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The contribution of gene–environment interaction to psychopathology

  • Anita Thapar (a1), Gordon Harold (a1), Frances Rice (a1), Kate Langley (a1) and Michael O'Donovan (a1)...
Abstract
Abstract

The study of gene–environment interaction (G × E) constitutes an area of significant social and clinical significance. Different types of research study designs are being used to investigate the contribution of G × E to psychopathology, although the term G × E has also been used and interpreted in different ways. Despite mixed evidence that G × E contributes to psychopathology, some promising and consistent findings are emerging. Evidence is reviewed in relation to depression, antisocial behavior, schizophrenia, and attention-deficit/hyperactivity disorder. Although findings from various research designs have different meaning, interestingly much of the evidence with regard to the contribution of G × E that has arisen from twin and adoption studies has been for antisocial behavior and depression. It is for these same forms of psychopathology that molecular genetic evidence of G × E has also been most convincing. Finally, current and anticipated methodological challenges and implications for future research in this area are considered.

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Corresponding author
Address correspondence and reprint requests to: Anita Thapar, Department of Psychological Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK; E-mail: Thapar@cf.ac.uk.
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D. Altshuler , & A. G. Clark (2005). Harvesting medical information from the human family tree. Science, 307, 10521053.

R. A. Barkley , J. Karlsson , S. Pollard , & J. V. Murphy (1985). Developmental changes in the mother–child interactions of hyperactive boys: Effects of two dose levels of Ritalin. Journal of Child Psychology and Psychiatry, 26, 705715.

R. Q. Bell (1968). A reinterpretation of the direction of effects in studies of socialization. Psychological Review, 75, 8185.

A. T. Bhutta , M. A. Cleves , P. H. Casey , M. M. Cradock , & K. J. Anand (2002). Cognitive and behavioral outcomes of school-aged children who were born preterm: A meta-analysis. Journal of the American Medical Association, 288, 728737.

K. J. Brookes , J. Mill , C. Guindalini , S. Curran , X. Xu , J. Knight , (2006). A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Archives of General Psychiatry, 63, 7481.

H. G. Brunner , M. Nelen , X. O. Breakfield , H. H. Ropers , & B. A. Van Oost (1993). Abnormal behaviour associated with a point mutation in the structural gene for monoamine oxidase A. Science, 262, 578580.

T. M. Button , J. Scourfield , N. Martin , S. Purcell , & P. McGuffin (2005). Family dysfunction interacts with genes in the causation of antisocial symptoms. Behavior Genetics, 35, 115120.

R. J. Cadoret , C. A. Cain , & R. R. Crowe (1983). Evidence for gene–environment interaction in the development of adolescent antisocial behavior. Behavior Genetics, 13, 301310.

A. Caspi , J. McClay , T. E. Moffitt , J. Mill , J. Martin , I. W. Craig , (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851854.

A. Caspi , T. E. Moffitt , M. Cannon , J. McClay , R. Murray , H. Harrington , (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. Biological Psychiatry, 57, 11171127.

N. Chatterjee , Z. Kalaylioglu , R. Moslehi , U. Peters , & S. Wacholder (2006). Powerful multilocus tests of genetic association in the presence of gene–gene and gene–environment interactions. The American Journal of Human Genetics, 79, 10021017.

D. Cicchetti , & J. Blender (2004). A multiple-levels-of-analysis approach to the study of developmental processes in maltreated children. Proceedings of the National Academy of Sciences of the USA, 101, 1732517326.

J. Couzin , & J. Kaiser (2007). Genomic hunt captures “diabetes DNA.” Science, 316, 820822.

L. Eaves , J. Silberg , & A. Erkanli (2003). Resolving multiple epigenetic pathways to adolescent depression. Journal of Child Psychology and Psychiatry, 44, 10061014.

T. C. Eley , K. Sugden , A. Corsico , A. M. Gregory , P. Sham , P. McGuffin , (2004). Gene–environment interaction analysis of seretonin system markers with adolescent depression. Molecular Psychiatry, 9, 908915.

S. V. Faraone , R. H. Perlis , A. E. Doyle , J. W. Smoller , J. J. Goralnick , M. A. Holmgren , (2005). Molecular genetics of attention deficit/hyperactivity. Biological Psychiatry, 57, 13131323.

M. E. Feinberg , T. M. Button , J. M. Neiderhiser , D. Reiss , & E. M. Hetherington (2007). Parenting and adolescent antisocial behavior and depression: Evidence of Genotype × Parenting Environment interaction. Archives of General Psychiatry, 64, 457465.

D. L. Foley , L. J. Eaves , B. Wormley , J. L. Silberg , H. H. Maes , J. Kuhn , (2004). Childhood adversity, monoamine oxidase a genotype, and risk for conduct disorder. Archives of General Psychiatry, 61, 738744.

X. Ge , R. D. Conger , R. J. Cadoret , J. M. Neiderhiser , W. Yates , E. Troughton , (1996). The developmental interface between nature and nurture: A mutual influence model of child antisocial behavior and parent behaviors. Developmental Psychology, 32, 574589.

B. C. Haberstick , J. M. Lessen , C. J. Hopfer , A. Smolen , M. A. Ehringer , D. Timberlake , (2005). Monoamine oxidase A (MAOA) and antisocial behaviours in the presence of childhood and adolescent maltreatment. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 135B, 5964.

C. A. Haiman , N. Patterson , M. L. Freedman , S. R. Myers , M. C. Pike , A. Waliszewska , (2007). Multiple regions within 8q24 independently affect risk for prostate cancer. Nature & Genetics, 39, 638644.

A. R. Hariri , V. S. Mattay , A. Tessitore , F. Fera , W. G. Smith , & D. R. Weinberger (2005). Dextroamphetamine modulates the response of the human amygdala. Neuropsychopharmacology, 27, 10361040.

C. Henquet , R. Murray , D. Linszen , & J. van Os (2005). The environment and schizophrenia: The role of cannabis use. Schizophrenia Bulletin, 31, 608612.

C. Henquet , A. Rosa , L. Krabbendam , S. Papiol , L. Fananas , M. Drukker , (2006). An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology, 31, 27482757.

D. Huizinga , B. C. Haberstick , A. Smolen , S. Menard , S. E. Young , & R. P. Corley (2006). Childhood maltreatment, subsequent antisocial behavior, and the role of monoamine oxidase A genotype. Biological Psychiatry, 60, 677683.

C. M. Hultman , A. Torrang , C. Tuvblad , S. Cnattingius , J. O. Larsson , & P. Lichtenstein (2007). Birth weight and attention-deficit/hyperactivity symptoms in childhood and early adolescence: A prospective Swedish twin study. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 370377.

S. R. Jaffee , A. Caspi , T. E. Moffitt , M. Polo-Tomas , T. S. Price , & A. Taylor (2004). The limits of child effects: Evidence for genetically mediated child effects on corporal punishment but not on physical maltreatment. Developmental Psychology, 40, 10471058.

R. S. Kahn , J. Khoury , W. C. Nichols , & B. P. Lanphear (2003). Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive–impulsive, inattentive, and oppositional behaviors. Journal of Pediatrics, 143, 104110.

J. Kaufman , B. Z. Yang , H. Douglas-Palumberi , D. Grasso , D. Lipschitz , S. Houshyar , (2006). Brain-derived neurotrophic factor–5-HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673680.

K. Kendler , J. Kuhn , J. Vittum , C. Prescott , & B. Riley (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: A replication. Archives of General Psychiatry, 62, 529535.

J. M. Kim , R. Stewart , S. W. Kim , S. J. Yang , I. S. Shin , Y. H. Kim , (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biological Psychiatry.

J. Kim-Cohen , A. Caspi , A. Taylor , B. Williams , R. Newcombe , I. W. Craig , (2006). MAOA, maltreatment, and gene–environment interaction predicting children's mental health: New evidence and a meta-analysis. Molecular Psychiatry, 11, 903913.

L. Krabbendam , & J. van Os (2005). Schizophrenia and urbanicity: A major environmental influence—Conditional on genetic risk. Schizophrenia Bulletin, 31, 795799.

P. Kraft , Y. C. Yen , D. O. Stram , J. Morrison , & W. J. Gauderman (2007). Exploiting gene–environment interaction to detect genetic associations. Human Heredity, 63,111119.

M. Laucht , M. H. Skowronek , K. Becker , M. H. Schmidt , G. Esser , T. G. Schulze , (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. Archives of General Psychiatry, 64, 585590.

H. Lehn , E. M. Derks , J. J. Hudziak , P. Heutink , T. C. van Beijsterveldt , & D. I. Boomsma (2007). Attention problems and attention-deficit/hyperactivity disorder in discordant and concordant monozygotic twins: Evidence of environmental mediators. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 8391.

D. Michelson , H. A. Read , D. D. Ruff , J. Witcher , S. Zhang , & J. McCracken (2007). CYP2D6 and clinical response to atomoxetine in children and adolescents with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 46, 242251.

J. Mill , A. Caspi , B. S. Williams , I. Craig , A. Taylor , M. Polo-Tomas , C. W. Berridge , (2006). Prediction of heterogeneity in intelligence and adult prognosis by genetic polymorphisms in the dopamine system among children with attention-deficit/hyperactivity disorder: Evidence from 2 birth cohorts. Archives of General Psychiatry, 63, 462469.

T. E. Moffitt , A. Caspi , & M. Rutter (2005). Strategy for investigating interactions between measured genes and measured environments. Archives of General Psychiatry, 62, 473481.

T. E. Moffitt , A. Caspi , & M. Rutter (2006). Measured gene–environment interactions in psychopathology: Concepts, research strategies, and implications for research, intervention, and public understanding of genetics. Perspectives on Psychological Science, 1, 527.

R. J. Neuman , E. Lobos , W. Reich , C. A. Henderson , L. W. Sun , & R. D. Todd (2007). Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype. Biological Psychiatry, 61, 13201328.

T. G. O'Connor , K. Deater-Deckard , D. Fulker , M. Rutter , & R. Plomin (1998). Genotype–environment correlations in late childhood and early adolescence: Antisocial behavioral problems and coercive parenting. Developmental Psychology, 34, 970981.

L. Pezawas , A. Meyer-Lindberg , E. M. Drabant , B. A. Verchinski , K. E. Munoz , B. S. Kolachana , (2005). 5-HTTPR polymorphism impacts human cingulate–amygdala interactions: A genetic susceptibility mechanism for depression. Nature Neuroscience, 8, 828834.

R. Plomin , J. C. DeFries , I. W. Craig , & P. McGuffin (Eds.). (2003). Behavioral genetics in the postgenomic era. Washington, DC: APA Books.

G. Polanczyk , C. Zeni , J. P. Genro , A. P. Guimaraes , T. Roman , M. H. Hutz , (2007). Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder. Archives of General Psychiatry, 64, 218224.

S. Purcell (2002). Variance components models for gene–environment interaction in twin analysis. Twin Research, 5, 554571.

R. A. Ramadas , A. Sadeghnejad , W. Karmaus , S. H. Arshad , S. Matthews , M. Huebner , (2007). Interleukin-1R antagonist gene and pre-natal smoke exposure are associated with childhood asthma. European Respiratory Journal, 29, 502508.

F. Rice , G. T. Harold , K. H. Shelton , & A. Thapar (2006). Family conflict interacts with genetic liability in predicting childhood and adolescent depression. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 841848.

F. Rice , G. T. Harold , & A. Thapar (2003). Negative life events as an account of age related differences in the genetic aetiology of depression in childhood and adolescence. Journal of Child Psychology and Psychiatry, 44, 977987.

M. Rutter (2006). Genes and behavior: Nature–nurture interplay explained. London: Blackwell.

M. Rutter (2007). Gene–environment interdependence. Developmental Science, 10, 1218.

M. Rutter , T. E. Moffitt , & A. Caspi (2006). Gene–environment interplay and psychopathology: Multiple varieties but real effects. Journal of Child Psychology and Psychiatry, 47, 226261.

M. Rutter , A. Pickles , R. Murray , & L. Eaves (2001). Testing hypotheses on specific environmental causal effects on behavior. Psychological Bulletin, 127, 291324.

R. Schachar , E. Taylor , M. Wieselberg , G. Thorley , & M. Rutter (1987). Changes in family function and relationships in children who respond to methylphenidate. Journal of the American Academy of Child & Adolescent Psychiatry, 26, 728732.

J. M. Scheid , C. B. Holzman , N. Jones , K. H. Friderici , K. A. Nummy , L. L. Symonds , (2007). Depressive symptoms in mid-pregnancy, lifetime stressors and the 5-HTTLPR genotype. Genes, Brain and Behavior, 6, 453464.

S. Schmidt , X. Qin , M. A. Schmidt , E. R. Martin , & E. R. Hauser (2007). Interpreting analyses of continuous covariates in affected sibling pair linkage studies. Genetics and Epidemiology.

G. Seeger , P. Schloss , M. H. Schmidt , A. Ruter-Jungfleisch , & F. A. Henn (2004). Gene–environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism. Neuroscience Letters, 366, 282286.

S. M. Sengupta , N. Grizenko , N. Schmitz , G. Schwartz , L. Ben Amor , & J. Bellingham (2006). COMT Val108/158Met gene variant, birth weight, and conduct disorder in children with ADHD. Journal of the American Academy of Child & Adolescent Psychiatry, 45, 13631369.

J. Silberg , A. Pickles , M. Rutter , J. Hewitt , E. Simonoff , H. Maes , (1999). The influence of genetic factors and life stress on depression among adolescent girls. Archives of General Psychiatry, 56, 225232.

J. Silberg , M. Rutter , M. Neale , & L. Eaves (2001). Genetic moderation of environmental risk for depression and anxiety in adolescent girls. British Journal of Psychiatry, 179, 116121.

D. St. Clair , M. Xu , P. Wang , Y. Yu , Y. Fang , F. Zhang , (2005). Rates of adult schizophrenia following prenatal exposure to the Chinese famine of 1959–1961. Journal of the American Medical Association, 294, 557562.

E. S. Susser , & S. P. Lin (1992). Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944–1945. Archives of General Psychiatry, 49, 983988.

P. Talmud , D. Flavell , K. Alfakih , J. Cooper , A. Balmforth , M. Sivananthan , (2007). The lipoprotein lipase gene serine 447 stop variant influences hypertension-induced left ventricular hypertrophy and risk of coronary heart disease. Clinical Science (London), 112, 617624.

A. Thapar , J. Holmes , K. Poulton , & R. Harrington (1999). Genetic basis of attention deficit and hyperactivity. British Journal of Psychiatry, 174, 105111.

A. Thapar , K. Langley , P. Asherson , & M. Gill (2007). Gene–environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective. British Journal of Psychiatry, 190, 13.

P. Tienari , L. C. Wynne , A. Sorri , I. Lahti , K. Laksy , J. Moring , (2004). Genotype–environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees. British Journal of Psychiatry, 184, 216222.

E. M. Tunbridge , P. J. Harrison , & D. R. Weinberger (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry, 60, 141151.

C. Tuvblad , M. Grann , & P. Lichtenstein (2006). Heritability for adolescent antisocial behavior differs with socioeconomic status: Gene–environment interaction. Journal of Child Psychology and Psychiatry, 47, 734743.

D.E. Vergne , & C. B. Nemeroff (2006). The interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major depression. Current Psychiatry Reports, 8, 452457.

C. S. Widom , & L. M. Brzustowicz (2006). MAOA and the “cycle of violence”: Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological Psychiatry, 60, 684689.

H. J. Williams , M. J. Owen , & M. C. O'Donovan (2007). Is COMT a susceptibility gene for schizophrenia? Schizophrenia Bulletin, 33, 635641.

G. Zalsman , Y. Y. Huang , M. A. Oquendo , A. K. Burke , X. Z. Hu , D. A. Brent , (2006). Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression. American Journal of Psychiatry, 163, 15881593.

S. Zammit , & M. J. Owen (2006). Stressful life events, 5-HTT genotype and risk of depression. British Journal of Psychiatry, 188, 199201.

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Development and Psychopathology
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