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Genetics of co-developing conduct and emotional problems during childhood and adolescence

Nature Human Behaviour volume 2, pages 514–521 (2018)Cite this article

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Abstract

Common genetic influences offer a partial explanation for comorbidity between different psychiatric disorders1,2,3. However, the genetics underlying co-development—the cross-domain co-occurrence of patterns of change over time—of psychiatric symptoms during childhood and adolescence has not been well explored. Here, we show genetic influence on joint symptom trajectories of parent-reported conduct and emotional problems (overall N = 15,082) across development (4–16 years) using both twin- and genome-wide polygenic score analyses (genotyped N = 2,610). Specifically, we found seven joint symptom trajectories, including two characterized by jointly stable and jointly increasing symptoms of conduct and emotional problems, respectively (7.3% of the sample, collectively). Twin modelling analyses revealed substantial genetic influence on trajectories (heritability estimates range of 0.41–0.78). Furthermore, individuals’ risk of being classified in the most symptomatic trajectory classes was significantly predicted by polygenic scores for years-of-education-associated alleles and depressive symptoms-associated alleles. Complementary analyses of child self-reported symptoms across late childhood and early adolescence yielded broadly similar results. Taken together, our results indicate that genetic factors are involved in the co-development of conduct and emotional problems across childhood and adolescence, and that individuals with co-developing symptoms across multiple domains may represent a clinical subgroup characterized by increased levels of genetic risk.

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Fig. 1: Joint trajectory latent class growth model for parent-reported symptoms of conduct and emotional problems with intercept and linear and quadratic slopes.
Fig. 2: Joint developmental trajectory classes of parent-reported symptoms of conduct and emotional problems from the best-fitting 7-class model.
Fig. 3: Distribution of education years and depressive symptoms GPS among each of the seven joint developmental trajectory classes of parent-reported symptoms of conduct and emotional problems.

References

  1. Kendler, K. S., Prescott, C. A., Myers, J. & Neale, M. C. The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch. Gen. Psychiatry 60, 929–937 (2003).

    Article  PubMed  Google Scholar 

  2. Lee, S. H. et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).

    Article  PubMed  CAS  Google Scholar 

  3. Pettersson, E., Larsson, H. & Lichtenstein, P. Common psychiatric disorders share the same genetic origin: a multivariate sibling study of the Swedish population. Mol. Psychiatry 21, 717–721 (2016).

    Article  PubMed  CAS  Google Scholar 

  4. Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R. & Walters, E. E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 617–627 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Krueger, R. F. & Markon, K. E. Reinterpreting comorbidity: a model-based approach to understanding and classifying psychopathology. Annu. Rev. Clin. Psychol. 2, 111–133 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Battaglia, M., Przybeck, T. R., Bellodi, L. & Cloninger, C. R. Temperament dimensions explain the comorbidity of psychiatric disorders. Compr. Psychiatry 37, 292–298 (1996).

    Article  PubMed  CAS  Google Scholar 

  7. Rhee, S. H., Lahey, B. B. & Waldman, I. D. Comorbidity among dimensions of childhood psychopathology: converging evidence from behavior genetics. Child Dev. Perspect. 9, 26–31 (2015).

    Article  PubMed  Google Scholar 

  8. Merikangas, K. R. et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication—Adolescent Supplement (NCS-A). J. Am. Acad. Child Adolesc. Psychiatry 49, 980–989 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Lewinsohn, P. M., Rohde, P. & Seeley, J. R. Adolescent psychopathology: III. The clinical consequences of comorbidity. J. Am. Acad. Child Adolesc. Psychiatry 34, 510–519 (1995).

    Article  PubMed  CAS  Google Scholar 

  10. Angold, A., Costello, E. J. & Erkanli, A. Comorbidity. J. Child Psychol. Psychiatry 40, 55–87 (1999).

    Article  Google Scholar 

  11. Costello, E. J., Mustillo, S., Erkanli, A., Keeler, G. & Angold, A. Prevalence and development of psychiatric disorders in childhood and adolescence. Arch. Gen. Psychiatry 60, 837–844 (2003).

    Article  PubMed  Google Scholar 

  12. Merikangas, K. R. et al. Prevalence and treatment of mental disorders among US children in the 2001–2004 NHANES. Pediatrics 125, 75–81 (2010).

    Article  PubMed  Google Scholar 

  13. Cunningham, N. R. & Ollendick, T. H. Comorbidity of anxiety and conduct problems in children: implications for clinical research and practice. Clin. Child Fam. Psychol. Rev. 13, 333–347 (2010).

    Article  PubMed  Google Scholar 

  14. Riglin, L. et al. Profiling depression in childhood and adolescence: the role of conduct problems. J. Child Psychol. Psychiatry 57, 481–490 (2016).

    Article  PubMed  Google Scholar 

  15. Wolff, J. C. & Ollendick, T. H. The comorbidity of conduct problems and depression in childhood and adolescence. Clin. Child Fam. Psychol. Rev. 9, 201–220 (2006).

    Article  PubMed  Google Scholar 

  16. Hofstra, M. B., van der Ende, J. & Verhulst, F. C. Continuity and change of psychopathology from childhood into adulthood: a 14-year follow-upstudy. J. Am. Acad. Child Adolesc. Psychiatry 39, 850–858 (2000).

    Article  PubMed  CAS  Google Scholar 

  17. Costello, E. J., Copeland, W. E. & Angold, A. Trends in psychopathology across the adolescent years: What changes when children become adolescents, and when adolescents become adults? J. Child Psychol. Psychiatry 52, 1015–1025 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Letcher, P., Smart, D., Sanson, A. & Toumbourou, J. W. Psychosocial precursors and correlates of differing internalizing trajectories from 3 to 15 years. Soc. Dev. 18, 618–646 (2009).

    Article  Google Scholar 

  19. Odgers, C. L. et al. Female and male antisocial trajectories: from childhood origins to adult outcomes. Dev. Psychopathol. 20, 673–716 (2008).

    Article  PubMed  Google Scholar 

  20. Lahey, B. B., Zald, D. H., Hakes, J. K., Krueger, R. F. & Rathouz, P. J. Patterns of heterotypic continuity associated with the cross-sectional correlational structure of prevalent mental disorders in adults. JAMA Psychiatry 71, 989–996 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Reinke, W. M. & Ostrander, R. Heterotyic and homotypic continuity: the moderating effects of age and gender. J. Abnorm. Child Psychol. 36, 1109–1121 (2008).

    Article  PubMed  Google Scholar 

  22. Rutter, M., Kim-Cohen, J. & Maughan, B. Continuities and discontinuities in psychopathology between childhood and adult life. J. Child Psychol. Psychiatry 47, 276–295 (2006).

    Article  PubMed  Google Scholar 

  23. Fanti, K. Using a person-centered methodology to investigate the co-occurrence between psychopathological problems. Ann. Depress. Anxiety 1, 1–5 (2014).

    Google Scholar 

  24. Barker, E. D. & Maughan, B. Differentiating early-onset persistent versus childhood-limited conduct problem youth. Am. J. Psychiatry 166, 900–908 (2009).

    Article  PubMed  Google Scholar 

  25. Moffitt, T. E., Caspi, A., Dickson, N., Silva, P. & Stanton, W. Childhood-onset versus adolescent-onset antisocial conduct problems in males: natural history from ages 3 to 18 years. Dev. Psychopathol. 8, 399–424 (1996).

    Article  Google Scholar 

  26. Maughan, B., Pickles, A., Rowe, R., Costello, E. J. & Angold, A. Developmental trajectories of aggressive and non-aggressive conduct problems. J. Quant. Criminol. 16, 199–221 (2000).

    Article  Google Scholar 

  27. Bongers, I. L., Koot, H. M., van der Ende, J. & Verhulst, F. C. Developmental trajectories of externalizing behaviors in childhood and adolescence. Child Dev. 75, 1523–1537 (2004).

    Article  PubMed  Google Scholar 

  28. Wildeboer, A. et al. Early childhood aggression trajectories: associations with teacher-reported problem behaviour. Int. J. Behav. Dev. 39, 221–234 (2015).

    Article  Google Scholar 

  29. Leve, L. D., Kim, H. K. & Pears, K. C. Childhood temperament and family environment as predictors of internalizing and externalizing trajectories from ages 5 to 17. J. Abnorm. Child Psychol. 33, 505–520 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shaw, D. S., Lacourse, E. & Nagin, D. S. Developmental trajectories of conduct problems and hyperactivity from ages 2 to 10. J. Child Psychol. Psychiatry Allied Discip. 46, 931–942 (2005).

    Article  Google Scholar 

  31. Feng, X., Shaw, D. S. & Silk, J. S. Developmental trajectories of anxiety symptoms among boys across early and middle childhood. J. Abnorm. Psychol. 117, 32–47 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Davis, S., Votruba‐Drzal, E. & Silk, J. S. Trajectories of internalizing symptoms from early childhood to adolescence: associations with temperament and parenting. Soc. Dev. 24, 501–520 (2015).

    Article  Google Scholar 

  33. Dekker, M. C. et al. Developmental trajectories of depressive symptoms from early childhood to late adolescence: gender differences and adult outcome. J. Child Psychol. Psychiatry 48, 657–666 (2007).

    Article  PubMed  Google Scholar 

  34. Nagin, D. S. & Tremblay, R. E. Analyzing developmental trajectories of distinct but related behaviors: a group-based method. Psychol. Methods 6, 18–33 (2001).

    Article  PubMed  CAS  Google Scholar 

  35. Gilliom, M. & Shaw, D. Codevelopment of externalizing and internalizing problems in early childhood. Dev. Psychopathol. 16, 313–333 (2004).

    Article  PubMed  Google Scholar 

  36. Fanti, K. & Henrich, C. C. Trajectories of pure and co-occurring internalizing and externalizing problems from age 2 to age 12: findings from the National Institute of Child Health and Human Development Study of Early Child Care. Dev. Psychol. 46, 1159–1175 (2010).

    Article  PubMed  Google Scholar 

  37. Nivard, M. G. et al. Joint developmental trajectories of internalizing and externalizing disorders between childhood and adolescence. Dev. Psychopathol. 29, 919–928 (2017).

    Article  PubMed  Google Scholar 

  38. Reinke, W. M., Eddy, J. M., Dishion, T. J. & Reid, J. B. Joint trajectories of symptoms of disruptive behavior problems and depressive symptoms during early adolescence and adjustment problems during emerging adulthood. J. Abnorm. Child Psychol. 40, 1123–1136 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Wiesner, M. & Kim, H. K. Co-occurring delinquency and depressive symptoms of adolescent boys and girls: a dual trajectory modeling approach. Dev. Psychol. 42, 1220–1235 (2006).

    Article  PubMed  Google Scholar 

  40. Anttila, A. V. et al. Analysis of shared heritability in common disorders of the brain. Preprint at https://www.biorxiv.org/content/early/2017/09/06/048991 (2017).

  41. Hannigan, L. J., Walaker, N., Waszczuk, M., McAdams, T. & Eley, T. C. Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review. Psychopathol. Rev. 4, 1–57 (2016).

    Article  Google Scholar 

  42. Lacourse, E. et al. A longitudinal twin study of physical aggression during early childhood: evidence for a developmentally dynamic genome. Psychol. Med. 44, 2617–2627 (2014).

    Article  PubMed  CAS  Google Scholar 

  43. Pingault, J.-B., Rijsdijk, F., Zheng, Y., Plomin, R. & Viding, E. Developmentally dynamic genome: evidence of genetic influences on increases and decreases in conduct problems from early childhood to adolescence. Sci. Rep. 5, 10053 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Lubke, G. H. et al. A powerful phenotype for gene-finding studies derived from trajectory analyses of symptoms of anxiety and depression between age seven and 18. Am. J. Med. Genet. B Neuropsychiatr. Genet. 171, 948–957 (2016).

    Article  PubMed  Google Scholar 

  45. Harden, K. P., Quinn, P. D. & Tucker-Drob, E. M. Genetically influenced change in sensation seeking drives the rise of delinquent behavior during adolescence. Dev. Sci. 15, 150–163 (2012).

    Article  PubMed  Google Scholar 

  46. Fontaine, N. M. G., Rijsdijk, F. V., McCrory, E. J. P. & Viding, E. Etiology of different developmental trajectories of callous-unemotional traits. J. Am. Acad. Child Adolesc. Psychiatry 49, 656–664 (2010).

    PubMed  Google Scholar 

  47. Plomin, R., DeFries, J. C., Knopik, V. S. & Neiderhiser, J. M. Top 10 replicated findings from behavioral genetics. Perspect. Psychol. Sci. 11, 3–23 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Dudbridge, F. Power and predictive accuracy of polygenic risk scores. PLoS Genet. 9, e1003348 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Krapohl, E. et al. Multi-polygenic score approach to trait prediction. Mol. Psychiatry 23, 1368–1374 (2018).

    Article  PubMed  CAS  Google Scholar 

  50. Krapohl, E. et al. Phenome-wide analysis of genome-wide polygenic scores. Mol. Psychiatry 21, 1188–1193 (2016).

    Article  PubMed  CAS  Google Scholar 

  51. Belsky, D. W. et al. The genetics of success. Psychol. Sci. 27, 957–972 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  52. McDonald, R. P. & Ho, M. H. Principles and practice in reporting structural equation analyses. Psychol. Methods 7, 64–82 (2002).

    Article  PubMed  Google Scholar 

  53. Costello, D., Swendsen, J., Roes, J. & Dierker, L. C. Risk and protective factors associated with trajectories of depressed mood from adolescence to early adulthood. J. Consult. Clin. Psychol. 76, 173–183 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Toumbourou, J. W., Williams, I., Letcher, P., Sanson, A. & Smart, D. Developmental trajectories of internalising behaviour in the prediction of adolescent depressive symptoms. Aust. J. Psychol. 63, 214–223 (2011).

    Article  Google Scholar 

  55. Lahey, B. B., Loeber, R., Burke, J., Rathouz, P. J. & McBurnett, K. Waxing and waning in concert: dynamic comorbidity of conduct disorder with other disruptive and emotional problems over 7 years among clinic-referred boys. J. Abnorm. Psychol. 111, 556–567 (2002).

    Article  PubMed  Google Scholar 

  56. Frick, P. J. & Morris, A. S. Temperament and developmental pathways to conduct problems. J. Clin. Child Adolesc. Psychol. 33, 54–68 (2004).

    Article  PubMed  Google Scholar 

  57. Dodge, K. A. Social-cognitive mechanisms in the development of conduct disorder and depression. Annu. Rev. Psychol. 44, 559–584 (1993).

    Article  PubMed  CAS  Google Scholar 

  58. Burt, S. A., McGue, M., Krueger, R. F. & Iacono, W. G. How are parent–child conflict and childhood externalizing symptoms related over time? Results from a genetically informative cross-lagged study. Dev. Psychopathol. 17, 145–165 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Avinun, R. & Knafo, A. Parenting as a reaction evoked by children’s genotype: a meta-analysis of children-as-twins studies. Personal. Soc. Psychol. Rev. 18, 87–102 (2014).

    Article  Google Scholar 

  60. Caspi, A. et al. The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clin. Psychol. Sci. 2, 119–137 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Eley, T. C. General genes: a new theme in developmental psychopathology. Curr. Dir. Psychol. Sci. 6, 90–95 (1997).

    Article  Google Scholar 

  62. Lahey, B. B., Van Hulle, Ca, Singh, A. L., Waldman, I. D. & Rathouz, P. J. Higher-order genetic and environmental structure of prevalent forms of child and adolescent psychopathology. Arch. Gen. Psychiatry 68, 181–189 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Visscher, P. M. Human complex trait genetics in the 21st century. Genetics 202, 377–379 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Enders, C., & Bandalos, D. The relative performance of full information maximum likelihood estimation for missing data in structural equation models. Struct. Equ. Modeling 8, 430–457 (2001).

    Article  Google Scholar 

  65. Haworth, C. Ma, Davis, O. S. P. & Plomin, R. Twins Early Development Study (TEDS): a genetically sensitive investigation of cognitive and behavioral development from childhood to young adulthood. Twin Res. Hum. Genet. 16, 117–125 (2013).

    Article  PubMed  Google Scholar 

  66. Goodman, R. The Strengths and Difficulties Questionnaire: a research note. J. Child Psychol. Psychiatry 38, 581–586 (1997).

    Article  PubMed  CAS  Google Scholar 

  67. Gadermann, A. M., Guhn, M. & Zumbo, B. D. Estimating ordinal reliability for Likert-type and ordinal item response data: a conceptual, empirical, and practical guide. Pract. Assess. Res. Eval. 17, 1–13 (2012).

    Google Scholar 

  68. Lo, Y., Mendell, N. R. & Rubin, D. B. Testing the number of components in a normal mixture. Biometrika 88, 767–778 (2001).

    Article  Google Scholar 

  69. Vuong, Q. Likelihood ratio tests for model selection and nonnested hypotheses. Econometrica 57, 307–333 (1989).

    Article  Google Scholar 

  70. Ram, N. & Grimm, K. J. Growth mixture modeling: a method for identifying differences in longitudinal change among unobserved groups. Int. J. Behav. Dev. 33, 565–576 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Sivakumaran, S. et al. Abundant pleiotropy in human complex diseases and traits. Am. J. Hum. Genet. 89, 607–618 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539–542 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 48, 624–633 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Muthén, L. K. & Muthén, B. O. Mplus User’s Guide 8th edn (Muthén & Muthén, Los Angeles, CA, 2017).

  75. Hallquist, M. N. & Wiley, J. F. MplusAutomation: an R Package for facilitating large-scale latent variable analyses in Mplus. Struct. Equ. Modeling 25, 621–638 (2018).

    Article  PubMed  Google Scholar 

  76. Neale, M. C. et al. OpenMx 2.0: extended structural equation and statistical modeling. Psychometrika 26, 99–127 (2015).

    Google Scholar 

  77. Jelicić, H., Phelps, E. & Lerner, R. M. Use of missing data methods in longitudinal studies: the persistence of bad practices in developmental psychology. Dev. Psychol. 45, 1195–1199 (2009).

    Article  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge the ongoing contribution of the participants in the TEDS and their families. TEDS is supported by a programme grant from the UK Medical Research Council (MR/M021475/1 and previously G0901245), with additional support from the US National Institutes of Health (AG046938) and the European Commission (602768 and 295366). L.J.H. is supported by a 1 + 3 PhD studentship from the UK Economic and Social Research Council (ESRC). J.-B.P. is a fellow of MQ: Transforming Mental Health. E.K. is supported by the MRC/IoPPN Excellence Award. T.A.M. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (107706/Z/15/Z). This study presents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank R. Plomin for his input and advice.

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  1. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Laurie J. Hannigan, Jean-Baptiste Pingault, Eva Krapohl, Tom A. McAdams, Frühling V. Rijsdijk & Thalia C. Eley

  2. Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

    Laurie J. Hannigan

  3. Division of Psychology and Language Sciences, University College London, London, UK

    Jean-Baptiste Pingault

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Contributions

L.J.H., T.C.E., T.A.M. and F.V.R. conceived of the investigation. L.J.H., J.-B.P. and E.K. discussed the analytic strategy, and L.J.H. and E.K. carried out the statistical analyses. L.J.H., T.C.E., T.A.M. and F.V.R. worked on interpreting the results and refining the analyses. L.J.H. wrote the manuscript, and all authors critically reviewed the manuscript.

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Correspondence to Thalia C. Eley.

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Hannigan, L.J., Pingault, JB., Krapohl, E. et al. Genetics of co-developing conduct and emotional problems during childhood and adolescence. Nat Hum Behav 2, 514–521 (2018). https://doi.org/10.1038/s41562-018-0373-9

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