Skip to main content Accessibility help

Differential susceptibility to rearing environment depending on dopamine-related genes: New evidence and a meta-analysis

  • Marian J. Bakermans-Kranenburg (a1) and Marinus H. van Ijzendoorn (a1)


In the current paper we present new empirical data and meta-analytic evidence for the role of dopamine-related genes as a susceptibility factor interacting with the rearing environment for better and for worse, that is, increasing children's susceptibility to both the adverse effects of unsupportive environments and the beneficial effects of supportive rearing. In Study 1 we examined the readiness of 91 7-year-old children to donate their money to a charity (UNICEF). We tested whether the association between attachment and donating behavior was moderated by the presence of the dopamine receptor D4 (DRD4) 7-repeat allele. The attachment story completion task was used to assess attachment as an index of the quality of the rearing environment. Children with secure attachment representations donated more but only if they had the DRD4 7-repeat allele. In Study 2 we present the results of a meta-analysis of gene–environment studies on children up to 10 years of age involving dopamine-related genes (dopamine receptor D2, DRD4, dopamine transporter). The cumulative negative effects of these “risk genes” and adverse rearing environments have been stressed, but potentially cumulative positive effects of these same genes interacting with positive rearing environments remained largely unnoticed. We examined the associations between negative and positive rearing environments and developmental outcomes as moderated by dopamine-related gene polymorphisms. Children with the less efficient dopamine-related genes did worse in negative environments than the comparisons without the “genetic risk,” but they also profited most from positive environments. Findings are discussed in light of evolutionary theory, and illustrated with some practical implications of differential susceptibility.


Corresponding author

Address correspondence and reprint requests to: Marian J. Bakermans-Kranenburg or Marinus H. van IJzendoorn, Centre for Child and Family Studies, Leiden University, P.O. Box 9555, Leiden 2300 RB, The Netherlands; E-mail: or


Hide All
Aron, E. N., & Aron, A. (1997). Sensory-processing sensitivity and its relation to introversion and emotionality. Journal of Personality and Social Psychology, 73, 345368.
Bachner-Melman, R., Gritsenko, I., Nemanov, L., Zohar, A. H., Dina, C., & Ebstein, R. P. (2005). Dopaminergic polymorphisms associated with selfreport measures of human altruism: A fresh phenotype for the dopamine D4 receptor. Molecular Psychiatry, 10, 333335.
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2006). Gene–environment interaction of the dopamine D4 receptor (DRD4) and observed maternal insensitivity predicting externalizing behavior in preschoolers. Developmental Psychobiology, 48, 406409.
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007). Genetic vulnerability or differential susceptibility in child development: The case of attachment. Journal of Child Psychology and Psychiatry, 48, 11601173.
Bakermans-Kranenburg, M. J., van IJzendoorn, M. H., Pijlman, F. T. A., Mesman, J., & Juffer, F. (2008). Experimental evidence for differential susceptibility: Dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers' externalizing behavior in a randomized control trial. Developmental Psychology, 44, 293300.
Barr, C. L., & Kidd, K. K. (1993). Population frequencies of the A1 allele at the dopamine D2 receptor locus. Biological Psychiatry, 34, 204209.
Belsky, J. (1997). Variation in susceptibility to environmental influence: An evolutionary argument. Psychological Inquiry, 8, 182185.
Belsky, J., Bakermans-Kranenbug, M. J., & van IJzendoorn, M. H. (2007). For better and for worse: Differential susceptibility to environmental influences. Current Directions in Psychological Science, 16, 300304.
Belsky, J., & Pluess, M. (2009). Beyond diathesis–stress: Differential susceptibility to environmental influence. Psychological Bulletin, 135, 885908.
Berman, S., Ozkaragoz, T., Young, R. M., & Noble, E. P. (2002). D2 dopamine receptor gene polymorphism discriminates two kinds of novelty seeking. Personality and Individual Differences, 33, 867882.
Blair, C. (2002). Early intervention for low birth weight preterm infants: The role of negative emotionality in the specification of effects. Development and Psychopathology, 14, 311332.
Borenstein, M., Hedges, L. V., & Higgins, J. P. T. (2009) Introduction to meta-analysis. Chichester: Wiley.
Bowles, S. (2008). Being human: Conflict: Altruism's midwife. Nature, 456, 326328.
Boyce, W. T., Chesney, M., Alkon, A., Tschann, J. M., Adams, S., Chesterman, B., et al. (1995). Psychobiologic reactivity to stress and childhood respiratory illnesses: Results of two prospective studies. Psychosomatic Medicine, 57, 411422.
Boyce, W. T., & Ellis, B. J. (2005). Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and function of stress reactivity. Development and Psychopathology, 17, 271301.
Bretherton, I., Prentiss, C., & Ridgeway, D. (1990). Family relationships as represented in a story-completion task at thirty-seven and fifty-four months of age. New Directions for Child and Adolescent Development, 48, 85105.
Bronfenbrenner, U. (1979). The ecology of human development: Experiments by nature and design. Cambridge, MA: Harvard University Press.
Carlson, E. A. (1998). A prospective longitudinal study of attachment disorganization/disorientation. Child Development, 69, 11071128.
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., et al. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851854.
Cassidy, J. (1988). Child mother attachment and the self in six year olds. Child Development, 59, 121134.
Congdon, E., Lesch, K. P., & Canli, T. (2008); Analysis of DRD4 and DAT polymorphisms and behavioral inhibition in healthy adults: Implications for impulsivity. American Journal of Medical Genetics, 147B, 2732.
Darwin, C. (1982). The descent of man, and selection in relation to sex. Princeton, NJ: Princeton University Press. [Original work published 1871]
Deater-Deckard, K., Dodge, K. A., Bates, J. E., & Pettit, G. S. (1996). Discipline among African American and European American mothers: Links to children's externalizing behaviors. Developmental Psychology, 32, 10651072.
De Waal, F. B. M. (2008). Putting the altruism back into altruism: The evolution of empathy. Annual Review of Psychology, 59, 279300.
Ding, Y. C., Chi, H. C., Grady, D. L., Morishima, A., Kidd, J. R., Kidd, K. K., et al. (2002). Evidence of positive selection acting at the human dopamine receptor D4 gene locus. Proceedings of the National Academy of Sciences of the United States of America, 99, 309314.
Ebstein, R. P., Israel, S., Chew, S. H., Zhong, S., & Knafo, A. (2010). Genetics of human social behavior. Neuron, 65, 831844,
Eisenberg, D. T. A., Campbell, B., Gray, P. B., & Sorenson, M. D. (2008). Dopamine receptor genetic polymorphisms and body composition in undernourished pastoralists: An exploration of nutrition indices among nomadic and recently settled Ariaal men of northern Kenya. BMC Evolutionary Biology, 8, 173.
Eisenberg, N., Guthrie, I. K., Murphy, B. C., Shepard, S. A., Cumberland, A., & Carlo, G. (1999). Consistency and development of prosocial dispositions: A longitudinal study. Child Development, 70, 13601372.
Eisenberg, N., Shell, R., Pasternack, J., Lennon, R., Beller, R., & Mathy, R. M. (1987). Prosocial development in middle childhood: A longitudinal study. Developmental Psychology, 23, 712718.
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 728.
Espy, K. A. & Cwik, M. F. (2004). The development of a Trail Making Test in young children: The Trails-P. Clinical Neuropsychologist, 18, 411422.
Evans, D. E. & Rothbart, M. K. (2007). Developing a model for adult temperament. Journal of Research in Personality, 41, 868888.
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., et al. 2005. Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, 13131323.
Fearon, R. M. P., Bakermans-Kranenburg, M. J., van IJzendoorn, M. H., Lapsley, A., & Roisman, G. I. (2010). The significance of insecure attachment and disorganization in the development of children's externalizing behavior: A meta-analytic study. Child Development, 81, 435456.
Fox, N. A., Hane, A. A., & Pine, D. S. (2007). Plasticity for affective neurocircuitry. How the environment affects gene expression. Current Directions in Psychological Science, 16, 15.
Froehlich, T. E., Lanphear, B. P., Dietrich, K. N., Cory-Slechta, D. A., Wang, N., & Kahn, R. S. (2007). Interactive effects of a DRD4 polymorphism, lead, and sex on executive functions in children. Biological Psychiatry, 62, 243249.
Gervai, J., Novak, A., Lakatos, K., Toth, I., Danis, I., Ronai, Z., et al. (2007). Infant genotype may moderate sensitivity to maternal affective communications: Attachment disorganization, quality of care, and the DRD4 polymorphism. Social Neuroscience, 2, 307319.
Gilissen, R., Bakermans-Kranenburg, M. J., van IJzendoorn, M. H., & Van der Veer, R. (2008). Parent–child relationship, temperament, and physiological reactions to fear-inducing film clips: Further evidence for differential susceptibility. Journal of Experimental Child Psychology, 99, 182195.
Goldstein, H., & Healy, M. J. R. (1995). The graphical presentation of a collection of means, Journal of the Royal Statistical Society, 158A, 175177.
Grunberg, N. E., Maycock, V. A., & Anthony, B. J. (1985). Material altruism in children. Basic and Applied Social Psychology, 6, 111.
Hesse, E. (2008). The Adult Attachment Interview: Protocol, method of analysis, and empirical studies. In Cassidy, J. & Shaver, P. R. (Eds.), Handbook of attachment: Theory, research, and clinical applications (pp. 552598). New York: Guilford Press.
Hoffman, M. L. (1984). Interaction of affect and cognition in empathy. In Izard, C. E., Kagan, J., & Zajone, R. B. (Eds.), Emotions, cognitions, and behavior (pp. 103131). Cambridge: Cambridge University Press.
Hrdy, S. B. (2009). Mothers and others: The evolutionary origins of mutual understanding. Cambridge, MA: Harvard University Press.
Kaffman, A., & Meaney, M. J. (2007). Neurodevelopmental sequelae of postnatal maternal care in rodents: Clinical and research implications of molecular insights. Journal of Child Psychology and Psychiatry, 48, 224244.
Kahn, R. S., Khoury, J., Nichols, W. C., & Lanphear, B. P. (2003). Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive–impulsive, inattentive, and oppositional behaviors. Journal of Pediatrics, 143, 104110.
Kim-Cohen, J., Caspi, A., Taylor, A., Williams, B., Newcombe, R., Craig, I. W., et al. (2006). MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11, 903913.
Klein, T. A., Neumann, J., Reuter, M., Hennig, J., Von Cramon, D. Y., & Ullsperger, M. (2007). Genetically determined learning from errors. Science, 318, 16421645.
Klein Velderman, M., Bakermans-Kranenburg, M. J., Juffer, F., & van IJzendoorn, M. H. (2006). Effects of attachment-based interventions on maternal sensitivity and infant attachment: Differential susceptibility of highly reactive infants. Journal of Family Psychology, 20, 266274.
Knafo, A. (2009). Prosocial development: The intertwined roles of children's genetics and their parental environment. Paper presented at the Biennial Meeting of the Society for Research in Child Development, Denver, CO, April 2–4.
Knafo, A., Zahn-Waxler, C., Van Hulle, C., Robinson, J. L., & Rhee, S. H. (2008). The developmental origins of a disposition towards empathy: Genetic and environmental contributions. Emotion, 8, 737752.
Kochanska, G., Askan, N., & Joy, M. E. (2007). Children's fearfulness as a moderator of parenting in early socialization: Two longitudinal studies. Developmental Psychology, 43, 222237.
Krevans, J., & Gibbs, J. C. (1996). Parents' use of inductive discipline: Relations to children's empathy and prosocial behavior. Child Development, 67, 32633277.
Levitan, R. D., Masellis, M., Basile, V. S., Lam, R. W., Kaplan, A. S., Davis, C., et al. (2004). The dopamine-4 receptor gene associated with binge eating and weight gain in women with seasonal affective disorder: An evolutionary perspective. Biological Psychiatry, 56, 665669.
Li, Y., Shao, C., Zhang, D., Zhao, M.Lin, L., Yan, P., et al. (2006). The effect of dopamine D2, D5 receptor and transporter (SLC6A3) polymorphisms on the cue-elicited heroin craving in Chinese. American Journal of Medical Genetics, 141B, 269273.
Maher, B. S., Marazita, M. L., Ferrell, R. E., & Vanyukov, M. M. 2002. Dopamine system genes and attention deficit hyperactivity disorder: A meta-analysis. Psychiatric Genetics 12, 207215.
Mikulincer, M., & Shaver, P. R. (2008). “Can't buy me love”: An attachment perspective on social support and money as psychological buffers. Psychological Inquiry, 19, 167173.
Noble, E. P. (2003). D2 dopamine receptor gene in psychiatric and neurological disorders and its phenotypes. American Journal of Medical Genetics, 116B, 103125.
Posner, M. I., & Rothbart, M. K. (2007). Research on attention networks as a model for the integration of psychological science. Annual Review of Psychology, 58, 123.
Propper, C., Willoughby, M., Halpern, C. T., Cox, M., & Carbone, M. A. (2007). Parenting quality, DRD4, and the prediction of externalizing and internalizing behaviors in early childhood. Developmental Psychobiology, 49, 619632.
Richters, J. E., & Waters, E. (1992). Attachment and socialization: The positive side of social influence. In Lewis, M. & Feinman, S. (Eds.), Social influences and behavior. New York: Plenum Press.
Robbins, T. W., & Everitt, B. J. (1999). Motivation and reward. In Bloom, F. E., Landis, S. C., Robert, J. L., Squire, L. R., & Zigmond, M. J. (Eds.), Fundamental neuroscience (pp. 12461260). San Diego, CA: Academic Press.
Rushton, J. P., Littlefield, C. H., & Lumsden, C. J. (1986). Gene culture coevolution of complex social behavior: Human altruism and mate choice. Proceedings of the National Academy of Sciences of the United States of America, 83, 73407343.
Rushton, J. P., & Wheelwright, M. (1980). Validation of donating to charity as a measure of children's altruism. Psychological Reports, 47, 803806.
Rutter, M. (2006). Genes and Behavior. Nature–nurture interplay explained. Oxford: Blackwell.
Rutter, M. (2007). Gene–environment interdependence. Developmental Science, 10, 1218.
Sheese, B. E., Voelker, P. M., Rothbart, M. K., & Posner, M. I. (2007). Parenting quality interacts with genetic variation in dopamine receptor D4 to influence temperament in early childhood. Development and Psychopathology, 19, 10391046.
Spiecker, B. (1991). Emoties en morele opvoeding [Emotions and moral education]. Meppel, The Netherlands: Boom.
Suomi, S. (1997). Early determinants of behaviour. British Medical Bulletin, 53, 170184.
Swanson, J., Flodman, P., Kennedy, J., Spence, M. A., Moyzis, R., Schuck, S., et al. (2000). Dopamine genes and ADHD. Neuroscience and Biobehavioral Reviews, 24, 2125.
Tabachnik, B. G., & Fidell, L. S. (2006). Using multivariate statistics. Boston: Allyn & Bacon.
Tripp, G., & Wickens, J. R. (2008). Dopamine transfer deficit: A neurobiological theory of altered reinforcement mechanisms in ADHD. Journal of Child Psychology and Psychiatry, 49, 691704.
Van IJzendoorn, M. H. (1997). Attachment, emergent morality, and aggression: Toward a developmental socioemotional model of antisocial behavior. International Journal of Behavioral Development, 21, 703727.
Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., & Mesman, J. (2008). Dopamine system genes associated with parenting in the context of daily hassles. Genes, Brain and Behavior, 7, 403410.
Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., Pannebakker, F., & Out, D. (2010). In defense of situational morality: Genetic, dispositional and situational determinants of children's donating to charity. Journal of Moral Education, 39, 120.
Van IJzendoorn, M. H., Caspers, K., Bakermans-Kranenburg, M. J., Beach, S. R. H., & Philibert, R. (2010). Methylation matters: Interaction between methylation density and 5HTT genotype predicts unresolved loss or trauma. Biological Psychiatry, 68, 405407.
Van IJzendoorn, M. H., Juffer, F., & Klein Poelhuis, C. W. (2005). Adoption and cognitive development: A meta-analytic comparison of adopted and nonadopted children's IQ and school performance. Psychological Bulletin, 131, 301316.
Verschueren, K., & Marcoen, A. (1994). Test met gehechtheidsverhalen classificatiesysteem: Aanpassing van de Doll Stories Completion Task van Cassidy (1986) [Adaptation of the Doll Stories Completion Task of Cassidy (1986)]. Unpublished manuscript, Katholieke Universiteit Leuven, Center for Developmental Psychology.
Verschueren, K., & Marcoen, A. (1999). Representation of self and socioemotional competence in kindergartners: Differential and combined effects of attachment to mother and father. Child Development, 70, 183201.
Volbrecht, M. M., Lemery-Chalfant, K., Akzan, N., Zahn-Waxler, C., & Goldsmith, H. H. (2007). Examining the familial link between positive effect and empathy development in the second year. Journal of Genetic Psychology, 168, 105130.
Wachs, T. D. (1983). The use and abuse of environment in behavior–genetic research. Child Development, 54, 396407.
Wachs, T. D. (1991). Synthesis: Promising research designs, measures, and strategies. In Wachs, T. D. & Plomin, R. (Eds.), Conceptualization and measurement of organism–environment interaction (pp. 162182). Washington, DC: American Psychological Association.
Waldman, I. D. (2007). Gene–environment interactions reexamined: Does mother's marital stability interact with the dopamine D2 gene in the etiology of childhood attention-deficit/hyperactivity disorder? Development and Psychopathology, 19, 11171128.
Wang, E. T., Ding, Y.-C., Flodman, P., Kidd, J. R., Kidd, K. K., Grady, D. L., et al. (2004). The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. American Journal of Human Genetics, 74, 931944.
Wiebe, S. A., Espy, K. A., Stopp, C., Respass, J., Stewart, P., Jameson, T. R., et al. (2009). Gene–environment interactions across development: Exploring DRD2 genotype and prenatal smoking effects on self-regulation. Developmental Psychology, 45, 3144.
Williams, R. B., Marchuk, D. A., Gadde, K. M., Barefoot, J. C., Crichnik, K., Helms, M. J., et al. (2003). Serotonin-related gene polymorphisms and central nervous system serotonin function. Neuropsychopharmacology, 28, 533541.
Wolf, M., Van Doorn, G. S., & Weissing, F. J. (2008). Evolutionary emergence of responsive and unresponsive personalities. Proceedings of the National Academy of Sciences of the United States of America, 105, 1582515830.


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed