Interaction effects between the 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype and family conflict on adolescent alcohol use and misuse
Jueun Kim
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorCorresponding Author
Aesoon Park
Department of Psychology, Syracuse University, Syracuse, NY, USA
Correspondence to: Aesoon Park, Syracuse University, Department of Psychology, 430 Huntington Hall, Syracuse, NY 13244, USA. E-mail: [email protected]Search for more papers by this authorStephen J. Glatt
The Psychiatric Genetic Epidemiology and Neurobiology Laboratory, Medical Genetics Research Center, Department of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
Search for more papers by this authorTanya L. Eckert
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorPeter A. Vanable
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorLori A. J. Scott-Sheldon
Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI, USA
Department of Psychiatry, Human Behavior, Alpert Medical School, Brown University, Providence, RI, USA
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorKate B. Carey
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorCraig K. Ewart
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorMichael P. Carey
Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI, USA
Department of Psychiatry, Human Behavior, Alpert Medical School, Brown University, Providence, RI, USA
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorJueun Kim
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorCorresponding Author
Aesoon Park
Department of Psychology, Syracuse University, Syracuse, NY, USA
Correspondence to: Aesoon Park, Syracuse University, Department of Psychology, 430 Huntington Hall, Syracuse, NY 13244, USA. E-mail: [email protected]Search for more papers by this authorStephen J. Glatt
The Psychiatric Genetic Epidemiology and Neurobiology Laboratory, Medical Genetics Research Center, Department of Psychiatry and Behavioral Sciences and Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA
Search for more papers by this authorTanya L. Eckert
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorPeter A. Vanable
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorLori A. J. Scott-Sheldon
Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI, USA
Department of Psychiatry, Human Behavior, Alpert Medical School, Brown University, Providence, RI, USA
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorKate B. Carey
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorCraig K. Ewart
Department of Psychology, Syracuse University, Syracuse, NY, USA
Search for more papers by this authorMichael P. Carey
Centers for Behavioral and Preventive Medicine, The Miriam Hospital, Providence, RI, USA
Department of Psychiatry, Human Behavior, Alpert Medical School, Brown University, Providence, RI, USA
Department of Behavioral and Social Sciences, Brown University, School of Public Health, Providence, RI, USA
Search for more papers by this authorAbstract
Aims
To investigate whether the effects of family conflict on adolescent drinking differed as a function of 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype cross-sectionally and prospectively in two independent samples of adolescents.
Design
Path analysis and multi-group analysis of two prospective datasets were conducted.
Settings
United States and United Kingdom.
Participants
Sample 1 was 175 adolescents in the United States (mean age = 15 at times 1 and 2 with a 6-month interval); Sample 2 was 4916 adolescents in the United Kingdon (mean age = 12 at time 1 and 15 at time 2).
Measurements
In both samples, demographics, tri-allelic 5-HTTLPR genotype and perceived family conflict were assessed at time 1. Alcohol use (frequency of drinking) and alcohol misuse (frequency of intoxication, frequency of drinking three or more drinks, maximum number of drinks) were assessed at times 1 and 2.
Findings
A significant gene–environment interaction on alcohol misuse at time 1 was found in both sample 1 (β = 0.57, P = 0.001) and sample 2 (β = 0.19, P = 0.01), indicating that the 5-HTTLPR low-activity allele carriers exposed to higher levels of family conflict were more likely to engage in alcohol misuse than non-carriers. A significant gene–environment interaction effect on change in alcohol misuse over time was found only in sample 1 (β = 0.48, P = 0.04) but not in sample 2.
Conclusions
Compared with non-carriers, adolescents carrying the 5-HTTLPR low-activity allele are more susceptible to the effects of family conflict on alcohol misuse.
Supporting Information
| Filename | Description |
|---|---|
| add12753-sup-0001-si.docxapplication/unknown, 306.2 KB | Figure S1 Results from interaction analyses between the 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype and family conflict using data from all adolescents, including non-Caucasians who had genetic data in sample 2 (n = 5108). (a,b,c) Results on alcohol outcomes at time 1 (T1); (d,e) results on changes in alcohol outcomes between T1 and T2. Standardized estimates are shown; self-reported race, age, gender and caregiver's education were controlled for in all analyses (paths are not shown). d = disturbance residual variance. *P < 0.05; **P < 0.01; ***P < 0.001. Figure S2 Results from interaction analyses between the 5-hydroxy tryptamine transporter-linked polymorphic region (5-HTTLPR) genotype and family conflict using data from Caucasians who reported having ever had a drink at time 1 (T1) (i.e. drinkers) and had genetic data in sample 2 (n = 1137). (a,b,c) Results on alcohol outcomes at T1; (d,e) results on changes in alcohol outcomes between T1 and T2. Standardized estimates are shown; age, gender and caregiver's education were controlled for in all analyses (paths are not shown). d = disturbance residual variance. *P < 0.05; **P < 0.01; ***P < 0.001. Table S1 Means or percentages of study variables as a function of the DNA sample donation and attrition in two samples. Table S2 Pearson's correlation coefficients among study variables in sample 1. Table S3 Pearson's correlation coefficients among study variables in sample 2. Description S1 Sensitivity analyses. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Johnson L. D., O'Malley P. M., Bachman J. G., Schulenberg J. E. Monitoring the Future National Survey Results on Drug Use, 1975–2012. Volume I: Secondary School Students. Ann Arbor: Institue for Social Research, The University of Michigan; 2013.
- 2 Friese B., Grube J. W. Youth drinking rates and problems: a comparison of European countries and the United States. Contract no.: NCJ 211446. Rockville, MD: Pacific Institute for Research and Evaluation; 2005.
- 3 Cloninger C. R., Bohman M., Sigvardsson S. Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Arch Gen Psychiatry 1981; 38: 861–868.
- 4 Sigvardsson S., Bohman M., Cloninger C. R. Replication of the Stockholm Adoption Study of alcoholism. Confirmatory cross-fostering analysis. Arch Gen Psychiatry 1996; 53: 681–687.
- 5 Fowler T., Lifford K., Shelton K., Rice F., Thapar A., Neale M. C. et al. Exploring the relationship between genetic and environmental influences on initiation and progression of substance use. Addiction 2007; 102: 413–422.
- 6 Maes H. H., Woodard C. E., Murrelle L., Meyer J. M., Silberg J. L., Hewitt J. K. et al. Tobacco, alcohol and drug use in eight- to sixteen-year-old twins: the Virginia Twin Study of Adolescent Behavioral Development. J Stud Alcohol 1999; 60: 293–305.
- 7 Rhee S. H., Hewitt J. K., Young S. E., Corley R. P., Crowley T. J., Stallings M. C. Genetic and environmental influences on substance initiation, use, and problem use in adolescents. Arch Gen Psychiatry 2003; 60: 1256–1264.
- 8 Viken R. J., Kaprio J., Koskenvuo M., Rose R. J. Longitudinal analyses of the determinants of drinking and of drinking to intoxication in adolescent twins. Behav Genet 1999; 29: 455–461.
- 9 Lesch K. P., Bengel D., Heils A., Sabol S. Z., Greenberg B. D., Petri S. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1531.
- 10 Heils A., Teufel A., Petri S., Stober G., Riederer P., Bengel D. et al. Allelic variation of human serotonin transporter gene expression. J Neurochem 1996; 66: 2621–2624.
- 11 Hu X. Z., Lipsky R. H., Zhu G., Akhtar L. A., Taubman J., Greenberg B. D. et al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive–compulsive disorder. Am J Hum Genet 2006; 78: 815–826.
- 12 LeMarquand D., Pihl R. O., Benkelfat C. Serotonin and alcohol intake, abuse, and dependence: findings of animal studies. Biol Psychiatry 1994; 36: 395–421.
- 13 Gerra G., Garofano L., Castaldini L., Rovetto F., Zaimovic A., Moi G. et al. Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents. J Neural Transm 2005; 112: 1397–1410.
- 14 Merenakk L., Maestu J., Nordquist N., Parik J., Oreland L., Loit H. M. et al. Effects of the serotonin transporter (5-HTTLPR) and alpha2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study. Psychopharmacology (Berl) 2011; 215: 13–22.
- 15 van der Zwaluw C. S., Engels R. C., Vermulst A. A., Rose R. J., Verkes R. J., Buitelaar J. et al. A serotonin transporter polymorphism (5-HTTLPR) predicts the development of adolescent alcohol use. Drug Alcohol Depend 2010; 112: 134–139.
- 16 Dawes M. A., Roache J. D., Javors M. A., Bergeson S. E., Richard D. M., Mathias C. W. et al. Drinking histories in alcohol-use-disordered youth: preliminary findings on relationships to platelet serotonin transporter expression with genotypes of the serotonin transporter. J Stud Alcohol Drugs 2009; 70: 899–907.
- 17 Hinckers A. S., Laucht M., Schmidt M. H., Mann K. F., Schumann G., Schuckit M. A. et al. Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents. Biol Psychiatry 2006; 60: 282–287.
- 18 Caspi A., Hariri A. R., Holmes A., Uher R., Moffitt T. E. Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 2010; 167: 509–527.
- 19 Karg K., Burmeister M., Shedden K., Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 2011; 68: 444–454.
- 20 Risch N., Herrell R., Lehner T., Liang K. Y., Eaves L., Hoh J. et al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009; 301: 2462–2471.
- 21 Covault J., Tennen H., Armeli S., Conner T. S., Herman A. I., Cillessen A. H. et al. Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biol Psychiatry 2007; 61: 609–616.
- 22 Kranzler H. R., Scott D., Tennen H., Feinn R., Williams C., Armeli S. et al. The 5-HTTLPR polymorphism moderates the effect of stressful life events on drinking behavior in college students of African descent. Am J Med Genet B Neuropsychiatr Genet 2012; 159B: 484–490.
- 23 Kaufman J., Yang B. Z., Douglas-Palumberi H., Crouse-Artus M., Lipschitz D., Krystal J. H. et al. Genetic and environmental predictors of early alcohol use. Biol Psychiatry 2007; 61: 1228–1234.
- 24 Nilsson K. W., Sjoberg R. L., Damberg M., Alm P. O., Ohrvik J., Leppert J. et al. Role of the serotonin transporter gene and family function in adolescent alcohol consumption. Alcohol Clin Exp Res 2005; 29: 564–570.
- 25 Laucht M., Treutlein J., Schmid B., Blomeyer D., Becker K., Buchmann A. F. et al. Impact of psychosocial adversity on alcohol intake in young adults: moderation by the LL genotype of the serotonin transporter polymorphism. Biol Psychiatry 2009; 66: 102–109.
- 26 Olsson C. A., Byrnes G. B., Lotfi-Miri M., Collins V., Williamson R., Patton C. et al. Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health. Mol Psychiatry 2005; 10: 868–876.
- 27 Duncan L. E., Keller M. C. A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. Am J Psychiatry 2011; 168: 1041–1049.
- 28 Windle M., Spear L. P., Fuligni A. J., Angold A., Brown J. D., Pine D. et al. Transitions into underage and problem drinking: summary of developmental processes and mechanisms: ages 10–15. Alcohol Res Health 2009; 32: 30–40.
- 29 Rose R. J., Dick D. M. Gene–environment interplay in adolescent drinking behavior. Alcohol Res Health 2004; 4: 222–229.
- 30 Bray J. H., Adams G. J., Getz J. G., Baer P. E. Developmental, family, and ethnic influences on adolescent alcohol usage: a growth curve approach. J Fam Psychol 2001; 15: 301–314.
- 31 Mason W. A., Hitchings J. E., McMahon R. J., Spoth R. L. A test of three alternative hypotheses regarding the effects of early delinquency on adolescent psychosocial functioning and substance involvement. J Abnorm Child Psychol 2007; 35: 831–843.
- 32 McKelvey L. M., Whiteside-Mansell L., Bradley R. H., Casey P. H., Conners-Burrow N. A., Barrett K. W. Growing up in violent communities: do family conflict and gender moderate impacts on adolescents' psychosocial development? J Abnorm Child Psychol 2011; 39: 95–107.
- 33 Bookman E. B., McAllister K., Gillanders E., Wanke K., Balshaw D., Rutter J. et al. Gene–environment interplay in common complex diseases: forging an integrative model—recommendations from an NIH workshop. Genet Epidemiol 2011; 35: 217–225.
- 34 Sellers E. M., Higgins G. A., Tompkins D. M., Romach M. K. Serotonin and alcohol drinking. NIDA Res Monogr 1992; 119: 141–145.
- 35 Fraser A., Macdonald-Wallis C., Tilling K., Boyd A., Golding J., Davey Smith G. et al. Cohort profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int J Epidemiol 2013; 42: 97–110.
- 36 Downs W. R., Robertson J. F. Adolescent alcohol consumption by age and sex of respondent. J Stud Alcohol 1982; 43: 1027–1032.
- 37 Kelly A. B., Toumbourou J. W., O'Flaherty M., Patton G. C., Homel R., Connor J. P. et al. Family relationship quality and early alcohol use: evidence for gender-specific risk processes. J Stud Alcohol Drugs 2011; 72: 399–407.
- 38 Droomers M., Schrijvers C. T., Casswell S., Mackenbach J. P. Occupational level of the father and alcohol consumption during adolescence; patterns and predictors. J Epidemiol Community Health 2003; 57: 704–710.
- 39 Pritchard J. K., Stephens M., Donnelly P. Inference of population structure using multilocus genotype data. Genetics 2000; 155: 945–959.
- 40 Wendland J. R., Moya P. R., Kruse M. R., Ren-Patterson R. F., Jensen C. L., Timpano K. R. et al. A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive–compulsive disorder. Hum Mol Genet 2008; 17: 717–723.
- 41 Moos R., Moos B. Family Environment Scale Manual: Development, Applications, and Research, 3rd edn. Palo Alto, CA: Consulting Psychologist Press; 1994.
- 42 Barnett N. P., Lebeau-Craven R., O'Leary T. A., Colby S. M., Rohsenow D. J., Monti P. M. et al. Predictors of motivation to change after medical treatment for drinking-related events in adolescents. Psychol Addict Behav 2002; 16: 106–112.
- 43 Migneault J. P., Pallonen U. E., Velicer W. F. Decisional balance and stage of change for adolescent drinking. Addict Behav 1997; 22: 339–351.
- 44 Saccone N. L., Kwon J. M., Corbett J., Goate A., Rochberg N., Edenberg H. J. et al. A genome screen of maximum number of drinks as an alcoholism phenotype. Am J Med Genet 2000; 96: 632–637.
- 45 IBM Corporation. IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corporation; 2010.
- 46 Muthén L., Muthén B. Mplus User's Guide, 6th edn. Los Angeles, CA: Muthén & Muthén; 1998–2010.
- 47
Graham J. W.,
Cumsille P. E.,
Elek-Fisk E. Methods for handling missing data. In: J. A. S. W. F. Velicer, editor. Research Methods in Psychology Handbook of Psychology (I. B. Weiner, Editor-in-Chief). New York: John Wiley & Sons; 2003, pp. 87–114.
10.1002/0471264385.wei0204 Google Scholar
- 48 Gauderman W., Morrison J. Quanto 1.2.4: A computer program for power and sample size calculations for genetic-epidemiology studies. 2009. Available at: http://biostats.usc.edu/Quanto.html (accessed 28 October 2014) (Archived at http://www.webcitation.org/6TfWWrGfE on 28 October 2014).
- 49 Park C. L., Armeli S., Tennen H. The daily stress and coping process and alcohol use among college students. J Stud Alcohol 2004; 65: 126–135.
- 50 Brummett B. H., Boyle S. H., Siegler I. C., Kuhn C. M., Ashley-Koch A., Jonassaint C. R. et al. Effects of environmental stress and gender on associations among symptoms of depression and the serotonin transporter gene linked polymorphic region (5-HTTLPR). Behav Genet 2008; 38: 34–43.
- 51 Polanczyk G., Caspi A., Williams B., Price T. S., Danese A., Sugden K. et al. Protective effect of CRHR1 gene variants on the development of adult depression following childhood maltreatment: replication and extension. Arch Gen Psychiatry 2009; 66: 978–985.
- 52 Royall R. M. The effect of sample size on the meaning of significance tests. Am Stat 1986; 40: 313–315.
- 53 Munafo M. R., Durrant C., Lewis G., Flint J. Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 2009; 65: 211–219.
- 54 Brody G. H., Ge X. Linking parenting processes and self-regulation to psychological functioning and alcohol use during early adolescence. J Fam Psychol 2001; 15: 82–94.
- 55 Sieving R. E., Maruyama G., Williams C. L., Perry C. L. Pathways to adolescent alcohol use: potential mechanisms of parent influence. J Res Adolesc 2000; 10: 489–514.
- 56 Read J. P., Wood M. D., Kahler C. W., Maddock J. E., Palfai T. P. Examining the role of drinking motives in college student alcohol use and problems. Psychol Addict Behav 2003; 17: 13–23.
- 57 Mann L. M., Chassin L., Sher K. J. Alcohol expectancies and the risk for alcoholism. J Consult Clin Psychol 1987; 55: 411–417.
- 58 Hariri A. R., Mattay V. S., Tessitore A., Kolachana B., Fera F., Goldman D. et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 2002; 297: 400–403.
- 59 Hariri A. R., Drabant E. M., Munoz K. E., Kolachana B. S., Mattay V. S., Egan M. F. et al. A susceptibility gene for affective disorders and the response of the human amygdala. Arch Gen Psychiatry 2005; 62: 146–152.
- 60 Pezawas L., Meyer-Lindenberg A., Drabant E. M., Verchinski B. A., Munoz K. E., Kolachana B. S. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005; 8: 828–834.
- 61 Kuntsche E., Rehm J., Gmel G. Characteristics of binge drinkers in Europe. Soc Sci Med 2004; 59: 113–127.
- 62 Horwitz A. V., White H. R. Becoming married, depression, and alcohol problems among young adults. J Health Soc Behav 1991; 32: 221–237.
- 63 Cooper M. L., Russell M., Frone M. R. Work stress and alcohol effects: a test of stress-induced drinking. J Health Soc Behav 1990; 31: 260–276.
- 64 Bristol City Council. State of city report. 2013. Available at: http://www.bristol.gov.uk/page/council-and-democracy/statistics-and-census-information (accessed 28 October 2014) (Archived at http://www.webcitation.org/6TfWc4W2q on 28 October 2014).
- 65 U.S. Census Bureau. State and County QuickFacts. 2014. Available at: http://quickfacts.census.gov/qfd/states/36/3673000.html (accessed 28 October 2014) (Archived at http://www.webcitation.org/6TfWIjMpY on 28 October 2014).
- 66 Loeber R., Drinkwater M., Yin Y., Anderson S., Schmidt L., Crawford A. Stability of family interaction from ages 6 to 18. J Abnorm Child Psychol 2000; 28: 353–369.
