European Child & Adolescent Psychiatry

, Volume 19, Issue 3, pp 199–210 | Cite as

From nature versus nurture, via nature and nurture, to gene × environment interaction in mental disorders

  • Anne-Kathrin Wermter
  • Manfred Laucht
  • Benno G. Schimmelmann
  • Tobias Banaschweski
  • Edmund J. S. Sonuga-Barke
  • Marcella Rietschel
  • Katja Becker


It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G × E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G × E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G × E in mental disorders. Strategies for G × E research are introduced. G × E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G × E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G × E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G × E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.


Gene–environment interaction Depressive disorders ADHD Obesity Schizophrenia Substance use disorders 


  1. 1.
    Agurs-Collins T, Bouchard C (2008) Gene-nutrition and gene–physical activity interactions in the etiology of obesity. Introduction. Obesity (Silver Spring) 16(Suppl 3):S2–S4Google Scholar
  2. 2.
    Alexander N, Kuepper Y, Schmitz A, Osinsky R, Kozyra E, Hennig J (2009) Gene–environment interactions predict cortisol responses after acute stress: implications for the etiology of depression. Psychoneuroendocrinology 34:1294–1303PubMedCrossRefGoogle Scholar
  3. 3.
    Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, Tanzi RE, Bertram L (2008) Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40:827–834PubMedCrossRefGoogle Scholar
  4. 4.
    Andreasen CH, Andersen G (2009) Gene–environment interactions and obesity—further aspects of genomewide association studies. Nutrition 25:998–1003PubMedCrossRefGoogle Scholar
  5. 5.
    Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen A, Borch-Johnsen K, Rasmussen SS, Clausen JO, Sandbaek A, Lauritzen T, Hansen L, Jorgensen T, Pedersen O, Hansen T (2008) Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57:95–101PubMedCrossRefGoogle Scholar
  6. 6.
    Banaschweski T, Becker K, Scherag S, Franke B, Coghill D (2009) Molecular genetics in attention-deficit/hyperactivity disorders: an overview. Eur Child Adolesc PsychiatryGoogle Scholar
  7. 7.
    Barr CS, Newman TK, Lindell S, Shannon C, Champoux M, Lesch KP, Suomi SJ, Goldman D, Higley JD (2004) Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates. Arch Gen Psychiatry 61:1146–1152PubMedCrossRefGoogle Scholar
  8. 8.
    Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004) Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 55:733–738PubMedCrossRefGoogle Scholar
  9. 9.
    Becker K, El-Faddagh M, Schmidt MH, Esser G, Laucht M (2008) Interaction of dopamine transporter genotype with prenatal smoke exposure on ADHD symptoms. J Pediatr 152:263–269PubMedCrossRefGoogle Scholar
  10. 10.
    Belsky J, Bakermans-Kranenburg M, van Itzendoorn M (2007) For better and for worse: differential susceptibility to environmental influences. Curr Dir Psychol Sci 16:300–304CrossRefGoogle Scholar
  11. 11.
    Belsky J, Jonassaint C, Pluess M, Stanton M, Brummett B, Williams R (2009) Vulnerability genes or plasticity genes? Mol Psychiatry 14:746–754PubMedCrossRefGoogle Scholar
  12. 12.
    Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M (2008) Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 63:146–151PubMedCrossRefGoogle Scholar
  13. 13.
    Bouchard C (2008) Gene–environment interactions in the etiology of obesity: defining the fundamentals. Obesity (Silver Spring) 16(Suppl 3):S5–S10Google Scholar
  14. 14.
    Bray MS (2008) Implications of gene–behavior interactions: prevention and intervention for obesity. Obesity (Silver Spring) 16(Suppl 3):S72–S78Google Scholar
  15. 15.
    Brookes KJ, Mill J, Guindalini C, Curran S, Xu X, Knight J, Chen CK, Huang YS, Sethna V, Taylor E, Chen W, Breen G, Asherson P (2006) A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch Gen Psychiatry 63:74–81PubMedCrossRefGoogle Scholar
  16. 16.
    Brookes ST, Whitley E, Peters TJ, Mulheran PA, Egger M, Davey Smith G (2001) Subgroup analyses in randomised controlled trials: quantifying the risks of false-positives and false-negatives. Health Technol Assess 5:1–56PubMedGoogle Scholar
  17. 17.
    Brown GW, Harris TO (2008) Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene–environment interaction. J Affect Disord 111:1–12PubMedCrossRefGoogle Scholar
  18. 18.
    Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854PubMedCrossRefGoogle Scholar
  19. 19.
    Caspi A, Moffitt TE (2006) Gene–environment interactions in psychiatry: joining forces with neuroscience. Nat Rev Neurosci 7:583–590PubMedCrossRefGoogle Scholar
  20. 20.
    Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, Taylor A, Arseneault L, Williams B, Braithwaite A, Poulton R, Craig IW (2005) Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-o-methyltransferase gene: longitudinal evidence of a gene × environment interaction. Biol Psychiatry 57:1117–1127PubMedCrossRefGoogle Scholar
  21. 21.
    Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389PubMedCrossRefGoogle Scholar
  22. 22.
    Cervilla JA, Molina E, Rivera M, Torres-Gonzalez F, Bellon JA, Moreno B, Luna JD, Lorente JA, Mayoral F, King M, Nazareth I, Gutierrez B (2007) The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort. Mol Psychiatry 12:748–755PubMedCrossRefGoogle Scholar
  23. 23.
    Chipman P, Jorm AF, Prior M, Sanson A, Smart D, Tan X, Easteal S (2007) No interaction between the serotonin transporter polymorphism (5-HTTLPR) and childhood adversity or recent stressful life events on symptoms of depression: results from two community surveys. Am J Med Genet B Neuropsychiatr Genet 144B:561–565PubMedCrossRefGoogle Scholar
  24. 24.
    Chorbov VM, Lobos EA, Todorov AA, Heath AC, Botteron KN, Todd RD (2007) Relationship of 5-HTTLPR genotypes and depression risk in the presence of trauma in a female twin sample. Am J Med Genet B Neuropsychiatr Genet 144B:830–833PubMedCrossRefGoogle Scholar
  25. 25.
    Cloninger CR, Sigvardsson S, Gilligan SB, von Knorring AL, Reich T, Bohman M (1988) Genetic heterogeneity and the classification of alcoholism. Adv Alcohol Subst Abuse 7:3–16PubMedGoogle Scholar
  26. 26.
    Coghill D, Banaschewski T (2009) The genetics of attention-deficit/hyperactivity disorder. Expert Rev Neurother 9:1547–1565PubMedCrossRefGoogle Scholar
  27. 27.
    Covault J, Tennen H, Armeli S, Conner TS, Herman AI, Cillessen AH, Kranzler HR (2007) Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biol Psychiatry 61:609–616PubMedCrossRefGoogle Scholar
  28. 28.
    Dempfle A, Scherag A, Hein R, Beckmann L, Chang-Claude J, Schafer H (2008) Gene–environment interactions for complex traits: definitions, methodological requirements and challenges. Eur J Hum Genet 16:1164–1172PubMedCrossRefGoogle Scholar
  29. 29.
    Drachmann Bukh J, Bock C, Vinberg M, Werge T, Gether U, Vedel Kessing L (2009) Interaction between genetic polymorphisms and stressful life events in first episode depression. J Affect Disord 119:107–115PubMedCrossRefGoogle Scholar
  30. 30.
    Eaves LJ (2006) Genotype × environment interaction in psychopathology: fact or artifact? Twin Res Hum Genet 9:1–8PubMedCrossRefGoogle Scholar
  31. 31.
    El-Faddagh M, Laucht M, Maras A, Vohringer L, Schmidt MH (2004) Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age. J Neural Transm 111:883–889PubMedCrossRefGoogle Scholar
  32. 32.
    El Hage W, Powell JF, Surguladze SA (2009) Vulnerability to depression: what is the role of stress genes in gene × environment interaction? Psychol Med 39:1407–1411Google Scholar
  33. 33.
    Eley TC, Sugden K, Corsico A, Gregory AM, Sham P, McGuffin P, Plomin R, Craig IW (2004) Gene–environment interaction analysis of serotonin system markers with adolescent depression. Mol Psychiatry 9:908–915PubMedCrossRefGoogle Scholar
  34. 34.
    Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1313–1323PubMedCrossRefGoogle Scholar
  35. 35.
    Feder A, Nestler EJ, Charney DS (2009) Psychobiology and molecular genetics of resilience. Nat Rev Neurosci 10:446–457PubMedCrossRefGoogle Scholar
  36. 36.
    Ficks CA, Waldman ID (2009) Gene–environment interactions in attention-deficit/hyperactivity disorder. Curr Psychiatry Rep 11:387–392PubMedCrossRefGoogle Scholar
  37. 37.
    Flint J, Munafo MR (2008) Forum: Interactions between gene and environment. Curr Opin Psychiatry 21:315–317PubMedCrossRefGoogle Scholar
  38. 38.
    Foley DL, Eaves LJ, Wormley B, Silberg JL, Maes HH, Kuhn J, Riley B (2004) Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Arch Gen Psychiatry 61:738–744PubMedCrossRefGoogle Scholar
  39. 39.
    Gillespie NA, Whitfield JB, Williams B, Heath AC, Martin NG (2005) The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med 35:101–111PubMedCrossRefGoogle Scholar
  40. 40.
    Goldman D, Oroszi G, Ducci F (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6:521–532PubMedCrossRefGoogle Scholar
  41. 41.
    Grabe HJ, Lange M, Wolff B, Volzke H, Lucht M, Freyberger HJ, John U, Cascorbi I (2005) Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden. Mol Psychiatry 10:220–224PubMedCrossRefGoogle Scholar
  42. 42.
    Haberstick BC, Lessem JM, Hopfer CJ, Smolen A, Ehringer MA, Timberlake D, Hewitt JK (2005) Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment. Am J Med Genet B Neuropsychiatr Genet 135B:59–64PubMedCrossRefGoogle Scholar
  43. 43.
    Hariri AR, Mattay VS, Tessitore A, Kolachana B, Fera F, Goldman D, Egan MF, Weinberger DR (2002) Serotonin transporter genetic variation and the response of the human amygdala. Science 297:400–403PubMedCrossRefGoogle Scholar
  44. 44.
    Henquet C, Di Forti M, Morrison P, Kuepper R, Murray RM (2008) Gene–environment interplay between cannabis and psychosis. Schizophr Bull 34:1111–1121PubMedCrossRefGoogle Scholar
  45. 45.
    Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L, Drukker M, Ramaekers JG, van Os J (2006) An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 31:2748–2757PubMedCrossRefGoogle Scholar
  46. 46.
    Hunter DJ (2005) Gene–environment interactions in human diseases. Nat Rev Genet 6:287–298PubMedCrossRefGoogle Scholar
  47. 47.
    Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG (2001) Replication validity of genetic association studies. Nat Genet 29:306–309PubMedCrossRefGoogle Scholar
  48. 48.
    Ioannidis JP, Trikalinos TA (2007) An exploratory test for an excess of significant findings. Clin Trials 4:245–253PubMedCrossRefGoogle Scholar
  49. 49.
    Kahn RS, Khoury J, Nichols WC, Lanphear BP (2003) Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr 143:104–110PubMedCrossRefGoogle Scholar
  50. 50.
    Kaufman J, Yang BZ, Douglas-Palumberi H, Crouse-Artus M, Lipschitz D, Krystal JH, Gelernter J (2007) Genetic and environmental predictors of early alcohol use. Biol Psychiatry 61:1228–1234PubMedCrossRefGoogle Scholar
  51. 51.
    Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841PubMedGoogle Scholar
  52. 52.
    Keri S, Kiss I, Seres I, Kelemen O (2009) A polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) affects reactivity to expressed emotion in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 150B:418–420PubMedCrossRefGoogle Scholar
  53. 53.
    Khoury MJ, Adams MJ Jr, Flanders WD (1988) An epidemiologic approach to ecogenetics. Am J Hum Genet 42:89–95PubMedGoogle Scholar
  54. 54.
    Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE (2006) MAOA, maltreatment, and gene–environment interaction predicting children’s mental health: new evidence and a meta-analysis. Mol Psychiatry 11:903–913PubMedCrossRefGoogle Scholar
  55. 55.
    Kim JM, Stewart R, Kim SW, Yang SJ, Shin IS, Kim YH, Yoon JS (2007) Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biol Psychiatry 62:423–428PubMedCrossRefGoogle Scholar
  56. 56.
    Langley K, Fowler TA, Grady DL, Moyzis RK, Holmans PA, van den Bree MB, Owen MJ, O’Donovan MC, Thapar A (2009) Molecular genetic contribution to the developmental course of attention-deficit hyperactivity disorder. Eur Child Adolesc Psychiatry 18:26–32PubMedCrossRefGoogle Scholar
  57. 57.
    Langley K, Turic D, Rice F, Holmans P, van den Bree MB, Craddock N, Kent L, Owen MJ, O’Donovan MC, Thapar A (2008) Testing for gene x environment interaction effects in attention deficit hyperactivity disorder and associated antisocial behavior. Am J Med Genet B Neuropsychiatr Genet 147B:49–53PubMedCrossRefGoogle Scholar
  58. 58.
    Laucht M, Skowronek MH, Becker K, Schmidt MH, Esser G, Schulze TG, Rietschel M (2007) Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Arch Gen Psychiatry 64:585–590PubMedCrossRefGoogle Scholar
  59. 59.
    Laucht M, Treutlein J, Blomeyer D, Buchmann AF, Schmid B, Becker K, Zimmermann US, Schmidt MH, Esser G, Rietschel M, Banaschewski T (2009) Interaction between the 5-HTTLPR serotonin transporter polymorphism and environmental adversity for mood and anxiety psychopathology: evidence from a high-risk community sample of young adults. Int J Neuropsychopharmacol 12:737–747Google Scholar
  60. 60.
    Laucht M, Treutlein J, Schmid B, Blomeyer D, Becker K, Buchmann AF, Schmidt MH, Esser G, Jennen-Steinmetz C, Rietschel M, Zimmermann US, Banaschewski T (2009) Impact of psychosocial adversity on alcohol intake in young adults: moderation by the LL genotype of the serotonin transporter polymorphism. Biol Psychiatry 66:102–109PubMedCrossRefGoogle Scholar
  61. 61.
    Levin BE (2009) Synergy of nature and nurture in the development of childhood obesity. Int J Obes (Lond) 33(Suppl 1):S53–S56Google Scholar
  62. 62.
    Loos RJ, Bouchard C (2008) FTO: the first gene contributing to common forms of human obesity. Obes Rev 9:246–250PubMedCrossRefGoogle Scholar
  63. 63.
    Luan JA, Wong MY, Day NE, Wareham NJ (2001) Sample size determination for studies of gene–environment interaction. Int J Epidemiol 30:1035–1040PubMedCrossRefGoogle Scholar
  64. 64.
    Manolio TA, Bailey-Wilson JE, Collins FS (2006) Genes, environment and the value of prospective cohort studies. Nat Rev Genet 7:812–820PubMedCrossRefGoogle Scholar
  65. 65.
    Middeldorp CM, Cath DC, Beem AL, Willemsen G, Boomsma DI (2008) Life events, anxious depression and personality: a prospective and genetic study. Psychol Med 38:1557–1565PubMedCrossRefGoogle Scholar
  66. 66.
    Middeldorp CM, de Geus EJ, Beem AL, Lakenberg N, Hottenga JJ, Slagboom PE, Boomsma DI (2007) Family based association analyses between the serotonin transporter gene polymorphism (5-HTTLPR) and neuroticism, anxiety and depression. Behav Genet 37:294–301PubMedCrossRefGoogle Scholar
  67. 67.
    Mittal VA, Ellman LM, Cannon TD (2008) Gene–environment interaction and covariation in schizophrenia: the role of obstetric complications. Schizophr Bull 34:1083–1094PubMedCrossRefGoogle Scholar
  68. 68.
    Moffitt TE, Caspi A, Rutter M (2006) Measured gene–environment interactions in psychopathology: concepts, research strategies, and implications for research, intervention, and public understanding of genetics. Perspect Psychol Sci 1:5–27CrossRefGoogle Scholar
  69. 69.
    Moffitt TE, Caspi A, Rutter M (2005) Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry 62:473–481PubMedCrossRefGoogle Scholar
  70. 70.
    Munafo MR, Durrant C, Lewis G, Flint J (2009) Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry 65:211–219PubMedCrossRefGoogle Scholar
  71. 71.
    Neuman RJ, Lobos E, Reich W, Henderson CA, Sun LW, Todd RD (2007) Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biol Psychiatry 61:1320–1328PubMedCrossRefGoogle Scholar
  72. 72.
    Nicodemus KK, Marenco S, Batten AJ, Vakkalanka R, Egan MF, Straub RE, Weinberger DR (2008) Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 13:873–877PubMedCrossRefGoogle Scholar
  73. 73.
    Nilsson KW, Sjoberg RL, Damberg M, Alm PO, Ohrvik J, Leppert J, Lindstrom L, Oreland L (2005) Role of the serotonin transporter gene and family function in adolescent alcohol consumption. Alcohol Clin Exp Res 29:564–570PubMedCrossRefGoogle Scholar
  74. 74.
    Nilsson KW, Sjoberg RL, Damberg M, Leppert J, Ohrvik J, Alm PO, Lindstrom L, Oreland L (2006) Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity. Biol Psychiatry 59:121–127PubMedCrossRefGoogle Scholar
  75. 75.
    Olsson CA, Byrnes GB, Lotfi-Miri M, Collins V, Williamson R, Patton C, Anney RJ (2005) 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 10:868–876PubMedCrossRefGoogle Scholar
  76. 76.
    Plomin R, DeFries JC, Loehlin JC (1977) Genotype-environment interaction and correlation in the analysis of human behavior. Psychol Bull 84:309–322PubMedCrossRefGoogle Scholar
  77. 77.
    Power T, Stewart R, Ancelin ML, Jaussent I, Malafosse A, Ritchie K 5-HTTLPR genotype, stressful life events and late-life depression: No evidence of interaction in a French population. Neurobiol AgingGoogle Scholar
  78. 78.
    Psychogiou L, Daley DM, Thompson MJ, Sonuga-Barke EJ (2008) Do maternal attention-deficit/hyperactivity disorder symptoms exacerbate or ameliorate the negative effect of child attention-deficit/hyperactivity disorder symptoms on parenting? Dev Psychopathol 20:121–137PubMedCrossRefGoogle Scholar
  79. 79.
    Rampersaud E, Mitchell BD, Pollin TI, Fu M, Shen H, O’Connell JR, Ducharme JL, Hines S, Sack P, Naglieri R, Shuldiner AR, Snitker S (2008) Physical activity and the association of common FTO gene variants with body mass index and obesity. Arch Intern Med 168:1791–1797PubMedCrossRefGoogle Scholar
  80. 80.
    Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR (2009) Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 301:2462–2471PubMedCrossRefGoogle Scholar
  81. 81.
    Rutter M (2008) Biological implications of gene–environment interaction. J Abnorm Child Psychol 36:969–975PubMedCrossRefGoogle Scholar
  82. 82.
    Rutter M (2003) Commentary: nature–nurture interplay in emotional disorders. J Child Psychol Psychiatry 44:934–944PubMedCrossRefGoogle Scholar
  83. 83.
    Rutter M (2007) Gene–environment interdependence. Dev Sci 10:12–18PubMedCrossRefGoogle Scholar
  84. 84.
    Rutter M (2006) Implications of resilience concepts for scientific understanding. Ann N Y Acad Sci 1094:1–12PubMedCrossRefGoogle Scholar
  85. 85.
    Rutter M (2002) The interplay of nature, nurture, and developmental influences: the challenge ahead for mental health. Arch Gen Psychiatry 59:996–1000PubMedCrossRefGoogle Scholar
  86. 86.
    Rutter M, Beckett C, Castle J, Colvert E, Kreppner JM, Metha M, Stevens SE, Sonuga-Barke EJ (2007) Effects of profound early institutional deprivation: an overview of findings from a UK longitudinal study of Romanian adoptees. Eur J Dev Psychol 4:332–350CrossRefGoogle Scholar
  87. 87.
    Rutter M, Moffitt TE, Caspi A (2006) Gene–environment interplay and psychopathology: multiple varieties but real effects. J Child Psychol Psychiatry 47:226–261PubMedCrossRefGoogle Scholar
  88. 88.
    Rutter M, Silberg J (2002) Gene–environment interplay in relation to emotional and behavioral disturbance. Annu Rev Psychol 53:463–490PubMedCrossRefGoogle Scholar
  89. 89.
    Rutter M, Silberg J, O’Connor T, Simonoff E (1999) Genetics and child psychiatry: I Advances in quantitative and molecular genetics. J Child Psychol Psychiatry 40:3–18PubMedCrossRefGoogle Scholar
  90. 90.
    Schmid B, Blomeyer D, Treutlein J, Zimmermann US, Buchmann AF, Schmidt MH, Esser G, Rietschel M, Banaschewski T, Schumann G, Laucht M (2009) Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds. Int J Neuropsychopharmacol 17:1–12Google Scholar
  91. 91.
    Serretti A, Mandelli L, Lorenzi C, Pirovano A, Olgiati P, Colombo C, Smeraldi E (2007) Serotonin transporter gene influences the time course of improvement of “core” depressive and somatic anxiety symptoms during treatment with SSRIs for recurrent mood disorders. Psychiatry Res 149:185–193PubMedCrossRefGoogle Scholar
  92. 92.
    Shaw P, Gornick M, Lerch J, Addington A, Seal J, Greenstein D, Sharp W, Evans A, Giedd JN, Castellanos FX, Rapoport JL (2007) Polymorphisms of the dopamine D4 receptor, clinical outcome, and cortical structure in attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 64:921–931PubMedCrossRefGoogle Scholar
  93. 93.
    Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158:343–359CrossRefGoogle Scholar
  94. 94.
    Smeraldi E, Zanardi R, Benedetti F, Di Bella D, Perez J, Catalano M (1998) Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol Psychiatry 3:508–511PubMedCrossRefGoogle Scholar
  95. 95.
    Sonuga-Barke EJ, Lasky-Su J, Neale BM, Oades R, Chen W, Franke B, Buitelaar J, Banaschewski T, Ebstein R, Gill M, Anney R, Miranda A, Mulas F, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Thompson M, Asherson P, Faraone SV (2008) Does parental expressed emotion moderate genetic effects in ADHD? An exploration using a genome wide association scan. Am J Med Genet B Neuropsychiatr Genet 147B:1359–1368PubMedCrossRefGoogle Scholar
  96. 96.
    Sonuga-Barke EJ, Oades RD, Psychogiou L, Chen W, Franke B, Buitelaar J, Banaschewski T, Ebstein RP, Gil M, Anney R, Miranda A, Roeyers H, Rothenberger A, Sergeant J, Steinhausen HC, Thompson M, Asherson P, Faraone SV (2009) Dopamine and serotonin transporter genotypes moderate sensitivity to maternal expressed emotion: the case of conduct and emotional problems in attention deficit/hyperactivity disorder. J Child Psychol Psychiatry 50:1052–1063PubMedCrossRefGoogle Scholar
  97. 97.
    Sonuga-Barke EJ, Rubia K (2008) Inattentive/overactive children with histories of profound institutional deprivation compared with standard ADHD cases: a brief report. Child Care Health Dev 34:596–602PubMedCrossRefGoogle Scholar
  98. 98.
    Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, Werge T, Pietilainen OP, Mors O, Mortensen PB, Sigurdsson E, Gustafsson O, Nyegaard M, Tuulio-Henriksson A, Ingason A, Hansen T, Suvisaari J, Lonnqvist J, Paunio T, Borglum AD, Hartmann A, Fink-Jensen A, Nordentoft M, Hougaard D, Norgaard-Pedersen B, Bottcher Y, Olesen J, Breuer R, Moller HJ, Giegling I, Rasmussen HB, Timm S, Mattheisen M, Bitter I, Rethelyi JM, Magnusdottir BB, Sigmundsson T, Olason P, Masson G, Gulcher JR, Haraldsson M, Fossdal R, Thorgeirsson TE, Thorsteinsdottir U, Ruggeri M, Tosato S, Franke B, Strengman E, Kiemeney LA, Melle I, Djurovic S, Abramova L, Kaleda V, Sanjuan J, de Frutos R, Bramon E, Vassos E, Fraser G, Ettinger U, Picchioni M, Walker N, Toulopoulou T, Need AC, Ge D, Yoon JL, Shianna KV, Freimer NB, Cantor RM, Murray R, Kong A, Golimbet V, Carracedo A, Arango C, Costas J, Jonsson EG, Terenius L, Agartz I, Petursson H, Nothen MM, Rietschel M, Matthews PM, Muglia P, Peltonen L, St Clair D, Goldstein DB, Stefansson K, Collier DA (2009) Common variants conferring risk of schizophrenia. Nature 460:744–747PubMedGoogle Scholar
  99. 99.
    Stevens SE, Kumsta R, Kreppner JM, Brookes KJ, Rutter M, Sonuga-Barke EJ (2009) Dopamine transporter gene polymorphism moderates the effects of severe deprivation on ADHD symptoms: developmental continuities in gene–environment interplay. Am J Med Genet B Neuropsychiatr Genet 150B:753–761PubMedCrossRefGoogle Scholar
  100. 100.
    Stevens SE, Sonuga-Barke EJ, Kreppner JM, Beckett C, Castle J, Colvert E, Groothues C, Hawkins A, Rutter M (2008) Inattention/overactivity following early severe institutional deprivation: presentation and associations in early adolescence. J Abnorm Child Psychol 36:385–398PubMedCrossRefGoogle Scholar
  101. 101.
    Surtees PG, Wainwright NW, Willis-Owen SA, Luben R, Day NE, Flint J (2006) Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biol Psychiatry 59:224–229PubMedCrossRefGoogle Scholar
  102. 102.
    Takeshita T, Mao XQ, Morimoto K (1996) The contribution of polymorphism in the alcohol dehydrogenase beta subunit to alcohol sensitivity in a Japanese population. Hum Genet 97:409–413PubMedCrossRefGoogle Scholar
  103. 103.
    Taylor SE, Way BM, Welch WT, Hilmert CJ, Lehman BJ, Eisenberger NI (2006) Early family environment, current adversity, the serotonin transporter promoter polymorphism, and depressive symptomatology. Biol Psychiatry 60:671–676PubMedCrossRefGoogle Scholar
  104. 104.
    Thapar A, Harold G, Rice F, Langley K, O’Donovan M (2007) The contribution of gene–environment interaction to psychopathology. Dev Psychopathol 19:989–1004PubMedCrossRefGoogle Scholar
  105. 105.
    Thapar A, Langley K, Asherson P, Gill M (2007) Gene–environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective. Br J Psychiatry 190:1–3PubMedCrossRefGoogle Scholar
  106. 106.
    Thapar A, Langley K, Fowler T, Rice F, Turic D, Whittinger N, Aggleton J, Van den Bree M, Owen M, O’Donovan M (2005) Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 62:1275–1278PubMedCrossRefGoogle Scholar
  107. 107.
    Uher R (2008) Gene–environment interaction: overcoming methodological challenges. Novartis Found Symp 293:13–26; discussion 26–30, 68–70Google Scholar
  108. 108.
    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. Mol Psychiatry 13:131–146PubMedCrossRefGoogle Scholar
  109. 109.
    van Os J, Rutten BP, Poulton R (2008) Gene-environment interactions in schizophrenia: review of epidemiological findings and future directions. Schizophr Bull 34:1066–1082PubMedCrossRefGoogle Scholar
  110. 110.
    van Winkel R, Henquet C, Rosa A, Papiol S, Fananas L, De Hert M, Peuskens J, van Os J, Myin-Germeys I (2008) Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. Am J Med Genet B Neuropsychiatr Genet 147B:10–17PubMedCrossRefGoogle Scholar
  111. 111.
    Wilhelm K, Mitchell PB, Niven H, Finch A, Wedgwood L, Scimone A, Blair IP, Parker G, Schofield PR (2006) Life events, first depression onset and the serotonin transporter gene. Br J Psychiatry 188:210–215PubMedCrossRefGoogle Scholar
  112. 112.
    Young SE, Smolen A, Hewitt JK, Haberstick BC, Stallings MC, Corley RP, Crowley TJ (2006) Interaction between MAO-A genotype and maltreatment in the risk for conduct disorder: failure to confirm in adolescent patients. Am J Psychiatry 163:1019–1025PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Anne-Kathrin Wermter
    • 1
  • Manfred Laucht
    • 2
  • Benno G. Schimmelmann
    • 3
  • Tobias Banaschweski
    • 2
  • Edmund J. S. Sonuga-Barke
    • 4
    • 5
  • Marcella Rietschel
    • 6
  • Katja Becker
    • 1
    • 2
  1. 1.Department of Child and Adolescent Psychiatry and PsychotherapyPhilipps-University of MarburgMarburgGermany
  2. 2.Department of Child and Adolescent Psychiatry and PsychotherapyCentral Institute of Mental HealthMannheimGermany
  3. 3.University Hospital of Child and Adolescent Psychiatry, University of BernBernSwitzerland
  4. 4.Developmental Brain-Behaviour Laboratory, Department of PsychologyUniversity of SouthamptonSouthamptonUK
  5. 5.Department of Experimental Clinical and Health PsychologyUniversity of GentGhentBelgium
  6. 6.Division of Genetic Epidemiology in PsychiatryCentral Institute of Mental HealthMannheimGermany

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