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Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele

Published online by Cambridge University Press:  23 March 2015

Elisa M. Trucco*
Affiliation:
University of Michigan
Sandra Villafuerte
Affiliation:
University of Michigan
Mary M. Heitzeg
Affiliation:
University of Michigan
Margit Burmeister
Affiliation:
University of Michigan
Robert A. Zucker
Affiliation:
University of Michigan
*
Address correspondence and reprint request to: Elisa M. Trucco, University of Michigan, Addiction Research Center, 4250 Plymouth Road, Ann Arbor, MI 48109-2700; E-mail: etrucco@med.umich.edu.

Abstract

Understanding factors increasing susceptibility to social contexts and predicting psychopathology can help identify targets for prevention. Persistently high externalizing behavior in adolescence is predictive of psychopathology in adulthood. Parental monitoring predicts low externalizing behavior, yet youth likely vary in the degree to which they are affected by parents. Genetic variants of GABA receptor subunit alpha-2 (GABRA2) may increase susceptibility to parental monitoring, thus impacting externalizing trajectories. We had several objectives: (a) to determine whether GABRA2 (rs279827, rs279826, rs279858) moderates the relationship between a component of parental monitoring, parental knowledge, and externalizing trajectories; (b) to test the form of this interaction to assess whether GABRA2 variants reflect risk (diathesis–stress) or susceptibility (differential susceptibility) factors; and (c) to clarify GABRA2 associations on the development of problem behavior. This prospective study (N = 504) identified three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. A GABRA2 × Parental Monitoring effect on class membership was observed, such that A-carriers were largely unaffected by parental monitoring, whereas class membership for those with the GG genotype was affected by parental monitoring. Findings support differential susceptibility in GABRA2.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Achenbach, T. M., & Rescorla, L. A. (2001). Youth Self-Report for ages 11-18. Burlington, VT: ASEBA.Google Scholar
Agrawal, A., Edenberg, H., Foroud, T., Bierut, L. J., Dunne, G., Hinrichs, A. L., et al. (2006). Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample. Behavior Genetics, 36, 640650. doi:10.1007/s10519-006-9069-4 Google Scholar
Aiken, L. S., & West, S. G. (1991). Multiple regression: Testing and interpreting interactions (p. 212). Newbury Park, CA: SAGE.Google Scholar
Barnes, G. M., Hoffman, J. H., Welte, J. W., Farrell, M. P., & Dintcheff, B. A. (2006). Effects of parental monitoring and peer deviance on substance use and delinquency. Journal of Marriage and Family, 68, 10841104. doi:10.1111/j.1741-3737.2006.00315.x CrossRefGoogle Scholar
Bauer, L. O., Covault, J., Harel, O., Das, S., Gelernter, J., Anton, R., et al. (2007). Variation in GABRA2 predicts drinking behavior in Project MATCH subjects. Alcoholism: Clinical and Experimental Research, 31, 17801787. doi:10.1111/j.1530-0277.2007.00517.x CrossRefGoogle ScholarPubMed
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, 300304. doi:10.1111/j.1467-8721.2007.00525.x Google Scholar
Belsky, J., & Beaver, K. M. (2011). Cumulative-genetic plasticity, parenting and adolescent self-regulation. Journal of Child Psychology and Psychiatry, 52, 619626. doi:10.1111/j.1469-7610.2010.02327.x CrossRefGoogle ScholarPubMed
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908. doi:10.1037/a0017376 CrossRefGoogle ScholarPubMed
Brody, G. H., Chen, Y., & Beach, S. R. (2013). Differential susceptibility to prevention: GABAergic, dopaminergic, and multilocus effects. Journal of Child Psychology and Psychiatry, 54, 863871. doi:10.1111/jcpp.12042 Google Scholar
Bronfenbrenner, U., & Morris, P. (1998). The ecology of developmental processes. In Lerner, R. M. (Ed.), Handbook of child psychology: Theoretical models of human development (Vol. 1, 5th ed., pp. 9931028). New York: Wiley.Google Scholar
Chilcoat, H. D., & Anthony, J. C. (1996). Impact of parent monitoring on initiation of drug use through late childhood. Journal of the American Academy of Child & Adolescent Psychiatry, 35, 91100. doi:10.1097/00004583-199601000-00017 Google Scholar
Chung, I. J., Hill, K. G., Hawkins, J., Gilchrist, L. D., & Nagin, D. S. (2002). Childhood predictors of offense trajectories. Journal of Research in Crime and Delinquency, 39, 6090. doi:10.1177/002242780203900103 Google Scholar
Covault, J., Gelernter, J., Hesselbrock, V., Nellissery, M., & Kranzler, H. R. (2004). Allelic and haplotypic association of GABRA2 with alcohol dependence. American Journal of Medical Genetics, 129B, 104109. doi:10.1002/ajmg.b.30091 Google ScholarPubMed
Dick, D. M., Bierut, L., Hinrichs, A., Fox, L., Bucholz, K. K., Kramer, J., et al. (2006). The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Behavior Genetics, 36, 577590. doi:10.1007/s10519-005-9041-8 CrossRefGoogle ScholarPubMed
Dick, D. M., Latendresse, S. J., Lansford, J. E., Budde, J. P., Goate, A., Dodge, K. A., et al. (2009). Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring. Archives of General Psychiatry, 66, 649657. doi:10.1001/archgenpsychiatry.2009.48 Google Scholar
Dick, D. M., Latendresse, S. J., Lansford, J. E., Budde, J. P., Goate, A., Dodge, K. A., et al. (2011). Error in table and results in: Role of GABRA2 in trajectories of externalizing behavior across development and evidence of moderation by parental monitoring. Archives of General Psychiatry, 68, 980. doi:10.1001/archgenpsychiatry.2011.90 Google Scholar
DiClemente, R. J., Wingood, G. M., Crosby, R., Sionen, C., Cobb, B. K., Harrington, K., et al. (2001). Parental monitoring: Association with adolescents' risk behaviors. Pediatrics, 107, 13631368. doi:10.1542/peds.107.6.1363 Google Scholar
Dishion, T. J., & McMahon, R. J. (1998). Parental monitoring and the prevention of child and adolescent problem behavior: A conceptual and empirical formulation. Clinical Child and Family Psychology Review, 1, 6175.CrossRefGoogle ScholarPubMed
Edenberg, H. J., Dick, D. M., Xuei, X., Tian, H., Almasy, L., Bauer, L. O., et al. (2004). Variations in GABRA2, encoding the α2 subunit of the GABAA receptor, are associated with alcohol dependence and with brain oscillations. American Journal of Human Genetics, 74, 705714. doi:10.1086/383283 Google Scholar
Enoch, M. A., Schwartz, L., Albaugh, B., Virkkunen, M., & Goldman, D. (2006). Dimensional anxiety mediates linkage of GABRA2 haplotypes with alcoholism. American Journal of Medical Genetics, 141B, 599607. doi:10.1002/ajmg.b.30336 Google ScholarPubMed
Fairchild, G., van Goozen, S. H. M., Calder, A. J., & Goodyer, I. M. (2013). Research review: Evaluating and reformulating the developmental taxonomic theory of antisocial behaviour. Journal of Child Psychology and Psychiatry, 54, 924940. doi:10.1111/jcpp.12102 Google Scholar
Hodgkinson, C. A., Yuan, Q., Xu, K., Shen, P. H., Heinz, E., Lobos, E. A., et al. (2008). Addictions biology: Haplotype-based analysis for 130 candidate genes on a single array. Alcohol and Alcoholism, 43, 505515. doi:10.1093/alcalc/agn032 Google Scholar
International HapMap Consortium. (2003). The International HapMap Project. Nature, 426, 789796.Google Scholar
Ioannidis, J. P. A., Trikalinos, T. A., & Khoury, M. J. (2006). Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. American Journal of Epidemiology, 164, 609614. doi:10.1093/aje/kwj259 Google Scholar
Jung, T., & Wickrama, K. (2008). An introduction to latent class growth analysis and growth mixture modeling. Social and Personality Psychology Compass, 2, 302317. doi:10.1111/j.1751-9004.2007.00054.x Google Scholar
Kendler, K. S. (2011). A conceptual overview of gene–environment interaction and correlation in a developmental context. In Kendler, K. S., Jaffee, S., & Romer, D. (Eds.), The Dynamic Genome and Mental Health. New York: Oxford University Press.Google Scholar
Kerr, M., & Stattin, H. (2000). What parents know, how they know it, and several forms of adolescent adjustment: Further support for a reinterpretation of monitoring. Developmental Psychology, 36, 366380. doi:10.1037/0012-1649.36.3.366 Google Scholar
Kerr, M., & Stattin, H. (2003). Straw men, untested assumptions, and bi-directional models: A response to Capaldi and Brody. In Crouter, A. C. & Booth, A. (Eds.), Children's influence on family dynamics: The neglected side of family relationships (pp. 181188). Mahwah, NJ: Erlbaum.Google Scholar
Kerr, M., Stattin, H., & Burk, W. J. (2010). A reinterpretation of parental monitoring in longitudinal perspective. Journal of Research on Adolescence, 20, 3964. doi:10.1111/j.1532-7795.2009.00623.x 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, 605616. doi:10.1017/S0954579411000071 Google Scholar
Kuppens, S., Grietens, H., Onghena, P., & Michiels, D. (2009). Associations between parental control and children's overt and relational aggression. British Journal of Developmental Psychology, 27, 607623. doi:10.1348/026151008X345591 CrossRefGoogle ScholarPubMed
Lacourse, E., Nagin, D. S., Tremblay, R. E., Vitaro, F., & Claes, M. (2003). Developmental trajectories of boys' delinquent group membership and facilitation of violent behaviors during adolescence. Development and Psychopathology, 14, 909924. doi:10.1017/S0954579403000105 Google Scholar
Laird, R. D., Pettit, G. S., Bates, J. E., & Dodge, K. A. (2003). Parents' monitoring-relevant knowledge and adolescent's delinquent behavior: Evidence of correlated developmental changes and reciprocal influences. Child Development, 74, 752768. doi:10.1111/1467-8624.00566 Google Scholar
Leve, L. D., Kim, H. K., & Pears, K. C. (2005). Childhood temperament and family environment as predictors of internalizing and externalzing trajectories from age 5 to age 17. Journal of Abnormal Child Psychology, 33, 505520. doi:10.1007/s10802-005-6734-7 Google Scholar
Moffitt, T. E. (1993). Adolescence-limited and life-course-persistent antisocial behavior: A developmental taxonomy. Psychological Review, 100, 674701. doi:10.1037/0033-295X.100.4.674 Google Scholar
Muthén, B. (2004). Latent variable analysis: Growth mixture modeling and related techniques for longitudinal data. In Kaplan, D. (Ed.), The Sage handbook of quantitative methodology for the social sciences (pp. 345368). Thousand Oaks, CA: Sage.Google Scholar
Muthén, B., & Muthén, L. K. (2000). Integrating person-centered and variable-centered analyses: Growth mixture modeling with latent trajectory classes. Alcoholism: Clinical and Experimental Research, 24, 882891. doi:10.1111/j.1530-0277.2000.tb02070.x Google Scholar
Muthén, L. K., & Muthén, B. O. (1998–2012). MPlus user's guide (7th ed.). Los Angeles: Author.Google Scholar
Nigg, J. T. (2006). Temperament and developmental psychopathology. Journal of Child Psychology and Psychiatry, 47, 395422. doi:10.1111/j.1469-7610.2006.01612.x Google Scholar
Nylund, K. L., Asparouhov, T., & Muthén, B. O. (2007). Deciding on the number of classes in latent class analysis and growth mixture modeling: A Monte Carlo simulation study. Structural Equation Modeling, 14, 535569. doi:10.1080/10705510701575396 Google Scholar
Odgers, C. L., Moffitt, T. E., Broadbent, J. M., Dickson, N., Hancox, R. J., Harrington, H., et al. (2008). Female and male antisocial trajectories: From childhood origins to adult outcomes. Development and Psychopathology, 20, 673716. doi:10.1017/S0954579408000333 Google Scholar
Pierucci-Lagha, A., Covault, J., Feinn, R., Nellissery, M., Hernandez-Avila, C., Oncken, C., et al. (2005). GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Neuropsychopharmacology, 30, 11931203. doi:10.1038/sj.npp.1300688 Google Scholar
Preacher, K. J., Curran, P. J., & Bauer, D. J. (2006). Computational tools for probing interactions in multiple linear regression, multilevel modeling, and latent curve analysis. Journal of Educational and Behavioral Statistics, 31, 437448. doi:10.3102/10769986031004437 Google Scholar
Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., et al. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. Journal of the American Medical Association, 301, 24622471. doi:10/1001/jama.2009.878 Google Scholar
Rutter, M., Moffitt, T. E., & Caspi, A. (2006). Gene-environment interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry and Allied Disciplines, 47, 226261. doi:10.1111/j.1469-7610.2005.01557.x Google Scholar
Schwarzer, C., Berresheim, U., Pirker, S., Wieselthaler, A., Fuchs, K., Sieghart, W., et al. (2001). Distribution of the major gamma-aminobutyric acid(A) receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat. Journal of Comparative Neurology, 433, 526549. doi:10.1002/cne.1158 Google Scholar
Shaw, D. S., Hyde, L. W., & Brennan, L. M. (2012). Early predictors of boys' antisocial trajectories. Development and Psychopathology, 24, 871888. doi:10.1017/S0954579412000429 Google Scholar
Simons, R. L., & Lei, M. K. (2013). Enhanced susceptibility to context: A promising perspective on the interplay of genes and the social environment. In Gibson, C. L. & Krohn, M. D. (Eds.), Handbook of life-course criminology: Emerging trends and directions for future research (pp. 5767). New York: Springer.Google Scholar
Smith, C., & Krohn, M. D. (1995). Delinquency and family life among male adolescents: The role of ethnicity. Journal of Youth and Adolescence, 24, 6993. doi:10.1007/BF01537561 Google Scholar
Stanger, C., & Lewis, M. (1993). Agreement among parents, teachers, and children on internalizing and externalizing behavior problems. Journal of Clinical Child Psychology, 22, 107115. doi:10.1207/s15374424jccp2201_11 Google Scholar
Stattin, H., & Kerr, M. (2000). Parental monitoring: A reinterpretation. Child Development, 71, 10721085. doi:10.1111/1467-8624.00210 Google Scholar
Tian, H., Chen, H. J., Cross, T. H., & Edenberg, H. (2005). Alternative splicing and promoter use in the human GABRA2 gene. Molecular Brain Research, 137, 174183. doi:10.1016/j.molbrainres.2005.03.001 Google Scholar
Uher, R., & McGuffin, P. (2008). The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: Review and methodological analysis. Molecular Psychiatry, 13, 131146. doi:10.1038/sj.mp.4002067 Google Scholar
Villafuerte, S., Heitzeg, M. M., Foley, S., Yau, W., Majczenko, K., Zubieta, J. K., et al. (2012). Impulsiveness and insula activation during reward anticipation are associated with genetic variants in GABRA2 in a family sample enriched for alcoholism. Molecular Psychiatry, 17, 511519. doi:10.1038/mp.2011.33 Google Scholar
Villafuerte, S., Strumba, V., Stoltenberg, S., Zucker, R. A., & Burmeister, M. (2013). Impulsiveness mediates the association between GABRA2 SNPs and lifetime alcohol problems. Genes Brain and Behavior, 12, 525531. doi:10.1111/gbb.12039 Google Scholar
Walters, G. D. (2011). The latent structure of life-course-persistent antisocial behavior: Is Moffitt's developmental taxonomy a true taxonomy? Journal of Consulting and Clinical Psychology, 79, 96105. doi:10.1037/a0021519 CrossRefGoogle ScholarPubMed
Weisner, M., & Windle, M. (2004). Assessing covariates of adolescent delinquency trajectories: A latent growth mixture modeling approach. Journal of Youth and Adolescence, 33, 431442. doi:10.1023/B:JOYO.0000037635.06937.13 Google Scholar
Widaman, K. F., Helm, J. L., Castro-Schilo, L., Pluess, M., Stallings, M. C., & Belsky, J. (2012). Distinguishing ordinal and disordinal interactions. Psychological Methods, 17, 615622. doi:10.1037/a0030003 Google Scholar
Zucker, R. A., Ellis, D. A., Fitzgerald, H. E., Bingham, C. R., & Sanford, K. (1996). Other evidence for at least two alcoholisms II: Life course variation in antisociality and heterogeneity of alcoholic outcome. Development and Psychopathology, 8, 831848. doi:10.1017/S0954579400007458 Google Scholar
Zucker, R. A., Fitzgerald, H. E., Refior, S. K., Puttler, L. I., Pallas, D. M., & Ellis, D. A. (2000). The clinical and social ecology of childhood for children of alcoholics: Description of a study and implications for a differentiated social policy. In Fitzgerald, H. E., Lester, B. M., & Zuckerman, B. S. (Eds.), Children of addiction: Research, health and policy issues (pp. 109141). New York: Routledge Falmer.Google Scholar
Zuckerman, M. (1999). Vulnerability to psychopathology: A biosocial model. Washington, DC: American Psychological Association.Google Scholar