Skip to main content Accessibility help

Dopamine receptor D2 (DRD2), dopamine transporter solute carrier family C6, member 4 (SLC6A3), and catechol-O-methyltransferase (COMT) genes as moderators of the relation between maternal history of maltreatment and infant emotion regulation

  • Vanessa Villani (a1), Jaclyn Ludmer (a1), Andrea Gonzalez (a2), Robert Levitan (a3) (a4), James Kennedy (a3) (a4), Mario Masellis (a5), Vincenzo S. Basile (a5), Christine Wekerle (a2) and Leslie Atkinson (a1)...


Although infants less than 18 months old are capable of engaging in self-regulatory behavior (e.g., avoidance, withdrawal, and orienting to other aspects of their environment), the use of self-regulatory strategies at this age (as opposed to relying on caregivers) is associated with elevated behavioral and physiological distress. This study investigated infant dopamine-related genotypes (dopamine receptor D2 [DRD2], dopamine transporter solute carrier family C6, member 4 [SLC6A3], and catechol-O-methyltransferase [COMT]) as they interact with maternal self-reported history of maltreatment to predict observed infant independent emotion regulation behavior. A community sample (N = 193) of mother–infant dyads participated in a toy frustration challenge at infant age 15 months, and infant emotion regulation behavior was coded. Buccal cells were collected for genotyping. Maternal maltreatment history significantly interacted with infant SLC6A3 and COMT genotypes, such that infants with more 10-repeat and valine alleles of SLC6A3 and COMT, respectively, relative to infants with fewer or no 10-repeat and valine alleles, utilized more independent (i.e., maladaptive) regulatory behavior if mother reported a more extensive maltreatment history, as opposed to less. The findings indicate that child genetic factors moderate the intergenerational impact of maternal maltreatment history. The results are discussed in terms of potential mechanism of Gene × Environment interaction.


Corresponding author

Address correspondence and reprint requests to: Leslie Atkinson, Department of Psychology, Ryerson University, 350 Victoria Street, Toronto, Ontario M5B 2K3, Canada; E-mail:


Hide All

This research was supported by funds from the Canadian Institutes of Health Research (MOP-64301), Ryerson University, and the Centre for Addiction and Mental Health. The authors acknowledge the contributions of Dr. Susan Goldberg, a Co-Principal Investigator on the grant that supported this work. She died prior to completion of the project, but her influence pervades the manuscript. We thank Emilie Boucher and Monica Tan, as well as other research assistants and students who contributed a great many hours to this project. Of course, we also greatly appreciate the time and effort of the mothers and babies who volunteered to participate in this project.



Hide All
Ainsworth, M. D. S., Blehar, M. C., Waters, E., & Wall, S. (1978). Patterns of attachment: A psychological study of the strange situation. Hillsdale, NJ: Erlbaum.
Atkinson, L., Gonzalez, A., Kashy, D. A., Basile, V. S., Masellis, M., Pereira, J., … Levitan, R. (2013). Maternal sensitivity and infant and mother adrenocortical function across challenges. Psychoneuroendocrinology, 38, 29432951. doi:10.1016/j.psyneuen.2013.08.001
Atkinson, L., Jamieson, B., Khoury, J., Ludmer, J., & Gonzalez, A. (2016). Stress physiology in infancy and early childhood: Cortisol flexibility, attunement and coordination. Journal of Neuroendocrinology, 28. doi:10.1111/jne.12408
Atkinson, L., Paglia, A., Coolbear, J., Niccols, A., Poulton, L., Leung, E., & Chisholm, V. C. (2000). L’ évaluation de la sensibilité maternelle dans le contexte de la sécurité d'attachment: Une méta-analyse [Assessing maternal sensitivity in the context of attachment security: A meta-analysis]. In Tarabulsy, G. M., Larose, S., Pederson, D. R., & Moran, G. (Eds.), Attachement et développement: Le rôle des premieres relations dans le développement humain [Attachment and development: The role of first relationships in human development] (pp. 2756). Québec: Presses de l'Université du Québec.
Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Manual for the Beck Depression Inventory (2nd ed.). San Antonio, TX: Psychological Corporation.
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908. doi:10.1037/a0017376
Bernstein, D. P., & Fink, L. (1998). Childhood Trauma Questionnaire: A retrospective self-report. Professional manual. New York: Psychological Corporation.
Bernstein, D. P., Fink, L., Handelsman, L., Foote, J., Lovejoy, M., Wenzel, K., … Ruggeriero, J. (1994). Initial reliability and validity of a new retrospective measure of child abuse and neglect. American Journal of Psychiatry, 151, 11321136. doi:10.1176/ajp.151.8.1132
Bernstein, D. P., Stein, J. A., Newcomb, M. D., Walker, E., Pogge, D., Ahluvalia, T., … Zule, W. (2003). Development and validation of a brief screening version of the childhood trauma questionnaire. Child Abuse and Neglect, 27, 169190. doi:10.1016/S0145-2134(02)00541-0
Bos, S. C., Pereira, A. T., Marques, M., Maia, B., Soares, M. J., Valente, J., … Azevedo, M. H. (2009). The BDI-II factor structure in pregnancy and postpartum: Two or three factors? European Psychiatry, 24, 334340. doi:10.1016/j.eurpsy.2008.10.003
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., … Heim, C. (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. doi:10.1017/S0954579411000162
Brand, S. R., & Brennan, P. A. (2009). Impact of antenatal and postpartum maternal mental illness: How are the children? Clinical Obstetrics and Gynecology, 52, 441455. doi:10.1097/GRF.0b013e3181b52930
Braungart-Rieker, J. M., & Stifter, C. A. (1996). Infants’ responses to frustrating situations: Continuity and change in reactivity and regulation. Child Development, 67, 17671779. doi:10.1111/j.1467-8624.1996.tb01826.x
Brooks, K., Xu, X., Zhou, K., Neale, B., Lowe, N., Aneey, R., … Johansson, L. (2006). The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: Association signals in DRD4, DAT1, and 16 other genes. Molecular Psychiatry, 11, 934953. doi:10.1038/
Brummelte, S., & Galea, L. A. M. (2010). Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones. Progress in Neuro-Psychoparmacology and Biological Psychiatry, 34, 766776. doi:10.1016/j.pnpbp.2009.09.006
Calkins, S. D., Gill, K. L., Johnson, M. C., & Smith, C. L. (1999). Emotional reactivity and emotional regulation strategies as predictors of social behaviour with peers during toddlerhood. Social Development, 8, 310334. doi:10.1111/1467-9507.00098
Cardon, L. R., & Palmer, L. J. (2003). Population stratification and spurious allelic association. Lancet, 361, 598604. doi:10.1016/S0140-6736(03)12520-2
Carpenter, L. L., Carvalho, J. P., Tyrka, A. R., Wier, L. M., Mello, A. F., Mello, M. F., … Price, L. H. (2007). Decreased adrenocorticotropic hormone and cortisol responses to stress in health adults reporting significant childhood maltreatment. Biological Psychiatry, 62, 10801087. doi:10.1016/j.biopsych.2007.05.002
Cicchetti, D. (Ed.). (1989). Rochester symposium on developmental psychopathology: The emergence of a discipline (Vol. 1). Hillsdale, NJ: Erlbaum.
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. doi:10.1017/S0954579406060329
Cicchetti, D., & Toth, S. L. (2009). The past achievements and future promises of developmental psychopathology: The coming of age of a discipline. Journal of Child Psychology and Psychiatry, 50, 1625. doi:10.1111/j.1469-7610.2008.01979.x
Cirulli, F., Berry, A., & Alleva, E. (2003). Early disruption of the mother–infant relationship: Effects on brain plasticity and implications for psychopathology. Neuroscience & Biobehavioral Reviews, 27, 7382. doi:10.1016/S0149-7634(03)00010-1
Collins, L. M., Schafer, J. L., & Kam, C. M. (2001). A comparison of inclusive and restrictive strategies in modern missing data procedures. Psychological Methods, 6, 330351. doi:10.1037//1082-989X.6.4.330
Collishaw, S., Dunn, J., O'Connor, T. G., & Golding, J. (2007). Maternal childhood abuse and offspring adjustment over time. Development and Psychopathology, 19, 367383. doi:10.1017/S0954579407070186
Diener, M. L., Mangelsdorf, S. C., McHale, J. L., & Frosch, C. A. (2002). Infants’ behavioral strategies for emotion regulation with fathers and mothers: Associations with emotional expressions and attachment quality. Infancy, 3, 153174. doi:10.1207/S15327078IN302_3
Dozois, D. J. A., Dobson, K. S., & Ahnberg, J. L. (1998). A psychometric evaluation of the Beck Depression Inventory—II. Psychological Assessment, 10, 8389.
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049. doi:10.1176/appi.aip.2011.11020191
Eisenberg, N., Cumberland, A., Spinrad, T. L., Fabes, R. A., Shepard, S. A., Reiser, M., … Guthrie, I. K. (2001). The relations of regulation and emotionality to children's externalizing and internalizing problem behavior. Child Development, 72, 11121134. doi:10.1111/1467-8624.00337
Enlow, M. B., Kullowatz, A., Staudenmayer, J., Spasojevic, J., Ritz, T., & Wright, R. J. (2009). Associations of maternal lifetime trauma and perinatal traumatic stress symptoms with infant cardiorespiratory reactivity to psychological challenge. Psychosomatic Medicine, 71, 607614. doi:10.1097/PSY.0b013e3181ad1c8b
Frigerio, A., Ceppi, E., Rusconi, M., Giorda, R., Raggi, M. E., & Fearon, P. (2009). The role played by the interaction between genetic factors and attachment in the stress response in infancy. Journal of Child Psychology and Psychiatry, 50, 15131522. doi:10.1111/j.1469-7610.2009.02126.x
Galvin, M., Shekhar, A., Simon, J., Stilwell, B., Eyck, R. T., Laite, G., … Blix, S. (1991). Low dopamine-beta-hydroxylase: A biological sequale of abuse and neglect? Psychiatry Research, 39, 111.
Hane, A. A., & Philbrook, L. E. (2012). Beyond licking and grooming: Maternal regulation of infant stress in the context of routine care. Parenting: Science and Practice, 12, 144153. doi:10.1080/15295192.2012.683341
Holmboe, K., Nemoda, Z., Fearon, R. M. P., Csibra, G., Sasvari-Szakely, M., & Johnson, M. H. (2010). Polymorphisms in dopamine system genes are associated with individual differences in attention in infants. Developmental Psychology, 46, 404416. doi:10.1037/a0018180
Keller, M. C. (2014). Gene × Environment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75, 1824. doi:10.1016/j.biopsych.2013.09.006
Khoury, J. E., Gonzalez, A., Levitan, R., Masellis, M., Basile, V., & Atkinson, L. (2015). Infant emotion regulation strategy moderates relations between self-reported maternal depressive symptoms and infant HPA activity. Infant and Child Development, 25, 6483. doi:10.1002/icd.1916
Kopp, C. (1989). Regulation of distress and negative emotions: A development view. Developmental Psychology, 25, 243254.
Lam, S., Dickerson, S. S., Zoccola, P. M., & Zalvidar, F. (2009). Emotion regulation and cortisol reactivity to a social-evaluative speech task. Psychoneuroendocrinology, 34, 13551362. doi:10.1016/j.psyneuen.2009.04.006
Laucht, M., Skowronek, M. H., Becker, K., Schmidt, M. H., Esser, G., Schulze, T. G., & Rietschel, M. (2007). Interacting effects of dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Archives of General Psychiatry, 64, 585590.
Little, R. J. (1988). A test of missing completely at random for multivariate data with missing values. Journal of the American Statistical Association, 83, 11981202.
Ludmer, J. A., Levitan, R., Gonzalez, A., Kennedy, J., Villani, V., Masellis, M., … Atkinson, L. (2015). DRD2 and SLC6A3 moderate impact of maternal depressive symptoms on infant cortisol. Psychoneuroendocrinology, 62, 243251. doi:10.1016/j.psyneuen.2015.08.026
Manian, N., & Bornstein, M. H. (2009). Dynamics of emotion regulation in infants of clinically depressed and nondepressed mothers. Journal of Child Psychology and Psychiatry, 50, 14101418. doi:10.1111/j.1469-7610.2009.02166.x
Markant, J., Cicchetti, D., Hetzel, S., & Thomas, K. M. (2014). Contributions of COMT Val158Met to cognitive stability and flexibility in infancy. Developmental Science, 17, 396411. doi:10.1111/desc.12128
Meaney, M. J., Brake, W., & Gratton, A. (2002). Environmental regulation of the development of mesolimbic dopamine systems: A neurobiologicqal mechanism for vulnerability to drug abuse. Psychoneuroendocrinology, 27, 127138.
Miller, E. A., Green, A. E., Fettes, D. L., & Aarons, G. A. (2011). Prevalence of maltreatment among youths in public sectors of care. Child Maltreatment, 16, 196204. doi:10.1177/1077559511415091
Mills-Koonce, W., Propper, C. B., Gariepy, J., Blair, C., Garrett-Peters, P., & Cox, M. J. (2007). Bidirectional genetic and environmental influences on mother and child behavior: The family system as the unit of analyses. Development and Psychopathology, 19, 10731087. doi:10.1017/S0954579407000545
Min, M. O., Singer, L. T, Minnes, S., Kim, H., & Short, E. (2012). Mediating links between maternal childhood trauma and preadolescent behavioral adjustment. Journal of Interpersonal Violence, 28, 831851. doi:10.1177/0886260512455868
Miranda, J. K., de la Osa, N., Granero, R., & Ezpeleta, L. (2013). Maternal childhood abuse, intimate partner violence, and child psychopathology: The mediator role of mothers’ mental health. Violence Against Women, 19, 5068. doi:10.1177/1077801212475337
Murray, L., & Cooper, P. J. (1997). Postpartum depression and child development. Psychological Medicine, 27, 253260.
Paivio, S. C., & Cramer, K. M. (2004). Factor structure and reliability of the Childhood Trauma Questionnaire in a Canadian undergraduate student sample. Child Abuse and Neglect, 28, 889904.
Pears, K. C., & Capaldi, D. M. (2001). Intergenerational transmission of abuse: A two-generational prospective study of an at-risk sample. Child Abuse and Neglect, 25, 14391461. doi:10.1016/S0145-2134(01)00286-1
Pederson, D. R., Moran, G., Sitko, C., & Campbell, K. (1990). Maternal sensitivity and the security of infant-mother attachment: A Q-sort study. Child Development, 61, 19741983.
Pereira, J., Vickers, K., Atkinson, L., Gonzalez, A., Wekerle, C., & Levitan, R. (2012). Parenting stress mediates between maternal maltreatment history and maternal sensitivity in a community sample. Child Abuse and Neglect, 36, 433437. doi:10.1016/j.chiabu.2012.01.006
Prentice, D. A., & Miller, D. T. (1992). When small effects are impressive. Psychological Bulletin, 112, 160164.
Propper, C., Moore, G. A., Mills-Koonce, W., Halpern, C. T., Hill-Soderlund, A., Calkins, S. D., … Cox, M. (2008). Gene-environment contributions to the development of infant vagal reactivity: The interaction of dopamine and maternal sensitivity. Child Development, 79, 13771394. doi:10.1111/j.1467-8624.2008.01194
Roberts, R., O'Connor, T., Dunn, J., & Golding, J. (2004). The effects of child sexual abuse in later family life; mental health, parenting and adjustment of offspring. Child Abuse and Neglect, 28, 525545. doi:10.1016/j.chiabu.2003.07.006
Roisman, G. I., Newman, D. A., Fraley, C., Haltigan, J. D., Groh, A. M., & Haydon, K. C. (2012). Distinguishing differential susceptibility from diathesis–stress: Recommendations for evaluating interaction effects. Development and Psychopathology, 24, 389409. doi:10.1017/S0954579412000065
Rothbart, M., & Derryberry, D. (1981). Development of individual differences in infant temperament. In Lamb, M. & Brown, A. (Eds.), Advances in developmental psychology (Vol. 1, pp. 3787). Hillsdale, NJ: Erlbaum.
Salgado-Pineda, P., Delaveau, P., Blin, O., & Nieoullon, A. (2005). Dopaminergic contribution to the regulation of emotional perception. Clinical Neuropharmacology, 28, 228237.
Schofield, T. J., Lee, R. D., & Merrick, M. T. (2013). Safe, stable, nurturing relationships as a moderator of intergenerational continuity of child maltreatment: A meta-analysis. Journal of Adolescent Health, 53, 532538. doi:10.1016/j.adohealth.2013.05.004
Spinhoven, P., Penninx, B. W., Hickendorff, M., van Hemert, A. M., Bernstein, D. P., & Elzinga, B. M. (2014). Childhood Trauma Questionnaire: Factor structure, measurement invariance, and validity across emotional disorders. Psychological Assessment, 26, 717729. doi:10.1037/pas0000002
Stifter, C. A., & Braungart, J. M. (1995). The regulation of negative reactivity in infancy: Function and development. Developmental Psychology, 31, 448455.
Streiner, D. L. (2003). Being inconsistent about consistency: When coefficient alpha does and doesn't matter. Journal of Personality Assessment, 80, 217222.
Streiner, D. L., & Norman, G. R. (2008). Health measurement scales: A practical guide to their development and use. New York: Oxford University Press.
Vandenbergh, D. J., Persico, A. M., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., & Uhi, G. R. (1992). Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics, 14, 11041106.
Voelker, P., Sheese, B. E., Rothbart, M. K., & Posner, M. I. (2009). Variations in catechol-O-methyltransferase gene interact with parenting to influence attention in early development. Neuroscience, 164, 121130. doi:10.1016/j.neuroscience.2009.05.059
Wager, T. D., Davidson, M. L., Hughes, B. L., Lindquist, M. A., & Ochsner, K. N. (2008). Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron, 59, 10371050.

Dopamine receptor D2 (DRD2), dopamine transporter solute carrier family C6, member 4 (SLC6A3), and catechol-O-methyltransferase (COMT) genes as moderators of the relation between maternal history of maltreatment and infant emotion regulation

  • Vanessa Villani (a1), Jaclyn Ludmer (a1), Andrea Gonzalez (a2), Robert Levitan (a3) (a4), James Kennedy (a3) (a4), Mario Masellis (a5), Vincenzo S. Basile (a5), Christine Wekerle (a2) and Leslie Atkinson (a1)...


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