Hostname: page-component-8448b6f56d-42gr6 Total loading time: 0 Render date: 2024-04-24T08:07:58.696Z Has data issue: false hasContentIssue false
  • English
  • Français

The conditioning of intervention effects on early adolescent alcohol use by maternal involvement and dopamine receptor D4 (DRD4) and serotonin transporter linked polymorphic region (5-HTTLPR) genetic variants

Published online by Cambridge University Press:  02 February 2015

H. Harrington Cleveland ,
Gabriel L. Schlomer ,
David J. Vandenbergh ,
Mark Feinberg ,
Mark Greenberg ,
Richard Spoth ,
Cleve Redmond ,
Mark D. Shriver ,
Arslan A. Zaidi  and
Kerry L. Hair
H. Harrington Cleveland*
Affiliation:
Pennsylvania State University
Gabriel L. Schlomer
Affiliation:
Pennsylvania State University
David J. Vandenbergh
Affiliation:
Pennsylvania State University
Mark Feinberg
Affiliation:
Pennsylvania State University
Mark Greenberg
Affiliation:
Pennsylvania State University
Richard Spoth
Affiliation:
Iowa State University
Cleve Redmond
Affiliation:
Iowa State University
Mark D. Shriver
Affiliation:
Pennsylvania State University
Arslan A. Zaidi
Affiliation:
Pennsylvania State University
Kerry L. Hair
Affiliation:
Pennsylvania State University
*
Address correspondence and reprint requests to: H. Harrington Cleveland, Department of Human Development and Family Studies, Pennsylvania State University, 315 East Human Development Building, University Park, PA 16802; E-mail: cleveland@psu.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.

Type
Special Section Articles
Information
Development and Psychopathology , Volume 27 , Issue 1: What Works for Whom? Genetic Moderation of Intervention Efficacy , February 2015 , pp. 51 - 67
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anchordoquy, H. C., McGeary, C., Liu, L., Krauter, K. S., & Smolen, A. (2003). Genotyping of three candidate genes after whole-genome preamplification of DNA collected from buccal cells. Behavior Genetics, 33, 73–78.Google Scholar
Asghari, V., Sanyal, S., Buchwaldt, S., Paterson, A., Jovanovic, V., & Van Tol, H. H. (1995). Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. Journal of Neurochemistry, 65, 1157–1165.Google Scholar
Bakermans-Kranenberg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to rearing environment depending on dopamine related genes: New evidence and meta-analysis. Development and Psychopathology, 23, 39–52.CrossRefGoogle Scholar
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (in press). The hidden efficacy of interventions: Gene × Environment experiments from a differential susceptibility perspective. Annual Review of Psychology.Google Scholar
Bakermans-Kranenberg, M. J., van IJzendoorn, M. H., Pijlman, F. T. A., Mesman, J., & Juffer, F. (2008). Experimental evidence for differential susceptibility: Dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers’ externalizing behavior in a randomized controlled trial. Developmental Psychology, 44, 293–300.Google Scholar
Barnes, J. J., Dean, A. J., Nandam, L. S., O'Connell, R. G., & Bellgrove, M. A. (2011). The molecular genetics of executive function: Role of monoamine system genes. Biological Psychiatry, 69, e127–e143.Google Scholar
Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007). For better and for worse: Differential susceptibility to environmental influences. Current Directions in Psychological Science, 16, 300–304.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis–stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885–908.Google Scholar
Belsky, J., & Pluess, M. (2013). Beyond risk, resilience and dysregulation: Phenotypic plasticity and human development. Development and Psychopathology, 25, 1243–1261.Google Scholar
Benjamin, J., Li, L., Patterson, C., Greenberg, B. D., Murphy, D. L., & Hamer, D. H. (1996). Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nature Genetics, 12, 81–84.Google Scholar
Botvin, G. J. (2000). Life Skills Training teacher's manual 3. Princeton, NJ: Princeton Heath Press, Inc.Google Scholar
Bradley, S. L., Dodelzon, K., Sandhu, H. K., & Philibert, R. A. (2005) Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA transcription. American Journal of Medical Genetics, 136B, 58–61.Google Scholar
Brody, G. H., Beach, S. R. H., Hill, K. G., Howe, G. W., & Prado, G. (2013). Using genetically informed, randomized prevention trials to test. American Journal of Public Health. Advance online publication.Google Scholar
Brody, G. H., Beach, S. R., Philibert, R. A., Chen, Y. F., & Murry, V. M. (2009) Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene × Environment hypotheses tested via a randomized prevention design. Child Development, 80, 645–661.Google Scholar
Brody, G. H., Beach, S. R., Philibert, R. A., Chen, Y. F., Lei, M. K., Murry, V. M., et al. (2009). Parenting moderates a genetic vulnerability factor in longitudinal increases in youths’ substance use. Journal of Consulting and Clinical Psychology, 77, 1–11. doi:10.1037/a0012996.Google Scholar
Bromberg-Martin, E. S., Matsumoto, M., & Hikosaka, O. (2010). Dopamine in motivational control: Rewarding, aversive, and alerting. Neuron, 68, 815–834. doi:10.1016/j.neuron.2010.11.022.CrossRefGoogle ScholarPubMed
Brook, J. S., Brook, D. W., Gordon, A. S., Whiteman, M., & Cohen, A. (1990). The psychosocial etiology of adolescent drug use: A family interactional approach. Genetic, Social and General Psychology Monographs, 116, 111–267.Google Scholar
Cardon, L. R., & Palmer, L. J. (2003). Population stratification and spurious allelic association. Lancet, 361, 598–604.Google Scholar
Covault, J., Tennen, H., Armeli, S., Conner, T. S., Herman, A. I., Cillessen, A. H. N., et al. (2007) Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biological Psychiatry, 61, 609–616.CrossRefGoogle ScholarPubMed
Creswell, K. G., Sayette, M. A., Manuck, S. B., Ferrell, R. E., Hill, S. Y., Dimoff, J. D., et al. (2012). DRD4 polymorphism moderates the effect of alcohol consumption on social bonding. PLOS ONE, 7, e28914. doi:10.1371/journal.pone.0028914.Google Scholar
Don, R. H., Cox, P. T., Wainwright, B. J., Baker, K., & Mattick, J. S. (1991). ‘Touchdown’ PCR to circumvent spurious priming during gene amplification. Nucleic Acids Research, 19, 4008.Google Scholar
Ebstein, R. P., Novick, O., Umansky, R., Priel, B., Osher, Y., Blaine, D., et al. (1996). Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nature Genetics, 12, 78–80.Google Scholar
Ellickson, P. L., McCaffrey, D. F., Ghosh-Dastidar, B., & Longshore, D. L. (2003). New inroads in preventing adolescent drug use: Results from a large-scale trial of Project ALERT in middle schools. American Journal of Public Health, 93, 1830–1836.Google Scholar
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 7–28.Google Scholar
Faraone, S. V., & Mick, E. (2010). Molecular genetics of attention deficit hyperactivity disorder. Psychiatric Clinics of North America, 33, 159–180. doi:10.1016/j.psc.2009.12.004.Google Scholar
Feinn, R., Nellissery, M., & Kranzler, H. R. (2005). Meta-analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence. American Journal of Medical Genetics, 133B, 79–84.Google ScholarPubMed
Figueredo, A. J., McKnight, P. E., McKnight, K. M., & Sidani, S. (2000). Multivariate modeling of missing data within and across assessment waves. Addiction, 95, 361–380.Google Scholar
Flint, J., & Munafò, M. R. (2013). Candidate and non-candidate genes in behavior genetics. Current Opinion in Neurobiology, 23, 57–61.Google Scholar
Frazier, P. A., Tix, A. P., & Barron, K. E. (2004). Testing moderator and mediator effects in counseling psychology research. Journal of Counseling Psychology, 51, 115–134.CrossRefGoogle Scholar
Freedman, M. L., Reich, D., Penney, K. L., McDonald, G. J., Mignault, A. A., Patterson, N., et al. (2004). Assessing the impact of population stratification on genetic association studies. Nature Genetics, 36, 388–393.CrossRefGoogle ScholarPubMed
Freeman, B., Smith, N., Curtis, C., Huckett, L., Mill, J., & Craig, I. W. (2003). DNA from buccal swabs recruited by mail: Evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavior Genetics, 33, 67–72.Google Scholar
Gardner, F., Hutchings, J., Bywater, T., & Whitaker, C. (2010). Who benefits and how does it work? Moderators and mediators of outcome in an effectiveness trial of a parenting intervention. Journal of Clinical Child and Adolescent Psychology, 39, 568–580. doi:10.1080/15374416.2010.486315Google Scholar
Gelernter, J., Cubells, J. F., Kidd, J. R., Pakstis, A. J., & Kidd, K. K. (1999). Population studies of polymorphisms of the serotonin transporter protein gene. American Journal of Medical Genetics, 88, 61–66.Google Scholar
Gilsbach, S., Neufang, S., Scherag, S., Vloet, T. D., Fink, G. R., Herpertz-Dahlmann, B., et al. (2012) Effects of the DRD4 genotype on neural networks associated with executive functions in children and adolescents. Developmental Cognitive Neuroscience, 2, 417–427.Google Scholar
Goncy, E. A., & van Dulmen, M. H. M. (2010). Fathers do make a difference: Parental involvement and adolescent alcohol use. Fathering, 8, 93–108.Google Scholar
Guyll, M., Spoth, R. L., Chao, W., Wickrama, K. A. S., & Russell, D. (2004). Family-focused preventive interventions: Evaluating parental risk moderation of substance use trajectories. Journal of Family Psychology, 18, 293–301.Google Scholar
Halder, I., Shriver, M., Thomas, M., Fernandez, J. R., & Frudakis, T. (2008). A panel of ancestry informative markers for estimating individual biogeographical ancestry and admixture from four contents: Utility and applications. Human Mutation, 29, 648–658.Google Scholar
Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., et al. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66, 2621–2624.CrossRefGoogle ScholarPubMed
Herman, A., Philbeck, J., Vassilopoulos, N., & Depetrillo, P. (2003) Serotonin transporter promoter polymorphism and differences in alcohol consumption behavior in a college student population. Alcohol, 38, 446–449.CrossRefGoogle Scholar
Holmes, A. (2008). Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease. Neuroscience & Biobehavioral Reviews, 32, 1293–1314. doi:10.1016/j.neubiorev.2008.03.006.Google Scholar
Jaffee, S. R., & Price, T. S. (2007). Gene–environment correlations: A review of the evidence and implications for prevention of mental illness. Molecular Psychiatry, 12, 432–442.Google Scholar
Jasinska, A. J., Lowry, C. A., & Burmeister, M. (2012). Serotonin transporter gene, stress and raphe–raphe interactions: A molecular mechanism of depression. Trends in Neuroscience, 35, 395–402. doi:10.1016/j.tins.2012.01.001Google Scholar
Jonassen, R., & Landro, N. I. (2014). Serotonin transporter polymorphisms (5-HTTLPR) in emotion processing implications from current neurobiology. Progress in Neurobiology, 117, 41–53.Google Scholar
Jones, D. J., Olson, A. L., Forehand, R., Gaffney, C. A., Zens, M. S., & Bau, J. J. (2005). A family-focused randomized controlled trial to prevent adolescent alcohol and tobacco use: The moderating roles of positive parenting and adolescent gender. Behavior Therapy, 36, 347–355.Google Scholar
Jordan, L. C., & Lewis, M. L. (2005). Paternal relationship quality as a protective factor: Preventing alcohol use among African American adolescents. Journal of Black Psychology, 31, 152–171.CrossRefGoogle Scholar
Kaufman, J., Gelernter, J., Kaffman, A., Caspi, A., & Moffitt, T. (2010) Arguable assumptions, debatable conclusions. Biological Psychiatry, 67, e19–e20.CrossRefGoogle ScholarPubMed
Keller, M., (2014). Gene × Environment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75, 18–24.Google Scholar
Kenna, G. A., Roder-Hanna, N., Leggio, L., Zywiak, W. H., Clifford, J., Edwards, S., et al. (2012). Association of the 5-HTT gene-linked promoter region (5-HTTLPR) polymorphism with psychiatric disorders: Review of psychopathology and pharmacotherapy. Pharmacogenomics and Personalized Medicine, 5, 19–35. doi:10.2147/PGPM.S23462.Google Scholar
Kluger, A. N., Siegfried, Z., & Ebstein, R. P. (2002). A meta-analysis of the association between DRD4 polymorphism and novelty seeking. Molecular Psychiatry, 7, 712–717.Google Scholar
Kochanska, G., Kim, S., Barry, R. A., & Philibert, R. A. (2011). Children's genotypes interact with maternal responsive care in predicting children's competence: Diathesis–stress or differential susceptibility? Development and Psychopathology, 23, 605–616.Google Scholar
Kreek, M. J., Nielsen, D. A., Butelman, E. R., & LaForge, K. S. (2005). Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nature Neuroscience, 8, 1450–1457.CrossRefGoogle ScholarPubMed
Larsen, H., van der Zwaluw, C. S., Overbeek, G., Granic, I., Franke, B., & Engels, R. C. (2010). A variable-number-of-tandem-repeats polymorphism in the dopamine D4 receptor gene affects social adaptation of alcohol use: Investigation of a gene–environment interaction. Psychological Science, 21, 1064–1068. doi:10.1177/0956797610376654.CrossRefGoogle ScholarPubMed
Le Moal, M., & Simon, H. (1991) Mesocorticolimbic dopaminergic network: Functional and regulatory roles. Physiology Review, 71, 155–234.Google Scholar
Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527–1531.CrossRefGoogle ScholarPubMed
Lichter, J. B., Barr, C. L., Kennedy, J. L., Van Tol, H. H., Kidd, K. K., & Livak, K. J. (1993). A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Human Molecular Genetics, 2, 767–773.Google Scholar
Lippold, M. A., Greenberg, M. T., & Collins, L. (in press). Youths’ substance use and changes in parental knowledge-related behaviors during middle school: A person-oriented approach. Journal of Youth and Adolescence.Google Scholar
Little, K. Y., Mclaughlin, D. P., Zhang, L., Livermore, C. S., Dalack, G. W., McFinton, P. R., et al. (1998) Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. American Journal of Psychiatry, 155, 207–213.Google Scholar
Mackie, J. L. (1965), Causes and conditionals. American Philosophical Quarterly, 2, 245–265.Google Scholar
Malhotra, A. K., Virkkunen, M., Rooney, W., Eggert, M., Linnoila, M., & Goldman, D. (1996). The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Molecular Psychiatry, 1, 388–391.Google Scholar
Marshal, M. P., & Chassin, L. (2000). Peer influence on adolescent alcohol use: The moderating role of parental support and discipline. Applied Developmental Science, 4, 80–88.CrossRefGoogle Scholar
McClelland, G. H., & Judd, C. M. (1993). Statistical difficulties of detecting interactions and moderator effects. Psychological Bulletin, 114, 376–390.Google Scholar
McNeal, R. B., Hansen, W. B., Harrington, N. G., & Giles, S. M. (2004). How All Stars works: An examination of program effects on mediating variables. Health Education & Behavior, 31, 165–178.Google Scholar
Munafò, M. R., Durrant, C., Lewis, G., & Flint, J. (2009) Gene × Environment interactions at the serotonin transporter locus. Biological Psychiatry, 65, 211–219.Google Scholar
Munafò, M. R., Yalcin, B., Willis-Owen, S. A., & Flint, J. (2008). Association of the dopamine D4 receptor (DRD4) gene and approach-related personality traits: Meta-analysis and new data. Biological Psychiatry, 63, 197–206.Google Scholar
Nikolova, Y. S., Ferrell, R. E., Manuck, S. B., & Hariri, A. R. (2011). Multilocus genetic profile for dopamine signaling predicts ventral striatum reactivity. Neuropsychopharmacology, 36, 1940–1947.Google Scholar
Odgers, C. L., Caspi, A., Nagin, D. S., Piquero, A. R., Slutske, W. S., Milne, B. J., et al. (2008). Is it important to prevent early exposure to drugs and alcohol among adolescents? Psychological Science, 19, 1037–1044.Google Scholar
Pérez-Edgar, K., Hardee, J. E., Guyer, A. E., Benson, B. E., Nelson, E. E., Gorodetsky, E., et al. (2013). DRD4 and striatal modulation of the link between childhood behavioral inhibition and adolescent anxiety. Social Cognitive and Affective Neuroscience, 9, 445–453. doi:10.1093/scan/nst001.Google Scholar
Petraitis, J., Flay, B. R., & Miller, T. Q. (1995). Reviewing theories of adolescent substance use: Organizing pieces of the puzzle. Psychological Bulletin, 117, 67–86.Google Scholar
Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., et al. (2005). 5-HTTLPR polymorphism impacts human cingulate–amygdala interactions: A genetic susceptibility mechanism for depression. Nature Neuroscience, 8, 828–834.Google Scholar
Pilgrim, C. C., Schulenberg, J. E., O'Malley, P. M., Bachman, J. G., & Johnston, L. D. (2006). Mediatiors and moderators of parental involvement on substance use: A national study of adolescents. Prevention Science, 7, 75–89.Google Scholar
Preacher, K. J., Curran, P. J., & Bauer, D. J. (2006). Computational tools for probing interaction effects in multiple linear regression, multilevel modeling, and latent curve analysis. Journal of Educational and Behavioral Statistics, 31, 437–448.Google Scholar
Price, T. S., & Jaffee, S. R. (2008). Effects of the family environment: Gene–environment interaction and passive gene–environment correlation. Developmental Psychology, 44, 305–315. http://dx.doi.org/10.1037/0012-1649.44.2.305Google Scholar
Roisman, G. I., Newman, D. A., Fraley, C., Haltigan, J. D., Groh, A. M., & Haydon, K. C. (2012). Distinguishing differential susceptibility from diathesis–stress: Recommendations for evaluating interaction effects. Development and Psychopathology, 24, 389–409.Google Scholar
Rowe, D. C., Stever, C. L., Giedinghagen, N., Gard, J. M. C., Cleveland, H. H., Terris, S. T., et al. (1999). Dopamine DRD4 receptor polymorphism and attention deficit disorder. Molecular Psychiatry, 3, 419–426.Google Scholar
Rutter, M., Thapar, A., & Pickles, A. (2009). Gene–environment interactions: Biologically valid pathway or artifact? Archives of General Psychiatry, 66, 1287–1289.Google Scholar
Ryan, S. M., Jorm, A. F., & Lubman, D. I. (2010). Parenting factors associated with reduced adolescent alcohol use: A systematic review of longitudinal studies. Australian and New Zealand Journal of Psychiatry, 44, 774–783.Google Scholar
Sander, T., Harms, H., Dufeu, P., Kuhn, S., Rommelspacher, H., & Schmidt, L. G. (1997). Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics. American Journal of Medical Genetics, 74, 483–487.Google Scholar
Schoots, O., & Van Tol, H. H. (2003). The human dopamine D4 receptor repeat sequences modulate expression. Pharmacogenomics Journal, 3, 343–348.Google Scholar
Sheese, B. E., Voelker, P. M., Rothbart, M. K., & Posner, M. I. (2007). Parenting quality interacts with genetic variation in dopamine receptor D4 to influence temperament in early childhood. Developmental Psychopathology, 19, 1039–1048.Google Scholar
Skowronek, M. H., Laucht, M., Hohm, E., Becker, K., & Schmidt, M. H. (2006). Interaction between the dopamine D4 receptor and the serotonin transporter promoter polymorphisms in alcohol and tobacco use among 15-year-olds. Neurogenetics, 7, 239–246.Google Scholar
Smit, E., Verdumen, J., Monshouwer, K., & Smit, F. (2008). Family interventions and their effect on adolescent alcohol use in general populations: A meta-analysis of randomized controlled trials. Drug and Alcohol Dependence, 97, 195–206.Google Scholar
Spoth, R., Greenberg, M., Bierman, K., & Redmond, C. (2004) PROSPER community–university partnership model for public education systems: Capacity-building for evidence-based, competence-building prevention. Prevention Science, 5, 31–39.Google Scholar
Spoth, R., Greenberg, M., & Turrisi, R. (2008). Preventive interventions addressing underage drinking: State of the evidence and steps toward public health impact. Pediatrics, 121(Suppl. 4), S311–S336.Google Scholar
Spoth, R., Guyll, M., Lillehoj, C. J., Redmond, C., & Greenberg, M. (2007). PROSPER study of evidence-based intervention implementation quality by community–university partnerships. Journal of Community Psychology, 35, 981–999. doi:10.1002/jcop.20207Google Scholar
Spoth, R., Redmond, C., Clair, S., Shin, C., Greenberg, M., & Feinberg, M. (2011). Preventing substance misuse through community–university partnerships: Randomized controlled trial outcomes 4½ years past baseline. American Journal of Preventive Medicine, 40, 440–447.Google Scholar
Spoth, R., Redmond, C., Shin, C., Greenberg, M., Feinberg, M., & Schainker, L. (2013). Longitudinal effects of universal PROSPER community–university partnership delivery system effects on substance misuse through 6 1/2 years past baseline from a cluster randomized controlled intervention trial. Preventive Medicine, 56, 190–196.Google Scholar
van IJzendoorn, M., Bakermans-Kranenburg, M., Belsky, J., Beach, S., Brody, G., Dodge, K., et al. (2011). Gene by environment experiments: A new approach to find missing heritability. Nature Reviews Genetics, 12, 881.Google Scholar
Windle, M., Spear, L. P., Fulgni, A. J., Angold, A., Brown, J. D., Pine, D., et al. (2008). Transitions into underage and problem drinking: Developmental processes and mechanisms between 10 and 15 years of age. Pediatrics, 121, s273–s289.Google Scholar
Zohsel, K., Buchmann, A. F., Blomeyer, D., Hohm, E., Schmidt, M. H., Esser, G., et al. (2014). Mothers’ prenatal stress and their children's antisocial outcomes—A moderating role for the dopamine D4 receptor (DRD4) gene. Journal of Child Psychology and Psychiatry, 55, 69–76. doi:10.1111/jcpp.12138.Google Scholar