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ADHD Symptoms in Middle Adolescence Predict Exposure to Person-Related Life Stressors in Late Adolescence in 5-HTTLPR S-allele Homozygotes

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Abstract

Literature suggests that life stressors predict attention-deficit/hyperactivity disorder (ADHD) symptoms and that this relationship is moderated by the serotonin transporter polymorphism (5-HTTLPR). It is less clear whether, on reverse, ADHD symptoms may influence the risk of exposure to life stressors. Furthermore, the role of life stressors may vary across development depending on the type of life stressor. We used threewave longitudinal data of 1,306 adolescents from the general population and clinicreferred cohort of the TRacking Adolescents’ Individual Lives Survey. The 5-HTTLPR genotype (SS, LS, LL), parent-reported ADHD symptoms at three time points (T1: Mage = 11.2; T2: Mage = 13.5; T3: Mage = 16.2 years), and the number of personrelated (‘dependent’) and environment-related (‘independent’) life stressors occurring between measurements (T1-T2, T2-T3) were assessed. Using path analyses, we examined bidirectional relations between exposure to these life stressors and ADHD symptoms between the separate waves moderated by 5-HTTLPR status. Exposure to life stressors did not predict ADHD symptoms. Rather, we found that in 5-HTTLPR Sallele homozygotes, ADHD symptoms in middle adolescence (T2) predicted exposure to the number of person-related life stressors later in adolescence (T2-T3, p = 0.001). There was no relation with environment-related life stressors. Our study suggests that S-allele homozygotes with higher levels of ADHD symptoms in middle adolescence are more vulnerable to becoming exposed to person-related (‘dependent’) life stressors in late adolescence. Findings emphasize the need to be aware of social-emotional adversities that may occur in genetically vulnerable adolescents with ADHD symptoms in the transition into adulthood.

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References

  • Achenbach, T. (1991). Manual for the child behavior checklist/4–18 and 1991 profile. Burlington: University of Vermont Department of Psychiatry.

    Google Scholar 

  • Amone-P’Olak, K., Ormel, J., Huisman, M., Verhulst, F. C., Oldehinkel, A. J., & Burger, H. (2009). Life stressors as mediators of the relation between socioeconomic position and mental health problems in early adolescence: The TRAILS study. Journal of the American Academy of Child and Adolescent Psychiatry, 48(10), 1031–1038.

    Article  PubMed  Google Scholar 

  • Arnett, J. J. (1999). Adolescent storm and stress, reconsidered. American Psychology, 51(4), 317–326.

    Article  Google Scholar 

  • Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135(6), 885–908.

    Article  PubMed  Google Scholar 

  • Brune, C. W., Kim, S.-J., Salt, J., Leventhal, B. L., Lord, C., & Cook, E. H. (2006). 5-HTTLPR genotype-specific phenotype in children and adolescents with autism. American Journal of Psychiatry, 163(12), 2148–2156.

    Article  PubMed  Google Scholar 

  • Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389.

    Article  PubMed  Google Scholar 

  • Caspi, A., Roberts, B. W., & Shiner, R. L. (2005). Personality development: Stability and change. Annual Review of Psychology, 56, 453–484.

    Article  PubMed  Google Scholar 

  • Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. The American Journal of Psychiatry, 167(5), 509–527.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ciu, M., Donnellan, M. B., & Conger, R. D. (2007). Reciprocal influences between parents' marital problems and adolescent internalizing and externalizing behavior. Developmental Psychology, 43(6), 1544–1552.

    Article  Google Scholar 

  • Combs, M. A., Canu, W. H., Broman-Fulks, J. J., Rocheleau, C. A., & Nieman, D. C. (2015). Perceived stress and ADHD symptoms in adults. Journal of Attention Disorders, 19(5), 425–434.

    Article  PubMed  Google Scholar 

  • Conway, C. C., Slavich, G. M., & Hammen, C. (2014). Daily stress reactivity and serotonin transporter gene (5-HTTLPR) variation: Internalizing responses to everyday stress as a possible transdiagnostic phenotype. Biology of Mood & Anxiety, 4(2), 2.

    Article  Google Scholar 

  • Cox, M. J., Mills-Koonce, R., Propper, C., & Garpiéry, J. L. (2010). Systems theory and cascades in developmental psychopathology. Development and Psychopathology, 22, 497–506.

    Article  PubMed  Google Scholar 

  • Dick, D. M. (2011). Gene-environment interaction in psychological traits and disorders. Annual Review of Clinical Psychology, 7, 383–409.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dick, D. M., Rose, R. J., & Kaprio, J. (2006). The next challenge for psychiatric genetics: Characterizing the risk associated with identified genes. Annals of Clinical Psychiatry, 18(4), 223–231.

    Article  PubMed  PubMed Central  Google Scholar 

  • Drabant, E. M., Ramel, W., Edge, M. D., Hyde, L. W., Kuo, J. R., Goldin, P. R., et al. (2012). Neural mechanisms underlying 5-HTTLPR related sensitivity to acute stress. American Journal of Psychiatry, 169(4), 397–405.

    Article  PubMed  Google Scholar 

  • Erikson, E. H. (1968). Identity: Youth and crisis. New York: Norton.

    Google Scholar 

  • Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: A meta-analytic review. Human Genetics, 126(1), 51–90.

    Article  PubMed  Google Scholar 

  • Gunther, N., Drukker, M., Feron, F., & van Os, J. (2007). No ecological effect modification of the association between negative life experiences and later psychopathology in adolescence: A longitudinal community study in adolescents. European Psychiatry, 22(5), 296–304.

    Article  PubMed  Google Scholar 

  • Hamaker, E. L., Kuiper, R. M., & Grasman, R. P. (2015). A critique of the cross-lagged panel model. Psychological Methods, 20(1), 102–116.

    Article  PubMed  Google Scholar 

  • Hampson, S. E. (2008). Mechanisms by which childhood personality traits influence adult well-being. Current Directions in Psychological Science, 17, 264–268.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science, 297(5580), 400–403.

    Article  PubMed  Google Scholar 

  • Hu, L. T., & Bentler, P. M. (1999). Cutoff criteria for fit indexes in covariance structure analysis: Conventional criteria versus new alternatives. Structural Equation Modeling, 6(1), 1–55.

    Article  Google Scholar 

  • Hu, X. Z., Lipsky, R. H., Zhu, G., Akhtar, L. A., Taubman, J., Greenberg, B. D., et al. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics, 78(5), 815–826.

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnson, D. P., Rhee, S. H., Whisman, M. A., Corley, R. P., & Hewitt, J. K. (2013). Genetic and environmental influences on negative life events from late childhood to adolescence. Child Development, 84(5), 1823–1839.

    Article  PubMed  PubMed Central  Google Scholar 

  • Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68(5), 444–454.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kendler, K. S., Kessler, R. C., Walters, E. E., MacLean, C., Neal, M. C., Heath, A. C., et al. (1995). Stressful life events, genetic liability, and onset of an episode of major depression in women. American Journal of Psychiatry, 152(6), 833–842.

    Article  PubMed  Google Scholar 

  • Kendler, K. S., Gardner, C. O., & Prescott, C. A. (2003). Personality and the experience of environmental adversity. Psychological Medicine, 33(7), 1193–1202.

    Article  PubMed  Google Scholar 

  • Kim, K. J., Conger, R. D., Elder Jr., G. H., & Lorenz, F. O. (2003). Reciprocal influences between stressful life events and adolescent internalizing and externalizing problems. Child Development, 74(1), 127–143.

    Article  PubMed  Google Scholar 

  • Kline, R. B. (2005). Principles and practice of structural equation modeling (2nd ed.). New York: The Guilford Press.

    Google Scholar 

  • Landrø, N. I., Jonassen, R., Clark, L., Foss Haug, K. B., Aker, M., Bø, R., et al. (2015). Serotonin transporter polymorphisms predict response inhibition in healthy volunteers. Neuroscience Letters, 584(1), 109–112.

    Article  PubMed  Google Scholar 

  • Laurens, B., Coy, K. C., & Collins, W. A. (1998). Reconsidering changes in parent-child conflict across adolescence: A meta-analysis. Child Development, 69(3), 817–832.

    Article  Google Scholar 

  • Lerner, R. M. (1991). Changing organism-context relations as the basic process of development: A developmental contextual perspective. Developmental Psychology, 27, 27–32.

    Article  Google Scholar 

  • Lesch, K. P., & Merschdorf, U. (2000). Impulsivity, aggression, and serotonin: A molecular psychobiological perspective. Behavioral Sciences & the Law, 18(5), 581–604.

    Article  Google Scholar 

  • Levy, F., Hay, D. A., McStephen, M., Wood, C., & Waldman, I. (1997). Attention-deficit hyperactivity disorder: A category or a continuum? Genetic analysis of a large-scale twin study. Journal of the American Academy of Adolescent Psychiatry, 36(3), 737–744.

    Article  Google Scholar 

  • Lifford, K. J., Harold, G. T., & Thapar, A. (2009). Parent–child hostility and child ADHD symptoms: A genetically sensitive and longitudinal analysis. Journal of Child Psychology and Psychiatry, 50(12), 1468–1476.

    Article  PubMed  Google Scholar 

  • Matthews, T., Danese, A., Wertz, J., Ambler, A., Kelly, M., Diver, A., et al. (2015). Social isolation and mental health at primary and secondary school entry: A longitudinal cohort study. Journal of the American Academy of Child and Adolescent Psychiatry, 54(3), 225–232.

    Article  PubMed  PubMed Central  Google Scholar 

  • van der Meer, D., Hartman, C. A., Richards, J., Bralten, J. B., Franke, B., Oosterlaan, J., et al. (2014). The serotonin transporter gene polymorphism 5-HTTLPR moderates the effects of stress on attention-deficit/hyperactivity disorder. Journal of Child Psychology and Psychiatry, 55(12), 1363–1371.

    Article  PubMed  Google Scholar 

  • Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research, 16, 1215.

    Article  PubMed  PubMed Central  Google Scholar 

  • Müller, D. J., Mandelli, L., Serretti, A., DeYoung, C. G., De Luca, V., Sicard, T., et al. (2008). Serotonin transporter gene and adverse life events in adult ADHD. American Journal of Medical Genetics. Part B, Neuropsychiatric. Genetics, 147B(8), 1461–1469.

    Article  Google Scholar 

  • Muthén, L. K., & Muthén, B. O. (1998–2012). Mplus user’s guide (6th ed.). Los Angeles: Muthén & Muthén.

    Google Scholar 

  • Nakamura, B. J., Ebesutani, C., Bernstein, A., & Chorpita, B. F. (2009). A psychometric analysis of the child behavior checklist DSM-oriented scales. Journal of Psychopathology and Behavioral Assessment, 31(3), 178–189.

    Article  Google Scholar 

  • Nijmeijer, J. S., Minderaa, R. B., Buitelaar, J. K., Mulligan, A., Hartman, C. A., & Hoekstra, P. J. (2008). Attention-deficit/hyperactivity disorder and social dysfunctioning. Clinical Psychology Review, 28(4), 692–708.

    Article  PubMed  Google Scholar 

  • Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011). Gene-environment interactions: Early life stress and risk for depressive anxiety disorders. Psychopharmacology, 214(1), 175–196.

    Article  PubMed  PubMed Central  Google Scholar 

  • Oades, R. D., Lasky-Su, J., Christiansen, H., Faraone, S. V., Sonuga-Barke, E. J., Banaschewski, T., et al. (2008). The influence of serotonin- and other genes on impulsive behavioral aggression and cognitive impulsivity in children with attention-deficit/hyperactivity disorder (ADHD): Findings from a family-based association test (FBAT) analysis. Behavioral and Brain Functions, 84(4), 48.

    Article  Google Scholar 

  • Oldehinkel, A. J., Verhulst, F. C., & Ormel, J. (2008). Low heart rate: A marker of stress resilience. The TRAILS study. Biological Psychiatry, 63(12), 1141–1146.

    Article  PubMed  Google Scholar 

  • Oldehinkel, A. J., Rosmalen, J. G. M., Buitelaar, J. K., Hoek, H. W., Ormel, J., Raven, D., et al. (2015). Cohort profile update: The tracking adolescents’ individual lives survey (TRAILS). International Journal of Epidemiology, 44(1), 76–76n.

  • Pingault, J., Viding, E., Galéra, C., Greven, C. U., Zhen, Y., Plomin, R., et al. (2015). Genetic and environmental influences on the developmental course of attention-deficit/hyperactivity disorder symptoms from childhood to adolescence. JAMA Psychiatry, 72(7), 651–658.

    Article  PubMed  Google Scholar 

  • Reiss, D. (2010). Genetic thinking in the study of social relationships: Five points of entry. Perspectives of Psychological Science, 5(5), 502–515.

    Article  Google Scholar 

  • Retz, W., Freitag, C. M., Retz-Junginger, P., Wenzler, D., Schneider, M., Kissling, C., et al. (2008). A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: Interaction with adverse childhood environment. Psychiatry Research, 158(2), 123–131.

    Article  PubMed  Google Scholar 

  • Rudolph, K. D., Hammen, C., Burge, D., Lindberg, N., Herzberg, D., & Daley, S. E. (2000). Toward an interpersonal life-stress model of depression: The developmental context of stress generation. Development and Psychopathology, 12(2), 215–234.

  • Sasser, T. R., Kalvin, C. B., & Bierman, K. L. (2016). Developmental trajectories of clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms from grade 3 through 12 in a high-risk sample: Predictors and outcomes. Journal of Abnormal Psychology, 125(2), 207–219.

    Article  PubMed  PubMed Central  Google Scholar 

  • Satorra, A., & Bentler, P. M. (2001). A scaled difference chi-square test statistic for moment structural analysis. Psychometrika, 66(4), 507–514.

    Article  Google Scholar 

  • Schneiders, J., Drukker, M., van der Ende, J., Verhulst, F. C., van Os, J., & Nicoloson, N. A. (2003). Neighbourhood socioeconomic disadvantage and behavioural problems from late childhood into early adolescence. Journal of Epidemiology and Community Health, 57(9), 699–703.

    Article  PubMed  PubMed Central  Google Scholar 

  • Schriber, R. A., & Gruyer, A. E. (2016). Adolescent neurobiological susceptibility to social context. Developmental Cognitive Neuroscience, 19(1), 1–18.

    Article  PubMed  Google Scholar 

  • Shanahan, M. J., & Boardman, J. D. (2009). Genetics and behavior in the life course: A promising frontier. In G. H. Elder Jr. & J. Z. Giele (Eds.), The Craft of Life Course Research (pp. 215–235). New York: The Guilford Press.

    Google Scholar 

  • Shaw, P. (2015). Gene and environment interactions in the brain: A pathway to ADHD? American Journal of Psychiatry, 172(8), 702–703.

    Article  PubMed  Google Scholar 

  • Shoval, G., Bar-Shira, O., Zalsman, G., John Mann, J., & Chechik, G. (2014). Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence. European Neuropsychopharmacology, 24(7), 1123–1132.

    Article  PubMed  Google Scholar 

  • Thapar, A., Langley, K., Asherson, P., & Gill, M. (2007). Gene-environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective. The British Journal of Psychiatry, 190, 1–3.

    Article  PubMed  Google Scholar 

  • Thissen, A. J. A. M., Bralten, J., Rommelse, N. N. J., Arias-Vasques, A., Greven, C. U., Heslenfeld, D., et al. (2015). The role of age in association analyses of ADHD and related neurocognitive functioning: A proof of concept for dopaminergic and serotonergic genes. American Journal of Medical Genetics Part B, Neuropsychiatric Genetics, 168(6), 471–479.

    Article  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(2), 131–146.

    Article  PubMed  Google Scholar 

  • Verhulst, F. C., & Achenbach, T. M. (1995). Empirically based assessment and taxonomy of psychopathology: Cross-cultural applications. A review. European Child and Adolescent Psychiatry, 4(2), 61–76.

    Article  PubMed  Google Scholar 

  • Verlinden, M., Jansen, P. W., Veenstra, R., Jaddoe, V. W. V., Hofman, A., Verhulst, F. C., et al. (2015). Preschool attention-deficit/hyperactivity and oppositional defiant problems as antecedents of school bullying. Journal of the American Academy of Child and Adolescent Psychiatry, 54(7), 571–579.

    Article  PubMed  Google Scholar 

  • de Winter, A. F., Oldehinkel, A. J., Veenstra, R., Agnes, J., Verhulst, F. C., & Ormel, J. (2005). Evaluation of non-response bias in mental health determinants and outcomes in a large in a large of non-response bias in mental health determinants and outcomes sample. European Journal of Epidemiology, 20(2), 173–181.

    Article  PubMed  Google Scholar 

  • Zandstra, A. R. E., Hartman, C. A., Nederhof, E., van den Heuvel, E. R., Dietrich, A., Hoekstra, P. J., & Ormel, J. (2015). Chronic stress and adolescents’ mental health: Modifying effects of basal cortisol and parental psychiatric history. The trails study. Journal of Abnormal Child Psychology, 43(6), 1119–1130.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research is part of the TRacking Adolescents’ Individual Lives Survey (TRAILS). Participating centers of TRAILS include various departments of the University Medical Center and University of Groningen, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. TRAILS has been financially supported by various grants from the Netherlands Organization for Scientific Research (NWO), ZonMW, GB-MaGW, the Dutch Ministry of Justice, the European Science Foundation, BBMRI-NL, and the participating universities. We are grateful to everyone who participated in this research or worked on this project to and make it possible.

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Djûke M. Brinksma, Pieter J. Hoekstra, Annelies de Bildt, Barbara J. van den Hoofdakker & Andrea Dietrich

  2. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Nijmegen, The Netherlands

    Jan K. Buitelaar

  3. Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands

    Jan K. Buitelaar

  4. Department of Clinical Psychology and Experimental Psychopathology, University of Groningen, Groningen, The Netherlands

    Barbara J. van den Hoofdakker

  5. Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), Department of Psychiatry, University of Groningen, University Medical Center, Groningen, The Netherlands

    Catharina A. Hartman

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  1. Djûke M. Brinksma
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  2. Pieter J. Hoekstra
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  3. Annelies de Bildt
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  4. Jan K. Buitelaar
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  7. Andrea Dietrich
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Correspondence to Djûke M. Brinksma.

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Conflict of Interest

Buitelaar declares interest through Advisory Board for Lundbeck and through speaker’s bureaus for Lilly, Janssen-Cilag, Shire, Medice and Novartis. Brinksma, de Bildt, Dietrich, Hartman, Hoekstra and van den Hoofdakker declare that they have no conflict of interest.

Ethical Approval

TRAILS was approved by the National Dutch Medical Ethics Committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Parents gave written informed consent prior to each assessment wave. Adolescents gave written informed assessment at the second and third waves. This manuscript contains no information that discloses the identity of our participants or violates their privacy.

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Brinksma, D.M., Hoekstra, P.J., de Bildt, A. et al. ADHD Symptoms in Middle Adolescence Predict Exposure to Person-Related Life Stressors in Late Adolescence in 5-HTTLPR S-allele Homozygotes. J Abnorm Child Psychol 46, 1427–1437 (2018). https://doi.org/10.1007/s10802-017-0377-3

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