 Feb 16.

  PMID: 20160081 BACKGROUND

• Guastella AJ, Einfeld SL, Gray KM, Rinehart NJ, Tonge BJ, Lambert TJ, Hickie IB. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry. 2010 Apr 1;67(7):692-4. doi: 10.1016/j.biopsych.2009.09.020. Epub 2009 Nov 7.

  PMID: 19897177 BACKGROUND

• Rossignol DA. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann Clin Psychiatry. 2009 Oct-Dec;21(4):213-36.

  PMID: 19917212 BACKGROUND

• Opar A. Search for potential autism treatments turns to 'trust hormone'. Nat Med. 2008 Apr;14(4):353. doi: 10.1038/nm0408-353. No abstract available.

  PMID: 18391923 BACKGROUND

• Bartz J, Simeon D, Hamilton H, Kim S, Crystal S, Braun A, Vicens V, Hollander E. Oxytocin can hinder trust and cooperation in borderline personality disorder. Soc Cogn Affect Neurosci. 2011 Oct;6(5):556-63. doi: 10.1093/scan/nsq085. Epub 2010 Nov 29.

  PMID: 21115541 BACKGROUND

• Bartz JA, Zaki J, Ochsner KN, Bolger N, Kolevzon A, Ludwig N, Lydon JE. Effects of oxytocin on recollections of maternal care and closeness. Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21371-5. doi: 10.1073/pnas.1012669107. Epub 2010 Nov 29.

  PMID: 21115834 BACKGROUND

• Hahn-Holbrook J, Holt-Lunstad J, Holbrook C, Coyne SM, Lawson ET. Maternal defense: breast feeding increases aggression by reducing stress. Psychol Sci. 2011 Oct;22(10):1288-95. doi: 10.1177/0956797611420729. Epub 2011 Aug 26.

  PMID: 21873570 BACKGROUND

• De Dreu CK, Greer LL, Van Kleef GA, Shalvi S, Handgraaf MJ. Oxytocin promotes human ethnocentrism. Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1262-6. doi: 10.1073/pnas.1015316108. Epub 2011 Jan 10.

  PMID: 21220339 BACKGROUND

• Domes G, Lischke A, Berger C, Grossmann A, Hauenstein K, Heinrichs M, Herpertz SC. Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology. 2010 Jan;35(1):83-93. doi: 10.1016/j.psyneuen.2009.06.016.

  PMID: 19632787 BACKGROUND

• Domes G, Heinrichs M, Glascher J, Buchel C, Braus DF, Herpertz SC. Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biol Psychiatry. 2007 Nov 15;62(10):1187-90. doi: 10.1016/j.biopsych.2007.03.025. Epub 2007 Jul 9.

  PMID: 17617382 BACKGROUND

• Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves "mind-reading" in humans. Biol Psychiatry. 2007 Mar 15;61(6):731-3. doi: 10.1016/j.biopsych.2006.07.015. Epub 2006 Nov 29.

  PMID: 17137561 BACKGROUND

• Dupont CP. Contact dermatitis in Dublin. Contact Dermatitis. 1979 Jan;5(1):61-2. doi: 10.1111/j.1600-0536.1979.tb05548.x. No abstract available.

  PMID: 421469 BACKGROUND

• Kirsch P, Esslinger C, Chen Q, Mier D, Lis S, Siddhanti S, Gruppe H, Mattay VS, Gallhofer B, Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci. 2005 Dec 7;25(49):11489-93. doi: 10.1523/JNEUROSCI.3984-05.2005.

  PMID: 16339042 BACKGROUND

• Petrovic P, Kalisch R, Singer T, Dolan RJ. Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci. 2008 Jun 25;28(26):6607-15. doi: 10.1523/JNEUROSCI.4572-07.2008.

  PMID: 18579733 BACKGROUND

• Pincus D, Kose S, Arana A, Johnson K, Morgan PS, Borckardt J, Herbsman T, Hardaway F, George MS, Panksepp J, Nahas Z. Inverse effects of oxytocin on attributing mental activity to others in depressed and healthy subjects: a double-blind placebo controlled FMRI study. Front Psychiatry. 2010 Oct 12;1:134. doi: 10.3389/fpsyt.2010.00134. eCollection 2010.

  PMID: 21423444 BACKGROUND

• Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ. Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain. Emotion. 2008 Dec;8(6):781-91. doi: 10.1037/a0014195.

  PMID: 19102589 BACKGROUND

• MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011 Sep;36(8):1114-26. doi: 10.1016/j.psyneuen.2011.02.015. Epub 2011 Mar 23.

  PMID: 21429671 BACKGROUND

Related Links

• Lab Website

Limitations and Caveats

Data collection has been completed, but data analysis is ongoing.

Results Point of Contact

• Title: Lilianne Mujica Parodi, PhD / Study Principal Investigator
• Organization: Stony Brook University

lilianne.strey@stonybrook.edu

631-632-1008

Study Officials

• Lilianne Mujica-Parodi, PhD

  Stony Brook University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2013
• First Posted: April 17, 2013
• Study Start: April 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: March 17, 2017
• Results First Posted: March 17, 2017

Record last verified: 2017-01

Locations

US (3)