What Are the Effects of the Social Neuropeptide Oxytocin on Social Cognitive Processing in Healthy Individuals vs Adult Antisocial Populations?

A short review of current research on the subject, submitted as one of my course’s essays at King’s.

Oxytocin (OT) as a neuropeptide has been widely regarded as a social one. It is intimately associated with various human behaviours pertaining to social relationships (Graustella & MacLeod, 2012; McCall & Singer, 2012). In literature, these processes are often referred to as social cognitive processing, and it entails (1) processing social information such as emotional expression (social perception), (2) understanding people’s emotional and cognitive states (social understanding), and (3) planning behaviours that consider others’ welfare, regarding one’s goals (social decision-making) (Arioli et al., 2018). Hence, OT presence is crucial for understanding the neural complexities of social processing and social cognitive deficits in both typically developing adults and those presenting with mental disorders, such as antisocial personality disorder (Jeung-Maarse et al., 2023). Nevertheless, conflicting findings, varying degrees of interactions, and methodological issues remain prevalent among such studies (McCall & Singer, 2012). In response, the present essay shall critically evaluate the effects of OT on social cognitive processing in both typically developing individuals and antisocial populations. It shall first review the former before linking its essential implications with the latter.

Extensive research has investigated the role of OT in affiliative behaviour among healthy adults, and we shall discuss these findings through three main themes: (a) emotional recognition/empathy, (b) trust and cooperation, and © memory for social information. To illustrate, this research builds upon evidence gathered from animal studies (Sansone et al., 2002; Ross & Young, 2009) and then tests for its effects in human subjects by administering a single dose of intranasal OT prior to an experimental task (Savaskan et al., 2008; Heinrichs & von Dawans, 2009; Guastella & Macleod, 2012). The neuroendocrinology framework of past research has identified brain regions that are meaningfully affected during such processes, particularly the amygdala. One of the initial studies on emotional recognition investigates the neural responses to threatening stimuli and facial expressions in the region. The results found that participants who were given OT treatment had lower amygdalar and brainstem activation compared to controls (Kirsch et al., 2005).

Similarly, another RCT study that utilises the fMRI discovered a reduced activation in the amygdala and the medial temporal gyrus in those given intranasal OT compared to placebos (Petrovic et al., 2008). Interestingly, the effects of OT within the amygdala are not entirely driven by negative stimuli. For instance, research conducted by Domes et al. (2007) found that reduced amygdala activities were observed during a passive-viewing task. Additionally, another study on healthy male adults found comparable results — in which the posterior amygdala mediates the effects of OT treatment on emotional valence processing and social attention (Gamer et al., 2010). These findings indicate that OT reduces amygdalar activities for fearful expressions but increases for ecstatic faces; a nuanced understanding of these neural mechanisms is crucial when interpreting results.

Regarding trust and cooperation, past initial studies have established the role of OT in increasing trust among healthy participants (Kosfeld et al., 2005). Specifically, Baumgartner et al.’s (2008) RCT study on healthy male adults found that OT maintains levels of trust after participants experienced social betrayal and attenuates neural responses related to experiencing a breach of trust. It does so through modulating regions in the brain responsible for fear-processing (i.e., the amygdala midbrain regions) and memory of social information (i.e., dorsal striatum) (Baumgartner et al., 2008). Furthermore, a more recent study supports the latter’s findings, in which healthy female participants who were given OT treatment had to respond to a task related to social feedback processing (Groppe et al., 2013). Specifically, participants had to respond as quickly as possible to a target stimulus to receive social rewards or avoid punishment. It was found that OT enhanced activities within the ventral tegmental area, positively predicting correct responses to socially rewarding conditions. Thus, these results imply that OT increases the saliency of socially rewarding and punishing cues (i.e., social information memory) (Groppe et al., 2013).

Much evidence supports the notion that OT modulates several mechanisms related to emotional recognition, trust, and social memory in adults. Nevertheless, it should be noted that most of these studies were conducted on typically developing and non-aggressive males. It remains unclear how these results translate to clinical populations such as aggression-prone and antisocial individuals. For instance, past studies that explored amygdala responses to aggression and anger-eliciting stimuli in violent offenders have produced conflicting results (Nikolic et al., 2022; Wen et al., 2022).

Due to the prior research gap, more recent studies have attempted to investigate the role of OT in antisocial populations further. The basic premise of conducting such research expands on previous findings on healthy and pathologised populations. For example, Coccaro et al.’s (2007) RCT discovered that there is amygdala hyperreactivity among male violent offenders compared to controls when looking at angry faces. However, more recent research on similar demographics could not confirm such findings (Schienle et al., 2017). Thus, since violent behaviours are a fundamental trait of antisocial personality disorder, it becomes highly crucial to better understand the mechanisms for research and clinical interventions. Jeung-Maarse et al.’s (2023) RCT study on 20 males and 18 females with ASPD discovered that OT attenuates amygdala activities in ASPD participants to levels much like their typically developing counterparts — particularly in females. Another study conducted on comparable participants with ASPD and psychopathy (N=34) also yielded similar results — in which oxytocin seems to modulate the empathic processing of violent offenders when looking at fearful expressions (Tully et al., 2023).

However, both studies employed relatively small sample sizes, with the majority being males without considering comorbidities. The former also did not consider the complexity of hormonal cycles within female participants that could significantly affect the results. Furthermore, an initial systematic review on the subject indicated that OT is generally helpful when correcting for deficits in recognising fearful or happy faces among the ASPD population. However, there was no systematic association regarding aggression (Gedeon et al., 2019). Similarly, a recent meta-analysis indicated the need to do more research on the subject to answer previous gaps on differences in findings regarding gender and aggression (Stark et al., 2023).

To summarise, although much research has established the effects of OT on healthy adult populations, studies on antisocial individuals still need to be more extensive and consistent. Future research should further investigate the influence of gender differences on aggressive behaviours, account for comorbidities, and employ much larger samples better to understand the role of OT on social cognitive processing.

References

Alcorn, J. L., 3rd, Rathnayaka, N., Swann, A. C., Moeller, F. G., & Lane, S. D. (2015). Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder. The Psychological record, 65(4), 691–703. https://doi.org/10.1007/s40732-015-0139-y

Arioli, M., Crespi, C., & Canessa, N. (2018). Social Cognition through the Lens of Cognitive and Clinical Neuroscience. BioMed research international, 2018, 4283427. https://doi.org/10.1155/2018/4283427

Baumgartner, T., Heinrichs, M., Vonlanthen, A., Fischbacher, U., & Fehr, E. (2008). Oxytocin shapes the neural circuitry of trust and trust adaptation in humans. Neuron, 58(4), 639–650. https://doi.org/10.1016/j.neuron.2008.04.009

Coccaro, E. F., McCloskey, M. S., Fitzgerald, D. A., & Phan, K. L. (2007). Amygdala and orbitofrontal reactivity to social threat in individuals with impulsive aggression. Biological psychiatry, 62(2), 168–178. https://doi.org/10.1016/j.biopsych.2006.08.024

Gamer, M., Zurowski, B., & Büchel, C. (2010). Different amygdala subregions mediate valence-related and attentional effects of oxytocin in humans. Proceedings of the National Academy of Sciences of the United States of America, 107(20), 9400–9405. https://doi.org/10.1073/pnas.1000985107

Gedeon, T., Parry, J., & Völlm, B. (2019). The role of oxytocin in antisocial personality disorders: A systematic review of the literature. Frontiers in Psychiatry, 10, Article 76. https://doi.org/10.3389/fpsyt.2019.00076

Groppe, S. E., Gossen, A., Rademacher, L., Hahn, A., Westphal, L., Gründer, G., & Spreckelmeyer, K. N. (2013). Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain. Biological psychiatry, 74(3), 172–179. https://doi.org/10.1016/j.biopsych.2012.12.023

Guastella, A. J., & MacLeod, C. (2012). A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions. Hormones and behavior, 61(3), 410–418. https://doi.org/10.1016/j.yhbeh.2012.01.002

Heinrichs, M., von Dawans, B., & Domes, G. (2009). Oxytocin, vasopressin, and human social behavior. Frontiers in neuroendocrinology, 30(4), 548–557. https://doi.org/10.1016/j.yfrne.2009.05.005

Jeung-Maarse, H., Schmitgen, M. M., Schmitt, R., et al. (2023). Oxytocin effects on amygdala reactivity to angry faces in males and females with antisocial personality disorder. Neuropsychopharmacology, 48, 946–953. https://doi.org/10.1038/s41386-023-01549-9

Kanat, M., Heinrichs, M., & Domes, G. (2014). Oxytocin and the social brain: neural mechanisms and perspectives in human research. Brain research, 1580, 160–171. https://doi.org/10.1016/j.brainres.2013.11.003

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. The Journal of neuroscience : the official journal of the Society for Neuroscience, 25(49), 11489–11493. https://doi.org/10.1523/JNEUROSCI.3984-05.2005

Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005). Oxytocin increases trust in humans. Nature, 435(7042), 673–676. https://doi.org/10.1038/nature03701

Krämer, U. M., Jansma, H., Tempelmann, C., & Münte, T. F. (2007). Tit-for-tat: the neural basis of reactive aggression. NeuroImage, 38(1), 203–211. https://doi.org/10.1016/j.neuroimage.2007.07.029

Meyer-Lindenberg, A., Domes, G., Kirsch, P., & Heinrichs, M. (2011). Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nature reviews. Neuroscience, 12(9), 524–538. https://doi.org/10.1038/nrn3044

McCall, C., & Singer, T. (2012). The animal and human neuroendocrinology of social cognition, motivation and behavior. Nature neuroscience, 15(5), 681–688. https://doi.org/10.1038/nn.3084

Nikolic, M., Pezzoli, P., Jaworska, N., & Seto, M. C. (2022). Brain responses in aggression-prone individuals: A systematic review and meta-analysis of functional magnetic resonance imaging (fMRI) studies of anger- and aggression-eliciting tasks. Progress in neuro-psychopharmacology & biological psychiatry, 119, 110596. https://doi.org/10.1016/j.pnpbp.2022.110596

Petrovic, P., Kalisch, R., Singer, T., & Dolan, R. J. (2008). Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(26), 6607–6615. https://doi.org/10.1523/JNEUROSCI.4572-07.2008

Sansone, G. R., Gerdes, C. A., Steinman, J. L., Winslow, J. T., Ottenweller, J. E., Komisaruk, B. R., & Insel, T. R. (2002). Vaginocervical stimulation releases oxytocin within the spinal cord in rats. Neuroendocrinology, 75(5), 306–315. https://doi.org/10.1159/000057340

Savaskan, E., Ehrhardt, R., Schulz, A., Walter, M., & Schächinger, H. (2008). Post-learning intranasal oxytocin modulates human memory for facial identity. Psychoneuroendocrinology, 33(3), 368–374. https://doi.org/10.1016/j.psyneuen.2007.12.004

Schienle, A., Wabnegger, A., Leitner, M., & Leutgeb, V. (2017). Neuronal correlates of personal space intrusion in violent offenders. Brain imaging and behavior, 11(2), 454–460. https://doi.org/10.1007/s11682-016-9526-5

Stark, N., Bobadilla, L., Michael, P., Saturn, S., & Portner, M. (2023). A meta-analytic review of the relationship between empathy and oxytocin: Implications for application in psychopathy research. Aggression and Violent Behavior, 70, 101828. https://doi.org/10.1016/j.avb.2023.101828

Timmermann, M., Jeung, H., Schmitt, R., Boll, S., Freitag, C. M., Bertsch, K., & Herpertz, S. C. (2017). Oxytocin improves facial emotion recognition in young adults with antisocial personality disorder. Psychoneuroendocrinology, 85, 158–164. https://doi.org/10.1016/j.psyneuen.2017.07.483

Tully, J., Sethi, A., Griem, J., Paloyelis, Y., Craig, M., Williams, S., Murphy, D., Blair, J., & Blackwood, N. (2023). Oxytocin normalizes the implicit processing of fearful faces in psychopathy: A randomized crossover study using fMRI. Nature Mental Health, 1, 420–427. https://doi.org/10.1038/s44220-023-00067-3

Wen, Z., Raio, C. M., Pace-Schott, E. F., Lazar, S. W., LeDoux, J. E., Phelps, E. A., & Milad, M. R. (2022). Temporally and anatomically specific contributions of the human amygdala to threat and safety learning. Proceedings of the National Academy of Sciences of the United States of America, 119(26), e2204066119. https://doi.org/10.1073/pnas.2204066119