Oxytocin is a hormone that is involved in many processes like birth and lactation, as well as attachment, prosocial behaviors and stress ^[1-4]. But despite its versatility, most certainly you have heard of it as “the love hormone” – and it is no wonder that you have this connection in mind: Many popular science articles equate love with oxytocin, and there are even companies selling oxytocin nasal sprays advertising it as the eagerly awaited recipe for a love potion. Make your crush sniff it – make them fall in love with you.

This is not completely far-fetched: Oxytocin definitely plays a role in parent-infant bonds and  romantic relationships ^[5-7]. Moreover, intranasal administration of oxytocin (see box) increased behaviors of trust and generosity ^{[8, 9]}, the ability to recognize faces ^{[10, 11]}, and mentalizing – the capability to infer the mental state of others ^[12].The body’s own (i.e. endogenous) release of oxytocin is triggered by stressful stimuli and elevated levels of the hormone help to regulate behavioral and physiological manifestations of stress and anxiety ^{[13, 14]}. You might think it is a perfect hormone. It makes us more generous and loving, more social and trusting, and it even helps us to cope with stress – wonderful! Well, maybe I have to disappoint you. Oxytocin definitely is a social hormone, being more implicated in social than in non-social contexts ^[15-17], but this does not necessarily mean its effects are merely positive. In fact, more and more researchers have found also negative or mixed effects, suggesting that the popular image of oxytocin may need an update.

The Effects of Oxytocin are Sex-dependent

Firstly, the influence of oxytocin on the behaviors mentioned above is dependent on your sex: As the hormone’s effect is highly mediated by the presence of the female sex hormone estrogen, this is only logical ^[22]. Different studies have found sex-dependent effects of the intranasal administration of oxytocin, ranging from social perception to moral judgments and responses to stress. The hormone increases the capability to perceive competition in men but not in women, and to perceive kinship in women but not in men ^[23]. I know what you are thinking: Oh please! Such a cliché! Well yeah, and it does not get better: Oxytocin motivated men to render moral judgments in a self-interested way, whereas women judged with increased altruistic tendencies and with less self-interest ^[24]. However, there are also findings that are not so clichéd: Another study found oxytocin compared to placebo to reduce negative affect after a social stressor in men but not in women, while women reported more anger ^[25]. Other studies found no sex differences concerning oxytocin, yielding a mixed picture ^[26].

The Influence of Context and Personality

Furthermore, the impact of oxytocin seems to differ as a function of context and personality. While the intranasal administration of oxytocin compared to placebo increased cooperation between participants when they had met before, it interestingly decreased cooperation when the interaction between participants was completely anonymous ^[27]. Another experiment investigating the effect of oxytocin on choices in moral dilemmas showed the hormone to increase ethnocentricity. After oxytocin administration compared to placebo, male participants were less likely to sacrifice one person in order to save five other nameless people, but only if this person was from an in-group, in the case of the study having a Dutch name. However, if the person was from an out-group, having an Arab name, the willingness to sacrifice was not decreased ^[28]. Wow, so apparently now oxytocin turned from the love hormone to the xenophobia hormone? What a huge change in so little time!

Moreover, in patients with Borderline Personality Disorder, a psychiatric condition characterized by affective instability, impulsive aggression and identity confusion, oxytocin administration decreased trust and cooperation. Importantly, this effect was strongest for those individuals that were both anxiously attached and avoidant, thus seeking for intimacy but at the same time feeling uncomfortable with emotional closeness ^[29]. In another study, healthy participants had to report memories of their mothers from when they were a child. When administered oxytocin compared to placebo, securely attached participants remembered their mothers as more caring and close, whereas anxiously attached individuals remembered them as less caring and close ^[30]. Thus, effects of oxytocin on social processes seem to be mediated by contextual factors such as the presence of a known vs. an unknown person or the person being in- or out-group, and inter-individual factors such as attachment style.

As you have read above, oxytocin also plays an important role in stress. And this role apparently depends on contextual factors: While some authors found oxytocin to decrease psychological and physiological responses to a stressor especially when combined with social support ^[31], other studies were not able to find this buffering effect. One study investigated the difference between social support from a friend vs. from a stranger in a stressful situation. Not surprisingly, if supported by a stranger, participants perceived the situation as awkward and uncomfortable, and less supporting than if they were supported by a friend. Interestingly, oxytocin administration made them perceive the friend-support situation as more positive, but the stranger-support situation as even more negative ^[25]. Moreover, when oxytocin was administered to patients with major depression before a therapy session, it did not decrease, but increase anxiety levels over the course of the session ^[32].

These findings indicate that oxytocin may actually exert different effects depending on the perception of the situation and the self. In another study, participants were stressed by little electrical shocks that were either administered only when participants saw a threat cue, or randomly. As an outcome measure, the researchers looked at the startle reflex, i.e. blinking in response to an aversive acoustic stimulus. As you probably have experienced yourself, one startles easier when already stressed out. Whereas in the predictable shock condition the administration of oxytocin had no effect, in the unpredictable shock condition it increased the startle response ^[33]. Thus, in an ambiguous – and therefore somewhat negative – situation, oxytocin seems to enhance stress rather than reduce it.

The Social Salience Hypothesis

Taken together, these findings suggest that effects of oxytocin are strongly dependent on the context and on inter-individual factors. Recently, researchers from the Universities of Haifa and Birmingham introduced a theoretical framework trying to explain these findings: The Social Salience Hypothesis ^[34]. So what is salience? Salience is a cognitive mechanism guiding your attention towards stimuli that are particularly salient, that is, somehow different from the rest. For example, a red apple in a box full of bananas is salient – because of its shape and, more importantly, its color. This mechanism does not only hold for basic perceptional processes, but also applies to more complex situations. The authors propose that oxytocin modulates the salience of social stimuli, which explains the contextual differences. According to this theory, effects of oxytocin are only positive, if the situation is already relatively positive: prosocial behaviors are enhanced if the context involves cooperative and positive emotions, because the attention is shifted on these. Likewise, the salience of safety signals in stressful situations is enhanced if the overall context is supportive. However, if oxytocin is administered in a context of competition or threat, attention is reoriented towards these negative contextual aspects, increasing competitive behaviors like envy and gloating ^[35] or anxiety. The theory also explains the ability of oxytocin to increase an in-group bias: as this attentional bias is already existent, its salience is only increased leading to more prosocial behavior towards in-group but not out-group members.

As a neural mechanism for this salience process, the authors propose oxytocin to influence dopaminergic signals in the brain. Dopamine is a neurotransmitter that is important for reward and motivation, and additionally regulates the detection of salient stimuli ^[36]. Oxytocin enhances activity in dopaminergic regions ^[37-39], and animal studies have shown the existence of numerous oxytocin receptors throughout the dopamine system ^{[40, 41]}. Thus, the authors propose this as a possible mechanism for a context dependence of oxytocin effects. However – as always – they also point out that further research is needed to really figure it out.

We’re almost there…

Phew. That was a lot of information. The most important message is: the effects of oxytocin are not universal. Depending on context and inter-individual differences it might promote pro- or antisocial behavior, might alleviate or increase anxiety and stress. Importantly, note that these possible negative effects are not unimportant or unwanted. If you were in a threatening situation, it would be disastrous to feel incredibly safe. By increasing the salience of already salient stimuli, it just strengthens the perception of contexts that are already existent – may they be ‘good’ or ‘bad’.

These findings also have implications for translational research – that is research trying to translate general scientific findings into medical practice. Researchers and clinicians have to be careful when trying to find an oxytocin-based medication for disorders such as autism or schizophrenia.

Another implication is that you might update your image of the ‘love hormone’ to a more differentiated and realistic view. This view is not that romantic, nor is it geared towards the media, but hey – that’s life.

Oh, and do not buy the nasal spray. If your crush perceives the situation as negative (maybe because this weird person wants them to sniff this creepy spray), the situation will only worsen. If not – well, you probably will not need the spray anyway.

References:

1. Neumann, I.D., Involvement of the brain oxytocin system in stress coping: interactions with the hypothalamo-pituitary-adrenal axis. Prog Brain Res, 2002. 139: p. 147-62. doi:10.1016/S0079-6123(02)39014-9
2. Heinrichs, M., B. von Dawans, and G. Domes, Oxytocin, vasopressin, and human social behavior. Front Neuroendocrinol, 2009. 30(4): p. 548-57. doi:10.1016/j.yfrne.2009.05.005
3. Richard, P., F. Moos, and M.J. Freund-Mercier, Central effects of oxytocin. Physiol Rev, 1991. 71(2): p. 331-70.
4. McCarthy, M.M. and M. Altemus, Central nervous system actions of oxytocin and modulation of behavior in humans. Mol Med Today, 1997. 3(6): p. 269-75. doi:10.1016/S1357-4310(97)01058-7
5. Schneiderman, I., et al., Oxytocin during the initial stages of romantic attachment: relations to couples’ interactive reciprocity. Psychoneuroendocrinology, 2012. 37(8): p. 1277-85. doi:10.1016/j.psyneuen.2011.12.021
6. Bartels, A. and S. Zeki, The neural correlates of maternal and romantic love. Neuroimage, 2004. 21(3): p. 1155-66. doi:10.1016/j.neuroimage.2003.11.003
7. Feldman, R., et al., Evidence for a neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychol Sci, 2007. 18(11): p. 965-70. doi:10.1111/j.1467-9280.2007.02010.x
8. Kosfeld, M., et al., Oxytocin increases trust in humans. Nature, 2005. 435(7042): p. 673-676. doi:10.1038/nature03701
9. Zak, P.J., A.A. Stanton, and S. Ahmadi, Oxytocin increases generosity in humans. PLoS One, 2007. 2(11): p. e1128. doi:10.1371/journal.pone.0001128
10. Lischke, A., et al., Intranasal oxytocin enhances emotion recognition from dynamic facial expressions and leaves eye-gaze unaffected. Psychoneuroendocrinology, 2012. 37(4): p. 475-81. doi:10.1016/j.psyneuen.2011.07.015
11. Marsh, A.A., et al., Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl), 2010. 209(3): p. 225-32. doi:10.1007/s00213-010-1780-4
12. Domes, G., et al., Oxytocin improves “mind-reading” in humans. Biol Psychiatry, 2007. 61(6): p. 731-3. doi:10.1016/j.biopsych.2006.07.015
13. Kumsta, R. and M. Heinrichs, Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system. Current Opinion in Neurobiology, 2013. 23(1): p. 11-16. doi:10.1016/j.conb.2012.09.004
14. Neumann, I.D. and D.A. Slattery, Oxytocin in General Anxiety and Social Fear: A Translational Approach. Biological Psychiatry, 2016. 79(3): p. 213-221. doi:10.1016/j.biopsych.2015.06.004
15. Kirsch, P., et al., Oxytocin modulates neural circuitry for social cognition and fear in humans. J Neurosci, 2005. 25(49): p. 11489-93. doi:10.1523/JNEUROSCI.3984-05.2005
16. Rimmele, U., et al., Oxytocin makes a face in memory familiar. J Neurosci, 2009. 29(1): p. 38-42. doi:10.1523/JNEUROSCI.4260-08.2009
17. Norman, G.J., et al., Selective influences of oxytocin on the evaluative processing of social stimuli. J Psychopharmacol, 2011. 25(10): p. 1313-9. doi:10.1177/0269881110367452
18. Ballabh, P., A. Braun, and M. Nedergaard, The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis, 2004. 16(1): p. 1-13. doi:10.1016/j.nbd.2003.12.016
19. Leng, G. and M. Ludwig, Intranasal Oxytocin: Myths and Delusions. Biol Psychiatry, 2016. 79(3): p. 243-50. doi:10.1016/j.biopsych.2015.05.003
20. Walum, H., I.D. Waldman, and L.J. Young, Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies. Biol Psychiatry, 2016. 79(3): p. 251-7. doi:10.1016/j.biopsych.2015.06.016
21. Bakermans-Kranenburg, M.J. and I.J.M.H. van Ijzendoorn, Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy. Transl Psychiatry, 2013. 3: p. e258. doi:10.1038/tp.2013.34
22. Gabor, C.S., et al., Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition. Behav Neurosci, 2012. 126(1): p. 97-109. doi:10.1037/a0026464
23. Fischer-Shofty, M., Y. Levkovitz, and S.G. Shamay-Tsoory, Oxytocin facilitates accurate perception of competition in men and kinship in women. Social Cognitive and Affective Neuroscience, 2013. 8(3): p. 313-317. doi:10.1093/scan/nsr100
24. Scheele, D., et al., Opposing effects of oxytocin on moral judgment in males and females. Hum Brain Mapp, 2014. 35(12): p. 6067-76. doi:10.1002/hbm.22605
25. Kubzansky, L.D., et al., A heartfelt response: Oxytocin effects on response to social stress in men and women. Biol Psychol, 2012. 90(1): p. 1-9. doi:10.1016/j.biopsycho.2012.02.010
26. Macdonald, K.S., Sex, receptors, and attachment: a review of individual factors influencing response to oxytocin. Front Neurosci, 2012. 6: p. 194. doi:10.3398/fnins.2012.00194
27. Declerck, C.H., C. Boone, and T. Kiyonari, Oxytocin and cooperation under conditions of uncertainty: The modulating role of incentives and social information. Hormones and Behavior, 2010. 57(3): p. 368-374. doi:10.1016/j.yhbeh.2010.01.006
28. De Dreu, C.K., et al., Oxytocin promotes human ethnocentrism. Proc Natl Acad Sci U S A, 2011. 108(4): p. 1262-6. doi:10.1073/pnas.1015316108
29. Bartz, J., et al., Oxytocin can hinder trust and cooperation in borderline personality disorder. Social Cognitive and Affective Neuroscience, 2011. 6(5): p. 556-563. doi:10.1093/scan/nsq085
30. Bartz, J.A., et al., Effects of oxytocin on recollections of maternal care and closeness. Proc Natl Acad Sci U S A, 2010. 107(50): p. 21371-5. doi:10.1073/pnas.1012669107
31. Heinrichs, M., et al., Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry, 2003. 54(12): p. 1389-98. doi:10.1016/S0006-3223(03)00465-7
32. MacDonald, K., et al., Oxytocin and psychotherapy: a pilot study of its physiological, behavioral and subjective effects in males with depression. Psychoneuroendocrinology, 2013. 38(12): p. 2831-43. doi:10.1016/j.psyneuen.2013.05.014
33. Grillon, C., et al., Oxytocin increases anxiety to unpredictable threat. Mol Psychiatry, 2013. 18(9): p. 958-60. doi:10.1038/mp.2012.156
34. Shamay-Tsoory, S.G. and A. Abu-Akel, The Social Salience Hypothesis of Oxytocin. Biol Psychiatry, 2016. 79(3): p. 194-202. doi:10.1016/j.biopsych.2015.07.020
35. Shamay-Tsoory, S.G., et al., Intranasal administration of oxytocin increases envy and schadenfreude (gloating). Biol Psychiatry, 2009. 66(9): p. 864-70. doi:10.1016/j.biopsych.2009.06.009
36. Berridge, K.C., The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology (Berl), 2007. 191(3): p. 391-431. doi:10.1007/s00213-006-0578-x
37. Groppe, S.E., et al., Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain. Biol Psychiatry, 2013. 74(3): p. 172-9. doi:10.1016/j.biopsych.2012.12.023
38. Rilling, J.K., et al., Effects of intranasal oxytocin and vasopressin on cooperative behavior and associated brain activity in men. Psychoneuroendocrinology, 2012. 37(4): p. 447-61. doi:10.1016/j.psyneuen.2011.07.013
39. Scheele, D., et al., Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proc Natl Acad Sci U S A, 2013. 110(50): p. 20308-13. doi:10.1073/pnas.1314190110
40. Gimpl, G. and F. Fahrenholz, The oxytocin receptor system: structure, function, and regulation. Physiol Rev, 2001. 81(2): p. 629-83.
41. Veinante, P. and M.J. Freund-Mercier, Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol, 1997. 383(3): p. 305-25. doi:10.1002/(SICI)1096-9861(19970707)383:33.3.CO;2-2

Pictures:

1. https://stocksnap.io/photo/EUWYCOBR4B
2.  By robin_24 [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)%5D, via Wikimedia Commons