Skip to main content

Advertisement

SpringerLink
Log in

Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse

  • Published:
Prevention Science Aims and scope Submit manuscript

Abstract

Accumulative evidence from recent genotype × intervention studies suggests that individuals carrying susceptible genotypes benefit more from intervention and provides one avenue to identify subgroups that respond differentially to intervention. This study examined the moderation by glucocorticoid receptor (NR3C1) gene variants of intervention effects on the developmental trajectories of alcohol abuse through adolescence. Participants were randomized into Fast Track intervention and control groups self-reported past-year alcohol abuse annually from grade 7 through 2 years post-high school and provided genotype data at age 21 (69% males; European Americans [EAs] = 270, African-Americans [AAs] = 282). Latent growth curve models were fit to examine developmental trajectories of alcohol abuse. The interactions of 10 single nucleotide polymorphisms (SNPs) in NR3C1 with intervention were examined separately. Both EAs and AAs showed significant increases in past-year alcohol abuse with substantial inter-individual differences in rates of linear growth. AAs showed lower general levels and slower rates of linear growth than EAs. Adjusting for multiple tests, one NR3C1 SNP (rs12655166) significantly moderated intervention effects on the developmental trajectories of alcohol abuse among AAs. Intervention effects on the rates of linear growth were stronger among AAs carrying minor alleles than those not carrying minor alleles. The findings highlight the importance of taking a developmental perspective on adolescent alcohol use and have implications for future intervention design and evaluation by identifying subgroups that could disproportionally benefit from intervention.

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

Fig. 1

Similar content being viewed by others

References

  • Achenbach, T. M. (1991a). Manual for the child behavior checklist and revised child behavior profile. Burlington: University of Vermont, Department of Psychiatry.

    Google Scholar 

  • Achenbach, T. M. (1991b). Manual for the teacher’s report form. Burlington: University of Vermont, Department of Psychiatry.

    Google Scholar 

  • Albert, D., Belsky, D. W., Crowley, D. M., Bates, J. E., Pettit, G. S., Lansford, J. E., Dick, D., & Dodge, K. A. (2015a). Developmental mediation of genetic variation in response to the Fast Track prevention program. Development and Psychopathology, 27, 81–95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Albert, D., Belsky, D. W., Crowley, D. M., Latendresse, S. J., Aliev, F., Riley, B., Sun, C., Conduct Problems Prevention Research Group, Dick, D. M., & Dodge, K. A. (2015b). Can genetics predict response to complex behavioral interventions? Evidence from a genetic analysis of the Fast Track Randomized Control Trial. Journal of Policy Analysis and Management, 34, 497–518.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bakermans-Kranenburg, M. J., & van Ijzendoorn, M. H. (2015). The hidden efficacy of interventions: Gene × environment experiments from a differential susceptibility perspective. Annual Review of Psychology, 66, 381–409.

    Article  PubMed  Google Scholar 

  • Beach, S. R. H., Brody, G. H., Lei, M. K., & Philibert, R. A. (2010). Differential susceptibility to parenting among African American youths: Testing the DRD4 hypothesis. Journal of Family Psychology, 24, 513–521.

    Article  PubMed  PubMed Central  Google Scholar 

  • Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885–908.

    Article  PubMed  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.

    Article  Google Scholar 

  • Bloom, H. S., & Michalopoulos, C. (2013). When is the story in the subgroups? Prevention Science, 14, 179–188.

    Article  PubMed  Google Scholar 

  • Brody, G. H., Beach, S. R., Philibert, R. A., Chen, Y. F., Lei, M. K., Murry, V. M., & Brown, A. C. (2009a). Parenting moderates a genetic vulnerability factor in longitudinal increases in youths’ substance use. Journal of Consulting and Clinical Psychology, 77, 1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brody, G. H., Beach, S. R., Philibert, R. A., Chen, Y. F., & Murry, V. M. (2009b). 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.

    Article  PubMed  Google Scholar 

  • Brody, G. H., Beach, S. R., Hill, K. G., Howe, G. W., Prado, G., & Fullerton, S. M. (2013a). Using genetically informed, randomized prevention trials to test etiological hypotheses about child and adolescent drug use and psychopathology. American Journal of Public Health, 103, S19–S24.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brody, G. H., Chen, Y. F., & Beach, S. R. (2013b). Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects. Journal of Child Psychology and Psychiatry, 54, 863–871.

    Article  PubMed  PubMed Central  Google Scholar 

  • Brody, G. H., Chen, Y. F., Beach, S. R., Kogan, S. M., Yu, T., DiClemente, R. J., Wingood, G. M., Windle, M., & Philibert, R. A. (2014). Differential sensitivity to prevention programming: A dopaminergic polymorphism-enhanced prevention effect on protective parenting and adolescent substance use. Health Psychology, 33, 182–191.

    Article  PubMed  Google Scholar 

  • Bureau of Labor Statistics. (2002). National Longitudinal Survey of Youth 1997 Cohort, 1997–2001. Chicago/Columbus, OH: University of Chicago, National Opinion Research Center/Ohio State University, Center for Human Resource Research.

  • Cardon, L. R., & Palmer, L. J. (2003). Population stratification and spurious allelic association. Lancet, 361, 598–604.

    Article  PubMed  Google Scholar 

  • Cleveland, H. H., Schlomer, G. L., Vandenbergh, D. J., Feinberg, M., Greenberg, M., Spoth, R., Redmond, C., Shriver, M. D., Zaidi, A. A., & Hair, K. L. (2015). 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. Development and Psychopathology, 27, 51–67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Conduct Problems Prevention Research Group. (1992). A developmental and clinical model for the prevention of conduct disorder: The FAST Track Program. Development and Psychopathology, 4, 509–527.

    Article  Google Scholar 

  • Conduct Problems Prevention Research Group. (1999). Initial impact of the Fast Track prevention trial for conduct problems: I. The high-risk sample. Journal of Consulting and Clinical Psychology, 67, 631–647.

    Article  PubMed Central  Google Scholar 

  • Conduct Problems Prevention Research Group. (2000). Merging universal and indicated prevention programs: The Fast Track model. Addictive Behaviors, 25, 913–927.

    Article  PubMed Central  Google Scholar 

  • Conduct Problems Prevention Research Group. (2011). The effects of the Fast Track preventive intervention on the development of conduct disorder across childhood. Child Development, 82, 331–345.

    Article  PubMed Central  Google Scholar 

  • Conduct Problems Prevention Research Group. (2015). Impact of early intervention on psychopathology, crime, and well-being at age 25. American Journal of Psychiatry, 172, 59–70.

    Article  Google Scholar 

  • DeRijk, R. H., van Leeuwen, N., Klok, M. D., & Zitman, F. G. (2008). Corticosteroid receptor-gene variants: Modulators of the stress-response and implications for mental health. European Journal of Pharmacology, 585, 492–501.

    Article  CAS  PubMed  Google Scholar 

  • Desrivieres, S., Lourdusamy, A., Muller, C., Ducci, F., Wong, C. P., Kaakinen, M., Pouta, A., Hartikainen, A. L., Isohanni, M., Charoen, P., Peltonen, L., Freimer, N., Elliott, P., Jarvelin, M. R., & Schumann, G. (2011). Glucocorticoid receptor (NR3C1) gene polymorphisms and onset of alcohol abuse in adolescents. Addiction Biology, 16, 510–513.

    Article  CAS  PubMed  Google Scholar 

  • Dick, D. M., Latendresse, S. J., & Riley, B. (2011). Incorporating genetics into your studies: A guide for social scientists. Frontiers in Psychiatry, 2, 1–11.

    Article  Google Scholar 

  • Dick, D. M., Agrawal, A., Keller, M. C., Adkins, A., Aliev, F., Monroe, S., Hewitt, J. K., Kendler, K. S., & Sher, K. J. (2015). Candidate gene–environment interaction research: Reflections and recommendations. Perspectives on Psychological Science, 10, 37–59.

    Article  PubMed  PubMed Central  Google Scholar 

  • Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 1041–1049.

    Article  PubMed  PubMed Central  Google Scholar 

  • Duncan, S. C., Alpert, A., Duncan, T. E., & Hops, H. (1997). Adolescent alcohol use development and young adult outcomes. Drug and Alcohol Dependence, 49, 39–48.

    Article  CAS  PubMed  Google Scholar 

  • Duncan, S. C., Duncan, T. E., & Strycker, L. A. (2006). Alcohol use from ages 9 to 16: A cohort-sequential latent growth model. Drug and Alcohol Dependence, 81, 71–81.

    Article  PubMed  Google Scholar 

  • Foxcroft, D. R., Ireland, D., Lister-Sharp, D. J., Lowe, G., & Breen, R. (2003). Longer-term primary prevention for alcohol misuse in young people: A systematic review. Addiction, 98, 397–411.

    Article  CAS  PubMed  Google Scholar 

  • French, K., Finkbiner, R., & Duhamel, L. (2002). Patterns of substance use among minority youth and adults in the United States: An overview and synthesis of national survey findings (National Evaluation Data Services [NEDS] Technical Report, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration [SAMHSA], contract no. 270-97-7016). Fairfax, VA: Caliber Associates.

  • Gabriel, S. B., Schaffner, S. F., Nguyen, H., Moore, J. M., Roy, J., Blumenstiel, B., Higgins, J., DeFelice, M., Lochner, A., Faggart, M., Liu-Cordero, S. N., Rotimi, C., Adeyemo, A., Cooper, R., Ward, R., Lander, E. S., Daly, M. J., & Altshuler, D. (2002). The structure of haplotype blocks in the human genome. Science, 296, 2225–2229.

    Article  CAS  PubMed  Google Scholar 

  • Hawes, D. J., Brennan, J., & Dadds, M. R. (2009). Cortisol, callous-unemotional traits, and pathways to antisocial behavior. Current Opinion in Psychiatry, 22, 357–362.

    Article  PubMed  Google Scholar 

  • Howe, G. W., Beach, S. R., & Brody, G. H. (2010). Microtrial methods for translating gene-environment dynamics into preventive interventions. Prevention Science, 11, 343–354.

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnston, L. D., O’Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (2010). Monitoring the future: National survey results on drug use, 1975–2009. Volume I: Secondary School Students (NIH Publication No. 10–7584). Bethesda, MD: National Institute on Drug Abuse.

  • Kusche, C. A., & Greenberg, M. T. (1995). The PATHS curriculum. Seattle: Developmental Research and Programs.

    Google Scholar 

  • Mason, W. A., Kosterman, R., Hawkins, J. D., Haggerty, K. P., & Spoth, R. L. (2003). Reducing adolescents’ growth in substance use and delinquency: Randomized trial effects of a parent-training prevention intervention. Prevention Science, 4, 203–212.

    Article  PubMed  Google Scholar 

  • Mason, W. A., Hitch, J. E., Kosterman, R., McCarty, C. A., Herrenkohl, T. I., & Hawkins, J. D. (2010). Growth in adolescent delinquency and alcohol use in relation to young adult crime, alcohol use disorders, and risky sex: A comparison of youth from low- versus middle-income backgrounds. Journal of Child Psychology and Psychiatry, 51, 1377–1385.

    Article  PubMed  PubMed Central  Google Scholar 

  • Masyn, K. E., Petras, H., & Liu, W. (2014). Growth curve models with categorical outcomes. In Encyclopedia of criminology and criminal justice (pp. 2013–2025). New York: Springer.

  • Metzger, I., Cooper, S. M., Zarrett, N., & Flory, K. (2013). Culturally sensitive risk behavior prevention programs for African American adolescents: A systematic analysis. Clinical Child and Family Psychology Review, 16, 187–212.

    Article  PubMed  Google Scholar 

  • Muthén, L. K., & Muthén, B. O. (1998–2012). Mplus user’s guide (7th ed.). Los Angeles, CA: Authors.

  • Newcomb, M. D., & Bentler, P. M. (1988). Consequences of adolescent drug use: Impact on the lives of young adults. Thousand Oaks: Sage Publications.

    Google Scholar 

  • Nyholt, D. R. (2004). A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. American Journal of Human Genetics, 74, 765–769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oyserman, D., Sanchez-Burks, J., & Harrison, K. (1996). Social identity and possible selves in adolescence. Unpublished manuscript, University of Michigan.

  • Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon, Y., & Patra, J. (2009). Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet, 373, 2223–2233.

    Article  PubMed  Google Scholar 

  • SAMHSA. (2002). Alcohol and cigarette use by race/ethnicity and age in the NHSDA Survey (NEDS fact sheet 136). Rockville, MD: Center for Substance Abuse Treatment.

  • SAMHSA. (2013). Results from the 2012 National Survey on Drug Use and Health: Summary of national findings (NSDUH Series H-46, HHS Publication No. (SMA) 13–4795). Rockville, MD: SAMHSA.

  • Schlomer, G. L., Cleveland, H. H., Vandenbergh, D. J., Fosco, G. M., & Feinberg, M. E. (2015). Looking forward in candidate gene research: Concerns and suggestions. Journal of Marriage and Family, 77, 351–354.

    Article  Google Scholar 

  • Schulenberg, J. E., & Maggs, J. L. (2002). A developmental perspective on alcohol use and heavy drinking during adolescence and the transition to young adulthood. Journal of Studies on Alcohol, S14, 54–70.

    Article  Google Scholar 

  • Smit, E., Verdurmen, 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.

    Article  PubMed  Google Scholar 

  • Taylor, B. J., Graham, J. W., Cumsille, P., & Hansen, W. B. (2000). Modeling prevention program effects on growth in substance use: Analysis of five years of data from the Adolescent Alcohol Prevention Trial. Prevention Science, 4, 183–197.

    Article  Google Scholar 

  • Tobler, N. S., Roona, M. R., Ochshorn, P., Marshall, D. G., Streke, A. V., & Stackpole, K. M. (2000). School-based adolescent drug prevention programs: 1998 meta-analysis. Journal of Primary Prevention, 20, 275–336.

    Article  Google Scholar 

  • van de Wiel, N. M., van Goozen, S. H., Matthys, W., Snoek, H., & van Engeland, H. (2004). Cortisol and treatment effect in children with disruptive behavior disorders: A preliminary study. Journal of the American Academy of Child & Adolescent Psychiatry, 43, 1011–1018.

    Article  Google Scholar 

  • van Ijzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2015). Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments. Development and Psychopathology, 27, 151–162.

    Article  PubMed  Google Scholar 

  • Wallace, J. M. (1999). Explaining race differences in adolescent and young adult drug use: The role of racialized social systems. Drugs & Society, 14, 21–36.

    Article  Google Scholar 

  • Watt, T. T., & Rogers, J. M. (2007). Factors contributing to differences in substance use among Black and White adolescents. Youth & Society, 39, 54–74.

  • Werthamer-Larsson, L., Kellam, S., & Wheeler, L. (1991). Effect of first-grade classroom environment on shy behavior, aggressive behavior, and concentration problems. American Journal of Community Psychology, 19, 585–602.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work used data from Fast Track project (for additional information concerning Fast Track, see http://www.fasttrackproject.org). We are grateful for the collaboration of the Durham Public Schools, the Metropolitan Nashville Public Schools, the Bellefonte Area Schools, the Tyrone Area Schools, the Mifflin County Schools, the Highline Public Schools, and the Seattle Public Schools. We appreciate the hard work and dedication of the many staff members who implemented the project, collected the evaluation data, and assisted with data management and analyses.

The Conduct Problems Prevention Research Group

Karen L. Bierman, Pennsylvania State University; John D. Coie, Duke University; Kenneth A. Dodge, Duke University; Mark T. Greenberg, Pennsylvania State University; John E. Lochman, University of Alabama; Robert J. McMahon, Simon Fraser University and BC Children’s Hospital; and Ellen E. Pinderhughes, Tufts University.

Author information

Authors and Affiliations

  1. Institute for the Reduction of Youth Violence, Department of Psychology, Simon Fraser University, RCB 5246, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada

    Yao Zheng & Robert J. McMahon

  2. BC Children’s Hospital, Vancouver, BC, Canada

    Yao Zheng & Robert J. McMahon

  3. Department of Psychology, Bryn Mawr College, Bryn Mawr, PA, USA

    Dustin Albert

  4. Center for Child and Family Policy, Duke University, Durham, NC, USA

    Kenneth Dodge

  5. Department of Psychology and Neuroscience, Duke University, Durham, NC, USA

    Kenneth Dodge

  6. College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA

    Danielle Dick

  7. Departments of Psychology, African American Studies, and Human & Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA

    Danielle Dick

Authors
  1. Yao Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dustin Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert J. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth Dodge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Danielle Dick
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Conduct Problems Prevention Research Group

  • Karen L. Bierman
  • , John D. Coie
  • , Kenneth A. Dodge
  • , Mark T. Greenberg
  • , John E. Lochman
  • , Robert J. McMahon
  •  & Ellen E. Pinderhughes

Corresponding author

Correspondence to Yao Zheng.

Ethics declarations

Funding

This work was supported by National Institute of Mental Health (NIMH) Grants R18 MH48043, R18 MH50951, R18 MH50952, R18 MH50953, K05MH00797, and K05MH01027; National Institute on Drug Abuse (NIDA) Grants DA016903, K05DA15226, and P30DA023026; and Department of Education Grant S184U30002. The Center for Substance Abuse Prevention also provided support through a memorandum of agreement with the NIMH. Additional support for the preparation of this work was provided by a LEEF B.C. Leadership Chair award, Child & Family Research Institute Investigator Salary and Investigator Establishment Awards, and a Canada Foundation for Innovation award to Robert J. McMahon.

Conflict of Interest

Drs. Bierman, Coie, Dodge, Greenberg, Lochman, McMahon, and Pinderhughes are the principal investigators on the Fast Track Project and have a publishing agreement with Guilford Publications, Inc. Royalties from that agreement will be donated to a professional organization. They are also authors of the PATHS curriculum and donate all royalties from Channing-Bete, Inc. to a professional organization. Dr. Greenberg is a developer of the PATHS curriculum and has a separate royalty agreement with Channing-Bete, Inc. Bierman, Coie, Dodge, Greenberg, Lochman, and McMahon are the developers of the Fast Track curriculum and have publishing and royalty agreements with Guilford Publications, Inc. Dr. McMahon is a coauthor of Helping the Noncompliant Child and has a royalty agreement with Guilford Publications, Inc.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Figure 1

(DOCX 42 kb)

Supplementary Figure 2

(DOCX 120 kb)

Supplementary Figure 3

(DOCX 39 kb)

Supplementary Table 1

(DOCX 24 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zheng, Y., Albert, D., McMahon, R.J. et al. Glucocorticoid Receptor (NR3C1) Gene Polymorphism Moderate Intervention Effects on the Developmental Trajectory of African-American Adolescent Alcohol Abuse. Prev Sci 19, 79–89 (2018). https://doi.org/10.1007/s11121-016-0726-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11121-016-0726-4

Keywords

Search

Navigation