Abstract
TaqI A D2 dopamine receptor (DRD2) alleles, family stress, and cognitive markers, including visuospatial ability (Benton's Line Orientation) and event-related potentials (P300 amplitude and latency), were obtained in preadolescent boys of alcoholic and nonalcoholic fathers. In the presence of the DRD2 minor allele (A1+), the Family Stress score negatively correlated with the Line Orientation score and P300 amplitude. No significant correlations were found in boys lacking this allele (A1−). The interaction of the A1+ allele and the Family Stress score produced significant regression coefficients for both Line Orientation score (p = .002) and P300 amplitude (p = .04). Together, these two cognitive markers account for 37% of the variance in the Family Stress score of 47 A1 allele boys (p = .0002) but less than 1% in 71 A1− allele boys (p > .9). This provides the first evidence of a specific gene–environment interaction involving human cognitive functioning.
Similar content being viewed by others
REFERENCES
Balldin, J. I,, Berggren, U. C., Lindstedt, G., and Sundkler, A. (1993). Further neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholism. Drug Alcohol Depend. 32:159-162.
Begleiter, H., Porjesz, B., Bihari, B., and Kissin, B. (1984). Event-related brain potentials in boys at risk for alcoholism. Science 225:1493-1496.
Benton, A. L., Varney, N. R., and Hamsher, K. (1978). Visuospatial judgment: A clinical test. Arch. Neural. 25:364-367.
Berman, S. M., and Noble, E. P. (1995). Reduced visuospatial performance in children with the D, dopamine receptor Al allele. Behav. Genet. 25:45-58.
Berman, S. M., and Noble, E. P. (1997). The P300 eventrelated potential as a putative marker for alcoholism: A review. In Miller, N. S. (ed.), Principles of Addiction Medicine, Update Series: Topics in Addiction Medicine, Vol. 1. No. 2, American Society of Addiction Medicine, Chevy Chase, MD (in press).
Berman, S. M., Whipple, S., Fitch, R. J., and Noble, E. P. (1993). P3 in young boys as a predictor of adolescent substance use. Alcohol 10:69-76.
Blum, K., Noble, E. P., Sheridan, P. J., Montgomery, A., Ritchie, T., Jagadeeswaraa, P., Nogami, H., Briggs, A. H., and Cohn, J. B. (1990). Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263:2055-2060.
Blum, K., Noble, E. P., Sheridan, P. J., Montgomery, A., Ritchie, T., Ozkaragoz, T., Fitch, R. J., Wood, R., Finley, D., and Sadlack, F. (1993). Genetic predisposition in alcoholism: Association of the D2 dopamine receptor Tagl B RFLP with severe alcoholics. Alcohol 10:59-67.
Cabib, S., Puglisi-AHegra, S., and Oliverio, A. (1985). A genetic analysis of stereotype in the mouse dopaminergic plasticity following chronic stress. Behav. Neural Bial. 44:239-248.
Cabib, S., Kempf, E., Schleef, C, Oliverio, A., and Puglisi-Allegra, S. (1988). Effects of immobilization stress on dopamine and its metabolites in different brain areas of the mouse: Role of genotype and stress duration. Brain Res. 441:153-160.
Callan, V. J., and Jackson, D. (1986). Children of alcoholic fathers and recovered alcoholic fathers: Personality and family functioning. J-Stud. Alcohol 47:180-182.
Catlaway, E. (1991). Discussion: Towards a pharmacology of information processing. Electroencephalogr. Clin. Neurophysiol. Suppl. 42:173-176.
Comings, D. E., Commings, B. G., Muhleman, D., Dietz, G., Shahbahrami, B., last, D., Knell, E., Kocsis, P., Baumgarten, R,, K ovacs, B. W., Levy, D. L., Smith, M., Borison, R. L., Evans, D. D., Klein, D, N., MacMurray, J,, Tosk, J, M., Sverd, J., Gysin, R., and Flanagan, S. D. (1991). The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 266:1793-1800.
Deminiere, J. M., Simon, H., Herman, J. P., and Lc Moal, M. (1984). 6-Hydroxydopamine lesion of the dopamine mesocorticolimbic cell bodies increase (+) amphetamine self-administration. Psychopharnmcology 83:281-284.
Deminiere, J. M., Taghzouti, K., Tassin, J. P., Le Moal, H., and Simon, H. (1988). Increased sensitivity to amphetamine and facilitation of amphetamine self-administration after 6-hydroxydopamine. Psychopharmacology 94:232-236.
Dunn, A. J. (1988). Stress-related activation of cerebral dopaminergic systems. Ana. N.Y. Acad. Sci. 537:188-205.
Estaugh, V., and Power, C. (1991). Family disruption in early life and drinking in young adulthood. Alcohol Alcohol. 26:639-644.
Fadda, F., Argiolas, A., Melis, M. R., Tissari, A. H., Onali, P. L., and Gessa G. L. (1978). Stress-induced increase in 3,4-dihydroxy-phenylacetic acid (DOPAC) levels in the cerebral cortex and the n. accumbens: Reversal by diazepam. Life Sci. 23:2219-2224.
Friedman, D., Putnam, L., Hamberger, M., and Berman, S. M. (1992). Mini-longitudinal study of the cognitive ERPs during picture-making in children, adolescents and adults: A replication. J. Psychophysiol. 6:29-46.
Gelernter, J., Goldman, D., and Risch, N. (1993). The Al allele of the D dopamine receptor gene and alcoholism. JAMA 269:1673-1677.
Grandy, D. K., Zhang, Y., and Civelli, O. (1993). PCR detection of the Taq A RFLP at the DRD2 locus. Hum. Mot. Genet. 2:2179.
Hansenne, M., Pitchot, W., Moreno, A. G., P apart, P., Timsit-Berthier, M., and Ansseau, M. (1995). Catecholamine function and P300 amplitude in major depressive disorder (P300 and catecholatnines). Electroencephalogr. Clin. Neurophysiol. 96:194-196.
Heinz, A., Dettling, M., Kuhn, S., Dufeu, P., Graf, K. J., Kurten, L, Rommelspacher, H., and Schmidt, I. G. (1995). Blunted growth hormone response is associated with early relapse in alcohol-dependent patients. Alcohol Clin. Exp. Res. 19:62-65.
Hendren, R. L. (1990). Stress and adolescence. In Arnold, L. E. (eds.), Childhood Stress. Wiley, New York, pp. 247-264.
Herve, D., T assin, J. P., Berthelemy, C., Blanc, G., Lavielle, S., and Glowinski, J. (1979). Difference in the reactivity of the mesocortical dopominergic neurons to stress in the BALB/C and C57BL/6 mice. Life Sci. 25:1659-1664.
Hussong, A. M., and Chassin, L. (1994). The stress-negative affect model of adolescent alcohol use: Disaggregating negative effect.J. Stud. Alcohol 55:707-718.
Kendler, K. S., Heath, A. C., Neale, M. C., Kessler, R. C., and Eaves, L. J. (1992). A population-based twin study of alcoholism in women. JAMA 268:1877-1882.
FCIorman, R., and Brumaghim, J. T. (1991). Stimulant drugs and ERPs. Electroencephalogr. Clin. Neurophysiol. Suppl. 42:135-141.
Koob, G. F. (1992). Drugs of abuse: Anatomy, pharmacology and function of reward. Trends Pharmacol. Sci. 13:177-184.
Kumpfer, K. L., and DeMash, J. (1986). Family environmental and genetic influences on children's future chemical dependency. In Griswold-Ezekoye, S., Kumpfer, K. L., and Bukoski, W. J. (eds.),Childhood and Chemical Abuse: Prevention and Intervention, Haworth Press, New York, pp. 46-91.
Lewontin, R. C., Kamin, L. J., and Rose, S. (1983). Not in Our Genes, Pantheon, New York.
Lindgren, S. D., and Benton, A. L. (1980). Developmental patterns of visuospatial judgment. J. Pediatr. Psychol. 5: 217-225.
Moos, R. H., and Billings, A. G. (1982). Children of alcoholics during their recovery process: Alcoholic and matched control families. Addict. Behav. 7:155-163.
Moos, R. H., and Moos, B. S. (1986). Family Environment Scale Manual, 2nd ed., Consulting Psychologist Press, Palo Alto, CA.
Neiswanger, K., Hill, S. Y., and Kaplan, B. B. (1995). Association and linkage studies of Tagl A alleles at the dopamine D2 receptor gene in samples of female and male alcoholics.Am. J. Med. Genet. (Neuropsychiat. Genet.) 60:267-271.
Newcomb, M. D., and Harlow, L. L. (1986). Life events and substance use among adolescents: Mediating effects of perceived loss of control and meaninglessness in life. J. Person. Soc. Psychol. 51:564-579.
Noble, E. P., and Blum, K. (1993). Alcoholism and the D2 receptor gene. JAMA 270:1547-1548.
Noble, E. P., Blum, K., Ritchie, T., Montgomery, A., and Sheridan, P. J. (1991). Allelic association of the D, dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch. Gen. Psychiatry 48:648-654.
Noble, E. P., Blum. K., Khalsa, M. E., Ritchie, T., Montgomery, A., Wood, R. D., Fitch, R. J., Ozkaragoz, T., Sheridan, P. J., Anglin, M. D., Paredes, A., Treiman, L. J., and Sparkes, R. S. (1993). Allelic association of the D3 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend. 33:271-285.
Noble, E. P., Berman, S. M., Ozkaragoz, T. Z., and Ritchie, T. (1994a). Prolonged P300 latency in children with the Dz dopamine receptor Al allele. Am. J. Hum. Genet. 54: 658-668.
Noble, E. P., St. Jeor, S. T., Ritchie, T., Syndulko, K., St. Jeor, S. C., Fitch, R. J., Brunner, R. L., and Sparkes, R. S. (1994b). D, dopamine receptor gene and cigarette smoking: A reward gene? Med. Hypotheses 42:257-260.
Ozkaragoz, T. Z,, and Noble, E. P. (1995). Neuropsychological differences between sons of active alcoholic and non-alcoholic fathers. Alcohol Alcohol. 30:115-123.
Pickens, R. R., Svikis, D. S., McGue, M., Lykken, D. T., Heston, L. L., and Clayton, P. J. (1991). Heterogeneity in the inheritance of alcoholism: A study of male and female twins. Arch. Gen. Psychiatry 48:19-28.
Plomin, R., DeFries, J. C., and Loehlin, J. C. (1977). Genotype-environmental interaction and correlation in the analysis of human behavior. Psychol. Bull. 84:309-322.
Plomin, R., Owen, R., and McGuffin, P. (1994). The genetic basis of complex human behaviors. Science 264:1733-1739.
Polich, J., Pollock, V. E., and Bloom, F. E. (1994), Metaanalysis of P300 amplitude from individuals at risk for alcoholism. Psyckol. Bull. 115:55-73.
Rosier, F., Manzey, D., and Sojka, B. (1985). Delineation of pharmacological effects by means of endogenous eventrelated brain potentials: An exemplification with flupentixol. Neurophysiology 13:81-92.
Schandler, S. L., Brannock, J. C., Cohen, M. J., and Mendez, J. (1993). Spatial learning deficits in adolescent children of alcoholics. Exp. Clin. Psychopharmacol. 1:207-214.
Schandler, S. L., Thomas, C. S., and Cohen, M. J. (1995). Spatial learning deficits in preschool children of alcoholics. Alcohol. Clin. Exp. Res. 19:1067-1072.
Sher, K. J. (1991). Children of Alcoholics, University of Chicago Press. Chicago.
Simon, H., Scatton, B., and Le Moal, M. (1979). Definitive disruption of spatial delayed alterations in rats after lesions in the ventral mesoencephalic tegmentum. Neurosci. Lest. 15:319-324.
Simon, H,, Scatton, B., and Le Moal, M. (1980). Dopaminergic A10 neurons are involved in cognitive functions. Nature 286:150-151.
Smith, S. S., O'Hara, B. F., Persico, A. M., Gorelick, D. A., Newlin, D. B., Vlahov, D., Solomon, L., Pickens, R., and Uhl, G. R. (1992). Genetic vulnerability to drug abuse. The dopamine D2 receptor Taql B RFLP is more frequent in polysubstance abusers. Arch. Gen. Psychiatry 49:723-727.
Steinhauer, S. R., and Hill, S. Y. (1993). Auditory event-related potentials in children at high risk for alcoholism. J. Stud. Alcohol54:408-421.
Tarter, R. E., Jacob, T., and Bremer, D. A. (1989). Cognitive status of sons of alcoholic men.Alcohol. Clin. Exp. Res. 13:232-235.
Thierry, A. M., Tassin, J. P., Blanc, G., and Glowinski, J. (1976). Selective activation of the mesocortical DA system by stress. Nature 263:242-243.
Tiihonen, J., Kuikka, J., Bergstrom, K., Hakola, P., Karhu, J., Ryynanen, O.-P. and Fohr, J. (1995). Altered striatat dopamine re-uptake site densities in habitually violent and non-violent alcoholics. Nature Med. 1:654-657.
Uhl, G. R., Elmer, G. I., LaBuda, M. C., and Pickens, R. W. (1995). Genetic influences in drug abuse. In Bloom, F. E., and Kupfer, D. J. (eds.), Psychopharmacology, The Fourth Generation of Progress, Raven Press, New York, pp. 1793-1806.
Wechsler, D. (1974). Wechsler Intelligence Scale for Children-Revised, The Psychological Corporation, New York.
Werner, E. E. (1986). Resilient offspring of alcoholics: A longitudinal study from birth to age 18. J. Stud. Alcohol 47:34-40.
Whipple, S. C., Parker, E. S., and Noble, E. P. (1988). An atypical neurocognitive profile in alcoholic fathers and their sons. J. Stud. Alcohol 49:240-244.
Whipple, S. C., Berman, S. M., and Noble, E. P. (1991). Event-related potentials in alcoholic fathers and their sons. Alcohol 8:321-327.
Windle, M., and Searles, J. S. (eds.) (1990). Children of Alcoholics: Critical Perspectives, Guilford Press, New York.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Berman, S.M., Noble, E.P. The D2 Dopamine Receptor (DRD2) Gene and Family Stress; Interactive Effects on Cognitive Functions in Children. Behav Genet 27, 33–43 (1997). https://doi.org/10.1023/A:1025611208475
Issue Date:
DOI: https://doi.org/10.1023/A:1025611208475