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Oxytocin

Dr. Simon Moss

Overview

Oxytocin is a hormone that encourages individuals to form relationships as well as provide support and care to relatives or friends. Similar effects are observed in animals.

Kosfeld, Heinrichs, Zak, Fischbacher, and Fehr (2005), for example, showed that administration of oxytocin through the nose increased the likelihood that individuals would trust another person. Zak, Kurzban, and Matzner (2005), indeed, demonstrated that oxytocin levels rise in individuals after someone else shows trust in their integrity.

Description

Structure

Oxytocin is a hormone in mammals that seems to encourage animals, including humans, to engage in affiliation rather than avoid interactions to preserve safety. Oxytocin is a peptide that comprises a sequence of nine amino acids: cysteine, tyrosine, isoleucine, glutamine, asparagines, cysteine, praline, leucine, and glycine, with a molecular mass of 1007 daltons. This sequence, apart from two amino acids, is the same as the structure of a related hormone, called vasopressin.

Production and release

Oxytocin is primarily produced in the hypothalamus-specifically in magnocellular neurosecretory cells of the supraoptic nucleus and paraventricular nucleus. The oxytocin is then stored in vesicles in the posterior lobe of the pituitary gland. Cells in the hypothalamus, when activated, generate actions potentials down axons to nerve endings in the pituitary gland, which then releases oxytocin, as well as vasopressin, into the blood. This lobe does not release any other hormones, except chemicals that act locally.

Several conditions evoke this release of oxytocin. First, oxytocin is released after distension of the cervix and vagina during labor to facilitate birth. Second, this hormone is released after stimulation of the nipples to enable press feeding. When the infant sucks the nipple, spinal nerves activate the hypothalamus, ultimately facilitating oxytocin release. Third, oxytocin is released during orgasm in both sexes. Any peripheral actions of oxytocin are mediated by specific oxytocin receptors.

Effects of oxytocin

The oxytocin that is secreted by the pituitary gland does not readily traverse the blood-brain barrier. Many of the psychological effects of oxytocin, therefore, might represent the release of oxytocin from central neurons. Oxytocin receptors are distributed across the amygdala, ventromedial hypothalamus, septum, and brainstem.

Peripheral versus central levels of oxytocin

Until recently, the effects of oxytocin were not understood definitely, because the studies in this domain were limited. In particular, rather than manipulate levels of oxytocin, most studies merely measured the levels of this hormone in the plasma. As a consequence, two problems arose. First, whether oxytocin is an antecedent or a consequence of social behavior was not certain. For example, Turner, Altemus, Enos, Cooper, and McGuinness (1999) showed that plasma levels of oxytocin correlated with relationship discord in young women. This finding might imply that oxytocin engenders perceptions of discord in relationships and thus constitutes an antecedent of social behavior. Taylor, Gonzaga, Klein, Hu, Greendale, and Seeman (2006), however, suggest that oxytocin is a consequence of relationship distress, encouraging individuals to enact behaviors that reinforce relationships. Although many studies, especially in animals, would corroborate this interpretation, this conclusion cannot be derived from these findings alone. Indeed, some third factor, such as age, might affect both oxytocin and relationship discord.

Second, the level of oxytocin in plasma does not necessarily correlate with the level of oxytocin in brain regions. To illustrate, whether oxytocin in plasma can traverse the putative blood-brain barrier is not entirely certain. Some researchers argue that active transport systems might convey specific peptides, such as oxytocin, from the blood to central regions (cf., McEwen, 2004). Alternatively, oxytocin might facilitate the transfer of other hormones and nutrients from the blood to the brain (McEwen, 2004). Furthermore, oxytocin might, instead, act on blood vessels to the brain to augment blood flow to specific regions, ultimately shaping the behavior of individuals.

Stress

To overcome these limitations, recent studies have been able to administer oxytocin, either through the veins or nose, rather than merely measure levels of this hormone. Previous studies had suggested that oxytocin might reduce levels of stress. For example, lactating women, who usually demonstrate elevated levels of oxytocin, show lower levels of cortisol responses, a gauge of stress, in response to physical stressors (for a review, see Bartz & Hollander, 2006).

Subsequent studies confirmed this role of oxytocin in experiments. Administration of oxytocin was shown to reduce cortisol response, as well as diminish levels of adrenocorticotropic hormone, in healthy humans (e.g., Chiodero & Coiro, 1987).

Heinrich Baumgartner, Kirschbaum, and Ehlert (2003) explored the conditions in which oxytocin is most likely to temper stress. In their study, healthy men received either intranasal oxytocin or a placebo. Furthermore, the level of social support that individuals received was also manipulated: only half the participants were permitted to arrive with a friend. Social support was especially likely to reduce cortisol levels in saliva and to curb subjective feelings of anxiety when oxytocin was administered. These findings intimate that social support might be more effective when oxytocin is available in the central nervous system.

Social affiliation

Researchers contend that oxytocin might encourage affiliation-forming relationships as well as showing care towards relatives and friends. This contention initially emanated from studies in animals. For example, administration of oxytocin antagonists in rats inhibited the onset, but the not the maintenance, of material behavior (Insel, 1992).

Kosfeld, Heinrichs, Zak, Fischbacher, and Fehr (2005) showed that oxytocin might also facilitate affiliation, at least trust, in humans as well. In their study, participants completed the trust game-a task that putatively assesses trust in other individuals. Some of the participants assumed the role of an investor, and other participants assumed the role of a trustee. The investor was granted a specific amount of money, any proportion of which they could transfer to the trustee. The money that was transferred to the trustee was then tripled. For example, if the investor transferred $4 to the trustee, the experimenter added $8. The trustee was then permitted to retain all the money or return a proportion to the investor.

Some investors might choose to transfer most, if not all, their money to the trustee, to maximize the amount of money the experimenter will add. Nevertheless, the trustee might be uncooperative, deciding to retain all the money, and the investor thus ends with no funds. Alternatively, the investor might choose to transfer none of the money to the trustee, concerned this person will retain all the funds.

Half of the participants received intranasal oxytocin instead of a placebo. Investors who had received oxytocin were more likely to transfer most, if not all, their money to the trustee. This finding indicates that oxytocin might boost trust, which ultimately facilitates the formation of relationships or the provision of support.

Several alternative explanations were rejected. First, oxytocin did not affect whether trustees retained, rather than returned, the money. This neuropeptide, therefore, does not merely encourage altruism. Second, oxytocin did not affect the behavior of investors who merely interacted with a computer, which they had been informed was governed by random forces. Oxytocin, therefore, does not merely increase tolerance of risks.

This trust might be mediated by a diminution in amygdala activation. In a study conducted by Kirsch, Esslinger, Chen, Mier, Lis, Siddhanti, Gruppe, Mattay, Gallhofer, and Meyer-Lindenberg (2005), participants either received intranasal oxytocin or a placebo. In addition, stimuli that traditionally induce fear were presented. Amygdala activation in response to these stimuli, as measured by functional magnetic resonance imaging, was diminished if participants had received oxytocin, and this reduction was especially pronounced if these stimuli related to the social context, such as angry faces. Presumably, oxytocin might curb the perceived fear attached to social entities, as manifested by the diminished activation of the amygdala, and thus encourage social interactions.

Aggression in aggressive people

Oxytocin does not always foster cooperation and altruism. In settings in which people tend to be aggressive, oxytocin can actually amplify this aggression. This finding is consistent with the assumptions that oxytocin facilitates maternal behavior, and mothers often need to be aggressive to defend their children.

DeWall, Gillath, Pressman, Black, Bartz, Moskovitz, and Stetler (2014) proposed and validated these arguments. In one study, participants completed tasks that are intended to provoke an aggressive state. In particular, they presented a speech in front of an unsupportive audience and were then asked to wrap an ice bandage around their forehead, purportedly for another study. In addition, half the participants received some oxytocin, administered through their nostrils. Finally, participants answered questions about the extent to which they tend to be aggressive as well as the likelihood they may act aggressively towards their romantic partner now.

As predicted, if participants reported they are often aggressive--and, for example, resort to violence to protect their rights--oxytocin increased the likelihood they may be aggressive towards their partner now. That is, they felt like shoving, grabbing, or throwing something at their partner. In contrast, if participants reported they are seldom if ever aggressive, oxytocin decreased the likelihood they may be aggressive towards their partner now.

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Arguably, oxytocin activates the schemas or tendencies that people have learned to apply in close relationships, such as with their parents, children, or partners. If they tend to be aggressive, oxytocin could thus exacerbate this aggression. In essence, oxytocin might activate the attachment system.

Overcoming threat

Many studies show that oxytocin and vasopressin diminish stress and promote affiliation, at least in some circumstances. Poulin, Holman, and Buffone (2012) integrated these two strands of literature to explain how oxytocin and vasopressin may foster cooperative behavior. Specifically, in response to various forms of threat, such as violence or illness, people tend to become more vigilant and distrusting rather than cooperative and altruistic. However, oxytocin and vasopressin may curb this effect of threat on cooperation. That is, when oxytocin and vasopressin levels are elevated, people can be cooperative and altruistic even in the midst of threat.

Poulin, Holman, and Buffone (2012) conducted a study that vindicates this possibility. In this study, participants completed a series of questions that gauged the extent to which they perceive the world as threatening, such as "There is more good in the world than bad" (reverse scored). Next, they answered questions that measure civic duty or the degree to which they feel obliged to sacrifice personal interests to help their community (e.g., "It is a citizen's duty to keep informed about politics even if it is time-consuming") and the extent to which they engage in charitable activities, such as blood donations.

For many participants, levels of threat were negatively associated with civic duty and charity. However, levels of oxytocin and vasopressin moderated these relationships. Specifically, in participants in which the OXTR rs53576 gene corresponded to two G alleles rather than one or two A alleles--enhancing the effect of oxytocin-- threat did not seem to diminish charitable behavior. Likewise, in participants in which the AVPR1a rs1 gene corresponded to two long alleles rather than one or two short alleles--enhancing the effect of vasopressin--threat did not seem to reduce civic duty.

These findings align with studies that show that oxytocin diminishes the reactions of both the amygdala and cardiovascular system in response to stress (for a review, see Poulin, Holman, & Buffone, 2012). Similarly, these findings align with research that demonstrates that vasopressin can reduce the startle response.

Empathic accuracy

Bartz, Zaki, Bolger, Hollander, Ludwig, Kolevzon, and Ochsner (2010) showed that oxytocin enhances empathic accuracy--the capacity to decipher the feelings and intentions of other people (see empathic accuracy). Specifically, participants watched various people in a video. During the video, they rated the extent to which they believed the person felt very positive or negative. In one condition, the participants were administered intranasal oxytocin. Furthermore, a measure of social competence, relating to autism, was assessed.

As social competence diminished, empathic accuracy--that is, accurate perceptions of the emotions of people in the videos--decreased. However, oxytocin curtailed this relationship. That is, after oxytocin administration, empathic accuracy was unrelated to social competence. Conceivably, oxytocin increases the perceived salience of social cues and, thus, benefits people who are usually oblivious to this information.

Autism

Limited levels of oxytocin are also implicated in autism. Children with autism show low levels of oxytocin in the plasma relative to their counterparts of the same age. The ratio of an oxytocin precursor to oxytocin is elevated (Green et al., 2001). Indeed, studies suggest that variabilkity in the oxytocin receptor gene might be related to autism (Wu et al., 2005).

Experimental studies also confirm the role of oxytocin in autism. Oxytocin, when administered to children with autism, curbed repetitive behaviors and improved the processing of social information (for a review, see Bartz & Hollander, 2006).

Borderline personality disorder

Bartz and Hollander (2006) cogently argue that limited levels of oxytocin might be implicated in borderline personality disorder. Borderline personality disorder, which tends to be manifested as an intense motivation to preclude abandonment, coupled with tumultuous relationships, often emerges after abuse or neglect during childhood. Likewise, Teicher et al. (2002) maintain that early stress, abuse, or neglect could compromise the subsequent release of oxytocin, ultimately undermining social relationships.

Antecedents to oxytocin

Zak, Kurzban, and Matzner (2005) revealed that oxytocin levels rise in individuals after someone else engaged in behavior that demonstrates trust. In this study, participants completed the trust game, as described by Kosfeld et al. (2005). In this game, one of the participants assumes the role of an investor and the other participant assumed the role of a trustee. Sometimes, the investor demonstrates trust, transferring money to the trustee, on the assumption this person will engage in some form of reciprocation later. In these instances, levels of oxytocin were elevated in the trustees. Oxytocin does not rise when these trustees randomly receive the same amount of money.

Controversies

Oxytocin and relationship distress

Several studies, indicate that oxytocin might coincide with elevated, rather than diminished, levels of stress (e.g., Taylor et al., 2006). Young women who reported relationship distress demonstrated higher levels of oxytonic in the plasma relative to their satisfied counterparts (Turner et al., 1999).

This finding might indicate that relationship distress elicits the release of oxytocin, ultimately to elicit behaviors that restore social connections (see also Tops, Van Peer, Korf, Wijers, &Tucker, 2007). Consistent with this interpretation, individuals are more inclined to perceive a person they have not met before as friendly--as well as more motivated to seek friends--after they feel rejected in some social setting (e.g., Maner, DeWall, Baumeister, & Schaller, 2006). Conceivably, feelings of rejection or exclusion boost levels of oxytocin, which promote behaviors that are intended to facilitate the formation of other friendships.

Differences between the sexes

The effects of oxytocin differ somewhat between males and females. For example, after children are born, levels of oxytocin increase in both mothers and fathers. Yet, in mothers, this increase is associated with affectionate behavior. In fathers, this increase in oxytocin is associated with behaviors that stimulate play (Gordon, Zagoory-Sharon, Leckman, & Feldman, 2010).

The neurological responses to oxytocin also seem to differ between men and women. Specifically, when oxytocin is administered, reactivity of the amygdala to emotional faces decreases in men but increases in women (Domes et al., 2007& Domes et al., 2010).

Furthermore, the consequences of variants to the oxytocin gene also differ between males and females. At least one copy of the A allele of the oxytocin receptor gene rs2254298, relative to two copies of the G allele, corresponds to elevated levels of attachment anxiety in females but not in males (attachment theory), as measured by the experiences in close relationships questionnaire (see measures of attachment). Instead, this one copy of the A allele of this gene correlates with traits associated with autism--such as deficits in social skills, attention switching, communication and imagination--in males but not in females (Chen & Johnson, 2012).

Manipulation of oxytocin levels

The relationship between blood and brain oxytocin has not been established definitively and, therefore, the implications of past studies in this domain are uncertain. Tsuji (2005) proposes that transport mechanisms that transfer peptides, such as oxytocin, to the brain could be activated or inhibited. Alternatively, smaller molecular agonists of oxytocin, which could traverse the blood-brain barrier more readily, could also be administered. These techniques could control brain levels of oxytocin more precisely.

Practical implications

Commercialization

Synthetic oxytocin is sold as medication under the trade names Pitocin and Syntocinon as well as generic oxytocin. Oxytocin must be injected or administered using a nasal spray, because the hormone disintegrates in the gastrointestinal tract.

Fostering affiliation

Some individuals are reluctant to form relationships and seem evasive. To overcome this tendency, you should demonstrate trust in these individuals. In particular, you should donate or offer these individuals something--perhaps a company car or some funds--maintaining that you trust they will reciprocate later. These demonstrations of trust boost levels of oxytocin, ultimately improving relationships (e.g., Zak et al., 2005).

References

Bartz, J. A., & Hollander, E. (2006). The neuroscience of affiliation: Forging links between basic and clinical research on neuropeptides and social behavior. Hormones and Behavior, 50, 518-528.

Bartz, J. A., Zaki, J., Bolger, N., Hollander, E., Ludwig, N. N., Kolevzon, A., & Ochsner, K. N. (2010). Oxytocin selectively improves empathic accuracy. Psychological Science, 21, 1426-1428.

Chen, F. S., & Johnson, S. C. (2012). An oxytocin receptor gene variant predicts attachment anxiety in females and autism-spectrum traits in males. Social Psychological and Personality, 3, 93-99.

Chiodera, P., & Coiro, V. (1987). Oxytocin reduces metyrapone-induced ACTH secretion in human subjects. Brain Research, 420, 178-181.

DeWall, C. N., Gillath, O., Pressman, S. D., Black, L. L., Bartz, J. A., Moskovitz, J., & Stetler, D. A. (2014). When the love hormone leads to violence: Oxytocin increases intimate partner violence inclinations among high trait aggressive people. Social Psychological and Personality Science, 5(6), 691-697. doi: 10.1177/1948550613516876

Domes, G., Heinrichs, M., Glascher, J., Buchel, C., Braus, D. F., & Herpertz, S. C. (2007). Oxytocin attenuates amygdala responses to emotional faces regardless of valence. Biological Psychiatry, 62, 1187-1190.

Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010). Effects of intranasal oxytocin on emotional face processing in women. Psychoneuroendocrinology, 35, 83-93.

Gordon, I., Zagoory-Sharon, O., Leckman, (2010). Oxytocin and the development Biological Psychiatry, 68, 377-382.

Green, L.Fein, D., Modahl, C. Feinstein, C., Waterhouse, L., & Morris, M. (2001). Oxytocin and autistic disorder: alterations in peptide forms. Biological Psychiatry, 50, 609-613.

Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry, 54, 1389-1398.

Insel, T. R. (1992). Oxytocin-a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies. Psychoneuroendocrinology, 17, 3-35.

Kirsch, P., Esslinger, C., Chen, Q., Mier, D., Lis, S., Siddhanti, S., Gruppe, H., Mattay, V.S., Gallhofer, B., & Meyer-Lindenberg, A. (2005). Oxytocin modulates neural circuitry for social cognition and fear in humans. Journal of Neuroscience, 25, 11489-11493.

Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005). Oxytocin increases trust in humans. Nature, 435, 673-676.

Maner, J. K., DeWall, C. N., Baumeister, R. F., & Schaller, M. (2006). Does social exclusion motivate interpersonal reconnection? Resolving the "porcupine problem". Journal of Personality and Social Psychology, 92, 42-55.

McEwen, B. B. (2004). Brain-fluid barriers: relevance for theoretical controversies regarding vasopressin and oxytocin memory research. Advances in Pharmacology, 50, 531-592.

Poulin, M. J., Holman, E. A., & Buffone, A. (2012). The neurogenetics of nice: Receptor genes for oxytocin and vasopressin interact with threat to predict prosocial behavior. Psychological Science, 23, 446-452. doi: 10.1177/0956797611428471

Taylor, S. E. Gonzaga, G. C. Klein, L. C., Hu, P. Greendale, G. A., & Seeman, T. E. (2006). Relation of oxytocin to psychological stress responses and hypothalamic-pituitary-adrenocortical axis activity in older women. Psychosomatic Medicine, 68, 238-245.

Tops, M., Van Peer, J. M., Korf, J., Wijers, A. A., & Tucker, D. M. (2007). Anxiety, cortisol, and attachment predict plasma oxytocin. Psychophysiology, 44, 444-449.

Tsuji, A. (2005). Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems. NeuroRx, 2, 54-62.

Turner, R. A., Altemus, M., Enos, T., Cooper, B., & McGuinness, T. (1999). Preliminary research on plasma oxytocin in normal cycling women: Investigating emotion and interpersonal distress. Psychiatry: Interpersonal & Biological Processes, 62, 97-113.

Turner, R. A., Altemus, M., Yip, D. N., Kupferman, E., Fletcher, D., & Bostrom, A.et al. (2002). Effects of emotion on oxytocin, prolactin, and ACTH in women. Stress: The International Journal on the Biology of Stress, 5, 269-276.

Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Shuang, M., Gong, X., Zhang, Y. Yang, X., & Zhang, D. (2005). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological Psychiatry, 58, 74-77.

Zak, P. J., Kurzban, R., & Matzner, W. T. (2005). Oxytocin is associated with human trustworthiness. Hormones and Behavior, 48, 522-527.








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Last Update: 6/8/2016