Skip to main content
SpringerLink
Log in

An Assessment of Transmission Disequilibrium Between Quantitative Measures of Childhood Problem Behaviors and DRD2/Taql and DRD4/48bp-Repeat Polymorphisms

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

In a pilot study of 120 children with reading disabilities, we assessed the presence of linkage and association between the DRD2/Taql and the DRD4/48bp-repeat polymorphisms and quantitative measures of behavioral problems derived from parental rated Child Behavior Checklist (CBCL) [Achenbach, T. M. (1991). TM Manual for the CBCL 14–18. Burlington, VT: University of Vermont]. Analyses included measures of between-family association, and a test of the presence of linkage and association by a logistic regression-based extension of the Transmission Disequilibrium Test (i.e., the logistic regression quantitative TDT). In between-family association analyses the “Social Problem” scale was weakly associated with the number of risk alleles of DRD2 and DRD4, while the “Withdrawn” scale was related to the number of risk alleles of DRD4 (the 7-repeat and the A1 allele respectively were considered the risk alleles). Logistic regression quantitative TDTs yielded statistically significant evidence in favor of linkage and association between DRD2 and “Social Problems” (Wald χ2 = 4.13, df = 1, p = 0.042, Odds Ratio = 1.97). A statistical trend in favor of linkage and association was found for “Withdrawn” and DRD4 (Wald χ2 = 2.65, df = 1, p = 0.104, Odds Ratio =1.44). Although preliminary, these findings are consistent with previous data that suggest a role of the same polymorphism in influencing individual sensitivity to reward and response to social cues and reinforcements in man and animal.

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

Similar content being viewed by others

REFERENCES

  • Achenbach, T. M., Conners, C. K. Quay, H. C., Verhulst, F. C., and Howell, C. T. (1989). Replication of empirically derived syndromes as a basis for taxonomy of child/adolescent psychopathology. J. Abnorm. Child Psychol. 17:299-323.

    PubMed  Google Scholar 

  • Achenbach, T. M. (1991). Manual for the CBCL/4-18 and 1991 Profile. Burlington, VT: University of Vermont Department of Psychiatry.

    Google Scholar 

  • Achenbach, T. M. (1992). Developmental Psychopathology. In M. E. Lamb and M. H. Bornstein (eds.), Developmental Psychology: an advanced textbook (3rd Ed.). Hillsdale, NJ: Erlbaum.

    Google Scholar 

  • Achenbach, T. M. (1993). Empirically based taxonomy: how to use syndromes and profile types derived from the CBCL/4-18, TRF, and YSR. Burlington, VT: University of Vermont Department of Psychiatry.

    Google Scholar 

  • American Psychiatric Association. (1994). Diagnostic and statistical manual of mental disorders (4th Ed.), Revised, Washington, DC: APA.

    Google Scholar 

  • Beitchman, J. H., and Young, A. R. (1997). Learning disorders with a special emphasis on reading disorders: a review of the past 10 years. J. Am. Acad. Child. Adolesc. Psychiatry36:1020-1032.

    Article  PubMed  Google Scholar 

  • Bender, W. N., and Wall, M. E. (1994). Social-emotional development of students with learning disabilities. Learn. Dis. Quart. 17:323-341.

    Google Scholar 

  • Benjamin, J., Li, L., Patterson, C., Greenberg, B. D., Murphy, D. L., and Hamer, D. H. (1996). Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat. Genet. 12:81-84.

    Article  PubMed  Google Scholar 

  • Blum, K., Noble, E. P., Sheridan P. J., Montgomery, A., Ritchie, T., Jagadeeswaran, P., Nogami, H., Briggs, A. H., and Conn, J. B. (1990). Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 18:2055-2060.

    Google Scholar 

  • Blum, K., Cull, J. G., Braveman, E. R., and Comings, D. E. (1996). Reward deficiency syndrome. Am. Sci. 84:132-145.

    Google Scholar 

  • Blum, K., Braverman, E. R., Wu, S., Cull, J. G., Chen, T. J., Gill, J., Wood, R., Eisenberg, A., Sherman, M., Davis, K. R., Matthews, D., Fischer, L., Schnautz, N., Walsh, W., Pontius, A. A., Zedar, M., Kaats, G., and Comings, D. E. (1997). Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/ avoidant behaviors (SAB). Mol. Psychiatry 2:239-246.

    Article  PubMed  Google Scholar 

  • Blum, K., Braverman, E. R., Holder, J. M, Lubar, J. F., Monastra, V. J., Miller, D., Lubar, J. O., Chen, T. J., and Comings, D. E. (2000). Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. J. Psychoactive Drugs 32 (Suppl:i-iv), 1-112.

    Google Scholar 

  • Boetsch, E., Green P. A., and Pennington B. F. (1996). Psychosocial correlates of dyslexia across the life span. Dev Psychopathol. 8:539-562.

    Google Scholar 

  • Boyle, M. H., Offord, D. R., and Racine, Y. (1993). Evaluation of the Diagnostic Interview for Children and Adolescents for use in general population samples. J. Abnorm. Child Psychol. 21:663-681.

    PubMed  Google Scholar 

  • Breier, A., Kestler, L., Adler, C., Elman, I., Wiesenfeld, N., Malhotra, A., and Pickar, D. (1998). Dopamine D2 receptor density and personal detachment in healthy subjects. Am. J., Psychiatry 155:1440-1442.

    Google Scholar 

  • Cornoldi, C., and Colpo, G. (1981). La verifica dell'apprendimento delta lettura. Firenze. Organizzazioni Speciali.

    Google Scholar 

  • Cornoldi, C., and Colpo, G. (1995). Nuove prove di lettura MT per la scuola media inferiore. Firenze. Organizzazioni Speciali.

    Google Scholar 

  • Current Protocols in Human Genetics (1995). Unit 9.7, New York: Wiley.

  • Curtis, D., and Sham, P. C. (1995). A note on the application of the transmission disequilibrium test when a parent is missing. Am. J. Hum. Genet. 56:811-812.

    PubMed  Google Scholar 

  • Edelbrock, C., Rende, R., Plomin, R., and Thompson, L. A. (1995). A twin study of competence and problem behavior in childhood and early adolescence. J. Child Psychology and Psychiatry 36:775-785.

    Google Scholar 

  • Faraone, S. V., Doyle, A. E., Mick, E., and Biederman, J. (2001). Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention defi-cit hyperactivity disorder. Am. J. Psychiatry 158:1052-1057.

    Article  PubMed  Google Scholar 

  • Farde, L., Gustavsson, J. P., and Jonsson, E. (1997). D2 dopamine receptors and personality traits. Nature. 13:385(6617):590.

    Google Scholar 

  • Fisher, S. E., Francks, C., McCracken, J. T., McGough, J. J., Marlow, A. J., MacPhie, I. L., Newbury, D. F., Crawford, L. R., Palmer, C. G., Woodward, J. A., Del'Homme, M., Cantwell, D. P., Nelson, S. F., Monaco, A. P., and Smalley, S. L. (2002). A genomewide scan for loci involved in attention-deficit/ hyperactivity disorder. Am J Hum. Genet. 70:1183-1196.

    Article  PubMed  Google Scholar 

  • Gingrich, B., Liu, Y., Cascio, C., Wang, Z., and Insel, T. R. (2000). Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). Behav. Neurosci. 114:173-183.

    Article  PubMed  Google Scholar 

  • Goldsmith, H. H., Gottesman, I. I., and Lemery, K. S. (1997). Epigenetic approaches to developmental psychopathology, Dev. Psychopathol. 9:365-387.

    PubMed  Google Scholar 

  • Grandy, D. H., Zhang, Y., and Civelli, O. (1993). PCR detection of the Taql A RFLP at the DRD2 locus Hum. Mol. Genet. 2:2197.

    Google Scholar 

  • Hill, S. Y., Zezza, N., Wipprecht, G., Locke, J., and Neiswanger, K. (1999). Personality traits and dopamine receptors (D2 and D4): linkage studies in families of alcoholics. Am. J. Med. Genet. 15:634-641.

    Article  Google Scholar 

  • Hinshaw, S. P. (1992). Externalizing behavior problems and academic underachievement in childhood and adolescence: causal relationships and underlying mechanisms. Psychol. Bull. 111:127-155.

    Article  PubMed  Google Scholar 

  • Hollingshead, A. B. (1975). Four-factor index of social status. Unpublished Manuscript. New Haven, CT: Yale University, Department of Sociology.

    Google Scholar 

  • Hudziak, J. J., Rudiger, L. P., Neale, M. C., Heath, A. C., and Todd, R. D. (2000). A twin study of inattentive, aggressive, and anxious/depressed behaviors. J. Am. Acad. Child Adolesc. Psychiatry 39:469-476.

    Article  PubMed  Google Scholar 

  • Hudziak, J. J., Copeland W., Rudiger, L. P., Achenbach T. M., Heath, A. C., and Todd, R. D. (2003). Genetic influences on childhood competencies: a twin study J. Am. Acad. Child Adolesc. Psychiatry 42:357-363.

    Article  PubMed  Google Scholar 

  • ICLD: National Joint Committee on Learning Disabilities Interagency Committee on Learning Disabilities. Learning Disabilities: A report to the US congress. Bethesda, MD, National Institutes of Health, 1987.

    Google Scholar 

  • Jonsson, E. G., Nothen, M. M., Grunhage, F., Farde, L., Nakashima, Y., Propping, P., and Sedvall, G. C. (1999). Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol. Psychiatry 4:290-296.

    Article  PubMed  Google Scholar 

  • Jonsson, E. G., Cichon, S., Gustavsson, J. P., Grunhage, F., Forslund, K., Mattila-Evenden, M., Rylander, G., Asberg, M., Farde, L., Propping, P., and Nothen, M. M. (2003). Association between a promoter dopamine D2 receptor gene variant and the personality trait detachment. Biol. Psychiatry 53:577-584.

    Article  PubMed  Google Scholar 

  • Kasius, M. C., Ferdinand, R. F., van den Berg, H., and Verhulst, F. C. (1997). Associations between different diagnostic approaches for child and adolescent psychopathology. J. Child Psychol. Psychiatry 38:625-632.

    PubMed  Google Scholar 

  • Lakatos, K., Toth, I., Nemoda, Z., Ney, K., Sasvari-Szekely, M., and Gervai, J. (2000), Dopamine D4 receptor (DRD4) gene polymorphism is associated with attachment disorganization in infants. Mol. Psychiatry 5:633-637.

    Article  PubMed  Google Scholar 

  • Lakatos, K., Nemoda, Z., Birkas E., Ronai Z., Kovacs E., Ney, K., M., Toth, I., Sasvari-Szekely, M., and Gervai, J (2003). Association of D4 dopamine receptor gene and serotonin transporter promoter polymorphisms with infants' response to novelty. Mol. Psychiatry 8:90-97.

    Article  PubMed  Google Scholar 

  • Lobos, E. A., and Todd, R. D. (1998). Association analysis in an evolutionary context: cladistic analysis of the DRD2 locus to test for association with alcoholism. Am. J. Med. Genet. 81:411-419.

    Article  PubMed  Google Scholar 

  • Macciardi, F., Petronis, A., Van Tol, H. H., Marino, C., Cavallini, M. C., Smeraldi, E., and Kennedy, J. L (1994). Analysis of the D4 dopamine receptor gene variant in an Italian schizophrenia kindred. Arch. Gen. Psychiatry 51:288-293.

    PubMed  Google Scholar 

  • Marino, C., Giorda, R., Vanzin, L., Molteni, M., Lorusso, M. L., Nobile, M., Baschirotto, C., Alda, M., and Battaglia, M. (2003). No evidence for association and linkage disequilibrium between dyslexia and markers of four dopamine-related genes. Eur. Child Adolesc. Psychiatry 12:198-202.

    Article  PubMed  Google Scholar 

  • Marino, C., Giorda, R., Vanzin, L., Nobile, M., Lorusso, M. L., Baschirotto, C., Riva, L., Molteni, M., and Battaglia, M. (2004). A locus on 15q15-15qter influences dyslexia: further support from a transmission/disequilibrium study in an Italian speaking population. J. Med. Genet. 41:42-46.

    Article  PubMed  Google Scholar 

  • McConaughy, S. H., Stanger, C., and Achenbach, T. M. (1992). Three-year course of behavioural/emotional problems in a national sample of 4 to 16 years old. Agreement among informants. J. Am. Acad. Child. Adolesc. Psychiatry 31:932-940.

    PubMed  Google Scholar 

  • Mirenowicz, J., and Schultz, W. (1996). Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature 379(6564):449-451.

    Article  PubMed  Google Scholar 

  • Munafò, M. R., Clark, T. G., Moore, L. R., Payne, E., Walton, R., and Flint, J. (2003). Genetic polymorphisms and personality in healthy adults: a systematic review and meta-analysis. Mol. Psychiatry 8:471-484.

    Article  PubMed  Google Scholar 

  • Noble, E. P., Oskaragoz, T. Z., Ritchie, T. L., Zhang, X., Belin, T. R., and Sparkes, R. S. (1998). D2 and D4 dopamine receptor polymorphisms and personality. Am. J. Med. Genet. 81:257-267.

    Article  PubMed  Google Scholar 

  • Noble, E. P. (2003). D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am. J. Med. Genet. 116B:103-125.

    Article  PubMed  Google Scholar 

  • Osman, B. (1995). No one to play with: social problems of LD and ADD children. Novato, CA: Academic Therapy Publications.

    Google Scholar 

  • Osman, B. B. (2000). Learning disabilities and the risk of psychiatric disorders in children and adolescents. In: Learning disabilities: implications for psychiatric treatment, Greenhiil, L.L., (eds.), Washington, DC, London, England: American Psychiatric Press, pp. 33-57.

    Google Scholar 

  • Petronis, A. (1999). The regulation of D2 dopamine receptor gene expression: epigenetic factors should not be forgotten. Mol. Psychiatry 4:212-213.

    Article  PubMed  Google Scholar 

  • Pohjalainen, T., Rinne, J. O., Nagren, K., Lehikoinen, P., Anttila, K., Syvalahti, E. K., and Hietala, J. (1998) The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Mol. Psychiatry 3:256-260.

    Article  PubMed  Google Scholar 

  • Reich, W., and Welner, Z. (1988). The Diagnostic Interview for Children and Adolescents-Revised. Washington University, St Louis, MO, Unpublished manuscript.

    Google Scholar 

  • Rende, R., and Plomin, R. (1995). Nature, Nurture and the development of psychopathology. In D. Cicchetti, and D. J. Cohen, (eds.), Developmental psychopathology, New York: Wiley, pp. 291-314.

    Google Scholar 

  • Rowe, D. C., Stever, C., Gard, J. M., Cleveland, H. H., Sanders, M. L., Abramowitz, A., Kozol, S. T., Mohr, J. H., Sherman, S. L., Waldman, I. D. (1998}a). The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders in children. Behav. Genet. 28:215-225.

    Article  PubMed  Google Scholar 

  • Rowe, D. C., Stever, C., Giedinghagen, L. N., Gard, J. M., Cleveland, H. H., Terris, S. T., Mohr, J. H., Sherman, S., Abramowitz, A., and Waldman, I. D. (1998}b). Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder. Mol. Psychiatry 3:419-426.

    Article  PubMed  Google Scholar 

  • Rowe, D. C., den Oord, E. J., Stever, C., Giedinghagen, L. N., Gard, J. M., Cleveland, H. H., Gilson, M., Terris, S. T., Mohr, J. H., Sherman, S., Abramowitz, A., and Waldman, I. D. (1999). The DRD2 TaqI polymorphism and symptoms of attention de.cit hyperactivity disorder. Mol. Psychiatry 4:580-586.

    Article  PubMed  Google Scholar 

  • Sabornie, E. J. (1994). Social-affective characteristics in early adolescents identi.ed as learning disabled and nondisabled. Learn. Dis. Quart. 17:268-279.

    Google Scholar 

  • Sartori. G., Job, R., and Tyressoldi, P. E. (1995). OS. Organizzazioni Speciali, Firenze.

    Google Scholar 

  • Schmitz, S., Fulker, D. W., and Mrazek, D. A. (1995). Problem behavior in early and middle childhood: an initial behaviorgenetic analysis. J. Child Psychol. Psychiat 36:1448-1458.

    Google Scholar 

  • Schneier, F. R., Liebowitz, M. R., Abi-Dargham, A., Zea-Ponce, Y., Lin, S. H., and Laruelle, M. (2000). Low dopamine D2 receptor binding potential in social phobia. Am. J. Psychiatry 157:457-459.

    Article  PubMed  Google Scholar 

  • Spielman, R. S., McGinnis, R. E., and Ewens, W. J. (1993). Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus. (IDDM). Am. J. Hum. Genet. 52:506-516.

    PubMed  Google Scholar 

  • SPSS Advanced Statistics 6.1. Norusis, M. J. (1994). SPSS Inc., Chicago, Illinois.

  • Tarazi, F. I., and Baldessarini, R. J. (1999). Dopamine D4 receptors: significance for molecular psychiatry at the millennium. Mol. Psychiatry 4:529-538.

    Article  PubMed  Google Scholar 

  • Tur-Kaspa, H., and Bryan, T. (1995). Teachers' ratings of the social competence and school adjustment of students with LD in elementary and junior high school. J. Learn. Disabil. 28:44-52.

    PubMed  Google Scholar 

  • Van den Oord, E. J., Boomsma, D. I., and Verhulst, F. C. (1994). A study of problem behaviors in 10-to 15-year-old biologically related and unrelated international adoptees. Behav. Genet. 24:193-205.

    PubMed  Google Scholar 

  • Van Tol, H. H., Bunzow, J. R., Guan, H. C., Sunahara, R. K., Seeman, P., Niznik, H. B., and Civelli, O. (1991). Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 18:610-614.

    Article  Google Scholar 

  • Waldman, I. D., Robinson, B. F., and Rowe, D. C. (1999). A logistic regression based extension of the TDT for continuous and categorical traits. Ann. Hum. Genet. 63:329-340.

    Article  PubMed  Google Scholar 

  • Wechsler, D. (1981). Wechsler intelligence scale for children, Revised. Examiner's manual. New York: Psychological Corp.

    Google Scholar 

  • Willcutt, E. G., and Pennington, B. F. (2000). Psychiatric comorbidity in children and adolescents with reading disability. J. Child Psychol. Psychiatry 41:1039-1048.

    Article  PubMed  Google Scholar 

  • Young, S. E., Smolen, A., Corley, R. P., Krauter, K. S., DeFries, J. C., Crowley, T. J., and Hewitt, J. K. (2002). Am. J. Med. Genet. 114:144–9 Dopamine transporter polymorphism associated with externalizing behavior problems in children.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Child Psychiatry, The Eugenio Medea Scientific Institute, Via Don Luigi Monza 20, Bosisio Parini, Lecco, Italy

    Cecilia Marino, Laura Vanzin, Alessandra Frigerio, Maria Luisa Lorusso, Maria Nobile, Massimo Molteni & Marco Battaglia

  2. Molecular Biology Laboratory, Bosisio Parini, Italy

    Roberto Giorda

  3. Department of Psychology, San Raffaele University, San Raffaele Scientific Institute, Milan, Italy

    Marco Battaglia

Authors
  1. Cecilia Marino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura Vanzin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Giorda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandra Frigerio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Luisa Lorusso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Nobile
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Massimo Molteni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marco Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marino, C., Vanzin, L., Giorda, R. et al. An Assessment of Transmission Disequilibrium Between Quantitative Measures of Childhood Problem Behaviors and DRD2/Taql and DRD4/48bp-Repeat Polymorphisms. Behav Genet 34, 495–502 (2004). https://doi.org/10.1023/B:BEGE.0000038487.80597.7e

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:BEGE.0000038487.80597.7e

Search

Navigation