Skip to main content

Advertisement

SpringerLink
Log in

Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers

  • Original Contribution
  • Published:
European Child & Adolescent Psychiatry Aims and scope Submit manuscript

Abstract

Research consistently chronicles a variety of mental health difficulties that plague institutionally reared children, including attention-deficit/hyperactivity disorder (ADHD), even if not all institutionalized children evince such problems. In seeking to extend work in this area, this research on gene × environment (GXE) interplay investigated whether the effect of the quality of institutional care—most notably, caregiver intrusiveness—on ADHD symptoms is moderated by the serotonin transporter (5-HTTLPR) polymorphism. One hundred and twenty-seven institutionalized preschoolers were evaluated using the Child Behavior Checklist. Caregiver-rated attention problems and hyperactivity were unrelated to both 5-HTTLPR polymorphism and caregiver intrusiveness. A significant GXE effect, independent of age at placement or duration of institutionalization, emerged, however, consistent with the differential-susceptibility hypothesis: s/s homozygotes manifest the most and least ADHD symptoms when they experienced, respectively, more and less intrusive caregiving. These results provide new insight into the reasons why some institutionalized children, but not others, exhibit ADHD symptoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. UNICEF (2010) At home or in a home? Formal care and adoption of children in Eastern Europe and Central Asia. http://www.unicef.org/ceecis/At_home_or_in_a_home_report.pdf. Accessed 7 Sept 2015

  2. Instituto de Segurança Social (2014) Caracterização anual da situação de acolhimento das crianças e jovens [Annual characterization of institutional care of children and young people]. http://www4.seg-social.pt/documents/10152/13326/Relatorio_CASA_2013. Accessed 7 Sept 2015

  3. Van Ijzendoorn M, Palacios J, Sonuga-Barke E et al (2011) Children in institutional care: delayed development and resilience. Monogr Soc Res Child Dev 76:8–30. doi:10.1111/j.1540-5834.2011.00626.x

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gunnar M, Van Dulmen M, The International Adoption Project Team (2007) Behavior problems in post institutionalized internationally adopted children. Dev Psychopathol 19:129–148. doi:10.1017/S0954579407070071

    Article  PubMed  Google Scholar 

  5. Sheridan MA, Drury S, McLaughlin KA et al (2010) Early institutionalization: neurobiological consequences and genetic modifiers. Neuropsychol Rev 20:414–429. doi:10.1007/s11065-010-9152-8

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zeanah C, Egger H, Smyke AT et al (2009) Institutional rearing and psychiatric disorders in Romanian preschool children. Am J Psychiatry 166:777–785. doi:10.1176/appi.ajp.2009.08091438

    Article  PubMed  Google Scholar 

  7. Kreppner J, Rutter M, Beckett C et al (2007) Normality and impairment following profound early institutional deprivation: a longitudinal follow-up into early adolescence. Dev Psychol 43:931–946. doi:10.1037/0012-1649.43.4.931

    Article  PubMed  Google Scholar 

  8. Rutter M, Kreppner J, O’Connor TG et al (2001) Specificity and heterogeneity in children’s responses to profound privation. Br J Psychiatry 179:97–103. doi:10.1192/bjp.179.2.97

    Article  CAS  PubMed  Google Scholar 

  9. Stevens S, Sonuga-Barke E, Kreppner J et al (2008) Inattention/overactivity following early severe institutional deprivation: presentation and associations in early adolescence. J Abnorm Child Psychol 36:385–398. doi:10.1007/s10802-007-9185-5

    Article  PubMed  Google Scholar 

  10. Wiik KL, Loman M, Van Ryzin MJ et al (2011) Behavioral and emotional symptoms of post-institutionalized children in middle childhood. J Child Psychol Psychiatry 52:56–63. doi:10.1111/j.1469-7610.2010.02294.x

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kreppner J, O’Connor TG, Rutter M (2001) Can inattention/overactivity be an institutional deprivation syndrome? J Abnorm Child Psychol 29:513–528. doi:10.1023/A:1012229209190

    Article  CAS  PubMed  Google Scholar 

  12. Kumsta R, Kreppner J, Rutter M et al (2010) Deprivation-specific psychological patterns. Monogr Soc Res Child Dev 75:48–78. doi:10.1111/j.1540-5834.2010.00550.x

    Article  PubMed  Google Scholar 

  13. Bobb AJ, Castellanos FX, Addington AM et al (2006) Molecular genetic studies of ADHD: 1991 to 2004. Am J Med Genet B Neuropsychiatr Genet 141b:551–565

    Article  CAS  Google Scholar 

  14. Wallis D, Russell HF, Muenke M (2008) Review: genetics of attention deficit/hyperactivity disorder. J Pediatr Psychol 33:1085–1099. doi:10.1093/jpepsy/jsn049

    Article  PubMed  Google Scholar 

  15. Wu J (2012) Role of dopamine receptors in ADHD: a systematic meta-analysis. Mol Neurobiol 45:605–620. doi:10.1007/s12035-012-8278-5

    Article  CAS  PubMed  Google Scholar 

  16. Smith TF (2010) Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: stronger association with AD/HD combined type. Am J Med Genet B Neuropsychiatr Genet B 153B:1189–1199. doi:10.1002/ajmg.b.31090

    CAS  Google Scholar 

  17. Heils A, Teufel A, Petri S et al (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66:2621–2624

    Article  CAS  PubMed  Google Scholar 

  18. Gatt J, Burton K, Williams L, Schofield P (2015) Specific and common genes implicated across major mental disorders: a review of meta-analytic studies. J Psychiatr Res 60:1–13. doi:10.1016/j.jpsychires.2014.09.014

    Article  PubMed  Google Scholar 

  19. Gadow K, DeVicent CJ, Siegal V et al (2013) Allelic-specific association of 5-HTTLPR/rs25531 with ADHD and autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 40:292–297. doi:10.1016/j.pnpbp.2012.10.019

    Article  CAS  PubMed  Google Scholar 

  20. Manor I, Eisenberg J, Tyano S et al (2001) Family-based association study of serotonin transporter promoter region polymorphism (5-HTTLPR) in attention deficit hyperactivity disorder. Am J Med Genet A 105:91–95

    Article  CAS  Google Scholar 

  21. Wargelius HL, Malmberg K, Larsson JO et al (2012) Associations of MAOA-VNTR or 5HTT-LPR alleles with attention-deficit hyperactivity disorder symptoms are moderated by platelet monoamine oxidase B activity. Psychiatr Genet 22:42–45. doi:10.1097/YPG.0b013e328347c1ab

    Article  CAS  PubMed  Google Scholar 

  22. Xu X, Mill J, Chen C, Brookes K, Taylor E, Asherson P (2005) Family-based association study of serotonin transporter gene polymorphisms in attention deficit hyperactivity disorder: no evidence for association in UK and Taiwanese samples. Am J Med Genet B: Neuropsychiatr Genet 139B:11–13. doi:10.1002/ajmg.b.30203

    Article  CAS  Google Scholar 

  23. Caspi A, Hariri A, Holmes A et al (2010) Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 167:509–527. doi:10.1176/appi.ajp.2010.09101452

    Article  PubMed  PubMed Central  Google Scholar 

  24. Van IJzendoorn MH, Belsky J, Bakermans-Kranenburg MJ (2012) Serotonin transporter genotype 5HTTLPR as a marker of differential susceptibility? A meta-analysis of child and adolescent gene-by-environment studies. Transl Psychiatry 2:e147. doi:10.1038/tp.2012.73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Retz W, Freitag CM, Retz-Junginger P et al (2008) A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: interaction with adverse childhood environment. Psychiatry Res 158:123–131

    Article  CAS  PubMed  Google Scholar 

  26. Kumsta R, Stevens S, Brookes K et al (2010) 5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study. J Child Psychol Psychiatry 51:755–762. doi:10.1111/j.1469-7610.2010.02249.x

    Article  PubMed  Google Scholar 

  27. Drury SS, Gleason MM, Theall KP et al (2012) Genetic sensitivity to the caregiving context: the influence of 5HTTLPR and BDNF val66met on indiscriminate social behavior. Physiol Behav 106:728–735. doi:10.1016/j.physbeh.2011.11.014

    Article  CAS  PubMed  Google Scholar 

  28. Belsky J (2005) Differential susceptibility to rearing influences: an evolutionary hypothesis and some evidence. In: Ellis B, Bjorklund D (eds) Origins of the social mind: evolutionary psychology and child development. Guildford, New York, pp 139–163

    Google Scholar 

  29. Belsky J, Bakermans-Kranenburg MJ, Van IJzendoorn MH (2007) For better and for worse differential susceptibility to environmental influences. Curr Dir Psychol Sci 16:300–304. doi:10.1111/j.1467-8721.2007.00525.x

    Article  Google Scholar 

  30. Belsky J, Pluess M (2009) Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull 135:885–908. doi:10.1037/a0017376

    Article  PubMed  Google Scholar 

  31. Belsky J, Pluess M (2013) Beyond risk, resilience and dysregulation: phenotypic plasticity and human development. Dev Psychopathol 25:1243–1261. doi:10.1017/S095457941300059X

    Article  PubMed  Google Scholar 

  32. Brett ZH, Humphreys KL, Smyke AT et al (2015) Serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates the longitudinal impact of early caregiving on externalizing behavior. Dev Psychopathol 27:7–18. doi:10.1017/S0954579414001266

    Article  PubMed  PubMed Central  Google Scholar 

  33. Smyke AT, Koga S, Johnson D et al (2007) The caregiving context in institution reared and family reared infants and toddlers in Romania. J Child Psychol Psychiatry 48:210–218. doi:10.1111/j.1469-7610.2006.01694.x

    Article  PubMed  Google Scholar 

  34. Oliveira P, Fearon P, Belsky J et al (2014) Quality of institutional care and early childhood development. Int J Behav Dev 39:161–170. doi:10.1177/0165025414552302

    Article  Google Scholar 

  35. American Psychiatric Association (2014) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Arlington

    Google Scholar 

  36. Jacobvitz D, Sroufe LA (1987) The early caregiver-child relationship and attention-deficit disorder with hyperactivity in kindergarten: a prospective study. Child Dev 58:1496–1504

    CAS  PubMed  Google Scholar 

  37. Carlson EA, Jacobvitz D, Sroufe LA (1995) A developmental investigation of inattentiveness and hyperactivity. Child Dev 66:37–54

    Article  CAS  PubMed  Google Scholar 

  38. Egeland B, Pianta R, O’Brien M (1993) Maternal intrusiveness in infancy and child maladaptation in early school years. Dev Psychopathol 5:359–370. doi:10.1017/S0954579400004466

    Article  Google Scholar 

  39. Landau R, Amiel-Laviad R, Berger A et al (2009) Parenting of 7-month-old infants at familial risk for ADHD during infant’s free play. Infant Behav Dev 32:173–182. doi:10.1016/j.infbeh.2008.12.007

    Article  PubMed  Google Scholar 

  40. Keown LJ (2012) Predictors of boys’ ADHD symptoms from early to middle childhood: the role of father–child and mother–child interactions. J Abnorm Child Psychol 40:569–581. doi:10.1007/s10802-011-9586-3

    Article  PubMed  Google Scholar 

  41. Harold GT, Leve LD, Barrett D et al (2013) Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture. J Child Psychol Psychiatry 54:1038–1046. doi:10.1111/jcpp.12100

    Article  PubMed  PubMed Central  Google Scholar 

  42. Fox E, Zougkou K, Ridgewell A et al (2011) The serotonin transporter gene alters sensitivity to attention bias modification: evidence for a plasticity gene. Biol Psychiatry 70:1049–1054. doi:10.1016/j.biopsych.2011.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gibb BE, Benas JS, Grassia M et al (2009) Children’s attentional biases and 5-HTTLPR genotype: potential mechanisms linking mother and child depression. J Clin Child Adolesc Psychol 38:415–426. doi:10.1080/15374410902851705

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ellis BJ, Boyce WT, Belsky J et al (2011) Differential susceptibility to the environment: a neurodevelopmental theory. Dev Psychopathol 23:7–28. doi:10.1017/S0954579410000611

    Article  PubMed  Google Scholar 

  45. Instituto de Segurança Social (2010) Recomendações técnicas para equipamentos sociais: Centros de acolhimento temporário [Technical recommendations for social facilities: temporary care centers]. http://www4.seg-social.pt/documents/10152/13337/rtes_creche. Accessed 7 Sept 2015

  46. Baptista J, Belsky J, Marques S et al (2014) The interactive effect of maltreatment in the family and unstable institutional caregiving in predicting behavior problems in toddlers. Child Abus Negl 38:2072–2079. doi:10.1016/j.chiabu.2014.10.015

    Article  Google Scholar 

  47. Achenbach TM, Rescorla LA (2000) Manual for the ASEBA preschool-age forms and profiles. University of Vermont, Research Center for Children, Youth, and Families, Burlington

    Google Scholar 

  48. Gonçalves M, Dias P, Machado BC (2007) Questionário de comportamentos da criança 1 ½–5. Unpublished manuscript. University of Minho, Braga

  49. Aebi M, Winkler Metzke C, Steinhausen HC (2010) Accuracy of the DSM-oriented attention problem scale of the child behavior checklist in diagnosing attention-deficit hyperactivity disorder. J Atten Disord 13:454–463. doi:10.1177/1087054708325739

    Article  PubMed  Google Scholar 

  50. Achenbach TM, Dumenci L, Rescorla LA (2003) Are American children’s problems still getting worse? A 23-year comparison. J Abnorm Child Psychol 31:1–11

    Article  PubMed  Google Scholar 

  51. Wendland JR, Martin BJ, Kruse MR, Schofield P (2006) Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Mol Psychiatry 11:224–226. doi:10.1038/sj.mp.4001789

    Article  CAS  PubMed  Google Scholar 

  52. Ainsworth MDS, Blehar MC, Waters E et al (1978) Patterns of attachment: a psychological study of the strange situation. Erlbaum, Hillsdale

    Google Scholar 

  53. Griffiths R (1984) The abilities of young children: a comprehensive system of mental measurement for the first eight years of life. The Test Agency, ARICD, High Wycombe

    Google Scholar 

  54. Gershon J (2002) A meta-analytic review of gender differences in ADHD. J Atten Disord 5:143–154

    Article  CAS  PubMed  Google Scholar 

  55. Lindström K, Lindblad F, Hjern A (2011) Preterm birth and attention-deficit/hyperactivity disorder in school children. Pediatrics 127:858–865. doi:10.1542/peds.2010-1279

    Article  PubMed  Google Scholar 

  56. Aiken LS, West SG (1991) Multiple regression: testing and interpreting interactions. Sage, California

    Google Scholar 

  57. Kochanska G, Kim S, Barry R et al (2011) Children’s genotype interact with maternal responsive care in predicting children’s competence: diathesis-stress or differential-susceptibility? Dev Psychopathol 23:605–616. doi:10.1017/S0954579411000071

    Article  PubMed  PubMed Central  Google Scholar 

  58. Hayes AF, Matthes J (2009) Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations. Behav Res Methods 41:924–936. doi:10.3758/BRM.41.3.924

    Article  PubMed  Google Scholar 

  59. Rescorla LA, Achenbach TM, Ianova MY et al (2011) International comparisons of behavioral and emotional problems in preschool children: parents reports from 24 societies. J Clin Child Adolesc Psychol 40:456–467. doi:10.1080/15374416.2011.563472

    Article  PubMed  PubMed Central  Google Scholar 

  60. Hariri AR, Drabant EM, Munoz KE et al (2005) A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 62:146–152

    Article  CAS  PubMed  Google Scholar 

  61. Hariri AR, Mattay VS, Tessitore A et al (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297:400–403

    Article  CAS  PubMed  Google Scholar 

  62. Heinz A, Braus DF, Smolka MN et al (2005) Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nat Neurosci 8:20–21. doi:10.1038/nn1366

    Article  CAS  PubMed  Google Scholar 

  63. Munafo MR, Brown SM, Hariri AR (2008) Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry 63:852–857

    Article  CAS  PubMed  Google Scholar 

  64. Pezawas L, Meyer-Lindenberg A, Drabant EM et al (2005) 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 8:828–834

    Article  CAS  PubMed  Google Scholar 

  65. Smolka MN, Buhler M, Schumann G et al (2007) Gene-gene effects on central processing of aversive stimuli. Mol Psychiatry 12:307–317

    CAS  PubMed  Google Scholar 

  66. Frazier TW, Demaree HA, Youngstrom EA (2004) Meta-analysis of intellectual and neuropsychological test performance in attention-deficit/hyperactivity disorder. Neuropsychology 18:543–555

    Article  PubMed  Google Scholar 

  67. Doom JR, Georgieff MK, Gunnar MR (2015) Institutional care and iron deficiency increase ADHD symptomatology and lower IQ 2.5–5 years post-adoption. Dev Sci 18:484–494. doi:10.1111/desc.12223

    Article  PubMed  Google Scholar 

  68. Dick D, Agrawal A, Keller M et al (2015) Candidate gene–environment interaction research: reflections and recommendations. Perspect Psychol Sci 10:137–159. doi:10.1177/1745691614556682

    Article  Google Scholar 

  69. Merz EC, McCall RB (2010) Behavior problems in children adopted from psychosocially depriving institutions. J Abnorm Child Psychol 38:459–470. doi:10.1007/s10802-009-9383-4

    Article  PubMed  PubMed Central  Google Scholar 

  70. The St. Petersburg-USA Orphanage Research Team (2008) The effects of early social-emotional and relationship experience on the development of young orphanage children. In: Collins WA (ed) Monographs of the society for research in child development 73: (3)

Download references

Acknowledgments

This study was conducted within the Psychology Research Centre, University of Minho, and partially supported by the Portuguese Foundation for Science and Technology (PTDC/PSI-PCL/101506/2008 and PTDC/PSI-PCL/116897/2010; also grant SFRH/BPD/100994/2014 assigned to the first author) and by the Portuguese Ministry of Education and Science through national funds and when applicable co-financed by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013). This study was also partially supported by grant 13/06 from Fundação BIAL. The authors are very grateful to the students who helped in data collection. Special thanks go to the children, caregivers, and other institutional staff who participated in the study.

Author information

Authors and Affiliations

  1. Psychology Research Center-CIPsi, School of Psychology, University of Minho, Campus de Gualtar, 4710-050, Braga, Portugal

    Joana Baptista, Ana Mesquita & Isabel Soares

  2. University of California, Davis, One Shields Avenue, Davis, CA, 95616, USA

    Jay Belsky

Authors
  1. Joana Baptista
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jay Belsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Mesquita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Isabel Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Isabel Soares.

Ethics declarations

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Ethical standards

The ethical requirements followed the guidelines present in the 1964 Declaration of Helsinki and its later amendments.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baptista, J., Belsky, J., Mesquita, A. et al. Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers. Eur Child Adolesc Psychiatry 26, 303–313 (2017). https://doi.org/10.1007/s00787-016-0890-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-016-0890-x

Keywords

Search

Navigation