Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Journal Mobile Options
Table of Contents
Vol. 18, No. 2, 2010
Issue release date: February 2011
Section title: Paper
Neurosignals 2010;18:82–97
(DOI:10.1159/000321035)

The Contribution of Oxytocin and Vasopressin to Mammalian Social Behavior: Potential Role in Autism Spectrum Disorder

Harony H. · Wagner S.
Department of Neurobiology and Ethology, Center for Gene Manipulation in the Brain, University of Haifa, Haifa, Israel
email Corresponding Author

Shlomo Wagner, PhD

Department of Biology and Department of Neurobiology and Ethology

RM 75, Biological Laboratories, University of Haifa, Mt. Carmel

IL–31905 Haifa (Israel)

Tel. +972 4 828 8773, Fax +972 4 828 8763, E-Mail shlomow@research.haifa.ac.il


References

  1. Caronna EB, Milunsky JM, Tager-Flusberg H: Autism spectrum disorders: clinical and research frontiers. Arch Dis Child 2008;93:518–523.
  2. Inglese MD, Elder JH: Caring for children with autism spectrum disorder. Part I: prevalence, etiology, and core features. J Pediatr Nurs 2009;24:41–48.
  3. Fombone E: Prevalence of childhood disintegrative disorder. Autism 2002;6:149–157.
  4. Steyaert JG, De la Marche W: What’s new in autism? Eur J Pediatr 2008;167:1091–1101.
  5. Geschwind DH: Advances in autism. Annu Rev Med 2009;60:367–380.
  6. Pardo CA, Eberhart CG: The neurobiology of autism. Brain Pathol 2007;17:434–447.
  7. Abrahams BS, Geschwind DH: Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 2008;9:341–355.
  8. Bill BR, Geschwind DH: Genetic advances in autism: heterogeneity and convergence on shared pathways. Curr Opin Genet Dev 2009;19:271–278.
  9. Happe F, Ronald A: The ‘fractionable autism triad’: a review of evidence from behavioural, genetic, cognitive and neural research. Neuropsychol Rev 2008;18:287–304.
  10. Kumar RA, Christian SL: Genetics of autism spectrum disorders. Curr Neurol Neurosci Rep 2009;9:188–197.
  11. Geschwind DH: Autism: many genes, common pathways? Cell 2008;135:391–395.
  12. Buxbaum JD: Multiple rare variants in the etiology of autism spectrum disorders. Dialogues Clin Neurosci 2009;11:35–43.
    External Resources
  13. Herbert MR: Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol;23:103–110.
  14. Newschaffer CJ, Croen LA, Daniels J, Giarelli E, Grether JK, Levy SE, Mandell DS, Miller LA, Pinto-Martin J, Reaven J, Reynolds AM, Rice CE, Schendel D, Windham GC: The epidemiology of autism spectrum disorders. Annu Rev Public Health 2007;28:235–258.
  15. Jones JR, Skinner C, Friez MJ, Schwartz CE, Stevenson RE: Hypothesis: dysregulation of methylation of brain-expressed genes on the X chromosome and autism spectrum disorders. Am J Med Genet A 2008;146A:2213–2220.
  16. Schanen NC: Epigenetics of autism spectrum disorders. Hum Mol Genet 2006;152:R138–R150.
    External Resources
  17. Berger SL, Kouzarides T, Shiekhattar R, Shilatifard A: An operational definition of epigenetics. Genes Dev 2009;23:781–783.
  18. Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003;33(Suppl):245–254.
  19. Miranda TB, Jones PA: DNA methylation: the nuts and bolts of repression. J Cell Physiol 2007;213:384–390.
  20. Klose RJ, Bird AP: Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 2006;31:89–97.
  21. Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY: MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320:1224–1229.
  22. Lasalle JM, Yasui DH: Evolving role of MeCP2 in Rett syndrome and autism. Epigenomics 2009;1:119–130.
  23. Garber KB, Visootsak J, Warren ST: Fragile X syndrome. Eur J Hum Genet 2008;16:666–672.
  24. Chahrour M, Zoghbi HY: The story of Rett syndrome: from clinic to neurobiology. Neuron 2007;56:422–437.
  25. LaSalle JM: The odyssey of MeCP2 and parental imprinting. Epigenetics 2007;2:5–10.
  26. Gonzales ML, LaSalle JM: The role of MeCP2 in brain development and neurodevelopmental disorders. Curr Psychiatry Rep 2010;12:127–134.
  27. D’Hulst C, Kooy RF: Fragile X syndrome: from molecular genetics to therapy. J Med Genet 2009;46:577–584.
  28. Belmonte MK, Bourgeron T: Fragile X syndrome and autism at the intersection of genetic and neural networks. Nat Neurosci 2006;9:1221–1225.
  29. Badcock C, Crespi B: Imbalanced genomic imprinting in brain development: an evolutionary basis for the aetiology of autism. J Evol Biol 2006;19:1007–1032.
  30. Hogart A, Nagarajan RP, Patzel KA, Yasui DH, Lasalle JM: 15q11–13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders. Hum Mol Genet 2007;16:691–703.
  31. Happe F, Ronald A, Plomin R: Time to give up on a single explanation for autism. Nat Neurosci 2006;9:1218–1220.
  32. Caldwell HK, Lee HJ, Macbeth AH, Young WS 3rd: Vasopressin: behavioral roles of an ‘original’ neuropeptide. Prog Neurobiol 2008;84:1–24.
  33. Lee HJ, Macbeth AH, Pagani JH, Young WS 3rd: Oxytocin: the great facilitator of life. Prog Neurobiol 2009;88:127–151.
  34. Gainer H, Yamashita M, Fields RL, House SB, Rusnak M: The magnocellular neuronal phenotype: cell-specific gene expression in the hypothalamo-neurohypophysial system. Prog Brain Res 2002;139:1–14.
  35. de Vries GJ, Miller MA: Anatomy and function of extrahypothalamic vasopressin systems in the brain. Prog Brain Res 1998;119:3–20.
  36. De Vries GJ, Panzica GC: Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints. Neuroscience 2006;138:947–955.
  37. Gainer H, Wray S: Oxytocin and vasopressin. From genes to peptides. Ann NY Acad Sci 1992;652:14–28.
  38. Gwee PC, Amemiya CT, Brenner S, Venkatesh B: Sequence and organization of coelacanth neurohypophysial hormone genes: evolutionary history of the vertebrate neurohypophysial hormone gene locus. BMC Evol Biol 2008;8:93.
  39. Stafflinger E, Hansen KK, Hauser F, Schneider M, Cazzamali G, Williamson M, Grimmelikhuijzen CJ: Cloning and identification of an oxytocin/vasopressin-like receptor and its ligand from insects. Proc Natl Acad Sci USA 2008;105:3262–3267.
  40. Hara Y, Battey J, Gainer H: Structure of mouse vasopressin and oxytocin genes. Brain Res Mol Brain Res 1990;8:319–324.
  41. Gainer H, Fields RL, House SB: Vasopressin gene expression: experimental models and strategies. Exp Neurol 2001;171:190–199.
  42. Fields RL, House SB, Gainer H: Regulatory domains in the intergenic region of the oxytocin and vasopressin genes that control their hypothalamus-specific expression in vitro. J Neurosci 2003;23:7801–7809.
  43. Landgraf R, Neumann ID: Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol 2004;25:150–176.
  44. Leng G, Ludwig M: Neurotransmitters and peptides: whispered secrets and public announcements. J Physiol 2008;586:5625–5632.
  45. Ludwig M, Leng G: Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 2006;7:126–136.
  46. Ross HE, Cole CD, Smith Y, Neumann ID, Landgraf R, Murphy AZ, Young LJ: Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 2009;162:892–903.
  47. Ross HE, Young LJ: Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front Neuroendocrinol 2009;30:534–547.
  48. Ludwig M, Sabatier N, Dayanithi G, Russell JA, Leng G: The active role of dendrites in the regulation of magnocellular neurosecretory cell behavior. Prog Brain Res 2002;139:247–256.
  49. Birnbaumer M: Vasopressin receptors. Trends Endocrinol Metab 2000;11:406–410.
  50. Gimpl G, Reitz J, Brauer S, Trossen C: Oxytocin receptors: ligand binding, signalling and cholesterol dependence. Prog Brain Res 2008;170:193–204.
  51. Manning M, Stoev S, Chini B, Durroux T, Mouillac B, Guillon G: Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res 2008;170:473–512.
  52. Inoue T, Kimura T, Azuma C, Inazawa J, Takemura M, Kikuchi T, Kubota Y, Ogita K, Saji F: Structural organization of the human oxytocin receptor gene. J Biol Chem 1994;269:32451–32456.
  53. Thibonnier M, Graves MK, Wagner MS, Auzan C, Clauser E, Willard HF: Structure, sequence, expression, and chromosomal localization of the human V1a vasopressin receptor gene. Genomics 1996;31:327–334.
  54. Thibonnier M, Coles P, Thibonnier A, Shoham M: Molecular pharmacology and modeling of vasopressin receptors. Prog Brain Res 2002;139:179–196.
  55. Gimpl G, Fahrenholz F: The oxytocin receptor system: structure, function, and regulation. Physiol Rev 2001;81:629–683.
  56. Lolait SJ, O’Carroll AM, Mahan LC, Felder CC, Button DC, Young WS 3rd, Mezey E, Brownstein MJ: Extrapituitary expression of the rat V1b vasopressin receptor gene. Proc Natl Acad Sci USA 1995;92:6783–6787.
  57. Caldwell HK, Wersinger SR, Young WS 3rd: The role of the vasopressin 1b receptor in aggression and other social behaviours. Prog Brain Res 2008;170:65–72.
  58. Vaccari C, Lolait SJ, Ostrowski NL: Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 1998;139:5015–5033.
  59. Insel TR: The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron 2010;65:768–779.
  60. Lim MM, Young LJ: Neuropeptidergic regulation of affiliative behavior and social bonding in animals. Horm Behav 2006;50:506–517.
  61. Carter CS: Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res 2007;176:170–186.
  62. Breton C, Di Scala-Guenot D, Zingg HH: Oxytocin receptor gene expression in rat mammary gland: structural characterization and regulation. J Mol Endocrinol 2001;27:175–189.
  63. Shughrue PJ, Dellovade TL, Merchenthaler I: Estrogen modulates oxytocin gene expression in regions of the rat supraoptic and paraventricular nuclei that contain estrogen receptor-beta. Prog Brain Res 2002;139:15–29.
  64. Ivell R, Kimura T, Muller D, Augustin K, Abend N, Bathgate R, Telgmann R, Balvers M, Tillmann G, Fuchs AR: The structure and regulation of the oxytocin receptor. Exp Physiol 2001;86:289–296.
  65. Zingg HH, Laporte SA: The oxytocin receptor. Trends Endocrinol Metab 2003;14:222–227.
  66. Hammock EA, Young LJ: Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol 2004;21:1057–1063.
  67. Mizumoto Y, Kimura T, Ivell R: A genomic element within the third intron of the human oxytocin receptor gene may be involved in transcriptional suppression. Mol Cell Endocrinol 1997;135:129–138.
  68. Kusui C, Kimura T, Ogita K, Nakamura H, Matsumura Y, Koyama M, Azuma C, Murata Y: DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochem Biophys Res Commun 2001;289:681–686.
  69. 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;7:62.
  70. Donaldson ZR, Young LJ: Oxytocin, vasopressin, and the neurogenetics of sociality. Science 2008;322:900–904.
  71. Rosenblatt JS: Prepartum and postpartum regulation of maternal behaviour in the rat. Ciba Found Symp 1975;33:17–37.
    External Resources
  72. Leng G, Meddle SL, Douglas AJ: Oxytocin and the maternal brain. Curr Opin Pharmacol 2008;8:731–734.
  73. Breton C, Zingg HH: Expression and region-specific regulation of the oxytocin receptor gene in rat brain. Endocrinology 1997;138:1857–1862.
  74. Young LJ, Muns S, Wang Z, Insel TR: Changes in oxytocin receptor mRNA in rat brain during pregnancy and the effects of estrogen and interleukin-6. J Neuroendocrinol 1997;9:859–865.
  75. Champagne F, Diorio J, Sharma S, Meaney MJ: Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proc Natl Acad Sci USA 2001;98:12736–12741.
  76. Rosenblatt JS, Mayer AD, Giordano AL: Hormonal basis during pregnancy for the onset of maternal behavior in the rat. Psychoneuroendocrinology 1988;13:29–46.
  77. Fahrbach SE, Morrell JI, Pfaff DW: Oxytocin induction of short-latency maternal behavior in nulliparous, estrogen-primed female rats. Horm Behav 1984;18:267–286.
  78. Bosch OJ, Meddle SL, Beiderbeck DI, Douglas AJ, Neumann ID: Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci 2005;25:6807–6815.
  79. van Leengoed E, Kerker E, Swanson HH: Inhibition of post-partum maternal behaviour in the rat by injecting an oxytocin antagonist into the cerebral ventricles. J Endocrinol 1987;112:275–282.
  80. Febo M, Numan M, Ferris CF: Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling. J Neurosci 2005;25:11637–11644.
  81. Keverne EB, Kendrick KM: Oxytocin facilitation of maternal behavior in sheep. Ann NY Acad Sci 1992;652:83–101.
  82. Kendrick KM, Da Costa AP, Broad KD, Ohkura S, Guevara R, Levy F, Keverne EB: Neural control of maternal behaviour and olfactory recognition of offspring. Brain Res Bull 1997;44:383–395.
  83. Hammock EA: Gene regulation as a modulator of social preference in voles. Adv Genet 2007;59:107–127.
  84. Aragona BJ, Wang Z: The prairie vole (Microtus ochrogaster): an animal model for behavioral neuroendocrine research on pair bonding. ILAR J 2004;45:35–45.
  85. Young KA, Liu Y, Wang Z: The neurobiology of social attachment: a comparative approach to behavioral, neuroanatomical, and neurochemical studies. Comp Biochem Physiol C Toxicol Pharmacol 2008;148:401–410.
  86. Insel TR, Young L, Wang Z: Molecular aspects of monogamy. Ann NY Acad Sci 1997;807:302–316.
  87. Hammock EA, Young LJ: Oxytocin, vasopressin and pair bonding: implications for autism. Philos Trans R Soc Lond B Biol Sci 2006;361:2187–2198.
  88. Young LJ, Wang Z: The neurobiology of pair bonding. Nat Neurosci 2004;7:1048–1054.
  89. Lim MM, Wang Z, Olazabal DE, Ren X, Terwilliger EF, Young LJ: Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 2004;429:754–757.
  90. Insel TR, Winslow JT, Wang Z, Young LJ: Oxytocin, vasopressin, and the neuroendocrine basis of pair bond formation. Adv Exp Med Biol 1998;449:215–224.
  91. Young LJ, Murphy Young AZ, Hammock EA: Anatomy and neurochemistry of the pair bond. J Comp Neurol 2005;493:51–57.
  92. Hammock EA, Young LJ: Variation in the vasopressin V1a receptor promoter and expression: implications for inter- and intraspecific variation in social behaviour. Eur J Neurosci 2002;16:399–402.
  93. Hammock EA, Young LJ: Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 2005;308:1630–1634.
  94. Dantzer R, Bluthe RM, Koob GF, Le Moal M: Modulation of social memory in male rats by neurohypophyseal peptides. Psychopharmacology (Berl) 1987;91:363–368.
  95. Bielsky IF, Young LJ: Oxytocin, vasopressin, and social recognition in mammals. Peptides 2004;25:1565–1574.
  96. Choleris E, Clipperton-Allen AE, Phan A, Kavaliers M: Neuroendocrinology of social information processing in rats and mice. Front Neuroendocrinol 2009;30:442–459.
  97. Ferguson JN, Young LJ, Insel TR: The neuroendocrine basis of social recognition. Front Neuroendocrinol 2002;23:200–224.
  98. Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT: Social amnesia in mice lacking the oxytocin gene. Nat Genet 2000;25:284–288.
  99. Takayanagi Y, Yoshida M, Bielsky IF, Ross HE, Kawamata M, Onaka T, Yanagisawa T, Kimura T, Matzuk MM, Young LJ, Nishimori K: Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proc Natl Acad Sci USA 2005;102:16096–16101.
  100. Winslow JT, Insel TR: The social deficits of the oxytocin knockout mouse. Neuropeptides 2002;36:221–229.
  101. Ferguson JN, Aldag JM, Insel TR, Young LJ: Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci 2001;21:8278–8285.
  102. Choleris E, Little SR, Mong JA, Puram SV, Langer R, Pfaff DW: Microparticle-based delivery of oxytocin receptor antisense DNA in the medial amygdala blocks social recognition in female mice. Proc Natl Acad Sci USA 2007;104:4670–4675.
  103. Dluzen DE, Muraoka S, Engelmann M, Landgraf R: The effects of infusion of arginine vasopressin, oxytocin, or their antagonists into the olfactory bulb upon social recognition responses in male rats. Peptides 1998;19:999–1005.
  104. Goodson JL, Kabelik D: Dynamic limbic networks and social diversity in vertebrates: from neural context to neuromodulatory patterning. Front Neuroendocrinol 2009;30:429–441.
  105. Skuse DH, Gallagher L: Dopaminergic-neuropeptide interactions in the social brain. Trends Cogn Sci 2009;13:27–35.
  106. Engelmann M, Landgraf R: Microdialysis administration of vasopressin into the septum improves social recognition in Brattleboro rats. Physiol Behav 1994;55:145–149.
  107. Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ: Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 2004;29:483–493.
  108. Bielsky IF, Hu SB, Ren X, Terwilliger EF, Young LJ: The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron 2005;47:503–513.
  109. Tobin VA, Hashimoto H, Wacker DW, Takayanagi Y, Langnaese K, Caquineau C, Noack J, Landgraf R, Onaka T, Leng G, Meddle SL, Engelmann M, Ludwig M: An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 2010;464:413–417.
  110. Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL: Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002;5:514–516.
  111. Amico JA, Johnston JM, Vagnucci AH: Suckling-induced attenuation of plasma cortisol concentrations in postpartum lactating women. Endocr Res 1994;20:79–87.
  112. Chiodera P, Salvarani C, Bacchi-Modena A, Spallanzani R, Cigarini C, Alboni A, Gardini E, Coiro V: Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women. Horm Res 1991;35:119–123.
  113. Heinrichs M, Meinlschmidt G, Neumann I, Wagner S, Kirschbaum C, Ehlert U, Hellhammer DH: Effects of suckling on hypothalamic-pituitary-adrenal axis responses to psychosocial stress in postpartum lactating women. J Clin Endocrinol Metab 2001;86:4798–4804.
  114. Turner RA, Altemus M, Enos T, Cooper B, McGuinness T: Preliminary research on plasma oxytocin in normal cycling women: investigating emotion and interpersonal distress. Psychiatry 1999;62:97–113.
  115. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U: Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 2003;54:1389–1398.
  116. Ditzen B, Schaer M, Gabriel B, Bodenmann G, Ehlert U, Heinrichs M: Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biol Psychiatry 2009;65:728–731.
  117. 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;35:83–93.
  118. Petrovic P, Kalisch R, Singer T, Dolan RJ: Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. J Neurosci 2008;28:6607–6615.
  119. 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;25:11489–11493.
  120. Meyer-Lindenberg A: Impact of prosocial neuropeptides on human brain function. Prog Brain Res 2008;170:463–470.
  121. Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E: Oxytocin increases trust in humans. Nature 2005;435:673–676.
  122. Baumgartner T, Heinrichs M, Vonlanthen A, Fischbacher U, Fehr E: Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron 2008;58:639–650.
  123. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC: Oxytocin improves ‘mind-reading’ in humans. Biol Psychiatry 2007;61:731–733.
  124. Guastella AJ, Mitchell PB, Dadds MR: Oxytocin increases gaze to the eye region of human faces. Biol Psychiatry 2008;63:3–5.
  125. Theodoridou A, Rowe AC, Penton-Voak IS, Rogers PJ: Oxytocin and social perception: oxytocin increases perceived facial trustworthiness and attractiveness. Horm Behav 2009;56:128–132.
  126. Di Simplicio M, Massey-Chase R, Cowen PJ, Harmer CJ: Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers. J Psychopharmacol 2009;23:241–248.
  127. Guastella AJ, Mitchell PB, Mathews F: Oxytocin enhances the encoding of positive social memories in humans. Biol Psychiatry 2008;64:256–258.
  128. Feldman R, Gordon I, Schneiderman I, Weisman O, Zagoory-Sharon O: Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent-infant contact. Psychoneuroendocrinology 2010;35:1133–1141.
  129. Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R: Oxytocin and the development of parenting in humans. Biol Psychiatry 2010;68:377–382.
  130. Naber F, van Ijzendoorn MH, Deschamps P, van Engeland H, Bakermans-Kranenburg MJ: Intranasal oxytocin increases fathers’ observed responsiveness during play with their children: a double-blind within-subject experiment. Psychoneuroendocrinology 2010, E-pub ahead of print.
  131. Shamay-Tsoory SG, Fischer M, Dvash J, Harari H, Perach-Bloom N, Levkovitz Y: Intranasal administration of oxytocin increases envy and schadenfreude (gloating). Biol Psychiatry 2009;66:864–870.
  132. Guastella AJ, Carson DS, Dadds MR, Mitchell PB, Cox RE: Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology 2009;34:220–225.
  133. Tops M: Oxytocin: envy or engagement in others? Biol Psychiatry 2010;67:e5–e6, author reply e7.
  134. De Dreu CK, Greer LL, Handgraaf MJ, Shalvi S, Van Kleef GA, Baas M, Ten Velden FS, Van Dijk E, Feith SW: The neuropeptide oxytocin regulates parochial altruism in intergroup conflict among humans. Science 2010;328:1408–1411.
  135. Ebstein RP, Israel S, Chew SH, Zhong S, Knafo A: Genetics of human social behavior. Neuron 2010;65:831–844.
  136. Israel S, Lerer E, Shalev I, Uzefovsky F, Reibold M, Bachner-Melman R, Granot R, Bornstein G, Knafo A, Yirmiya N, Ebstein RP: Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between. Prog Brain Res 2008;170:435–449.
  137. Knafo A, Israel S, Darvasi A, Bachner-Melman R, Uzefovsky F, Cohen L, Feldman E, Lerer E, Laiba E, Raz Y, Nemanov L, Gritsenko I, Dina C, Agam G, Dean B, Bornstein G, Ebstein RP: Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA. Genes Brain Behav 2008;7:266–275.
  138. Walum H, Westberg L, Henningsson S, Neiderhiser JM, Reiss D, Igl W, Ganiban JM, Spotts EL, Pedersen NL, Eriksson E, Lichtenstein P: Genetic variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans. Proc Natl Acad Sci USA 2008;105:14153–14156.
  139. Prichard ZM, Mackinnon AJ, Jorm AF, Easteal S: AVPR1A and OXTR polymorphisms are associated with sexual and reproductive behavioral phenotypes in humans. Mutation in brief No. 981. Online. Hum Mutat 2007;28:1150.
  140. Meyer-Lindenberg A, Kolachana B, Gold B, Olsh A, Nicodemus KK, Mattay V, Dean M, Weinberger DR: Genetic variants in AVPR1A linked to autism predict amygdala activation and personality traits in healthy humans. Mol Psychiatry 2009;14:968–975.
  141. Rodrigues SM, Saslow LR, Garcia N, John OP, Keltner D: Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proc Natl Acad Sci USA 2009;106:21437–21441.
  142. Bakermans-Kranenburg MJ, van Ijzendoorn MH: Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Soc Cogn Affect Neurosci 2008;3:128–134.
  143. Riem MM, Pieper S, Out D, Bakermans-Kranenburg MJ, van Ijzendoorn MH: Oxytocin receptor gene and depressive symptoms associated with physiological reactivity to infant crying. Soc Cogn Affect Neurosci 2010, E-pub ahead of print.
  144. Israel S, Lerer E, Shalev I, Uzefovsky F, Riebold M, Laiba E, Bachner-Melman R, Maril A, Bornstein G, Knafo A, Ebstein RP: The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task. PLoS One 2009;4:e5535.
  145. Ebstein RP, Israel S, Lerer E, Uzefovsky F, Shalev I, Gritsenko I, Riebold M, Salomon S, Yirmiya N: Arginine vasopressin and oxytocin modulate human social behavior. Ann NY Acad Sci 2009;1167:87–102.
  146. Insel TR, O’Brien DJ, Leckman JF: Oxytocin, vasopressin, and autism: is there a connection? Biol Psychiatry 1999;45:145–157.
  147. Baron-Cohen S, Ring HA, Bullmore ET, Wheelwright S, Ashwin C, Williams SC: The amygdala theory of autism. Neurosci Biobehav Rev 2000;24:355–364.
  148. Schulkin J: Autism and the amygdala: an endocrine hypothesis. Brain Cogn 2007;65:87–99.
  149. 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;62:1187–1190.
  150. Winslow JT, Insel TR: Neuroendocrine basis of social recognition. Curr Opin Neurobiol 2004;14:248–253.
  151. Yamasue H, Kuwabara H, Kawakubo Y, Kasai K: Oxytocin, sexually dimorphic features of the social brain, and autism. Psychiatry Clin Neurosci 2009;63:129–140.
  152. de Vries GJ: Sex differences in vasopressin and oxytocin innervation of the brain. Prog Brain Res 2008;170:17–27.
  153. Modahl C, Green L, Fein D, Morris M, Waterhouse L, Feinstein C, Levin H: Plasma oxytocin levels in autistic children. Biol Psychiatry 1998;43:270–277.
  154. Green L, Fein D, Modahl C, Feinstein C, Waterhouse L, Morris M: Oxytocin and autistic disorder: alterations in peptide forms. Biol Psychiatry 2001;50:609–613.
  155. 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 USA 2010;107:4389–4394.
  156. Jansen LM, Gispen-de Wied CC, Wiegant VM, Westenberg HG, Lahuis BE, van Engeland H: Autonomic and neuroendocrine responses to a psychosocial stressor in adults with autistic spectrum disorder. J Autism Dev Disord 2006;36:891–899.
  157. Lauritsen MB, Als TD, Dahl HA, Flint TJ, Wang AG, Vang M, Kruse TA, Ewald H, Mors O: A genome-wide search for alleles and haplotypes associated with autism and related pervasive developmental disorders on the Faroe Islands. Mol Psychiatry 2006;11:37–46.
  158. McCauley JL, Li C, Jiang L, Olson LM, Crockett G, Gainer K, Folstein SE, Haines JL, Sutcliffe JS: Genome-wide and Ordered-Subset linkage analyses provide support for autism loci on 17q and 19p with evidence of phenotypic and interlocus genetic correlates. BMC Med Genet 2005;6:1.
  159. Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, Yamrom B, Yoon S, Krasnitz A, Kendall J, Leotta A, Pai D, Zhang R, Lee YH, Hicks J, Spence SJ, Lee AT, Puura K, Lehtimaki T, Ledbetter D, Gregersen PK, Bregman J, Sutcliffe JS, Jobanputra V, Chung W, Warburton D, King MC, Skuse D, Geschwind DH, Gilliam TC, Ye K, Wigler M: Strong association of de novo copy number mutations with autism. Science 2007;316:445–449.
  160. Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH Jr: Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci Lett 2007;417:6–9.
  161. Liu X, Kawamura Y, Shimada T, Otowa T, Koishi S, Sugiyama T, Nishida H, Hashimoto O, Nakagami R, Tochigi M, Umekage T, Kano Y, Miyagawa T, Kato N, Tokunaga K, Sasaki T: Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. J Hum Genet 2010;55:137–141.
  162. Lerer E, Levi S, Salomon S, Darvasi A, Yirmiya N, Ebstein RP: Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition. Mol Psychiatry 2008;13:980–988.
  163. Wu S, Jia M, Ruan Y, Liu J, Guo Y, Shuang M, Gong X, Zhang Y, Yang X, Zhang D: Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol Psychiatry 2005;58:74–77.
  164. Yrigollen CM, Han SS, Kochetkova A, Babitz T, Chang JT, Volkmar FR, Leckman JF, Grigorenko EL: Genes controlling affiliative behavior as candidate genes for autism. Biol Psychiatry 2008;63:911–916.
  165. Tansey KE, Brookes KJ, Hill MJ, Cochrane LE, Gill M, Skuse D, Correia C, Vicente A, Kent L, Gallagher L, Anney RJ: Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: genetic and molecular studies. Neurosci Lett 2010;474:163–167.
  166. Kim SJ, Young LJ, Gonen D, Veenstra-VanderWeele J, Courchesne R, Courchesne E, Lord C, Leventhal BL, Cook EH Jr, Insel TR: Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol Psychiatry 2002;7:503–507.
  167. Wassink TH, Piven J, Vieland VJ, Pietila J, Goedken RJ, Folstein SE, Sheffield VC: Examination of AVPR1a as an autism susceptibility gene. Mol Psychiatry 2004;9:968–972.
  168. Yirmiya N, Rosenberg C, Levi S, Salomon S, Shulman C, Nemanov L, Dina C, Ebstein RP: Association between the arginine vasopressin 1a receptor (AVPR1a) gene and autism in a family-based study: mediation by socialization skills. Mol Psychiatry 2006;11:488–494.
  169. Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S: Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 2003;28:193–198.
  170. Hollander E, Bartz J, Chaplin W, Phillips A, Sumner J, Soorya L, Anagnostou E, Wasserman S: Oxytocin increases retention of social cognition in autism. Biol Psychiatry 2007;61:498–503.
  171. Bartz JA, Hollander E: Oxytocin and experimental therapeutics in autism spectrum disorders. Prog Brain Res 2008;170:451–462.
  172. 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;67:692–694.
  173. Heinrichs M, von Dawans B, Domes G: Oxytocin, vasopressin, and human social behavior. Front Neuroendocrinol 2009;30:548–557.