The Relation of the Dopamine Transporter Gene (DAT1) to Symptoms of Internalizing Disorders in Children
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The relation of the dopamine transporter gene (DAT1) to symptoms of internalizing disorders, Tourette's disorder, and obsessive-compulsive disorder was examined using both within- and between-family tests of association. The sample consisted of clinic-referred children and their siblings and controls and their siblings. Between-family association was examined via the association of DAT1 genotypes with disorder symptoms in the population. Symptoms of all eight disorders increased with a greater number of 10-repeat DAT1 alleles. Using a quantitative transmission disequilibrium test (QTDT), linkage and within-family association was indicated by increased symptoms in children who received 10 repeat alleles from heterozygous parents relative to children who received 9 repeat alleles. Four disorders were associated with DAT1 using the QTDT: generalized anxiety, social phobia, obsessive-compulsive, and Tourette's. The effects of comorbidity were investigated by repeating the same between- and within-family analyses on residual scores, with any effects of attention deficit hyperactivity disorder symptoms removed. Although the residuals were associated less strongly with DAT1 than were the original scores, three disorders continued to show association both between and within families: generalized anxiety, Tourette's, and social phobia.
- Allison, D. B. (1997). Transmission-disequilibrium tests for quantitative traits. Am. J. Hum. Genet. 60:676–690.
- Blum, K., Cull, J. G., Braverman, E. R., and Comings, D. E. (1996). Reward deficiency syndrome. Am. Sci. 84:132–145.
- Comings, D. E., Comings, B. G., and Knell, E. (1989). Hypothesis: Homozygosity in Tourette syndrome. Am. J. Med. Genet. 34:413–421.
- Comings, D. E., Wu, S., Chiu, C., Ring, R. H., Gade, R., Ahn, C., MacMurray, J. P., Dietz, G., and Muhleman, D. (1996). Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: The additive and subtractive effect of three dopaminergic genes—DRD2, DβH, and DAT1. Am. J. Med. Genet. (Neuropsychiatric Genetics) 67:264–288.
- Cook, E. H., Stein, M. A., Krasowski, M. D., Cox, N. J., Olkon, D. M., Kieffer, J. E., and Leventhal, B. L. (1995). Association of attention-deficit disorder and the dopamine transporter gene. Am. J. Hum. Genet. 56:993–998.
- Deater-Deckard, K., Reiss, D., Hetherington, E. M., and Plomin, R. (1997). Dimensions and disorders of adolescent adjustment: A quantitative genetic analysis of unselected samples and selected extremes. J. Child Psychol. Psychiatry 38:515–525.
- Doucette-Stamm, L. A., Blakely, D. J., Tian, J., Mockus, S., and Mao, J. (1995). Population study of the human dopamine transporter gene (DAT1). Genet. Epidemiol. 12:303–308.
- Fergusson, D. M., Horwood, L. J., and Lynskey, M. T. (1993). Prevalence and comorbidity of DSM-III-R diagnoses in a birth cohort of 15 year olds. J. Am. Acad. Child Adolesc. Psychiatry 32:1127–1134.
- Gill, M., Galy, G., Heron, S., Hawl, Z., and Fitzgerald, M. (1997). Confirmation of association between attention deficit hyperactivity disorder and a dopamine transporter polymorphism. Mol. Psychiatry 2:311–313.
- Giros, B., Jabar, M., Jones, S. R., Wightman, R. M., and Caron, M. G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 379:606–612.
- Goodwin, E. B., Okkema, P. G., Evans, T. C., and Kimble, J. (1993). Translational regulation of tra-2 by its 3′ untranslated region controls sexual identity in C. elegans. Cell 75:329–339.
- Hinshaw, S. P. (1994). Attention Deficits and Hyperactivity in Children, Sage, Thousand Oaks, CA.
- Kendler, K., Neale, M. C., Kessler, R. C., and Heath, A. C. (1992). Major depression and generalized anxiety disorder: Same genes, partly different environments. Arch. Gen. Psychiatry 49:716–722.
- Kendler, K., Neale, M. C., Kessler, R. C., Heath, A. C., and Eaves, L. J. (1993). Major depression and phobias: The genetic and environmental sources of comorbidity. Psychol. Med. 23:361–371.
- LaHoste, D. J., Wigal, S. B., Glade, C., Cook, E. H., Kennedy, J. L., and Swanson, J. M. (1995). Dopamine related genes and ADHD disorder. Paper presented at the meeting of the Society for Neurociences, San Diego.
- Malison, R. T., McDougle, C. J., van Dyck, C. H., Scahill, L., Baldwin, R. M., Seibyl, J. P., Price, L. H., Leckman, J. F., and Innis, R. B. (1995). [123I]B-CIT SPECT imaging of striatal dopamine transporter binding in Tourette's disorder. Am. J. Psychiatry 152:1359–1361.
- Neale, M. C., and Kendler, K. S. (1995). Multifactorial models of comorbidity. Am. J. Hum. Genet. 57:935–953.
- Nakatome, M., Honda, K., Islam, M. N., Terada, M., Yamazaki, M., Kuroki, H., Ogura, Y., Bai, H., and Wakasugi, C. (1995). Amplification of DAT1 (human dopamine transporter gene) 3′ variable region in the Japanese population. Hum. Hered. 45:262–265.
- Ritz, M. C., Lamb, R. J., Goldberg, S. R., and Kuhar, M. J. (1987). Cocaine receptors on the dopamine transporters are related to self-administration of cocaine. Science 237:1219–1223.
- Schweri, M. M., Thurkauf, A., Mattson, M. V., and Rice, K. C. (1992). Fourphit: A selective probe for the methylphenidate binding site on the dopamine transporter. J. Pharmacol. Exp. Ther. 261:936–942.
- Singer, H., Hahn, I., and Moran, T. (1991). Tourette's syndrome: Abnormal dopamine uptake sites in postmortem striatum from patients with Tourette's syndrome. Ann. Neurol. 30:558–562.
- Spielman, R. S., and Ewens, W. J. (1996). The TDT and other family-based tests for linkage disequilibrium and association. Am. J. Hum. Genet. 59:983–989.
- Spielman, R. S., McGinnis, R. E., and Ewens, W. J. (1993). Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent mellitus (IDDM). Am. J. Hum. Genet. 52:506–516.
- Vandenberg, D. J., Persico, A. M., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., and Uhl, G. R. (1992). Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics 14:1866–1868.
- Verhulst, F. C., and van der Ende, J. (1993). “Comorbidity” in an epidemiological sample: A longitudinal perspective. J. Child Psychol. Psychiatry 34:767–783.
- Waldman, I. D., Rowe, D. C., Abramowitz, A., Kozel, S., Mohr, J., Sherman, S. L., Cleveland, H. H., Sanders, M. L., and Stever, C. (1998). Association and linkage of the dopamine transporter gene (DAT1) and attention deficit hyperactivity disorder in children. (submitted for publication).
- The Relation of the Dopamine Transporter Gene (DAT1) to Symptoms of Internalizing Disorders in Children
Volume 28, Issue 3 , pp 215-225
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- dopamine transporter
- internalizing traits
- Author Affiliations
- 1. Family Studies and Interdisciplinary Graduate Committee on Genetics, University of Arizona, Tucson, Arizona, 85721
- 2. Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, 85721
- 3. Department of Psychiatry, Emory University, Atlanta, Georgia, 30322
- 4. Department of Psychology, Emory University, Atlanta, Georgia, 30322
- 5. Department of Genetics and Molecular Medicine, Emory University, Atlanta, Georgia, 30322