Journal of Neural Transmission

, Volume 126, Issue 2, pp 211–218 | Cite as

Oxytocin reactivity to an emotional challenge paradigm and its relation to social-cognitive functions in healthy volunteers

  • Nina KampkaEmail author
  • Nicole Frommann
  • Uwe Henning
  • Robert Schwark
  • Wolfgang Wölwer
  • Reinhard Pietrowsky
  • Christian Luckhaus
Psychiatry and Preclinical Psychiatric Studies - Original Article


The neuropeptide oxytocin (OT) is known to be an important modulator of social cognition. It has been shown that lower OT plasma concentrations are linked to impairments in social cognition. Studies have also shown that intranasal OT may enhance social-cognitive abilities in healthy subjects. We hypothesize that, besides baseline OT concentrations, the reactivity of the OT system may have an important role in social-cognitive functioning of individuals. In the present study, we explored if an emotional challenge paradigm is suitable to elicit OT release into plasma to make the reactivity of the OT system measurable. Therefore, 20 healthy male volunteers watched an emotional film clip, showing another person in pain during a severe dentist’s treatment, while blood draws were conducted pre and post challenge. OT concentrations in plasma were measured by ELISA after solid phase extraction from plasma. OT plasma concentrations at baseline were significantly negatively correlated to an empathetic rating of our film clip and to measures of emotional empathy for positive and negative emotions, whereas the difference between post-challenge value and baseline was significantly positively correlated with the latter measures. Our data thus show that a short emotional video can be successfully employed as a challenge paradigm for eliciting an increase of peripheral OT in healthy male subjects. Calculating the relative OT change post- vs. pre-challenge may give a measure of OT reactivity. The combination of low peripheral OT at baseline with high OT reactivity may be a psychoendocrine trait that is linked to higher emotional functioning.


Oxytocin Empathy Pain ELISA Emotional challenge Social cognition 



This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.


  1. Barraza JA, Zak PJ (2009) Empathy toward strangers triggers oxytocin release and subsequent generosity. Ann NY Acad Sci 1167:182–189Google Scholar
  2. Bartz JA, Zaki J, Bolger N, Hollander E, Ludwig NN, Kolevzon A, Ochsner KN (2010) Oxytocin selectively improves empathic accuracy. Psychol Sci 21:1426–1428Google Scholar
  3. Boll S, Almeida de Minas AC, Raftogianni A, Herpertz SC, Grinevich V (2017) Oxytocin and pain perception: from animal models to human research. Neuroscience 387:149–161Google Scholar
  4. Bora E, Berk M (2016) Theory of mind in major depressive disorder: a meta-analysis. J Affect Disord 191:49–55Google Scholar
  5. Bos PA, Montoya ER, Hermans EJ, Keysers C, van Honk J (2015) Oxytocin reduces neural activity in the pain circuitry when seeing pain in others. Neuroimage 113:217–224Google Scholar
  6. Davis MC, Green MF, Lee J, Horan WP, Senturk D, Clarke AD, Marder SR (2014) Oxytocin-augmented social cognitive skills training in schizophrenia. Neuropsychopharmacology 39:2070–2077Google Scholar
  7. De Wied M, Boxtel AV, Posthumus JA, Goudena PP, Matthys W (2009) Facial EMG and heart rate responses to emotion-inducing film clips in boys with disruptive behavior disorders. Psychophysiology 46:996–1004Google Scholar
  8. Decety J, Lamm C (2006) Human empathy through the lens of social neuroscience. Sci World J 6:1146–1163Google Scholar
  9. Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC (2007) Oxytocin improves “mind-reading” in humans. Biol Psychiatry 61:731–733Google Scholar
  10. Dziobek I, Rogers K, Fleck S, Bahnemann M, Heekeren HR, Wolf OT, Convit A (2008) Dissociation of cognitive and emotional empathy in adults with Asperger syndrome using the Multifaceted Empathy Test (MET). J Autism Dev Disord 38:464–473Google Scholar
  11. Ekman P, Friesen WV (1976) Pictures of facial affect. Consulting Psychologists Press, Palo AltoGoogle Scholar
  12. Feeser M, Fan Y, Weigand A, Hahn A, Gartner M, Boker H, Grimm S, Bajbouj M (2015) Oxytocin improves mentalizing—pronounced effects for individuals with attenuated ability to empathize. Psychoneuroendocrinology 53:223–232Google Scholar
  13. Fischer-Shofty M, Brune M, Ebert A, Shefet D, Levkovitz Y, Shamay-Tsoory SG (2013) Improving social perception in schizophrenia: the role of oxytocin. Schizophr Res 146:357–362Google Scholar
  14. Gibson CM, Penn DL, Smedley KL, Leserman J, Elliott T, Pedersen CA (2014) A pilot six-week randomized controlled trial of oxytocin on social cognition and social skills in schizophrenia. Schizophr Res 156:261–265Google Scholar
  15. Gimpl G, Fahrenholz F (2001) The oxytocin receptor system: structure, function, and regulation. Physiol Rev 81:629–683Google Scholar
  16. Goldman M, Marlow-O’Connor M, Torres I, Carter CS (2008) Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits. Schizophr Res 98:247–255Google Scholar
  17. Guastella AJ, Carson DS, Dadds MR, Mitchell PB, Cox RE (2009) Does oxytocin influence the early detection of angry and happy faces? Psychoneuroendocrinology 34:220–225Google Scholar
  18. Hogenelst K, Schoevers RA, Kema IP, Sweep FC, aan het Rot M (2016) Empathic accuracy and oxytocin after tryptophan depletion in adults at risk for depression. Psychopharmacology 233:111–120Google Scholar
  19. Hubble K, Daughters K, Manstead ASR, Rees A, Thapar A, van Goozen SHM (2017) Oxytocin increases attention to the eyes and selectively enhances self-reported affective empathy for fear. Neuropsychologia 106:350–357Google Scholar
  20. Hurlemann R, Patin A, Onur OA, Cohen MX, Baumgartner T, Metzler S, Dziobek I, Gallinat J, Wagner M, Maier W, Kendrick KM (2010) Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans. J Neurosci 30:4999–5007Google Scholar
  21. Jackson PL, Meltzoff AN, Decety J (2005) How do we perceive the pain of others? A window into the neural processes involved in empathy. Neuroimage 24:771–779Google Scholar
  22. Jobst A, Dehning S, Ruf S, Notz T, Buchheim A, Henning-Fast K, Meissner D, Meyer S, Bondy B, Muller N, Zill P (2014) Oxytocin and vasopressin levels are decreased in the plasma of male schizophrenia patients. Acta Neuropsychiatr 26:347–355Google Scholar
  23. Krueger F, Parasuraman R, Moody L, Twieg P, de Visser E, McCabe K, O’Hara M, Lee MR (2013) Oxytocin selectively increases perceptions of harm for victims but not the desire to punish offenders of criminal offenses. Soc Cogn Affect Neurosci 8:494–498Google Scholar
  24. Kuypers KP, Dolder PC, Ramaekers JG, Liechti ME (2017) Multifaceted empathy of healthy volunteers after single doses of MDMA: a pooled sample of placebo-controlled studies. J Psychopharmacol 31:589–598Google Scholar
  25. Lancaster K, Carter CS, Pournajafi-Nazarloo H, Karaoli T, Lillard TS, Jack A, Davis JM, Morris JP, Connelly JJ (2015) Plasma oxytocin explains individual differences in neural substrates of social perception. Front Hum Neurosci 9:132Google Scholar
  26. Losh M, Adolphs R, Poe MD, Couture S, Penn D, Baranek GT, Piven J (2009) Neuropsychological profile of autism and the broad autism phenotype. Arch Gen Psychiatry 66:518–526Google Scholar
  27. Lundqvist D, Flykt A, Öhman A (1998) The Karolinska Directed Emotional Faces—KDEF, CD ROM from Department of Clinical Neuroscience, Psychology section. In: P.S., Karolinska Institutet, CD ROM from Departement of Clinical Neuroscience. Karolinska Institutet, Solna, ISBN 91-630-7164-9Google Scholar
  28. McCullough ME, Churchland PS, Mendez AJ (2013) Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted? Neurosci Biobehav Rev 37:1485–1492Google Scholar
  29. Morrison I, Lloyd D, di Pellegrino G, Roberts N (2004) Vicarious responses to pain in anterior cingulate cortex: is empathy a multisensory issue? Cogn Affect Behav Neurosci 4:270–278Google Scholar
  30. Nishi D, Hashimoto K, Noguchi H, Kim Y, Matsuoka Y (2015) Serum oxytocin, posttraumatic coping and C-reactive protein in motor vehicle accident survivors by gender. Neuropsychobiology 71:196–201Google Scholar
  31. Pedersen CA, Gibson CM, Rau SW, Salimi K, Smedley KL, Casey RL, Leserman J, Jarskog LF, Penn DL (2011) Intranasal oxytocin reduces psychotic symptoms and improves theory of mind and social perception in schizophrenia. Schizophr Res 132:50–53Google Scholar
  32. Preston SD, de Waal FB (2002) Empathy: Its ultimate and proximate bases. Behav Brain Sci 25:1–20; (discussion 20–71)Google Scholar
  33. Radke S, de Bruijn ER (2015) Does oxytocin affect mind-reading? A replication study. Psychoneuroendocrinology 60:75–81Google Scholar
  34. Robinson KJ, Hazon N, Lonergan M, Pomeroy PP (2014) Validation of an enzyme-linked immunoassay (ELISA) for plasma oxytocin in a novel mammal species reveals potential errors induced by sampling procedure. J Neurosci Methods 226:73–79Google Scholar
  35. Rubin LH, Carter CS, Drogos L, Jamadar R, Pournajafi-Nazarloo H, Sweeney JA, Maki PM (2011) Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia. Schizophr Res 130:266–270Google Scholar
  36. Rubin LH, Carter CS, Bishop JR, Pournajafi-Nazarloo H, Drogos LL, Hill SK, Ruocco AC, Keedy SK, Reilly JL, Keshavan MS, Pearlson GD, Tamminga CA, Gershon ES, Sweeney JA (2014) Reduced levels of vasopressin and reduced behavioral modulation of oxytocin in psychotic disorders. Schizophr Bull 40:1374–1384Google Scholar
  37. Salonia A, Nappi RE, Pontillo M, Daverio R, Smeraldi A, Briganti A, Fabbri F, Zanni G, Rigatti P, Montorsi F (2005) Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women. Horm Behav 47:164–169Google Scholar
  38. Savla GN, Vella L, Armstrong CC, Penn DL, Twamley EW (2013) Deficits in domains of social cognition in schizophrenia: a meta-analysis of the empirical evidence. Schizophr Bull 39:979–992Google Scholar
  39. Shamay-Tsoory SG, Abu-Akel A, Palgi S, Sulieman R, Fischer-Shofty M, Levkovitz Y, Decety J (2013) Giving peace a chance: oxytocin increases empathy to pain in the context of the Israeli-Palestinian conflict. Psychoneuroendocrinology 38:3139–3144Google Scholar
  40. Singer T (2006) The neuronal basis and ontogeny of empathy and mind reading: review of literature and implications for future research. Neurosci Biobehav Rev 30:855–863Google Scholar
  41. Singer T, Lamm C (2009) The social neuroscience of empathy. Ann N Y Acad Sci 1156:81–96Google Scholar
  42. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD (2004) Empathy for pain involves the affective but not sensory components of pain. Science 303:1157–1162Google Scholar
  43. Singer T, Snozzi R, Bird G, Petrovic P, Silani G, Heinrichs M, Dolan RJ (2008) Effects of oxytocin and prosocial behavior on brain responses to direct and vicariously experienced pain. Emotion 8:781–791Google Scholar
  44. Strauss GP, Keller WR, Koenig JI, Gold JM, Ossenfort KL, Buchanan RW (2015) Plasma oxytocin levels predict olfactory identification and negative symptoms in individuals with schizophrenia. Schizophr Res 162:57–61Google Scholar
  45. Szeto A, McCabe PM, Nation DA, Tabak BA, Rossetti MA, McCullough ME, Schneiderman N, Mendez AJ (2011) Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin. Psychosom Med 73:393–400Google Scholar
  46. Tay SA, Hulbert CA, Jackson HJ, Chanen AM (2017) Affective and cognitive theory of mind abilities in youth with borderline personality disorder or major depressive disorder. Psychiatry Res 255:405–411Google Scholar
  47. Zaki J, Weber J, Bolger N, Ochsner K (2009) The neural bases of empathic accuracy. Proc Natl Acad Sci USA 106:11382–11387Google Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Nina Kampka
    • 1
    Email author
  • Nicole Frommann
    • 1
  • Uwe Henning
    • 1
  • Robert Schwark
    • 1
  • Wolfgang Wölwer
    • 1
  • Reinhard Pietrowsky
    • 2
  • Christian Luckhaus
    • 3
  1. 1.Department of Psychiatry and Psychotherapy, Medical FacultyHeinrich Heine University DüsseldorfDuesseldorfGermany
  2. 2.Department of Clinical Psychology, Institute of Experimental PsychologyHeinrich Heine University DuesseldorfDuesseldorfGermany
  3. 3.Department of Psychiatry Psychotherapy and Preventive Medicine, LWL University HospitalRuhr University BochumBochumGermany

Personalised recommendations