Skip to main content

Advertisement

SpringerLink
Log in

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14

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

Abstract

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10–14, we examined the association of the functional Val158Met COMT polymorphism and SES—both as linear and interactive effects—with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales. Multivariate- and subsequent univariate-analysis of covariance showed a significant association of COMT × SES interaction with CBCL 6/18 DOS attention deficit/hyperactivity problems (p = 0.004), and revealed higher scores among those children with Val/Val COMT genotype who belonged to low-SES families. We also found a significant association of SES with attention deficit/hyperactivity problems and conduct problems DOS (p = 0.04 and 0.01, respectively). Our data are consistent with a bulk of recent literature suggesting a role of environmental factors in moderating the contribution of specific genetic polymorphisms to human variability in ADHD. While future investigations will refine and better clarify which specific environmental and genetic mechanisms are at work in influencing the individual risk to ADHD in pre-adolescence, these data may contribute to identify/prevent the risk for ADHD problems in childhood.

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.

Fig. 1

Similar content being viewed by others

References

  1. Achenbach TM, McConaughy SH, Howell CT (1987) Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situation specificity. Psychol Bull 101:213–232

    Article  CAS  PubMed  Google Scholar 

  2. Achenbach TM, Rescorla LA (2001) Manual for the ASEBA school-age forms and profiles. University of Vermont, Department of Psychiatry, Burlington

  3. Barry TD, Dunlap ST, Cotten SJ, Lochman JE, Wells KC (2005) The influence of maternal stress and distress on disruptive behavior problems in boys. J Am Acad Child Adolesc Psychiatry 44:265–273

    Article  PubMed  Google Scholar 

  4. Battaglia M, Zanoni A, Giorda R, Pozzoli U, Citterio A, Beri S, Ogliari A, Nobile M, Marino C, Molteni M (2007) Effect of the catechol-O-methyltransferase val(158)met genotype on children's early phases of facial stimuli processing. Genes Brain Behav 6:364–374

    Article  CAS  PubMed  Google Scholar 

  5. Biederman J, Faraone SV, Monuteaux MC (2002) Differential effect of environmental adversity by gender: Rutter’s index of adversity in a group of boys and girls with and without ADHD. Am J Psychiatry 159:1556–1562

    Article  PubMed  Google Scholar 

  6. Blair C, Diamond A (2008) Biological processes in prevention and intervention: the promotion of self-regulation as a means of preventing school failure. Dev Psychopathol 20:899–911

    Article  PubMed  Google Scholar 

  7. Blasi G, Mattay VS, Bertolino A, Elvevåg B, Callicott JH, Das S, Kolachana BS, Egan MF, Goldberg TE, Weinberger DR (2005) Effect of catechol-O-methyltransferase val158met genotype on attentional control. J Neurosci 25:5038–5045

    Article  CAS  PubMed  Google Scholar 

  8. Burt SA, Krueger RF, McGue M, Iacono W (2003) Parent-child conflict and the comorbidity among childhood externalizing disorders. Arch Gen Psychiatry 60:505–513

    Article  PubMed  Google Scholar 

  9. Caspi A, Langley K, Milne B, Moffitt TE, O’Donovan M, Owen MJ, Polo Tomas M, Poulton R, Rutter M, Taylor A, Williams B, Thapar A (2008) A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 65:203–210

    Article  PubMed  Google Scholar 

  10. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854

    Article  CAS  PubMed  Google Scholar 

  11. Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807–821

    Article  CAS  PubMed  Google Scholar 

  12. Cheuk DK, Wong V (2006) Meta-analysis of association between a catechol-O-methyltransferase gene polymorphism and attention deficit hyperactivity disorder. Behav Genet 36:651–659

    Article  PubMed  Google Scholar 

  13. Collett BR, Ohan JL, Myers KM (2003) Ten-year review of rating scales. VI: scales assessing externalizing behaviors. J Am Acad Child Adolesc Psychiatry 42:1143–1170

    Article  PubMed  Google Scholar 

  14. Conger RD, Wallace LE, Sun Y, Simons RL, McLoyd VC, Brody GH (2002) Economic pressure in African American families: a replication and extension of the family stress model. Dev Psychol 38:179–193

    Article  PubMed  Google Scholar 

  15. Diamond A (2007) Consequences of variations in genes that affect dopamine in prefrontal cortex. Cereb Cortex 17:161–170

    Article  Google Scholar 

  16. Dodge KA, Pettit GS, Bates JE (1994) Socialization mediators of the relation between socioeconomic status and child conduct problems. Child Dev 65:649–665

    Article  CAS  PubMed  Google Scholar 

  17. Eaves LJ (2006) Genotype × environment interaction in psychopathology: fact or artifact? Twin Res Hum Genet 9:1–8

    Article  PubMed  Google Scholar 

  18. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function, risk for schizophrenia. Proc Natl Acad Sci USA 98:6917–6922

    Article  CAS  PubMed  Google Scholar 

  19. Egeland B (1997) Mediators of the effect of child maltreatment on developmental adaptation in adolescence. In: Cicchetti D, Toth SL (eds) Developmental perspectives on trauma: theory, research, and intervention. University of Rochester Press, Rochester, pp 403–434

    Google Scholar 

  20. Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1313–1323

    Article  CAS  PubMed  Google Scholar 

  21. Frigerio A, Cattaneo C, Cataldo MG, Schiatti A, Molteni M, Battaglia M (2004) Behavioral and emotional problems among Italian children and adolescents aged 4 to 18 years as reported by parents and teachers. Eur J Psychol Assess 20:124–133

    Article  Google Scholar 

  22. Frigerio A, Vanzin L, Pastore V, Nobile M, Giorda R, Marino C, Molteni M, Rucci P, Ammaniti M, Lucarelli L, Lenti C, Walder M, Martinuzzi A, Carlet O, Muratori F, Milone A, Zuddas A, Cavolina P, Nardocci F, Tullini A, Morosini P, Polidori G, De Girolamo G (2006) The Italian preadolescent mental health project (PrISMA): rationale and methods. Int J Methods Psychiatr Res 15:22–35

    Article  PubMed  Google Scholar 

  23. Frigerio A, Rucci P, Goodman R, Ammaniti M, Carlet O, Cavolina P, De Girolamo G, Lenti C, Lucarelli L, Mani E, Martinuzzi A, Micali N, Milone A, Morosini P, Muratori F, Nardocci F, Pastore V, Polidori G, Tullini A, Vanzin L, Villa L, Walter M, Zuddas A, Molteni M (2009) Prevalence and correlates of mental disorders among adolescents in Italy: the PrISMA study. Eur Child Adolesc Psychiatry 18:217–226

    Article  PubMed  Google Scholar 

  24. Gallinat J, Bajbouj M, Sander T, Schlattmann P, Xu K, Ferro EF, Goldman D, Winterer G (2003) Association of the G1947A COMT (Val(108/158)Met) gene polymorphism with prefrontal P300 during information processing. Biol Psychiatry 54:40–48

    Article  CAS  PubMed  Google Scholar 

  25. Hariri AR, Weinberger DR (2003) Functional neuroimaging of genetic variation in serotonergic neurotransmission. Genes Brain Behav 2:341–349

    Article  CAS  PubMed  Google Scholar 

  26. Hollingshead AB (1975) Four factor index of social status. Yale University, Department of Sociology, New Haven, CT (unpublished manuscript)

  27. Jaffee SR, Moffitt TE, Caspi A, Taylor A, Arseneault L (2002) Influence of adult domestic violence on children’s internalizing and externalizing problems: an environmentally informative twin study. J Am Acad Child Adolesc Psychiatry 41:1095–1103

    Article  PubMed  Google Scholar 

  28. Karoum F, Chrapusta SJ, Egan MF (1994) 3-Methoxytyramine is the major metabolite of released dopamine in the rat frontal cortex: reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model. J Neurochem 63:972–979

    CAS  PubMed  Google Scholar 

  29. Keiley MK, Bates JE, Dodge KA, Pettit GS (2000) A cross-domain growth analysis: externalizing and internalizing behaviors during 8 years of childhood. J Abnorm Child Psychol 28:161–179

    Article  CAS  PubMed  Google Scholar 

  30. Krol NP, De Bruyn EE, Coolen JC, van Aarle EJ (2006) From CBCL to DSM: a comparison of two methods to screen for DSM-IV diagnoses using CBCL data. J Clin Child Adolesc Psychol 35:127–135

    Article  PubMed  Google Scholar 

  31. Lambert MC, Knight F, Taylor R, Achenbach T (1994) Epidemiology of behavioral and emotional problems among children of Jamaica and the United States: parent reports for ages 6 to 11. J Abnorm Child Psychol 22:113–128

    Article  CAS  PubMed  Google Scholar 

  32. Larsson B, Frisk M (1999) Social competence and emotional/behavior problems in 6–16-year-old Swedish school children. Eur Child Adolesc Psychiatry 8:24–33

    Article  CAS  PubMed  Google Scholar 

  33. Lasky-Su J, Faraone SV, Lange C, Tsuang MT, Doyle AE, Smoller JW, Laird NM, Biederman J (2007) A study of how socioeconomic status moderates the relationship between SNPs encompassing BDNF and ADHD symptom counts in ADHD families. Behav Genet 37:487–497

    Article  CAS  PubMed  Google Scholar 

  34. Liu X, Kurita H, Guo C, Miyake Y, Ze J, Cao H (1999) Prevalence and risk factors of behavioral and emotional problems among Chinese children aged 6 through 11 years. J Am Acad Child Adolesc Psychiatry 38:708–715

    Article  CAS  PubMed  Google Scholar 

  35. Loeber R, Green SM, Keenan K, Lahey BB (1995) Which boys will fare worse? Early predictors of the onset of conduct disorder in a six-year longitudinal study. J Am Acad Child Adolesct Psychiatry 34:499–509

    Article  CAS  Google Scholar 

  36. Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melén K, Julkunen I, Taskinen J (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34:4202–4210

    Article  CAS  PubMed  Google Scholar 

  37. MacDonald VM, Tsiantis J, Achenbach TM, Motti-Stefanidi F, Richardson SC (1995) Competencies and problems reported by parents of Greek and American children, ages 6–11. Eur Child Adolesc Psychiatry 4:1–13

    Article  CAS  PubMed  Google Scholar 

  38. Manly JT, Kim JE, Rogosch FA, Cicchetti D (2001) Dimensions of child maltreatment and children’s adjustment: contributions of developmental timing and subtype. Dev Psychopathol 13:759–782

    CAS  PubMed  Google Scholar 

  39. Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR (2003) Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA 100:6186–6191

    Article  CAS  PubMed  Google Scholar 

  40. Mick E, Biederman J, Prince J, Fischer MJ, Faraone SV (2002) Impact of low birth weight on attention-deficit hyperactivity disorder. J Dev Behav Pediatr 23:16–22

    PubMed  Google Scholar 

  41. Nobile M, Giorda R, Marino C, Carlet O, Pastore V, Vanzin L, Bellina M, Molteni M, Battaglia M (2007) Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence. Dev Psychopathol 19:1147–1160

    Article  PubMed  Google Scholar 

  42. Nobile M, Rusconi M, Bellina M, Marino C, Giorda R, Carnet O, Vanzin L, Molteni M, Battaglia M (2009) TPH2 G-703T and the 5-HTTLPR serotonergic genes upon affective problems in children aged 10–14 years. J Child Psychol Psychiatry 50:317–325

    Article  PubMed  Google Scholar 

  43. Novik TS (1999) Validity of the child behavior checklist in a Norwegian sample. Eur Child Adolesc Psychiatry 8:247–254

    Article  CAS  PubMed  Google Scholar 

  44. Roussos A, Karantanos G, Richardson C, Hartman C, Karajiannis D, Kyprianos S, Lazaratou H, Mahaira O, Tassi M, Zoubou V (1999) Achenbach’s child behavior checklist and teacher’s report form in a normative sample of Greek children 6–12 years old. Eur Child Adolesc Psychiatry 8:165–172

    Article  CAS  PubMed  Google Scholar 

  45. Rutter M, Moffitt TE, Caspi A (2006) Gene-environment interplay and psychopathology: multiple varieties but real effects. J Child Psychol Psychiatry 47:226–261

    Article  PubMed  Google Scholar 

  46. Sengupta SM, Grizenko N, Schmitz N, Schwartz G, Ben Amor L, Bellingham J, de Guzman R, Polotskaia A, Ter Stepanian M, Thakur G, Joober R (2006) COMT Val108/158Met gene variant, birth weight, and conduct disorder in children with ADHD. J Am Acad Child Adolesc Psychiatry 45:1363–1369

    Article  PubMed  Google Scholar 

  47. Smolka MN, Schumann G, Wrase J, Grüsser SM, Flor H, Mann K, Braus DF, Goldman D, Büchel C, Heinz A (2005) Catechol-O-methyltransferase val158met genotype affects processing of emotional stimuli in the amygdala and prefrontal cortex. J Neurosci 25:836–842

    Article  CAS  PubMed  Google Scholar 

  48. Spatola CA, Fagnani C, Pesenti-Gritti P, Ogliari A, Stazi MA, Battaglia M (2007) A general population twin study of the CBCL/6–18 DSM-oriented scales. J Am Acad Child Adolesc Psychiatry 46:619–627

    Article  PubMed  Google Scholar 

  49. Spielman RS, Weinshilboum RM (1981) Genetics of red cell COMT activity: analysis of thermal stability and family data. Am J Med Genet 10:279–290

    Article  CAS  PubMed  Google Scholar 

  50. Steinhausen HC, Winkler Metzke C, Meier M, Kannenberg R (1997) Behavioral and emotional problems reported by parents for ages 6 to 17 in a Swiss epidemiological study. Eur Child Adolesc Psychiatry 6:136–141

    CAS  PubMed  Google Scholar 

  51. Thapar A, Langley K, Fowler T, Rice F, Turic D, Whittinger N, Aggleton J, Van den Bree M, Owen M, O’Donovan M (2005) Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 62:1275–1278

    Article  CAS  PubMed  Google Scholar 

  52. Wadsworth ME, Achenbach TM (2005) Explaining the link between low socioeconomic status and psychopathology: testing two mechanisms of the social causation hypothesis. J Consult Clin Psychol 73:1146–1153

    Article  PubMed  Google Scholar 

  53. Wahlstrom D, White T, Hooper CJ, Vrshek-Schallhorn S, Oetting WS, Brott MJ, Luciana M (2007) Variations in the catechol O-methyltransferase polymorphism and prefrontally guided behaviors in adolescents. Biol Psychiatry 61:626–632

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Grant R.F.2002-2003 N. 182 from the Italian Ministry of Health.

Author information

Authors and Affiliations

  1. Department of Child Psychiatry, Eugenio Medea Scientific Institute, via Don Luigi Monza 20, 23842, Bosisio Parini (LC), Italy

    Maria Nobile, Monica Bellina, Cecilia Marino, Laura Vanzin, Massimo Molteni & Marco Battaglia

  2. Molecular Biology Laboratory, Eugenio Medea Scientific Institute, Bosisio Parini, Italy

    Marianna Rusconi & Roberto Giorda

  3. Department of Psychiatry, CRULRG, Laval University, Quebec, G1K7P4, Canada

    Cecilia Marino

  4. Department of Child Psychiatry, Eugenio Medea Scientific Institute, Conegliano, Italy

    Ombretta Carlet

  5. Centre for the Study of Behavioural Plasticity, Vita-Salute San Raffaele University, 20127, Milan, Italy

    Marco Battaglia

Authors
  1. Maria Nobile
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marianna Rusconi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monica Bellina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cecilia Marino
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Roberto Giorda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ombretta Carlet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laura Vanzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Massimo Molteni
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marco Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Nobile.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nobile, M., Rusconi, M., Bellina, M. et al. COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10–14. Eur Child Adolesc Psychiatry 19, 549–557 (2010). https://doi.org/10.1007/s00787-009-0080-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00787-009-0080-1

Keywords

Search

Navigation