Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-14T16:48:40.921Z Has data issue: false hasContentIssue false

Oxytocin receptor gene polymorphism, perceived social support, and psychological symptoms in maltreated adolescents

Published online by Cambridge University Press:  12 March 2014

Camelia E. Hostinar*
Affiliation:
University of Minnesota Institute of Child Development
Dante Cicchetti
Affiliation:
University of Minnesota Institute of Child Development University of Rochester Mt. Hope Family Center
Fred A. Rogosch
Affiliation:
University of Rochester Mt. Hope Family Center
*
Address correspondence and reprint requests to: Camelia E. Hostinar, Institute of Child Development, University of Minnesota, 51 East River Road, Minneapolis, MN 55455; E-mail: hosti002@umn.edu.

Abstract

Despite the detrimental consequences of child maltreatment on developmental processes, some individuals show remarkable resilience, with few signs of psychopathology, while others succumb to dysfunction. Given that oxytocin has been shown to be involved in social affiliation, attachment, social support, trust, empathy, and other social or reproductive behaviors, we chose to examine the possible moderation of maltreatment effects on perceived social support and on psychological symptoms by a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene. We studied adolescents (N = 425) aged approximately 13–15, including participants with objectively documented maltreatment histories (N = 263) and a nonmaltreated comparison group from a comparable low socioeconomic status background (N = 162). There was a significant genotype by maltreatment interaction, such that maltreated adolescents with the G/G genotype perceived significantly lower social support compared to maltreated A-carriers, with no effect of genotype in the comparison group. Maltreated G/Gs also reported higher levels of internalizing symptoms than did A-carriers, even though they did not differ from them on objective measures of maltreatment (type, duration, or severity). G/G homozygotes may be more attuned to negative social experiences, such as family maltreatment, while maltreated A-carriers were indistinguishable from nonmaltreated adolescents in levels of mental health symptoms.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Achenbach, T. M. (1991). Integrative guide for the 1991 CBCL/4–18, YSR, and TRF profiles. Burlington, VT: University of Vermont, Department of Psychiatry.Google Scholar
Achenbach, T. M., & Rescorla, L. A. (2001). Manual for the ASEBA School-Age Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families.Google Scholar
Apicella, C. L., Cesarini, D., Johannesson, M., Dawes, C. T., Lichtenstein, P., Wallace, B., et al. (2010). No association between oxytocin receptor (OXTR) gene polymorphisms and experimentally elicited social preferences. PLOS ONE, 5, e11153.CrossRefGoogle ScholarPubMed
Avishai-Eliner, S., Gilles, E. E., Eghbal-Ahmadi, M., Bar-El, Y., & Baram, T. Z. (2001). Altered regulation of gene and protein expression of hypothalamic–pituitary–adrenal axis components in an immature rat model of chronic stress. Journal of Neuroendocrinology, 13, 799807.Google Scholar
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2008). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social Cognitive and Affective Neuroscience, 3, 128134.Google Scholar
Barnett, D., Manly, J. T., & Cicchetti, D. (1993). Defining child maltreatment: The interface between policy and research. In Cicchetti, D. & Toth, S. L. (Eds.), Child abuse, child development, and social policy (pp. 773). Norwood, NJ: Ablex.Google Scholar
Barraza, J. A., & Zak, P. J. (2009). Empathy toward strangers triggers oxytocin release and subsequent generosity. Annals of the New York Academy of Sciences, 1167, 182189.Google Scholar
Bolger, K. E., & Patterson, C. J. (2001). Pathways from child maltreatment to internalizing problems: Perceptions of control as mediators and moderators. Development and Psychopathology, 13, 913940.Google Scholar
Bolger, K. E., Patterson, C. J., & Kupersmidt, J. B. (1998). Peer relationships and self-esteem among children who have been maltreated. Child Development, 69, 11711197.Google Scholar
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., et al. (2011). Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene. Development and Psychopathology, 23, 439452.Google Scholar
Buchheim, A., Heinrichs, M., George, C., Pokorny, D., Koops, E., Henningsen, P., et al. (2010). Oxytocin enhances the experience of attachment security. Psychoneuroendocrinology, 34, 14171422.Google Scholar
Carter, C. S. (2007). Sex differences in oxytocin and vasopressin: Implications for autism spectrum disorders? Behavior and Brain Research, 176, 170186.Google Scholar
Caspi, A., & Moffitt, T. E. (2006). Gene–environment interactions in psychiatry: Joining forces with neuroscience. Nature Reviews Neuroscience, 7, 583590.Google Scholar
Champagne, F., Diorio, J., Sharma, S., & Meaney, M. J. (2001). Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. Proceedings of the National Academy of Sciences, 98, 1273612741.Google Scholar
Chen, F. S., Kumsta, R., von Dawans, B., Monakhov, M., Ebstein, R. P., & Heinrichs, M. (2011). Common oxytocin receptor gene (OXTR) polymorphism and social support interact to reduce stress in humans. Proceedings of the National Academy of Sciences, 108, 1993719942.Google Scholar
Chibbar, R., Toma, J. G., Mitchell, B. F., & Miller, F. D. (1990). Regulation of neural oxytocin gene expression by gonadal steroids in pubertal rats. Molecular Endocrinology, 4, 20302038.Google Scholar
Cicchetti, D. (2010). Resilience under conditions of extreme stress: A multilevel perspective. World Psychiatry, 9, 110.Google Scholar
Cicchetti, D. (2013). Resilient functioning in maltreated children: Past, present, and future perspectives. Journal of Child Psychology and Psychiatry, 54, 402422.Google Scholar
Cicchetti, D., & Barnett, D. (1991). Attachment organization in maltreated preschoolers. Development and Psychopathology, 3, 397411.Google Scholar
Cicchetti, D., & Blender, J. A. (2006). A multiple-levels-of-analysis perspective on resilience: Implications for the developing brain, neural plasticity, and preventive interventions. Annals of the New York Academy of Sciences, 1094, 248258.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Lynch, M. (1995). Failures in the expectable environment and their impact on individual development: The case of child maltreatment. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology: Risk, disorder, and adaptation (Vol. 2, pp. 3271). New York: Wiley.Google Scholar
Cicchetti, D., & Rogosch, F. A. (1997). The role of self-organization in the promotion of resilience in maltreated children. Development and Psychopathology, 9, 799817.Google Scholar
Cicchetti, D., & Rogosch, F. A. (2012). Gene × Environment interaction and resilience: Effects of child maltreatment and serotonin, corticotropin releasing hormone, dopamine, and oxytocin genes. Development and Psychopathology, 24, 411427.Google Scholar
Cicchetti, D., Rogosch, F. A., & Toth, S. L. (2006). Fostering secure attachment in infants in maltreating families through preventive interventions. Development and Psychopathology, 18, 623649.Google Scholar
Cicchetti, D., Toth, S. L., & Manly, J. T. (2003). Maternal Maltreatment Interview. Unpublished manuscript.Google Scholar
Cicchetti, D., & Valentino, K. (2006). An ecological transactional perspective on child maltreatment: Failure of the average expectable environment and its influence upon child development. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental psychopathology (Vol. 3, 2nd ed., pp. 129201). Hoboken, NJ: Wiley.Google Scholar
Cohen, S. (2004). Social relationships and health. American Psychologist, 59, 676684.Google Scholar
Costa, B., Pini, S., Gabelloni, P., Abelli, M., Lari, L., Cardini, A., et al. (2009). Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology, 34, 15061514.Google Scholar
Crone, E. A., & Dahl, R. E. (2012). Understanding adolescence as a period of social–affective engagement and goal flexibility. Nature Reviews Neuroscience, 13, 636650.CrossRefGoogle ScholarPubMed
Ditzen, B., Schaer, M., Gabriel, B., Bodenmann, G., Ehlert, U., & Heinrichs, M. (2009). Intranasal oxytocin increases positive communication and reduces cortisol levels during couple conflict. Biological Psychiatry, 65, 728731.Google Scholar
Domes, G., Heinrichs, M., Michel, A., Berger, C., & Herpertz, S. C. (2007). Oxytocin improves “mind-reading” in humans. Biological Psychiatry, 61, 731733.Google Scholar
Donaldson, Z. R., & Young, L. J. (2008). Oxytocin, vasopressin, and the neurogenetics of sociality. Science, 322, 900904.Google Scholar
Ebstein, R. P., Knafo, A., Mankuta, D., Chew, S. H., & Lai, P. S. (2012). The contributions of oxytocin and vasopressin pathway genes to human behavior. Hormones and Behavior, 61, 359379.Google Scholar
Feldman, R., Gordon, I., Schneiderman, I., Weisman, O., & Zagoory-Sharon, O. (2010). Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent–infant contact. Psychoneuroendocrinology, 35, 11331141.Google Scholar
Furman, W., & Buhrmester, D. (1992). Age and sex differences in perceptions of networks of personal relationships. Child Development, 63, 103115.Google Scholar
Galbally, M., Lewis, A. J., IJzendoorn, M., & Permezel, M. (2011). The role of oxytocin in mother–infant relations: A systematic review of human studies. Harvard Review of Psychiatry, 19, 114.Google Scholar
Gillath, O., Shaver, P. R., Baek, J.-M., & Chun, D. S. (2008). Genetic correlates of adult attachment style. Personality & Social Psychology Bulletin, 34, 13961405.Google Scholar
Gimpl, G., & Fahrenholz, F. (2001). The oxytocin receptor system: Structure, function, and regulation. Physiological Reviews, 81, 629683.Google Scholar
Gordon, I., Zagoory-Sharon, O., Leckman, J. F., & Feldman, R. (2010). Oxytocin and the development of parenting in humans. Biological Psychiatry, 68, 377382.Google Scholar
Grant, K. E., Compas, B. E., Stuhlmacher, A. F., Thurm, A. E., McMahon, S. D., & Halpert, J. A. (2003). Stressors and child and adolescent psychopathology: Moving from markers to mechanisms of risk. Psychological Bulletin, 129, 447466.Google Scholar
Heim, C., Young, L. J., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2009). Lower CSF oxytocin concentrations in women with a history of childhood abuse. Molecular Psychiatry, 14, 954958.Google Scholar
Heinrichs, M., & Domes, G. (2008). Neuropeptides and social behaviour: Effects of oxytocin and vasopressin in humans. Progress in Brain Research, 170, 337350.Google Scholar
Hennessy, M. B., Kaiser, S., & Sachser, N. (2009). Social buffering of the stress response: Diversity, mechanisms, and functions. Frontiers in Neuroendocrinology, 30, 470482.Google Scholar
Hostinar, C. E., Sullivan, R. M., & Gunnar, M. R. (2014). Psychobiological mechanisms underlying the social buffering of the HPA axis: A review of animal models and human studies across development. Psychological Bulletin, 140, 256282. doi:10.1037/a0032671 Google Scholar
Inoue, T., Kimura, T., Azuma, C., Inazawa, J., Takemura, M., Kikuchi, T., et al. (1994). Structural organization of the human oxytocin receptor gene. Journal of Biological Chemistry, 269, 3245132456.CrossRefGoogle ScholarPubMed
Insel, T. R., & Shapiro, L. E. (1992). Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proceedings of the National Academy of Sciences, 89, 59815985.Google Scholar
Jacob, S., Brune, C. W., Carter, C. S., Leventhal, B. L., Lord, C., & Cook, E. H. (2007). Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neuroscience Letters, 417, 69.Google Scholar
Jostins, L., Pickrell, J. K., MacArthur, D. G., & Barretta, J. C. (2012). Misuse of hierarchical linear models overstates the significance of a reported association between OXTR and prosociality. Proceedings of the National Academy of Sciences, 109, E1048.Google Scholar
Kaplow, J. B., & Widom, C. S. (2007). Age of onset of child maltreatment predicts long-term mental health outcomes. Journal of Abnormal Psychology, 116, 176187.Google Scholar
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444454.Google Scholar
Kim, H. S., Sherman, D. K., Sasaki, J. Y., Xu, J., Chu, T. Q., Ryu, et al. (2010). Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking. Proceedings of the National Academy of Sciences, 107, 1571715721.Google Scholar
Kogan, A., Saslow, L. R., Impett, E. A, Oveis, C., Keltner, D., & Rodrigues Saturn, S. (2011). Thin-slicing study of the oxytocin receptor (OXTR) gene and the evaluation and expression of the prosocial disposition. Proceedings of the National Academy of Sciences, 108, 1918919192.Google Scholar
Kosfeld, M., Heinrichs, M., Zak, P. J., Fischbacher, U., & Fehr, E. (2005). Oxytocin increases trust in humans. Nature, 435, 673676.Google Scholar
Krueger, F., Parasuraman, R., Iyengar, V., Thornburg, M., Weel, J., Lin, M., et al. (2012). Oxytocin receptor genetic variation promotes human trust behavior. Frontiers in Human Neuroscience, 6, 4.Google Scholar
Lucht, M. J., Barnow, S., Sonnenfeld, C., Rosenberger, A., Grabe, H. J., Schroeder, W., et al. (2009). Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 33, 860866.Google Scholar
Maestripieri, D. (2005). Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys. Proceedings of the National Academy of Sciences, 102, 97269729.Google Scholar
Malik, A. I., Zai, C. C., Abu, Z., Nowrouzi, B., & Beitchman, J. H. (2012). The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression. Genes, Brain, and Behavior, 11, 545551.Google Scholar
Manly, J. T., Cicchetti, D., & Barnett, D. (1994). The impact of subtype, frequency, chronicity, and severity of child maltreatment on social competence and behavior problems. Development and Psychopathology, 6, 121143.Google Scholar
Manly, J. T., Kim, J. E., Rogosch, F. A., & Cicchetti, D. (2001). Dimensions of child maltreatment and children's adjustment: Contributions of developmental timing and subtype. Development and Psychopathology, 13, 759782.Google Scholar
Manly, T. J. (2005). Advances in research definitions in child development. Child Abuse and Neglect, 29, 425439.Google Scholar
Masten, A. S. (2001). Ordinary magic: Resilience processes in development. American Psychologist, 56, 227238.Google Scholar
Meinlschmidt, G., & Heim, C. (2007). Sensitivity to intranasal oxytocin in adult men with early parental separation. Biological Psychiatry, 61, 11091111.Google Scholar
Merikangas, K. R., He, J. P., Burstein, M., Swanson, S. A., Avenevoli, S., Cui, L., et al. (2010). Lifetime prevalence of mental disorders in U.S. adolescents: Results from the National Comorbidity Survey Replication—Adolescent supplement (NCS-A). Journal of the American Academy of Child & Adolescent Psychiatry, 49, 980989.Google Scholar
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, 524538.Google Scholar
Monroe, S. M., & Reid, M. W. (2008). Gene–environment interactions in depression: Genetic polymorphisms and life stress polyprocedures. Psychological Science, 19, 947956.Google Scholar
Montag, C., Brockmann, E. M., Lehmann, A., Müller, D. J., Rujescu, D., & Gallinat, J. (2012). Association between oxytocin receptor gene polymorphisms and self-rated “empathic concern” in schizophrenia. PLOS One, 7, e51882.CrossRefGoogle Scholar
Morhenn, V., Park, J., Piper, E., & Zak, P. (2008). Monetary sacrifice among strangers is mediated by endogenous oxytocin release after physical contact. Evolution and Human Behavior, 29, 375383.Google Scholar
Naber, F., van IJzendoorn, M. H., Deschamps, P., van Engeland, H., & Bakermans-Kranenburg, M. J. (2010). Intranasal oxytocin increases fathers' observed responsiveness during play with their children: A double-blind within-subject experiment. Psychoneuroendocrinology, 35, 15831586.Google Scholar
Neumann, I. D. (2008). Brain oxytocin: A key regulator of emotional and social behaviours in both females and males. Journal of Neuroendocrinology, 20, 858865.Google Scholar
Nolen-Hoeksema, S. (2012). Emotion regulation and psychopathology: The role of gender. Annual Reviews in Clinical Psychology, 8, 161187.Google Scholar
Poulin, M., 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, 446452.Google Scholar
Raineki, C., Moriceau, S., & Sullivan, R. M. (2010). Developing a neurobehavioral animal model of infant attachment to an abusive caregiver. Biological Psychiatry, 67, 11371145.Google Scholar
Riem, M. M. E., Pieper, S., Out, D., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Oxytocin receptor gene and depressive symptoms associated with physiological reactivity to infant crying. Social Cognitive and Affective Neuroscience, 6, 294300.Google Scholar
Rodrigues, S. M., Saslow, L. R., Garcia, N., John, O. P., & Keltner, D. (2009). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proceedings of the National Academy of Sciences, 106, 2143721441.Google Scholar
Rogosch, F. A., Cicchetti, D., & Aber, J. L. (1995). The role of child maltreatment in early deviations in cognitive and affective processing abilities and later peer relationship problems. Development and Psychopathology, 7, 591.Google Scholar
Rogosch, F. A., Dackis, M. N., & Cicchetti, D. (2011). Child maltreatment and allostatic load: Consequences for physical and mental health in children from low-income families. Development and Psychopathology, 23, 11071124.Google Scholar
Rogosch, F. A., Oshri, A., & Cicchetti, D. (2010). From child maltreatment to adolescent cannabis abuse and dependence: A developmental cascade model. Development and Psychopathology, 22, 883897.CrossRefGoogle ScholarPubMed
Roth, T., & Sullivan, R. M. (2005). Memory of early maltreatment: Neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning. Biological Psychiatry, 57, 823831.Google Scholar
Rutter, M. (2010). Gene–environment interplay. Depression and Anxiety, 27, 14.Google Scholar
Sakai, J. T., Crowley, T. J., Stallings, M. C., McQueen, M., Hewitt, J. K., Hopfer, C., et al. (2012). Test of association between 10 single nucleotide polymorphisms in the oxytocin receptor gene and conduct disorder. Psychiatric Genetics, 22, 99102.Google Scholar
Saphire-Bernstein, S., Way, B. M., Kim, H. S., Sherman, D. K., & Taylor, S. E. (2011). Oxytocin receptor gene (OXTR) is related to psychological resources. Proceedings of the National Academy of Sciences, 108, 1511815122.Google Scholar
Scott, K. L., Wolfe, D. A., & Wekerle, C. (2003). Maltreatment and trauma: Tracking the connections in adolescence. Child and Adolescent Psychiatric Clinics of North America, 12, 211230.Google Scholar
Sedlak, A. J., Mettenburg, J., Basena, M., Petta, I., McPherson, K., Green, A., et al. (2010). The Fourth National Incidence Study of Child Abuse and Neglect (NIS-4): Report to Congress. Washington, DC: US Department of Health and Human Services, Administration for Children and Families.Google Scholar
Seltzer, L. J., Ziegler, T. E., & Pollak, S. D. (2011). Social vocalizations can release oxytocin in humans. Proceedings of the Royal Society B: Biological Sciences, 277, 26612666.Google Scholar
Sturge-Apple, M. L., Cicchetti, D., Davies, P. T., & Suor, J. H. (2012). Differential susceptibility in spillover between interparental conflict and maternal parenting practices: Evidence for OXTR and 5-HTT genes. Journal of Family Psychology, 26, 431442.Google Scholar
Takayanagi, Y., Yoshida, M., Bielsky, I. F., Ross, H. E., Kawamata, M., Onaka, T., et al. (2005). Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice. Proceedings of the National Academy of Sciences, 102, 1609616101.Google Scholar
Tharner, A., Luijk, M. P., Raat, H., Ijzendoorn, M. H., Bakermans-Kranenburg, M. J., Moll, H., et al. (2012). Breastfeeding and its relation to maternal sensitivity and infant attachment. Journal of Developmental and Behavioral Pediatrics, 33, 396404.Google Scholar
Tost, H., Kolachana, B., Hakimi, S., Lemaitre, H., Verchinski, B. A., Mattay, V. S., et al. (2010). A common allele in the oxytocin receptor gene (OXTR) impacts prosocial temperament and human hypothalamic–limbic structure and function. Proceedings of the National Academy of Sciences, 107, 1393613941.Google Scholar
van IJzendoorn, M. H., Belsky, J., & Bakermans-Kranenburg, M. J. (2012). Serotonin transporter genotype 5HTTLPR as a marker of differential susceptibility? A meta-analysis of child and adolescent gene-by-environment studies. Translational Psychiatry, 2, e147.Google Scholar
Wu, S., Jia, M., Ruan, Y., Liu, J., Guo, Y., Shuang, M., et al. (2005). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological Psychiatry, 58, 7477.Google Scholar
Zak, P. J., Kurzban, R., & Matzner, W. T. (2005). Oxytocin is associated with human trustworthiness. Hormones and Behavior, 48, 522527.Google Scholar
Zak, P. J., Stanton, A. A., & Ahmadi, S. (2007). Oxytocin increases generosity in humans. PLOS ONE, 2, e1128.Google Scholar