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The Role of Gene-Environment Interaction in Mental Health and Susceptibility to the Development of Psychiatric Disorders

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Beyond Our Genes

Abstract

The current chapter aims to present a concise but comprehensive review of the current state of gene-by-environment interaction (GxE) research in the field of psychiatric genetics, with a special focus on research from molecular genetic studies. The chapter starts with a review of GxE studies of mental health disorders which includes both recent genome-wide GxE studies, as well as candidate gene studies, since the latter comprise the majority of such studies conducted in the field so far. Next, we critically evaluate the research conducted in the field so far, taking into account the methodological limitations of these studies, as well as recent theoretical concepts of Environmental Sensitivity, such as Differential Susceptibility, that challenge historic assumptions underlying GxE models. The chapter ends with suggestions and directions for future GxE research in mental health.

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References

  1. Aguilera M, Arias B, Wichers M, Barrantes-Vidal N, Moya J, Villa H, et al. Early adversity and 5-HTT/BDNF genes: new evidence of gene–environment interactions on depressive symptoms in a general population. Psychol Med. 2009;39(09):1425–32.

    Article  CAS  PubMed  Google Scholar 

  2. Alemany S, Arias B, Aguilera M, Villa H, Moya J, Ibanez MI, et al. Childhood abuse, the BDNF-Val66Met polymorphism and adult psychotic-like experiences. Br J Psychiatry. 2011;199(1):38–42. https://doi.org/10.1192/bjp.bp.110.083808.

    Article  PubMed  Google Scholar 

  3. Almli LM, Duncan R, Feng H, Ghosh D, Binder EB, Bradley B, et al. Correcting systematic inflation in genetic association tests that consider interaction effects: application to a genome-wide association study of posttraumatic stress disorder. JAMA Psychiat. 2014;71(12):1392–9.

    Article  Google Scholar 

  4. Aron EN, Aron A. Sensory-processing sensitivity and its relation to introversion and emotionality. J Pers Soc Psychol. 1997;73(2):345–68.

    Article  CAS  PubMed  Google Scholar 

  5. Aschard H, Lutz S, Maus B, Duell EJ, Fingerlin TE, Chatterjee N, et al. Challenges and opportunities in genome-wide environmental interaction (GWEI) studies. Hum Genet. 2012;131(10):1591–613.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Assary E, Keers R, Krapohl E, Pluess M. Polygenic score of environmental senstivity moderates the effects of psychosocial environment on psychological distress across life-span. in preparation.

    Google Scholar 

  7. Bakermans-Kranenburg MJ, van Ijzendoorn MH. Differential susceptibility to rearing environment depending on dopamine-related genes: new evidence and a meta-analysis. Dev Psychopathol. 2011;23(01):39–52.

    Article  PubMed  Google Scholar 

  8. Bakermans-Kranenburg MJ, van IJzendoorn MH. The hidden efficacy of interventions: gene × environment experiments from a differential susceptibility perspective. Annu Rev Psychol. 2015;66:381–409.

    Article  PubMed  Google Scholar 

  9. Bakermans-Kranenburg MJ, Van IMH, Pijlman FT, Mesman J, Juffer F. Experimental evidence for differential susceptibility: dopamine D4 receptor polymorphism (DRD4 VNTR) moderates intervention effects on toddlers’ externalizing behavior in a randomized controlled trial. Dev Psychol. 2008;44(1):293–300. https://doi.org/10.1037/0012-1649.44.1.293.

    Article  PubMed  Google Scholar 

  10. Bar-Haim Y, Lamy D, Pergamin L, Bakermans-Kranenburg MJ, Van Ijzendoorn MH. Threat-related attentional bias in anxious and nonanxious individuals: a meta-analytic study. Psychol Bull. 2007;133(1):1–24.

    Article  PubMed  Google Scholar 

  11. Battle CL, Shea MT, Johnson DM, Yen S, Zlotnick C, Zanarini MC, et al. Childhood maltreatment associated with adult personality disorders: findings from the collaborative longitudinal personality disorders study. J Personal Disord. 2004;18(2):193–211. https://doi.org/10.1521/pedi.18.2.193.32777.

    Article  Google Scholar 

  12. Belsky J, Pluess M. Beyond diathesis stress: differential susceptibility to environmental influences. Psychol Bull. 2009;135(6):885–908. https://doi.org/10.1037/a0017376.

    Article  PubMed  Google Scholar 

  13. Belsky J, Pluess M. Beyond risk, resilience, and dysregulation: phenotypic plasticity and human development. Dev Psychopathol. 2013a;25(4 Pt 2):1243–61. https://doi.org/10.1017/S095457941300059X.

    Article  PubMed  Google Scholar 

  14. Belsky J, Pluess M. Genetic moderation of early child-care effects on social functioning across childhood: a developmental analysis. Child Dev. 2013b;84(4):1209–25. https://doi.org/10.1111/cdev.12058.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Belsky J, Bakermans-Kranenburg MJ, van IJzendoorn MH. For better and for worse: differential susceptibility to environmental influences. Curr Dir Psychol Sci. 2007a;16(6):300–4. https://doi.org/10.1111/j.1467-8721.2007.00525.x.

    Article  Google Scholar 

  16. Belsky J, Fearon RMP, Bell B. Parenting, attention and externalizing problems: testing mediation longitudinally, repeatedly and reciprocally. J Child Psychol Psychiatry. 2007b;48(12):1233–42.

    Article  PubMed  Google Scholar 

  17. Berry D, Deater-Deckard K, McCartney K, Wang Z, Petrill SA. Gene-environment interaction between dopamine receptor D4 7-repeat polymorphism and early maternal sensitivity predicts inattention trajectories across middle childhood. Dev Psychopathol. 2013;25(2):291–306. https://doi.org/10.1017/s095457941200106x.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bertelsen A, Harvald B, Hauge M. A Danish twin study of manic-depressive disorders. Br J Psychiatry. 1977;130(4):330–51.

    Article  CAS  PubMed  Google Scholar 

  19. Bosker FJ, Hartman CA, Nolte IM, Prins BP, Terpstra P, Posthuma D, et al. Poor replication of candidate genes for major depressive disorder using genome-wide association data. Mol Psychiatry. 2011;16(5):516–32. https://doi.org/10.1038/mp.2010.38.

    Article  CAS  PubMed  Google Scholar 

  20. Boyce WT, Ellis BJ. Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity. Dev Psychopathol. 2005;17(02):271–301.

    Article  PubMed  Google Scholar 

  21. Brunner HG, Nelen M, Breakefield X, Ropers H, Van Oost B. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science. 1993;262:578–80.

    Article  CAS  PubMed  Google Scholar 

  22. Burt A. A mechanistic explanation of popularity: genes, rule breaking, and evocative gene-environment correlations. J Pers Soc Psychol. 2009;96(4):783–94. https://doi.org/10.1037/a0013702.

    Article  PubMed  Google Scholar 

  23. Byrd AL, Manuck SB. MAOA, childhood maltreatment, and antisocial behavior: meta-analysis of a gene-environment interaction. Biol Psychiatry. 2014;75(1):9–17. https://doi.org/10.1016/j.biopsych.2013.05.004.

    Article  CAS  PubMed  Google Scholar 

  24. Cadoret RJ, Yates WR, Troughton E, Woodworth G, Stewart MA. Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Arch Gen Psychiatry. 1995;52(11):916–24.

    Article  CAS  PubMed  Google Scholar 

  25. Cannon TD, Keller MC. Endophenotypes in the genetic analyses of mental disorders. Annu Rev Clin Psychol. 2006;2:267–90.

    Article  PubMed  Google Scholar 

  26. Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, et al. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science. 1995;268(5218):1763–6. https://doi.org/10.1126/science.7792602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, et al. Role of genotype in the cycle of violence in maltreated children. Science. 2002;297(5582):851–4.

    Article  CAS  PubMed  Google Scholar 

  28. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science. 2003;301(5631):386–9.

    Article  CAS  PubMed  Google Scholar 

  29. Caspi A, Moffitt TE, Cannon M, McClay J, Murray R, Harrington H, et al. 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 X environment interaction. Biol Psychiatry. 2005;57(10):1117–27.

    Article  CAS  PubMed  Google Scholar 

  30. Cervilla JA, Molina E, Rivera M, Torres-Gonzalez F, Bellon JA, Moreno B, et al. 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. 2007;12(8):748–55.

    Article  CAS  PubMed  Google Scholar 

  31. Cicchetti D, Rogosch FA, Thibodeau EL. The effects of child maltreatment on early signs of antisocial behavior: genetic moderation by tryptophan hydroxylase, serotonin transporter, and monoamine oxidase a genes. Dev Psychopathol. 2012;24(3):907–28.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS, et al. Grand challenges in global mental health. Nature. 2011;475(7354):27–30. https://doi.org/10.1038/475027a.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Collins AL, Kim Y, Sklar P, O’Donovan MC, Sullivan PF. Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results. Psychol Med. 2012;42(3):607–16. https://doi.org/10.1017/s0033291711001607.

    Article  CAS  PubMed  Google Scholar 

  34. Collip D, van Winkel R, Peerbooms O, Lataster T, Thewissen V, Lardinois M, et al. COMT Val158Met-stress interaction in psychosis: role of background psychosis risk. CNS Neurosci Ther. 2011;17(6):612–9. https://doi.org/10.1111/j.1755-5949.2010.00213.x.

    Article  PubMed  Google Scholar 

  35. Cross-Disorder Group of the Psychiatric Genomics, C. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet, 45(9), 984–994. doi:https://doi.org/10.1038/ng.2711.http://www.nature.com/ng/journal/v45/n9/abs/ng.2711.html – supplementary-information.

  36. Culverhouse RC, Saccone NL, Horton AC, Ma Y, Anstey KJ, Banaschewski T, et al. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Mol Psychiatry. 2017;23:133–42. https://doi.org/10.1038/mp.2017.44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. DeWitt TJ, Sih A, Wilson DS. Costs and limits of phenotypic plasticity. Trends Ecol Evol. 1998;13(2):77–81. https://doi.org/10.1016/s0169-5347(97)01274-3.

    Article  CAS  PubMed  Google Scholar 

  38. Dick DM, Rose RJ, Viken RJ, Kaprio J, Koskenvuo M. Exploring gene-environment interactions: socioregional moderation of alcohol use. J Abnorm Psychol. 2001;110(4):625–32.

    Article  CAS  PubMed  Google Scholar 

  39. Domingue BW, Liu H, Okbay A, Belsky DW. Genetic heterogeneity in depressive symptoms following the death of a spouse: polygenic score analysis of the US Health and Retirement Study. Am J Psychiatry. 2017; https://doi.org/10.1176/appi.ajp.2017.16111209.

    Article  PubMed  Google Scholar 

  40. Donnelly P. Progress and challenges in genome-wide association studies in humans. Nature. 2008;456(7223):728–31.

    Article  CAS  PubMed  Google Scholar 

  41. Dudbridge F. Power and predictive accuracy of polygenic risk scores. PLoS Genet. 2013;9(3):e1003348. https://doi.org/10.1371/journal.pgen.1003348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Duncan LE, Keller MC. A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. Am J Psychiatr. 2011;168(10):1041–9. https://doi.org/10.1176/appi.ajp.2011.11020191.

    Article  PubMed  Google Scholar 

  43. Dunn EC, Wiste A, Radmanesh F, Almli LM, Gogarten SM, Sofer T, et al. Genome-Wide Association Study (gwas) and Genome-Wide by Environment Interaction Study (gweis) of depressive symptoms in african american and hispanic/latina women. Depress Anxiety. 2016;33(4):265–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Eaves L, Silberg J, Erkanli A. Resolving multiple epigenetic pathways to adolescent depression. J Child Psychol Psychiatry. 2003;44(7):1006–14.

    Article  PubMed  Google Scholar 

  45. Foley DL, Eaves LJ, Wormley B, Silberg JL, Maes HH, Kuhn J, Riley B. Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Arch Gen Psychiatry. 2004;61(7):738–44.

    Article  CAS  PubMed  Google Scholar 

  46. Fox E, Zougkou K, Ridgewell A, Garner K. The serotonin transporter gene alters sensitivity to attention bias modification: evidence for a plasticity gene. Biol Psychiatry. 2011;70(11):1049–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Frankenhuis WE, Panchanathan K. Individual differences in developmental plasticity may result from stochastic sampling. Perspect Psychol Sci. 2011;6(4):336–47. https://doi.org/10.1177/1745691611412602.

    Article  PubMed  Google Scholar 

  48. Frazzetto G, Di Lorenzo G, Carola V, Proietti L, Sokolowska E, Siracusano A, et al. Early trauma and increased risk for physical aggression during adulthood: the moderating role of MAOA genotype. PLoS One. 2007;2(5):e486.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. French L, Gray C, Leonard G, Perron M, Pike GB, Richer L, et al. Early cannabis use, polygenic risk score for schizophrenia and brain maturation in adolescence. JAMA Psychiat. 2015;72(10):1002–11.

    Article  Google Scholar 

  50. Gillespie NA, Whitfield JB, Williams B, Heath AC, Martin NG. The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression. Psychol Med. 2005;35(01):101–11.

    Article  PubMed  Google Scholar 

  51. Gillespie CF, Phifer J, Bradley B, Ressler KJ. Risk and resilience: genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26(11):984–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatr. 2003;160(4):636–45.

    Article  PubMed  Google Scholar 

  53. Grossman MH, Emanuel BS, Budarf ML. Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1→q11.2. Genomics. 1992;12(4):822–5. https://doi.org/10.1016/0888-7543(92)90316-K.

    Article  CAS  PubMed  Google Scholar 

  54. Haberstick BC, Lessem JM, Hopfer CJ, Smolen A, Ehringer MA, Timberlake D, Hewitt JK. Monoamine oxidase a (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment. Am J Med Genet B Neuropsychiatr Genet. 2005;135B(1):59–64. https://doi.org/10.1002/ajmg.b.30176.

    Article  PubMed  Google Scholar 

  55. Hakamata Y, Lissek S, Bar-Haim Y, Britton JC, Fox NA, Leibenluft E, et al. Attention bias modification treatment: a meta-analysis toward the establishment of novel treatment for anxiety. Biol Psychiatry. 2010;68(11):982–90.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Hallion LS, Ruscio AM. A meta-analysis of the effect of cognitive bias modification on anxiety and depression, vol. 137: American Psychological Association; 2011. p. 940–58.

    Google Scholar 

  57. Hankin BL, Nederhof E, Oppenheimer CW, Jenness J, Young JF, Abela JRZ, et al. Differential susceptibility in youth: evidence that 5-HTTLPR x positive parenting is associated with positive affect ‘for better and worse’. Transl Psychiatry. 2011;1:e44. https://doi.org/10.1038/tp.2011.44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Henquet C, Rosa A, Krabbendam L, Papiol S, Fananas L, Drukker M, et al. An experimental study of catechol-O-Methyltransferase Val158Met moderation of [Delta]-9-Tetrahy drocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology. 2006;31(12):2748–57.

    Article  CAS  PubMed  Google Scholar 

  59. Hosang GM, Uher R, Keers R, Cohen-Woods S, Craig I, Korszun A, et al. Stressful life events and the brain-derived neurotrophic factor gene in bipolar disorder. J Affect Disord. 2010;125(1–3):345–9. https://doi.org/10.1016/j.jad.2010.01.071.

    Article  CAS  PubMed  Google Scholar 

  60. Hosang GM, Shiles C, Tansey KE, McGuffin P, Uher R. Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis. BMC Med. 2014;12:7. https://doi.org/10.1186/1741-7015-12-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ikeda M, Shimasaki A, Takahashi A, Kondo K, Saito T, Kawase K, et al. Genome-wide environment interaction between depressive state and stressful life events. J Clin Psychiatry. 2016;77(1):e29–30.

    Article  PubMed  Google Scholar 

  62. Jaffee SR, Price TS. Gene-environment correlations: a review of the evidence and implications for prevention of mental illness. Mol Psychiatry. 2007;12(5):432–42. https://doi.org/10.1038/sj.mp.4001950.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Joormann J, Gotlib IH. Emotion regulation in depression: relation to cognitive inhibition. Cognit Emot. 2010;24(2):281–98.

    Article  Google Scholar 

  64. Kantrowitz JT, Nolan KA, Sen S, Simen AA, Lachman HM, Bowers MB Jr. Adolescent cannabis use, psychosis and catechol-O-methyltransferase genotype in African Americans and Caucasians. Psychiatry Q. 2009;80(4):213–8. https://doi.org/10.1007/s11126-009-9108-4.

    Article  Google Scholar 

  65. Karg K, Sen S. Gene × environment interaction models in psychiatric genetics. Curr Top Behav Neurosci. 2012;12:441–62. https://doi.org/10.1007/7854_2011_184.

    Article  PubMed  PubMed Central  Google Scholar 

  66. 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(5):444–54.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Keers R, Pluess M. Childhood quality influences genetic sensitivity to environmental influences across adulthood: a life-course gene× environment interaction study. Dev Psychopathol. 2017;29(5):1921–33.

    Article  PubMed  Google Scholar 

  68. Keers R, Coleman JR, Lester KJ, Roberts S, Breen G, Thastum M, et al. A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders. Psychother Psychosom. 2016;85(3):146–58.

    Article  PubMed  Google Scholar 

  69. Kendler KS, Eaves LJ. Models for the joint effect of genotype and environment on liability to psychiatric illness. Am J Psychiatry. 1986;

    Google Scholar 

  70. Kendler KS, Myers J. The genetic and environmental relationship between major depression and the five-factor model of personality. Psychol Med. 2010;40(5):801–6. https://doi.org/10.1017/S0033291709991140.

    Article  CAS  PubMed  Google Scholar 

  71. Kendler KS, Kessler RC, Walters EE, MacLean C, Neale MC, Heath AC, Eaves LJ. Stressful life events, genetic liability, and onset of an episode of major depression in women. Am J Psychiatry. 1995;152(6):833–42. https://doi.org/10.1176/ajp.152.6.833.

    Article  CAS  PubMed  Google Scholar 

  72. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51(1):8–19.

    Article  CAS  PubMed  Google Scholar 

  73. Kim-Cohen J, Caspi A, Taylor A, Williams B, Newcombe R, Craig IW, Moffitt TE. MAOA, maltreatment, and gene-environment interaction predicting children’s mental health: new evidence and a meta-analysis. Mol Psychiatry. 2006;11(10):903–13.

    Article  CAS  PubMed  Google Scholar 

  74. Klahr AM, Thomas KM, Hopwood CJ, Klump KL, Burt SA. Evocative gene-environment correlation in the mother-child relationship: a twin study of interpersonal processes. Dev Psychopathol. 2013;25(1):105–18. https://doi.org/10.1017/S0954579412000934.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Knafo A, Israel S, Ebstein RP. Heritability of children’s prosocial behavior and differential susceptibility to parenting by variation in the dopamine receptor D4 gene. Dev Psychopathol. 2011;23(1):53–67. https://doi.org/10.1017/s0954579410000647.

    Article  PubMed  Google Scholar 

  76. Lau JY, Eley TC. Disentangling gene-environment correlations and interactions on adolescent depressive symptoms. J Child Psychol Psychiatry. 2008;49(2):142–50. https://doi.org/10.1111/j.1469-7610.2007.01803.x.

    Article  PubMed  Google Scholar 

  77. Lemery-Chalfant K, Kao K, Swann G, Goldsmith HH. Childhood temperament: passive gene-environment correlation, gene-environment interaction, and the hidden importance of the family environment. Dev Psychopathol. 2013;25(1):51–63. https://doi.org/10.1017/S0954579412000892.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Leve LD, Neiderhiser JM, Scaramella LV, Reiss D. The early growth and development study: using the prospective adoption design to examine genotype-environment interplay. Xin Li Xue Bao. 2008;40(10):1106–15. https://doi.org/10.3724/SP.J.1041.2008.01106.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Lichtenstein P, Yip BH, Bjork C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet. 2009;373(9659):234–9. https://doi.org/10.1016/s0140-6736(09)60072-6.

    Article  CAS  PubMed  Google Scholar 

  80. MacLeod C, Hagan R. Individual differences in the selective processing of threatening information, and emotional responses to a stressful life event. Behav Res Ther. 1992;30(2):151–61.

    Article  CAS  PubMed  Google Scholar 

  81. MacLeod C, Rutherford E, Campbell L, Ebsworthy G, Holker L. Selective attention and emotional vulnerability: assessing the causal basis of their association through the experimental manipulation of attentional bias. J Abnorm Psychol. 2002;111(1):107–23.

    Article  PubMed  Google Scholar 

  82. Maher B. Personal genomes: the case of the missing heritability. Nature. 2008;456(7218):18–21. https://doi.org/10.1038/456018a.

    Article  CAS  PubMed  Google Scholar 

  83. Mathews A, MacLeod C. Cognitive vulnerability to emotional disorders. Annu Rev Clin Psychol. 2005;1:167–95.

    Article  PubMed  Google Scholar 

  84. McClelland GH, Judd CM. Statistical difficulties of detecting interactions and moderator effects. Psychol Bull. 1993;114(2):376–90.

    Article  CAS  PubMed  Google Scholar 

  85. McGuffin P, Rijsdijk F, Andrew M, Sham P, Katz R, Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch Gen Psychiatry. 2003;60(5):497–502. https://doi.org/10.1001/archpsyc.60.5.497.

    Article  PubMed  Google Scholar 

  86. Miller GA, Rockstroh B. Endophenotypes in psychopathology research: where do we stand? Annu Rev Clin Psychol. 2013;9:177–213.

    Article  PubMed  Google Scholar 

  87. Modinos G, Iyegbe C, Prata D, Rivera M, Kempton MJ, Valmaggia LR, et al. Molecular genetic gene–environment studies using candidate genes in schizophrenia: a systematic review. Schizophr Res. 2013;150(2):356–65.

    Article  PubMed  Google Scholar 

  88. Monroe SM, Simons AD. Diathesis-stress theories in the context of life stress research: implications for the depressive disorders. Psychol Bull. 1991;110(3):406–25. https://doi.org/10.1037/0033-2909.110.3.406.

    Article  CAS  PubMed  Google Scholar 

  89. Mullins N, Power R, Fisher H, Hanscombe K, Euesden J, Iniesta R, et al. Polygenic interactions with environmental adversity in the aetiology of major depressive disorder. Psychol Med. 2016;46(04):759–70.

    Article  CAS  PubMed  Google Scholar 

  90. Munafo MR, Flint J. Replication and heterogeneity in gene x environment interaction studies. Int J Neuropsychopharmacol. 2009;12(6):727–9. https://doi.org/10.1017/s1461145709000479.

    Article  CAS  PubMed  Google Scholar 

  91. Munafò MR, Durrant C, Lewis G, Flint J. Gene × environment interactions at the serotonin transporter locus. Biol Psychiatry. 2009;65(3):211–9. https://doi.org/10.1016/j.biopsych.2008.06.009.

    Article  CAS  PubMed  Google Scholar 

  92. Musliner KL, Seifuddin F, Judy JA, Pirooznia M, Goes FS, Zandi PP. Polygenic risk, stressful life events and depressive symptoms in older adults: a polygenic score analysis. Psychol Med. 2015;45(08):1709–20.

    Article  CAS  PubMed  Google Scholar 

  93. Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry. 2012;169(2):141–51. https://doi.org/10.1176/appi.ajp.2011.11020335.

    Article  PubMed  Google Scholar 

  94. Narusyte J, Neiderhiser JM, Andershed AK, D’Onofrio BM, Reiss D, Spotts E, et al. Parental criticism and externalizing behavior problems in adolescents: the role of environment and genotype-environment correlation. J Abnorm Psychol. 2011;120(2):365–76. https://doi.org/10.1037/a0021815.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Nay WT, Thorpe GL, Roberson-Nay R, Hecker JE, Sigmon ST. Attentional bias to threat and emotional response to biological challenge. J Anxiety Disord. 2004;18(5):609–27.

    Article  PubMed  Google Scholar 

  96. Organization, W. H. (2008). The global burden of disease: 2004 update. (9241563710). World Health Organization.

    Google Scholar 

  97. Otowa T, Kawamura Y, Tsutsumi A, Kawakami N, Kan C, Shimada T, et al. The first pilot genome-wide gene-environment study of depression in the Japanese population. PLoS One. 2016;11(8):e0160823.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Pe’er I, Yelensky R, Altshuler D, Daly MJ. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol. 2008;32(4):381–5.

    Article  PubMed  Google Scholar 

  99. Peerbooms O, Rutten BPF, Collip D, Lardinois M, Lataster T, Thewissen V, et al. Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. Acta Psychiatr Scand. 2012;125(3):247–56. https://doi.org/10.1111/j.1600-0447.2011.01806.x.

    Article  CAS  PubMed  Google Scholar 

  100. Peyrot WJ, Milaneschi Y, Abdellaoui A, Sullivan PF, Hottenga JJ, Boomsma DI, Penninx BW. Effect of polygenic risk scores on depression in childhood trauma. Br J Psychiatry. 2014;205(2):113–9.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Plomin R, DeFries JC, Knopik VS, Neiderhiser JM. Top 10 replicated findings from Behavioral genetics. Perspect Psychol Sci. 2016;11(1):3–23. https://doi.org/10.1177/1745691615617439.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Pluess M, Belsky J. Conceptual issues in psychiatric gene-environment interaction research. Am J Psychiatr. 2012;169(2):222–3. https://doi.org/10.1176/appi.ajp.2011.11111614.

    Article  PubMed  Google Scholar 

  103. Pluess M, Belsky J. Vantage sensitivity: individual differences in response to positive experiences. Psychol Bull. 2013;139(4):901–16. https://doi.org/10.1037/a0030196.

    Article  PubMed  Google Scholar 

  104. Pluess M, Belsky J, Way BM, Taylor SE. 5-HTTLPR moderates effects of life events on neuroticism: differential susceptibility to environmental influences. Prog Neuro-Psychopharmacol Biol Psychiatry. 2010;34:1070–4.

    Article  CAS  Google Scholar 

  105. Purcell S. Variance components models for gene-environment interaction in twin analysis. Twin Res. 2002;5(6):554–71. https://doi.org/10.1375/136905202762342026.

    Article  PubMed  Google Scholar 

  106. Purcell SM, Wray NR, Stone JL, Visscher PM, O’donovan MC, Sullivan PF, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460(7256):748–52.

    Article  CAS  PubMed  Google Scholar 

  107. Pury CL. Information-processing predictors of emotional response to stress. Cognit Emot. 2002;16(5):667–83.

    Article  Google Scholar 

  108. Rice F, Lewis G, Harold GT, Thapar A. Examining the role of passive gene-environment correlation in childhood depression using a novel genetically sensitive design. Dev Psychopathol. 2013;25(1):37–50. https://doi.org/10.1017/S0954579412000880.

    Article  PubMed  Google Scholar 

  109. Risch N, Herrell R, Lehner T, Liang KY, 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(23):2462–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Rutter M, Silberg J. Gene-environment interplay in relation to emotional and behavioral disturbance. Annu Rev Psychol. 2002;53:463–90. https://doi.org/10.1146/annurev.psych.53.100901.135223.

    Article  PubMed  Google Scholar 

  111. Rutter M, Moffitt TE, Caspi A. Gene-environment interplay and psychopathology: multiple varieties but real effects. J Child Psychol Psychiatry. 2006;47(3–4):226–61.

    Article  PubMed  Google Scholar 

  112. Schizophrenia Working Group of the Psychiatric Genomics, C. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. doi:https://doi.org/10.1038/nature13595http://www.nature.com/nature/journal/v511/n7510/abs/nature13595.html - supplementary-information.

  113. Sharpley CF, Palanisamy SK, Glyde NS, Dillingham PW, Agnew LL. An update on the interaction between the serotonin transporter promoter variant (5-HTTLPR), stress and depression, plus an exploration of non-confirming findings. Behav Brain Res. 2014;273:89–105.

    Article  CAS  PubMed  Google Scholar 

  114. Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’Er I, et al. Common variants on chromosome 6p22. 1 are associated with schizophrenia. Nature. 2009;460(7256):753–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Sih A. Effects of early stress on behavioral syndromes: an integrated adaptive perspective. Neurosci Biobehav Rev. 2011;35(7):1452–65. https://doi.org/10.1016/j.neubiorev.2011.03.015.

    Article  PubMed  Google Scholar 

  116. Silberg J, Rutter M, Neale M, Eaves L. Genetic moderation of environmental risk for depression and anxiety in adolescent girls. Br J Psychiatry. 2001;179:116–21.

    Article  CAS  PubMed  Google Scholar 

  117. Simons CJP, Wichers M, Derom C, Thiery E, Myin-Germeys I, Krabbendam L, Van Os J. Subtle gene–environment interactions driving paranoia in daily life. Genes Brain Behav. 2009;8(1):5–12. https://doi.org/10.1111/j.1601-183X.2008.00434.x.

    Article  CAS  PubMed  Google Scholar 

  118. Smoller JW, Finn CT. Family, twin, and adoption studies of bipolar disorder. Am J Med Genet C Semin Med Genet. 2003;123c(1):48–58. https://doi.org/10.1002/ajmg.c.20013.

    Article  PubMed  Google Scholar 

  119. Stefanis NC, Henquet C, Avramopoulos D, Smyrnis N, Evdokimidis I, Myin-Germeys I, et al. COMT Val158Met moderation of stress-induced psychosis. Psychol Med. 2007;37(11):1651–6.

    Article  PubMed  Google Scholar 

  120. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry. 2000;157(10):1552–62.

    Article  CAS  PubMed  Google Scholar 

  121. Sullivan PF, Kendler KS, Neale MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry. 2003;60(12):1187–92. https://doi.org/10.1001/archpsyc.60.12.1187.

    Article  PubMed  Google Scholar 

  122. Surtees PG, Wainwright NW, Willis-Owen SA, Luben R, Day NE, Flint J. Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biol Psychiatry. 2006;59(3):224–9.

    Article  CAS  PubMed  Google Scholar 

  123. Taylor A, Kim-Cohen J. Meta-analysis of gene-environment interactions in developmental psychopathology. Dev Psychopathol. 2007;19(4):1029–37. https://doi.org/10.1017/S095457940700051X.

    Article  PubMed  Google Scholar 

  124. Teicher MH, Samson JA. Childhood maltreatment and psychopathology: a case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatry. 2013;170(10):1114–33. https://doi.org/10.1176/appi.ajp.2013.12070957.

    Article  PubMed  PubMed Central  Google Scholar 

  125. Trotta A, Iyegbe C, Di Forti M, Sham PC, Campbell DD, Cherny SS, et al. Interplay between schizophrenia polygenic risk score and childhood adversity in first-presentation psychotic disorder: a pilot study. PLoS One. 2016;11(9):e0163319.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Uher R. Gene–environment interactions in severe mental illness. Front Psych. 2014;5:48.

    Google Scholar 

  127. Uher R, McGuffin P. The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry. 2010;15(1):18–22.

    Article  CAS  PubMed  Google Scholar 

  128. Van Den Hout M, Tenney N, Huygens K, Merckelbach H, Kindt M. Responding to subliminal threat cues is related to trait anxiety and emotional vulnerability: a successful replication of MacLeod and Hagan (1992). Behav Res Ther. 1995;33(4):451–4.

    Article  PubMed  Google Scholar 

  129. van Ijzendoorn MH, Bakermans-Kranenburg MJ. Genetic differential susceptibility on trial: meta-analytic support from randomized controlled experiments. Dev Psychopathol. 2015;27(01):151–62.

    Article  PubMed  Google Scholar 

  130. Van Ijzendoorn MH, Bakermans-Kranenburg MJ, Belsky J, Beach S, Brody G, Dodge KA, et al. Gene-by-environment experiments: a new approach to finding the missing heritability. Nat Rev Genet. 2011;12(12):881.

    Article  PubMed  CAS  Google Scholar 

  131. Van IJzendoorn M, Belsky J, Bakermans-Kranenburg M. Serotonin transporter genotype 5HTTLPR as a marker of differential susceptibility? A meta-analysis of child and adolescent gene-by-environment studies. Transl Psychiatry. 2012;2(8):e147.

    Article  PubMed  PubMed Central  Google Scholar 

  132. van Os J, Kenis G, Rutten BPF. The environment and schizophrenia. Nature. 2010;468(7321):203–12.

    Article  PubMed  CAS  Google Scholar 

  133. van Winkel R, Henquet C, Rosa A, Papiol S, Fananas L, De Hert M, et al. Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(1):10–7. https://doi.org/10.1002/ajmg.b.30559.

    Article  CAS  PubMed  Google Scholar 

  134. Verhaak CM, Smeenk JM, van Minnen A, Kraaimaat FW. Neuroticism, preattentive and attentional biases towards threat, and anxiety before and after a severe stressor: a prospective study. Personal Individ Differ. 2004;36(4):767–78.

    Article  Google Scholar 

  135. Visscher PM, Brown MA, McCarthy MI, Yang J. Five years of GWAS discovery. Am J Hum Genet. 2012;90(1):7–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Wilkinson PO, Trzaskowski M, Haworth CM, Eley TC. The role of gene-environment correlations and interactions in middle childhood depressive symptoms. Dev Psychopathol. 2013;25(1):93–104. https://doi.org/10.1017/S0954579412000922.

    Article  PubMed  Google Scholar 

  137. Zammit S, Spurlock G, Williams H, Norton N, Williams N, O’Donovan MC, Owen MJ. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry. 2007;191(5):402–7. https://doi.org/10.1192/bjp.bp.107.036129.

    Article  PubMed  Google Scholar 

  138. Zammit S, Owen MJ, Evans J, Heron J, Lewis G. Cannabis, COMT and psychotic experiences. Br J Psychiatry. 2011;199(5):380–5. https://doi.org/10.1192/bjp.bp.111.091421.

    Article  PubMed  Google Scholar 

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Assary, E., Vincent, J., Machlitt-Northen, S., Keers, R., Pluess, M. (2020). The Role of Gene-Environment Interaction in Mental Health and Susceptibility to the Development of Psychiatric Disorders. In: Teperino, R. (eds) Beyond Our Genes. Springer, Cham. https://doi.org/10.1007/978-3-030-35213-4_7

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