Journal of Substance Abuse Treatment
Volume 38, Issue 2 , Pages 178-190 , March 2010

Genetic, personality, and environmental predictors of drug use in adolescents

  • Bradley T. Conner, Ph.D.

      Affiliations

    • Department of Psychology, Temple University, Philadelphia, PA 19122, USA
    • ,
  • Gerhard S. Hellemann, Ph.D.

      Affiliations

    • Biostatistics Core, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    • ,
  • Terry L. Ritchie, Ph.D.

      Affiliations

    • Alcohol Research Center, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    • ,
  • Ernest P. Noble, Ph.D., M.D.

      Affiliations

    • Alcohol Research Center, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    • Corresponding Author InformationCorresponding author. UCLA Alcohol Research Center, 760 Westwood Plaza, Los Angeles, CA, USA. Tel.: +1 310 825 1891; fax: +1 310 206 7309.

Received 3 February 2009 ,Revised 23 June 2009 ,Accepted 21 July 2009.

References 

  1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders, 4th ed, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Press, Inc; 2000;
  2. Arnett J. Reckless behavior in adolescence: A developmental perspective. Developmental Review. 1992;12:339–373
  3. Aseltine RH, Gore S, Colten ME. The co-occurrence of depression and substance abuse in late adolescence. Development and Psychopathology. 1998;10:513–529
  4. Beck AT. Beck depression inventory-II (BDI-II). San Antonio, TX: The Psychological Corporation; 1996;
  5. Benton AL, Varney NR, Hamsher KD. Visuospatial judgment. A clinical test. Archives of Neurology. 1978;35:364–367
  6. Berggren U, Fahlke C, Aronsson E, Karanti A, Eriksson M, Blennow K, et al. The Taq1 DRD2 A1 allele is associated with alcohol-dependence although its effect size is small. Alcohol and Alcoholism. 2006;41:479–485
  7. Berman SM, Noble EP. Reduced visuospatial performance in children with the D2 dopamine receptor A1 allele. Behavioral Genetics. 1995;25:45–58
  8. Bowirrat A, Oscar-Berman M. Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2005;132B:29–37
  9. Breiman L, Freidman JH, Olshen RA, Stone CJ. Classification and regression trees. Belmont, CA: Wadsworth International; 1984;
  10. Bressan RA, Crippa JA. The role of dopamine in reward and pleasure behaviour—Review of data from preclinical research. Acta Psychiatrica Scandinavica. 2005;111(Suppl. 427):14–21
  11. Button TM, Hewitt JK, Rhee SH, Young SE, Corley RP, Stallings MC. Examination of the causes of covariation between conduct disorder symptoms and vulnerability to drug dependence. Twin Research & Human Genetics. 2006;9:38–45
  12. Chen C-Y, Storr CL, Anthony JC. Early-onset drug use and risk for drug dependence problems. Addictive Behaviors. 2009;34:319–322
  13. Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science. 1987;236:410–416
  14. Cloninger CR, Sigvardsson S, Bohman M. Childhood personality predicts alcohol abuse in young adults. Alcohol: Clinical and Experimental Research. 1988;12:494–505
  15. Cohen MX, Krohn-Grimberghe A, Elger CE, Weber B. Dopamine gene predicts the brain's response to dopaminergic drug. European Journal of Neuroscience. 2007;26:3652–3660
  16. Colhoun HM, McKeigue PM, Smith GD. Problems of reporting genetic associations with complex outcomes. Lancet. 2003;361:865–872
  17. Conner BT, Noble EP, Berman SM, Ozkaragoz T, Ritchie T, Antolin T, et al. DRD2 genotypes and substance use in adolescent children of alcoholics. Drug and Alcohol Dependence. 2005;79:379–387
  18. Deas D, Thomas S. Comorbid psychiatric factors contributing to adolescent alcohol and other drug use. Alcohol Research & Health. 2002;26:116–121
  19. de Courten-Myers GM. The human cerebral cortex: Gender differences in structure and function. Journal of Neuropatholology and Experimental Neurology. 1999;58:217–226
  20. Derringer J, Krueger RF, McGue M, Iacono WG. Genetic and environmental contributions to the diversity of substances used in adolescent twins: A longitudinal study of age and sex effects. Addiction. 2008;103:1744–1751
  21. Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proceedings of the National Academy of Sciences of the United States of America. 1988;85:5274–5278
  22. Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, et al. Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Human Molecular Genetics. 2003;12:205–216
  23. Edenberg HJ, Dick DM, Xuei X, Tian H, Almasy L, Bauer LO, et al. Variations in GABRA2 encoding the alpha 2 subunit of the GABAA receptor, are associated with alcohol dependence and with brain oscillations. American Journal of Human Genetics. 2004;74:705–714
  24. Eysenck HJ, Eysenck SBG. Manual of the Eysenck Personality Questionnaire (Junior and Adult). London: Hodder & Staughton; 1975;
  25. Feldstein SW, Miller WR. Substance use and risk-taking among adolescents. Journal of Mental Health. 2006;15:633–643
  26. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV Axis I disorders, clinician version (SCID-CV). Washington, DC: American Psychiatric Press, Inc; 1996;
  27. Flannery DJ, Vazsonyi AT, Torquati J, Fridrich A. Ethnic and gender differences in risk for early adolescent substance use. Journal of Youth and Adolescence. 1994;23:195–213
  28. Fleming CB, Mason WA, Mazza J, Abbott RD, Catalano RF. Latent growth modeling of the relationship between depressive symptoms and substance use during adolescence. Psychology of Addictive Behaviors. 2008;22:186–197
  29. Florsheim P, Shiozaki T, Hiraoka R, Tiffany ST, Heavin S, Hall S, et al. Craving among polysubstance-using adolescents. Journal of Child & Adolescent Substance Abuse. 2007;17:101–124
  30. Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, et al. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. American Journal of Human Genetics. 1989;45:778–785
  31. Grandy DK, Zhang Y, Civelli O. PCR detection of the Taq A RFLP at the DRD2 locus. Human Molecular Genetics. 1993;2:2197
  32. Grant BF, Dawson DA. Age at onset of drug use and its association with DSM-IV drug abuse and dependence: Results from the National Longitudinal Alcohol Epidemiologic Survey. Journal of Substance Abuse. 1998;10:163–173
  33. Guindalini C, Howard M, Haddley K, Laranjeira R, Collier D, Ammar N, et al. A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample. Proceedings of the National Academy of Sciences of the United States of America. 2006;103:4552–4557
  34. Han C, McGue MK, Iacono WG. Lifetime tobacco, alcohol, and other substance use in adolescent Minnesota twins: Univariate and multivariate behavioral genetic analyses. Addiction. 1999;94:981–993
  35. Harlaar N, Butcher LM, Meaburn E, Sham P, Craig IW, Plomin R. A behavioural genomic analysis of DNA markers associated with general cognitive ability in 7-year-olds. Journal of Child Psychology and Psychiatry. 2005;46:1097–1107
  36. Heath AC, Bucholz KK, Madden PAF, Dinwiddie SH, Slutske WS, Bierut LJ, et al. Genetic and environmental contributions to alcohol dependence risk in a national twin sample: Consistency of findings in women and men. Psychological Medicine. 1997;27:1381–1396
  37. Hellemann G, Conner BT, Anglin MD, Longshore D. Seeing the trees despite the forest: Applying recursive partitioning to the evaluation of drug treatment retention. Journal of Substance Abuse and Treatment. 2009;36:59–64
  38. Hill SY, Hoffman EK, Zezza N, Thalamuthu A, Weeks DE, Mathews AG, et al. Dopaminergic mutations: Within-family association and linkage multiplex alcohol dependence families. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2008;147B:517–526
  39. Hirvonen M, Laakso A, Någren K, Rinne JO, Pohjalainen T, Hietala J. C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo. Molecular Psychiatry. 2004;9:1060–1061
  40. Hoda F, Nicholl D, Bennett P, Arranz M, Aitchison KJ, Al-Chalabi A, et al. No association between Parkinson's disease and low-activity alleles of catechol-O-methyltransferase. Biochemical and Biophysical Research Communications. 1996;228:780–784
  41. Hutchison KE, Stallings M, McGeary J, Bryan A. Population stratification in the Candidate Gene Study: Fatal threat or red herring?. Psychological Bulletin. 2004;130:66–79
  42. Ikemoto S, Kohl RR, McBride WJ. GABAA receptor blockage in the ventral tegmental area increases extracellular levels of dopamine in the nucleus accumbens of rats. Journal of Neurochemistry. 1997;69:137–143
  43. Jang KL, Livesley WJ, Vernon PA. Gender-specific etiological differences in alcohol and drug problems: A behavioural genetic analysis. Addiction. 1997;92:1265–1276
  44. Jessor R, Donovan JE, Costa FM. Health Behavior Questionnaire. Boulder, CO: University of Colorado Institute of Behavioral Science; 1992;
  45. Johnson SW, North RA. Opioids excite dopamine neurons by hyperpolarization of loval interneurons. Journal of Neuroscience. 1992;12:483–488
  46. Jönsson EG, Nöthen MM, Grünhage F, Farde L, Nakashima Y, Propping P, et al. Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Molecular Psychiatry. 1999;4:290–296
  47. Kaasinen V, Nägren K, Hietala J, Farde L, Rinne JO. Sex differences in extrastriatal dopamine D2-like receptors in the human brain. American Journal of Psychiatry. 2001;158:308–311
  48. Kashdan TB, Vetter CJ, Collins RL. Substance use in young adults: Associations with personality and gender. Addictive Behaviors. 2005;30:259–269
  49. King SM, Iacono WG, McGue M. Childhood externalizing and internalizing psychopathology in the prediction of early substance use. Addiction. 2004;99:1548–1559
  50. Kirisci L, Tarter RE, Vanyukov M, Martin C, Mezzich A, Brown S. Application of item response theory to quantify substance use disorder severity. Addictive Behaviors. 2006;31:1035–1049
  51. Klein TA, Neumann J, Reuter M, Hennig J, von Cramon DY, Ullsperger M. Genetically determined differences in learning from errors. Science. 2007;318:1642–1645
  52. Köhnke MD, Batra A, Kolb W, Köhnke AM, Lutz U, Schick S, et al. Association of the dopamine transporter gene with alcoholism. Alcohol and Alcoholism. 2005;40:339–342
  53. Lachman H, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996;6:243–250
  54. Lachman HM. An overview of the genetics of substance use disorders. Current Psychiatry Reports. 2006;8:133–143
  55. Lemon SC, Roy J, Clark MA, Friedmann PD, Rakowski W. Classification and regression tree analysis in public health: Methodological review and comparison with logistic regression. Annals of Behavioral Medicine. 2003;26:172–181
  56. Lichter JB, Barr CL, Kennedy JL, Van Tol HHM, Kidd KK, Livak KJ. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Human Molecular Genetics. 1993;2:767–773
  57. Limosin F, Gorwood P, Loze J-Y, Dubertret C, Gouya L, Deybach J-C, et al. Male limited association of the dopamine receptor D2 gene TaqI A polymorphism and alcohol dependence. American Journal of Medical Genetics. 2002;112:343–346
  58. Luby JL, Svrakic DM, McCallum K, Przybeck TR, Cloninger CR. The Junior Temperament and Character Inventory: Preliminary validation of a child self-report measure. Psychological Reports. 1999;84:1127–1138
  59. Lusher JM, Chandler C, Ball D. Dopamine D4 receptor gene (DRD4) is associated with novelty seeking (NS) and substance abuse: The saga continues. Molecular Psychiatry. 2001;6:497–499
  60. Mâsse LC, Tremblay RE. Behavior of boys in kindergarten and the onset of substance use during adolescence. Archives of General Psychiatry. 1997;54:62–68
  61. McGeary JE, Esposito-Smythers C, Spirito A, Monti PM. Association of the dopamine D4 receptor gene VNTR polymorphism with drug use in adolescent psychiatric inpatients. Pharmacology, Biochemistry, and Behavior. 2007;86:401–406
  62. Melis M, Spiga S, Diana M. The dopamine hypothesis of drug addiction: Hypodopaminergic state. International Review of Neurobiology. 2005;63:101–154
  63. Merenäkk L, Harro M, Kiive E, Laidra K, Eensoo D, Allik J, et al. Association between substance use, personality traits, and platelet MAO activity in preadolescents and adolescents. Addictive Behaviors. 2003;28:1507–1514
  64. Michelhaugh SK, Fiskerstrand C, Lovejoy E, Bannon MJ, Quinn JP. The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons. Journal of Neurochemistry. 2001;79:1033–1038
  65. Moos RH, Moos BS. Life stressors and social resources inventory: Youth form manual. Odessa, FL: Psychological Assessment Resources; 1994;
  66. Mutirangura A, Ledbetter SA, Kuwano A, Chinault AC, Ledbetter DH. Dinucleotide repeat polymorphism at the GABAA receptor β3 (GABRB3) locus in the Angelman/Prader-Willi region (AS/PWS) of chromosome 15. Human Molecular Genetics. 1992;1:67
  67. Namkoong K, Cheon K-A, Kim J-W, Jun J-Y, Lee J-L. Association study of dopamine D2, D4 receptor gene, GABAA receptor β subunit gene, serotonin transporter gene polymorphism with children of alcoholics in Korea: A preliminary study. Alcohol. 2008;42:77–81
  68. Chanock SJ, Manolio T, Boehnke M, Boerwinkle E, Hunter DJ, Thomas G, et al. Replicating genotype–phenotype associations. Nature. 2007;447:655–660
  69. Nestler EJ. Genes and addiction. Nature Genetics. 2000;26:277–281
  70. Neville MJ, Johnstone EC, Walton RT. Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Human Mutation. 2004;23:540–545
  71. Noble EP. D2 dopamine receptor gene in psychiatric and neurological disorders and its phenotypes. American Journal of Medical Genetics. Part. B, Neuropsychiatric Genetics. 2003;116B:103–125
  72. Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ. Allelic association of the D2 dopamine receptor gene with receptor binding characteristics in alcoholism. Archives of General Psychiatry. 1991;48:648–654
  73. Noble EP, Zhang X, Ritchie T, Lawford BR, Grosser SC, Young RM, et al. D2 dopamine receptor and GABAA receptor β3 subunit genes and alcoholism. Psychiatry Research. 1998;81:133–147
  74. Oak JN, Oldenhof J, Van Tol HHM. The dopamine D4 receptor: One decade of research. European Journal of Pharmacology. 2000;405:303–327
  75. Pohjalainen T, Rinne JO, Någren K, Lehikoinen P, Anttila K, Syvälahti EKG, et al. The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers. Molecular Psychiatry. 1998;3:256–260
  76. Pohjalainen T, Rinne JO, Nägren K, Syvälahti E, Hietala J. Sex differences in the striatal dopamine D2 receptor binding characteristics in vivo. American Journal of Psychiatry. 1998;155:768–773
  77. Robins LN, Przybeck TR. Age of onset of drug use as a factor in drug and other disorders. In:  Jones CL,  Battjes RJ editor. Etiology of drug abuse: Implications for prevention. National Institute on Drug Abuse Research Monograph 56. Rockville, MD: U.S. Department of Health and Human Services; 1991;p. 178–192
  78. Sáiz PA, G-Portilla MP, Paredes B, Delgado J, Martínez S, Bascarán MT, et al. Use of cocaine by secondary school students in northern Spain. European Addiction Research. 2003;9:138–143
  79. Samochowiec J, Kucharska-Mazur J, Grzwacz A, Jabłoński M, Rommelspacher H, Samochowiec A, et al. Family-based and case-control study of DRD2, DAT, 5HTT, COMT genes polymorphisms in alcohol dependence. Neuroscience Letters. 2006;410:1–5
  80. Scheier LM, Botvin GJ, Miller NL. Life events, neighborhood stress, psychosocial functioning, and alcohol use among urban minority youth. Journal of Child & Adolescent Substance Abuse. 1999;30:19–50
  81. Schoots O, Van Tol HHM. The human dopamine D4 receptor repeat sequences modulate expression. Pharmacogenomics Journal. 2003;3:343–348
  82. Shoal G, Giancola P. Cognition, negative affectivity, and substance use in adolescent boys with and without a family history of a substance use disorder. Journal of Studies on Alcohol. 2001;62:675–686
  83. Song J, Koller DL, Foroud T, Carr K, Zhao J, Rice J, et al. Association of GABAA receptors and alcohol dependence and the effects of genetic imprinting. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 2003;117B:39–45
  84. Spanagel R, Weiss F. The dopamine hypothesis of reward: Past and current status. Trends in Neurosciences. 1999;22:521–527
  85. Spear LP. The adolescent brain and age-related behavioral manifestations. Neuroscience and Biobehavioral Reviews. 2000;24:417–463
  86. Steinberg L. A social neuroscience perspective on adolescent risk-taking. Developmental Review. 2008;28:78–106
  87. Taylor J. Life events and peer substance use and their relation to substance use problems in college students. Journal of Drug Education. 2006;36:179–191
  88. Tcheremissine OV, Lane SD, Cherek DR, Pietras CJ. Impulsiveness and other personality dimensions in substance use disorders and conduct disorders. Addictive Disorders & Their Treatment. 2003;2:1–7
  89. Theile JW, Morikawa H, Gonzales RA, Morrisett RA. Ethanol enhances GABAergic transmission onto dopamine neurons in the ventral tegmental area of the rat. Alcohol: Clinical & Experimental Research. 2008;32:1040–1048
  90. Therneau TM, Atkinson B. The rpart package. Retrieved October 6, 2006, from University of California, Los Angeles Statistics Department Comprehensive R Archive Network http://cran.stat.ucla.edu2006;
  91. Vandenbergh DJ, Bennett CJ, Grant MD, Strasser AA, O'Connor R, Stauffer RL, et al. Smoking status and the human transporter variable number of tandem repeats (VNTR) polymorphism: Failure to replicate and finding that never-smokers may be different. Nicotine & Tobacco Research. 2002;4:333–340
  92. Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, et al. Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics. 1992;14:1104–1106
  93. Vandenbergh DJ, Rodriguez LA, Miller IT, Uhl GR, Lachman HM. High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. 1997;74:439–442
  94. Volkow ND, Wang G-J, Begleiter H, Porjesz B, Fowler JS, Telang F, et al. High levels of dopamine D2 receptors in unaffected members of alcoholic families: Possible protective factors. Archives of General Psychiatry. 2006;63:999–1008
  95. Wang T, Franke P, Neidt H, Cichon S, Knapp M, Lichtermann D, et al. Association study of the low-activity allele of catechol-O-methyltransferase and alcoholism using a family-based approach. Molecular Psychiatry. 2001;6:109–111
  96. White FJ. Synaptic regulation of mesocorticolimbic dopamine neurons. Annual Review of Neuroscience. 1996;19:405–436
  97. Wills TA, Vaccaro D, McNamara G. The role of life events, family support, and competence in adolescent substance use: A test of vulnerability and protective factors. American Journal of Community Psychology. 1992;20:349–374
  98. Yang B-Z, Kranzler HR, Zhao H, Gruen JR, Luo X, Gelernter J. Haplotypic variants in DRD2, ANKK1, TTC12, and NCAM1 are associated with comorbid alcohol and drug dependence. Alcoholism: Clinical and Experimental Research. 2008;32:2117–2127
  99. Zaykin DV, Young SS. Large recursive partitioning analysis of complex disease pharmacogenetic studies. II. Statistical considerations. Pharmacogenomics. 2005;6:77–89
  100. Zhang H, Singer B. Recursive partitioning in the health sciences. New York: Springer-Verlag; 1999;

PII: S0740-5472(09)00122-6

doi: 10.1016/j.jsat.2009.07.004

Journal of Substance Abuse Treatment
Volume 38, Issue 2 , Pages 178-190 , March 2010

Article Tools

* Image Usage & Resolution