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Effects of an attachment-based intervention on daily cortisol moderated by dopamine receptor D4: A randomized control trial on 1- to 3-year-olds screened for externalizing behavior

Published online by Cambridge University Press:  07 July 2008

Marian J. Bakermans-Kranenburg*
Leiden University
Marinus H. Van IJzendoorn*
Leiden University
Judi Mesman
Leiden University
Lenneke R. A. Alink
Leiden University
Femmie Juffer
Leiden University
Address correspondence and reprint requests to: Marian Bakermans-Kranenburg or Marinus van IJzendoorn, Centre for Child and Family Studies, Leiden University, P.O. Box 9555, Leiden NL-2300 RB, The Netherlands; E-mail: or
Address correspondence and reprint requests to: Marian Bakermans-Kranenburg or Marinus van IJzendoorn, Centre for Child and Family Studies, Leiden University, P.O. Box 9555, Leiden NL-2300 RB, The Netherlands; E-mail: or


The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-repeat allele, but not in children without the DRD4 7-repeat allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-repeat DRD4 allele.

Research Article
Copyright © Cambridge University Press 2008

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This study is part of the research project on Screening and Intervention of Problem Behavior in Toddlerhood (SCRIPT). The study is supported by Grant 2200.0097 from The Netherlands Organization for Health Research and Development (ZonMw) to Marinus van IJzendoorn and Femmie Juffer. Support from The Netherlands Organization for Scientific Research NWO (Rubicon to Lenneke Alink, VENI to Judi Mesman, VIDI to Marian Bakermans-Kranenburg, and SPINOZA Prize to Marinus van IJzendoorn) is gratefully acknowledged. We thank Mirjam Stolk, Jantien van Zeijl, Femke Pijlman, and Hans Koot for their contributions to the various parts of the intervention study and Base-Clear for the genotyping. Last, but not least, we thank the parents and children who participated in our study, as well as the students who assisted in various phases of the SCRIPT project. The contributions of the first and the second author to this paper are equal.


Achenbach, T. M., & Rescorla, L. A. (2000). Manual for the ASEBA preschool forms & profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, & Families.Google Scholar
Alink, L. R. A., Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., Mesman, J., Juffer, F., & Koot, H. M. (in press). Cortisol and externalizing behavior in children and adolescents: Mixed meta-analytic evidence for the inverse relation of basal cortisol and cortisol reactivity with externalizing behavior. Developmental Psychobiology.Google Scholar
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.Google Scholar
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.Google Scholar
Bakermans-Kranenburg, M. J., Van IJzendoorn, M. H., & Juffer, F. (2003). Less is more: Meta-analyses of sensitivity and attachment interventions in early childhood. Psychological Bulletin, 129, 195215.Google Scholar
Bakermans-Kranenburg, M. J., Van IJzendoorn, M. H., Pijlman, F. T. A., Mesman, J., & Juffer, F. (2008). Differential susceptibility to intervention: Dopamine D4 receptor polymorphism (DRD4 VNTR) moderates effects on toddlers' externalizing behavior in a randomized control trial. Developmental Psychology, 44, 293300.Google Scholar
Barker, S. B., Knisely, J. S., Mccain, N. L., & Best, A. M. (2005). Measuring stress and immune response in healthcare professionals following interaction with a therapydog: A pilot study. Psychological Reports, 96, 713729.Google Scholar
Bates, J. E., Freeland, C. A. B., & Lounsbury, M. L. (1979). Measurement of infant difficultness. Child Development, 50, 794803.Google Scholar
Benjamin, J., Ebstein, R. P., & Belmaker, R. H. (2002). Personality genetics, 2002. Israel Journal of Psychiatry and Related Sciences, 39, 271279.Google Scholar
Chrousos, G. P., & Gold, P. W. (1992). The concepts of stress and stress system disorders: Overview of physical and behavioral homeostasis. Journal of the American Medical Association, 267, 12441252.Google Scholar
Cicchetti, D., & Rogosh, F. A. (2001a). Diverse patterns of neuroendocrine activity in maltreated children. Development and Psychopathology, 13, 677693.Google Scholar
Cicchetti, D., & Rogosh, F. A. (2001b). The impact of child maltreatment and psychopathology on neuroendocrine functioning. Development and Psychopathology, 13, 783804.Google Scholar
Colhoun, H. M., McKeigue, P. M., & Davey Smith, G. (2003). Problems of reporting genetic associations with complex outcomes. Lancet, 361, 865872.Google Scholar
Cruess, D. G., Antoni, M. H., Kumar, M., & Schneiderman, N. (2000). Reductions in salivary cortisol are associated with mood improvement during relaxation training among HIV-seropositive men. Journal of Behavioral Medicine, 23, 107122.Google Scholar
De Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6, 463475.Google Scholar
DeWolff, M. S., & Van IJzendoorn, M. H. (1997). Sensitivity and attachment: A meta-analysis on parental antecedents of infant attachment. Child Development, 68, 571591.Google Scholar
Dozier, M., Albus, K., Fisher, P. A., & Sepulveda, S. (2002). Interventions for foster parents: Implications for developmental theory. Development and Psychopathology, 14, 843860.Google Scholar
Dozier, M., Peloso, E., Lindhiem, O., Gordon, M. K., Manni, M., Sepulveda, S., et al. (2006). Developing evidence-based interventions for foster children: An example of a randomized clinical trial with infants and toddlers. Journal of Social Issues, 62, 767785.Google Scholar
D'souza, U. M., & Craig, I. W. (2006). Functional polymorphisms in dopamine and serotonin pathway genes. Human Mutation, 27, 113.Google Scholar
Ebstein, R. P., Benjamin, J., & Belmaker, R. H. (2002). Behavioral genetics, genomics, and personality. In Plomin, R., DeFries, J. C., Craig, I. W., & McGuffin, P. (Eds.), Behavioral genetics in the postgenomic era (pp. 365388). Washington, DC: American Psychological Association.Google Scholar
Field, T., Diego, M., & Hernandez-Reif, M. (2006). Prenatal depression effects on the fetus and newborn: A review. Infant Behavior & Development, 29, 445455.Google Scholar
Field, T., Hernandez-Reif, M., Diego, M., Feijo, L., Vera, Y., & Gil, K. (2004). Massage therapy by parents improves early growth and development. Infant Behavior & Development, 27, 435442.Google Scholar
Field, T. M., Scafidi, F., Pickens, J., Prodromidis, M., Pelaez-Nogueras, M., Torquati, J., et al. (1998). Polydrug-using adolescent mothers and their infants receiving early intervention. Adolescence, 33, 117143.Google Scholar
Fisher, P., Gunnar, M. R., Chamberlain, P., & Reid, J. B. (2000). Preventive intervention for maltreated preschool children: Impact on children's behavior, neuroendocrine activity, and foster parent functioning. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 13561364.Google Scholar
Fisher, P., Gunnar, M., Dozier, M., Bruce, J., & Pears, K. (2006). Effects of therapeutic interventions for foster children on behavioral problems, caregiver attachment, and stress regulatory neural systems. Annuals of the New York Academy of Sciences, 40, 111.Google Scholar
Fisher, P. A., & Kim, H. K. (2007). Intervention effects on foster preschoolers' attachment-related behaviors from a randomized trial. Prevention Science, 8, 161170.Google Scholar
Fries, E., Hesse, J., Hellhammer, J., & Hellhammer, D. H. (2005). A new view on hypocortisolism. Psychoneuroendocrinology, 30, 10101016.Google Scholar
Gunnar, M. R., Fisher, P. A., & The Early Experience, Stress, and Prevention Network. (2006). Bringing basic research on early experience and stress neurobiology to bear on preventive interventions for neglected and maltreated children. Development and Psychopathology, 18, 651677.Google Scholar
Gunnar, M. R., Morison, S. J., Chisholm, K., & Schuder, M. (2001). Salivary cortisol levels in children adopted from Romanian orphanages. Development and Psychopathology, 13, 611628.Google Scholar
Gunnar, M. R., & Quevedo, K. (2007). The neurobiology of stress and development. Annual Review of Psychology, 58, 145173.Google Scholar
Gunnar, M. R., & Vazquez, D. M. (2001). Low cortisol and a flattening of expected daytime rhythm: Potential indices of risk in human development. Development and Psychopathology, 13, 515538.Google Scholar
Hart, D., Burock, D., London, B., Atkins, R., & Bonilla-Santiago, G. (2005). The relation of personality types to physiological, behavioural, and cognitive processes. European Journal of Personality, 19, 391407.Google Scholar
Heim, C., Ehlert, U., & Hellhammer, D. H. (2000). The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology, 25, 135.Google Scholar
Heim, C., Newport, D. J., Heit, S., Graham, Y. P., Wilcox, M., Bonsall, R., et al. (2000). Pituitary–adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. Journal of the American Medical Association, 284, 592597.Google Scholar
Hoffman, M. L. (1984). Empathy, its limitations, and its role in a comprehensive moral theory. In Gewirtz, J. L. & Kurtines, W. (Eds.), Morality, moral development, and moral behavior (pp. 283302). New York: Wiley.Google Scholar
Juffer, F., Bakermans-Kranenburg, M. J., & Van IJzendoorn, M. H. (2005). The importance of parenting in the development of disorganized attachment: Evidence from a preventive intervention study in adoptive families. Journal of Child Psychology and Psychiatry, 46, 263274.Google Scholar
Juffer, F., Bakermans-Kranenburg, M. J., & Van IJzendoorn, M. H. (2008). Promoting positive parenting: An attachment-based intervention. New York: Taylor & Francis.Google Scholar
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.Google Scholar
Kalinauskiene, L., Cekuoliene, D., Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., & Juffer, F. (July, 2007). A short term video feedback intervention to promote maternal sensitivity and infant attachment security: The Vilnius study. Poster presented at the International Attachment Conference, Lisbon, July 10–13, 2007.Google Scholar
Kamei, T., Torui, Y., Kimura, H., Ohno, S., Kumano, H., & Kimura, K. (2000). Decrease in serum cortisol during yoga exercise is correlated with alpha wave activation. Perceptual and Motor Skills, 90, 10271032.Google Scholar
Kariyawasam, S. H., Zaw, F., & Handley, S. L. (2002). Reduced salivary cortisol in children with comorbid attention deficit hyperactivity disorder and oppositional defiant disorder. Neuroendocrinology Letters, 23, 4548.Google Scholar
Kirschbaum, C., & Hellhammer, D. H. (1989). Salivary cortisol in psychobiological research: An overview. Neuropsychobiology, 22, 150169.Google Scholar
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.Google Scholar
Klein Velderman, M., Bakermans-Kranenburg, M. J., Juffer, F., Van IJzendoorn, M. H., Mangelsdorf, S. C., & Zevalkink, J. (2006). Preventing preschool externalizing behavior problems through video-feedback intervention in infancy. Infant Mental Health Journal, 27, 466493.Google Scholar
Kohnstamm, G. A. (1984). Bates' Infant Characteristics Questionnaire (ICQ) in The Netherlands. Paper presented at the fourth biennial International Conference on Infant Studies, New York.Google Scholar
Koot, H. M., Van den Oord, E. J. C. G., Verhulst, F. C., & Boomsma, D. I. (1997). Behavioral and emotional problems in young preschoolers: Cross-cultural testing of the validity of the Child Behavior Checklist/2–3. Journal of Abnormal Child Psychology, 25, 183196.Google Scholar
Lee, M. S., Kang, C. W., Lim, H. J., & Lee, M. S. (2004). Effects of Qi-training on anxiety and plasma concentrations of cortisol, ACTH, and aldosterone: A randomized placebo-controlled pilot study. Stress and Health, 20, 243248.Google Scholar
Lieberman, A. F. (2004). Child–parent psychotherapy. A relationship-based approach to the treatment of mental health disorders in infancy and early childhood. In Sameroff, A. J., McDonough, S. C., & Rosenblum, K. L. (Eds.), Treating parent–infant relationship problems (pp. 97122). New York: Guilford Press.Google Scholar
Lindblad, F., Hogmark, Å., & Theorell, T. (2007). Music intervention for 5th and 6th graders—Effects on development and cortisol secretion. Stress and Health, 23, 914.Google Scholar
Luan, J. A., Wong, M. Y., Day, N. E., & Wareham, N. J. (2001). Sample size determination for studies of gene–environment interaction. International Journal of Epidemiology, 30, 10351040.Google Scholar
McBurnett, K., Lahey, B. B., Capasso, L., & Loeber, R. (1996). Aggressive symptoms and salivary cortisol in clinic-referred boys with conduct disorder. Annals of the New York Academy of Sciences, 794, 169178.Google Scholar
McKinney, C. H., Antoni, M. H., Kumar, M., Tims, F. C., & McCabe, P. M. (1997). Effects of Guided Imagery and Music (GIM) therapy on mood and cortisol in healthy adults. Health Psychology, 16, 390400.Google Scholar
Meaney, M. J. (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience, 24, 11611192.Google Scholar
Meaney, M. J. (2007, April). Maternal regulation of individual differences in reproductive behavior in the female offspring. Paper presented at the biennial meeting of the Society for Research in Child Development, Boston, March 29–April 1, 2007.Google Scholar
Meaney, M. J., & Szyf, M. (2005). Maternal care as a model for experience-dependent chromatin plasticity? Trends in Neurosciences, 28, 456463.Google Scholar
Mesman, J., Stolk, M. N., Van Zeijl, J., Alink, L. R. A., Juffer, F., Bakermans-Kranenburg, M. J. (2008). Extending the video-feedback intervention to sensitive discipline: The early prevention of antisocial behavior. In Juffer, F., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (Eds.), Promoting positive parenting: An attachment-based intervention. New York: Taylor & Francis.Google Scholar
Michel, G. F., & Moore, C. L. (1995). Developmental psychobiology. An interdisciplinary science. Cambridge, MA: MIT.Google Scholar
Moffitt, T. E. (2005). The new look of behavioral genetics in developmental psychopathology: Gene–environment interplay in antisocial behaviors. Psychological Bulletin, 131, 533554.Google Scholar
Moffitt, T. E., Caspi, A., & Rutter, M. (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62, 473481.Google Scholar
Pajer, K., Gardner, W., Rubin, R. T., Perel, J., & Neal, S. (2001). Decreased cortisol levels in adolescent girls with conduct disorder. Archives of General Psychiatry, 58, 297302.Google Scholar
Patterson, G. R. (1982). Coercive family process: A social learning approach. Eugene, OR: Castalia.Google Scholar
Pawlow, L. A., & Jones, G. E. (2005). The impact of abbreviated progressive muscle relaxation on salivary cortisol and salivary immunoglobulin a (sIga). Applied Psychophysiology and Biofeedback 30, 375387.Google Scholar
Pivonello, R., Ferone, D., Lombardi, G., Colao, A., Lamberts, S. W. J., & Hofland, L. J. (2007). Novel insights in dopamine receptor physiology. European Journal of Endocrinology, 156, 1321.Google Scholar
Pruessner, J. C., Kirschbaum, C., Meinlschmid, G., & Hellhammer, D. H. (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology, 28, 916931.Google Scholar
Robbins, T. W., & Everitt, B. J. (1999). Motivation and reward. In Zigmond, M. J., Bloom, F. E., Landis, S. C., Roberts, J. L., & Squire, L. R. (Eds.), Fundamental neuroscience (pp. 12461260). San Diego, CA: Academic Press.Google Scholar
Rutter, M. (2003). Commentary: Nature–nurture interplay in emotional disorders. Journal of Child Psychology and Psychiatry, 44, 934944.Google Scholar
Rutter, M. (2006). Genes and Behavior. Nature–nurture interplay explained. Oxford: Blackwell.Google Scholar
Savitz, J., Solms, M., & Ramesar, R. (2006). The molecular genetics of cognition: Dopamine, COMT and BDNF. Genes, Brain and Behavior 5, 311328.Google Scholar
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews, 21, 5589.Google Scholar
Scerbo, A. S., & Kolko, D. J. (1994). Salivary testosterone and cortisol in disruptive children: Relationship to aggressive, hyperactive, and internalizing behaviors. Journal of the American Academy of Child & Adolescent Psychiatry, 33, 11741184.Google Scholar
Schmidt, L. A., Fox, N. A., Rubin, K. H., Hu, S., & Hamer, D. H. (2002). Molecular genetics of shyness and aggression in preschoolers. Personality and Individual Differences, 33, 227238.Google Scholar
Schulz, K. P., Halperin, J. M., Newcorn, J. H., Sharma, V., & Gabriel, S. (1997). Plasma cortisol and aggression in boys with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 605609.Google Scholar
Spieker, S., Nelson, D., DeKlyen, M., & Staerkel, F. (2005). Enhancing early attachments in the context of early head start: Can programs emphasizing family support improve rates of secure infant–mother attachments in low-income families? In Berlin, L. J., Ziv, Y., Amaya-Jackson, L., & Greenberg, M. T. (Eds.), Enhancing early attachments: Theory, research, intervention, and policy (pp. 250275). New York: Guilford Press.Google Scholar
Stein, A., Woolley, H., Senior, R., Hertzmann, L., Lovel, M., Lee, J., et al. (2006). Treating disturbances in the relationship between mothers with bulimic eating disorders and their infants: A randomized, controlled trial of video feedback. The American Journal of Psychiatry, 163, 899906.Google Scholar
Tabachnick, B. G., & Fidell, L. S. (2001). Using multivariate statistics (4th ed.). London: Allyn & Bacon.Google Scholar
Urizar, G. G., Milazzo, M., Le, H. N., Delucchi, K., Sotelo, R., & Munoz, R. F. (2004). Impact of stress reduction instructions on stress and cortisol levels during pregnancy. Biological Psychology, 67, 275282.Google Scholar
Van Bokhoven, I., Van Goozen, S. H. M., Van Engeland, H., Schaal, B., Arseneault, L., Seguin, J. R., et al. (2005). Salivary cortisol and aggression in a population-based longitudinal study of adolescent males. Journal of Neural Transmission, 112, 10831096.Google Scholar
Van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2006). DRD4 7-repeat polymorphism moderates the association between maternal unresolved loss or trauma and infant disorganization. Attachment & Human Development, 8, 291307.Google Scholar
Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., & Juffer, F. (2005). Why less is more: From the dodo bird verdict to evidence-based interventions on sensitivity and early attachments. In Berlin, L. J., Ziv, Y., Amaya-Jackson, L., & Greenberg, M. T. (Eds.), Enhancing early attachments: Theory, research, intervention, and policy (pp. 297312). New York: Guilford Press.Google Scholar
Van Zeijl, J., Mesman, J., Stolk, M. N., Alink, L. R. A., Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., et al. (2006). Terrible ones? Assessment of externalizing behaviors in infancy with the Child Behavior Checklist. Journal of Child Psychology and Psychiatry, 47, 801810.Google Scholar
Van Zeijl, J., Mesman, J., Van IJzendoorn, M. H., Bakermans-Kranenburg, M. J., Juffer, F, Stolk, M. N., et al. (2006). Attachment-based intervention for enhancing sensitive discipline in mothers of one- to three-year-old children at risk for externalizing behavior problems: A randomized controlled trial. Journal of Consulting and Clinical Psychology, 74, 9941005.Google Scholar
West, J., Otte, C., Geher, K., Johnson, J., & Mohr, D. C. (2004). Effects of Hatha yoga and African dance on perceived stress, affect, and salivary cortisol. Annals of Behavioral Medicine, 28, 114118.Google Scholar
Wright, J. M. (2000). Stress responses of adolescents as a function of anger status and its concomittants. Dissertation Abstracts International, 62, 4811B.Google Scholar
Wong, M. Y., Day, N. E., Luan, J. A., Chan, K. P., & Wareham, N. J. (2003). The detection of gene–environment interaction for continuous traits: Should we deal with measurement error by bigger studies or better measurement? International Journal of Epidemiology, 32, 5157.Google Scholar