Modeling gene‐environment interaction in longitudinal data: Risk for neuroticism due to interaction between maternal care and the Dopamine 4 Receptor gene (DRD4)

Abstract The purpose of this study was to investigate risk for neuroticism due to the joint action of low maternal care and compromised mesocorticolimbic ‘reward’ system function linked to a variable number tandem repeat (VNTR) in the dopamine 4 receptor gene (DRD4). Data were drawn from the Victorian Adolescent Health Cohort Study, a longitudinal study of the health and well‐being of 2,000 young Australians followed from adolescence to young adulthood across 8 waves from 14‐ to 28‐years. Genetic risk was defined by carriage of at least one copy of the 7‐repeat allele or derivative alleles 5, 6, and 8 (labeled 7R+). Neuroticism was assessed in adolescence and young adulthood. We observed an approximately fourfold increase in the odds of reporting neurotic symptoms in carriers of the 7R+ disposition who reported low maternal care compared with non‐carriers who reported high maternal care. The percentage of risk attributable to mechanisms in which both factors played a role was 35%. Findings are discussed in terms of implications for prevention.

[1]  M. McInnis,et al.  Psychiatric genetics: progress amid controversy , 2008, Nature Reviews Genetics.

[2]  S. Zubrick,et al.  Identification and genetic determination of an early life risk disposition for depressive disorder: Atypical stress‐related behaviour in early childhood , 2011 .

[3]  M. Bakermans-Kranenburg,et al.  Gene-environment interaction of the dopamine D4 receptor (DRD4) and observed maternal insensitivity predicting externalizing behavior in preschoolers. , 2006, Developmental psychobiology.

[4]  M C Neale,et al.  A longitudinal twin study of personality and major depression in women. , 1993, Archives of general psychiatry.

[5]  Philip Seeman,et al.  Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine , 1991, Nature.

[6]  P. Sham,et al.  Neuroticism: a vulnerability marker for depression evidence from a family study. , 1995, Journal of affective disorders.

[7]  P. Costa,et al.  Influences of parenting on normal personality traits , 2002, Psychiatry Research.

[8]  B. Rodgers,et al.  Reported parental behaviour and adult affective symptoms. 1. Associations and moderating factors , 1996, Psychological Medicine.

[9]  G. Guo,et al.  Trajectories of depressive symptoms, dopamine D2 and D4 receptors, family socioeconomic status and social support in adolescence and young adulthood , 2009, Psychiatric genetics.

[10]  Brad E. Sheese,et al.  Parenting quality interacts with genetic variation in dopamine receptor D4 to influence temperament in early childhood , 2007, Development and Psychopathology.

[11]  M. Weissman,et al.  Low parental care as a risk factor to lifetime depression in a community sample. , 1995, Journal of affective disorders.

[12]  Nobumasa Kato,et al.  Association between dopamine D4 receptor (DRD4) exon III polymorphism and Neuroticism in the Japanese population , 2006, Neuroscience Letters.

[13]  D. Lichtermann,et al.  Personality traits in subjects at risk for unipolar major depression: a family study perspective. , 1992, Journal of affective disorders.

[14]  M. Bakermans-Kranenburg,et al.  Research Review: genetic vulnerability or differential susceptibility in child development: the case of attachment. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[15]  P. Sham,et al.  Quality of parenting and vulnerability to depression: results from a family study , 1998, Psychological Medicine.

[16]  P. Costa,et al.  NEO inventories for the NEO Personality Inventory-3 (NEO-PI-3), NEO Five-Factor Inventory-3 (NEO-FFI-3), NEO Personality Inventory-Revised (NEO PI-R) : professional manual , 2010 .

[17]  D. Grayson.  Latent trait analysis of the Eysenck Personality Questionnaire. , 1986, Journal of psychiatric research.

[18]  P. Seeman,et al.  Multiple dopamine D4 receptor variants in the human population , 1992, Nature.

[19]  Hans J. Eysenck,et al.  Manual of the Eysenck personality questionnaire , 1975 .

[20]  D. Rubin.  Multiple imputation for nonresponse in surveys , 1989 .

[21]  L. Botto.  Flavors in gene-environment interactions. , 2007, Epidemiology.

[22]  Josephine Key.  Perceptions of poor maternal care are associated with adolescent depression. , 1995, Journal of affective disorders.

[23]  J. Schafer,et al.  Computational Strategies for Multivariate Linear Mixed-Effects Models With Missing Values , 2002 .

[24]  K. Kendler,et al.  A population-based twin study of the relationship between neuroticism and internalizing disorders. , 2006, The American journal of psychiatry.

[25]  I. Craig,et al.  Functional polymorphisms in dopamine and serotonin pathway genes , 2006, Human mutation.

[26]  G. Parker.  Parental Overprotection : A Risk Factor in Psychosocial Development , 1983 .

[27]  J. Carlin,et al.  Parental ‘affectionless control’ in adolescent depressive disorder , 2001, Social Psychiatry and Psychiatric Epidemiology.

[28]  R. Ebstein,et al.  Personality and polymorphisms of genes involved in aminergic neurotransmission. , 2000, European journal of pharmacology.

[29]  J. Toumbourou,et al.  The relationship between social capital and depression during the transition to adulthood , 2011 .

[30]  M. Munafo,et al.  Genetic Polymorphisms and Personality in Healthy Adults: A systematic review and meta-analysis , 2003, Molecular Psychiatry.

[31]  Alan D. Lopez,et al.  Evidence-Based Health Policy--Lessons from the Global Burden of Disease Study , 1996, Science.

[32]  B. Cox,et al.  Parental bonding and adult psychopathology: results from the US National Comorbidity Survey , 2002, Psychological Medicine.

[33]  Jay Belsky,et al.  For Better and For Worse , 2007 .

[34]  W. Dragan,et al.  An association between dopamine D4 receptor and transporter gene polymorphisms and personality traits, assessed using NEO-FFI in a Polish female population , 2007 .

[35]  G. Parker,et al.  The stability of the Parental Bonding Instrument over a 20-year period , 2004, Psychological Medicine.

[36]  B. Cox,et al.  Personality Dimensions and Depression: Review and Commentary , 1997, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[37]  D. Murphy,et al.  Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking , 1996, Nature Genetics.

[38]  Gordon Parker,et al.  The parental bonding instrument , 1979 .

[39]  S. Merry,et al.  Psychological and/or educational interventions for the prevention of depression in children and adolescents. , 2004, The Cochrane database of systematic reviews.

[40]  M. Bakermans-Kranenburg,et al.  DRD4 7-repeat polymorphism moderates the association between maternal unresolved loss or trauma and infant disorganization , 2006, Attachment & human development.

[41]  G. Parker,et al.  The Parental Bonding Instrument: psychometric properties reviewed. , 1989, Psychiatric developments.

[42]  S. David,et al.  Genetic variation in the dopamine D4 receptor (DRD4) gene and smoking cessation: follow-up of a randomised clinical trial of transdermal nicotine patch , 2008, The Pharmacogenomics Journal.

[43]  P. Vernon,et al.  The relationship between Eysenck's P-E-N model of personality, the five-factor model of personality, and traits delineating personality dysfunction , 2002 .

[44]  M. Bourin,et al.  Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder , 2007, Acta psychiatrica Scandinavica. Supplementum.

[45]  John T. Mitchell,et al.  Reinforcement sensitivity and maternal style as predictors of psychopathology , 2007 .