Temperament and character profiles and the dopamine D4 receptor gene in ADHD.

OBJECTIVE This study was designed to investigate the link among attention deficit hyperactivity disorder (ADHD) in adults, novelty-seeking temperament, and the 48-base pair (bp) dopamine D4 receptor (DRD4) gene variant. METHOD This study drew from a larger molecular genetic study of ADHD in which the ascertainment criterion was having an affected sibling pair with ADHD. Parents (N=171) from 96 families provided data. Of the 171 parents, 56 (33%) had a lifetime history of ADHD, with 28 (50%) continuing to meet DSM-IV criteria (i.e., "persistent" ADHD). Latent variable modeling was used to test whether the DRD4 gene variant or Temperament and Character Inventory factors could predict ADHD. RESULTS Using latent variable modeling, the authors were able to confirm the first-order factor structure of the Temperament and Character Inventory. Furthermore, novelty seeking predicted ADHD lifetime diagnosis (R(2)=26%), while the DRD4 gene variant independently predicted ADHD (R(2)=5%) but not novelty seeking. CONCLUSIONS In this unique sample of parents from multiply affected ADHD families, novelty seeking and the 48-bp DRD4 variant were associated with a lifetime history of ADHD. However, the association between novelty seeking and ADHD does not appear to be due to variation in the 48-bp DRD4 variant.

[1]  R. Plomin Temperamental differences in infants and young children (Ciba Foundation Symposium 89) , 1982 .

[2]  M Linnoila,et al.  The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. , 1996, Molecular psychiatry.

[3]  J. Swanson,et al.  Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach , 1998, Molecular Psychiatry.

[4]  K. Lesch,et al.  No association between dopamine D4 receptor gene exon III and –521C/T polymorphism and Novelty Seeking , 2002, Molecular Psychiatry.

[5]  T. Belin,et al.  D2 and D4 dopamine receptor polymorphisms and personality. , 1998, American journal of medical genetics.

[6]  I. Waldman,et al.  Dopamine DRD4 receptor polymorphism and attention deficit hyperactivity disorder , 1998, Molecular Psychiatry.

[7]  S. Tomitaka,et al.  Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism in Japanese subjects. , 1999, American journal of medical genetics.

[8]  S. Kanba,et al.  Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects. , 1997, American journal of medical genetics.

[9]  Dragan M. Svrakic,et al.  The Tridimensional Personality Questionnaire: U.S. Normative Data , 1991, Psychological reports.

[10]  C. R. Cloninger,et al.  The temperament and character inventory (TCI) : a guide to its development and use , 1994 .

[11]  P. Sullivan,et al.  No association between novelty seeking and the type 4 dopamine receptor gene (DRD4) in two New Zealand samples. , 1998, The American journal of psychiatry.

[12]  A. Buss Temperaments as personality traits. , 1989 .

[13]  B K Suarez,et al.  A comparison of three affected-sib-pair scoring methods to detect HLA-linked disease susceptibility genes. , 1984, American journal of medical genetics.

[14]  B. Brocke,et al.  Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty Seeking in a German population , 1999, Molecular Psychiatry.

[15]  D. Comings,et al.  Comparison of the role of dopamine, serotonin, and noradrenaline genes in ADHD, ODD and conduct disorder: multivariate regression analysis of 20 genes , 2000, Clinical genetics.

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

[17]  P. Costa,et al.  Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis. , 2000, The American journal of psychiatry.

[18]  V. Kustanovich,et al.  Biased paternal transmission of SNAP-25 risk alleles in attention-deficit hyperactivity disorder , 2003, Molecular Psychiatry.

[19]  S. Faraone,et al.  Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. , 1999, The American journal of psychiatry.

[20]  M. Hutz,et al.  Dopamine D4 receptor gene and personality dimensions in Brazilian male alcoholics. , 1999, Psychiatric genetics.

[21]  B. Pennington,et al.  Big five dimensions and ADHD symptoms: links between personality traits and clinical symptoms. , 2002, Journal of personality and social psychology.

[22]  C. Francks,et al.  Genetic linkage of attention-deficit/hyperactivity disorder on chromosome 16p13, in a region implicated in autism. , 2002, American journal of human genetics.

[23]  M. Jarvelin,et al.  Association between novelty seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample. , 1999, The American journal of psychiatry.

[24]  S. Manuck,et al.  Human novelty-seeking personality traits and dopamine D4 receptor polymorphisms: a twin and genetic association study. , 1998, American journal of medical genetics.

[25]  C. Francks,et al.  A genomewide scan for loci involved in attention-deficit/hyperactivity disorder. , 2002, American journal of human genetics.

[26]  S. Cichon,et al.  No association between dopamine D4 receptor gene variants and Novelty Seeking , 2002, Molecular Psychiatry.

[27]  R. Ebstein,et al.  Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking , 1996, Nature Genetics.

[28]  R. Ebstein,et al.  Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT) , 2000, Molecular Psychiatry.

[29]  S. Nelson,et al.  No evidence of linkage or linkage disequilibrium between DAT1 and attention deficit hyperactivity disorder in a large sample. , 1999, Psychiatric genetics.

[30]  O. Pomerleau,et al.  Adult attention deficit hyperactivity disorder: psychological test profiles in a clinical population. , 1997, The Journal of nervous and mental disease.

[31]  T. Arinami,et al.  Identification of a polymorphism in the promoter region of DRD4associated with the human novelty seeking personality trait , 2000, Molecular Psychiatry.

[32]  A. Buss,et al.  The inheritance of temperaments. , 1973, Journal of personality.

[33]  S. Nelson,et al.  Evidence for linkage of a tandem duplication polymorphism upstream of the dopamine D4 receptor gene (DRD4) with attention deficit hyperactivity disorder (ADHD) , 2000, Molecular Psychiatry.

[34]  D. Klein,et al.  Schedule for Affective Disorders and Schizophrenia--Lifetime Version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual development. , 1986, Journal of psychiatric research.

[35]  G Saucier,et al.  Studies of the 48 bp repeat polymorphism of the DRD4 gene in impulsive, compulsive, addictive behaviors: Tourette syndrome, ADHD, pathological gambling, and substance abuse. , 1999, American journal of medical genetics.

[36]  M. Bornstein,et al.  Contemporary research on parenting. The case for nature and nurture. , 2000, The American psychologist.

[37]  J. Nigg,et al.  Parent personality traits and psychopathology associated with antisocial behaviors in childhood attention-deficit hyperactivity disorder. , 1998, Journal of child psychology and psychiatry, and allied disciplines.

[38]  P. Bentler,et al.  Cutoff criteria for fit indexes in covariance structure analysis : Conventional criteria versus new alternatives , 1999 .

[39]  J N Giedd,et al.  Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses , 1998, Molecular Psychiatry.

[40]  Getachew A Dagne,et al.  Hierarchical modeling of sequential behavioral data: an empirical Bayesian approach. , 2002, Psychological methods.

[41]  W. Roberts,et al.  Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder. , 2000, American journal of medical genetics.

[42]  G. Saucier,et al.  A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory , 2000, Clinical genetics.

[43]  M. Nöthen,et al.  Allelic variants of dopamine receptor D4 (DRD4) and serotonin receptor 5HT2c (HTR2c) and temperament factors: replication tests. , 1999, American journal of medical genetics.

[44]  J. McGough,et al.  Familial clustering of symptoms and disruptive behaviors in multiplex families with attention-deficit/hyperactivity disorder. , 2000, Journal of the American Academy of Child and Adolescent Psychiatry.

[45]  R. Ebstein,et al.  A haplotype relative risk study of the dopamine D4 receptor (DRD4) exon III repeat polymorphism and attention deficit hyperactivity disorder (ADHD). , 2000, American journal of medical genetics.

[46]  N. Ryan,et al.  Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[47]  R. Ebstein,et al.  Failure to replicate an excess of the long dopamine D4 exon III repeat polymorphism in ADHD in a family-based study. , 2000, American journal of medical genetics.

[48]  D. Cantwell Attention deficit disorder: a review of the past 10 years. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[49]  C. Francks,et al.  A genomewide scan for attention-deficit/hyperactivity disorder in an extended sample: suggestive linkage on 17p11. , 2003, American journal of human genetics.

[50]  D. Derryberry,et al.  Development of individual differences in temperament , 1981 .

[51]  R. Klein,et al.  Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status. , 1993, Archives of general psychiatry.

[52]  M. Nöthen,et al.  Lack of association between dopamine D4 receptor gene and personality traits , 1998, Psychological Medicine.

[53]  J. Benjamin,et al.  DRD4 related to infant attention and information processing: a developmental link to ADHD? , 2001, Psychiatric genetics.

[54]  S. Faraone,et al.  Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. , 2001, The American journal of psychiatry.

[55]  T. Sander,et al.  Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics. , 1997, American journal of medical genetics.

[56]  Melvin Lewis Child and Adolescent Psychiatry: A Comprehensive Textbook , 2002 .

[57]  Z. Rónai,et al.  Genotyping the ‐521C/T functional polymorphism in the promoter region of dopamine D4 receptor (DRD4) gene , 2001, Electrophoresis.

[58]  Y. Fukumaki,et al.  Association analysis of polymorphisms in the upstream region of the human dopamine D4 receptor gene (DRD4) with schizophrenia and personality traits , 2001, Journal of Human Genetics.

[59]  C. R. Cloninger,et al.  The genetics and psychobiology of the seven-factor model of personality. , 1998 .

[60]  P. Muglia,et al.  Adult attention deficit hyperactivity disorder and the dopamine D4 receptor gene. , 2000, American journal of medical genetics.

[61]  B. Muthén,et al.  Finite Mixture Modeling with Mixture Outcomes Using the EM Algorithm , 1999, Biometrics.

[62]  S. Faraone,et al.  Predictors of persistence and remission of ADHD into adolescence: results from a four-year prospective follow-up study. , 1996, Journal of the American Academy of Child and Adolescent Psychiatry.

[63]  C. R. Cloninger,et al.  A psychobiological model of temperament and character. , 1993, Archives of general psychiatry.

[64]  No association of the dopamine DRD4 receptor (DRD4) gene polymorphism with attention deficit hyperactivity disorder (ADHD) in the Irish population. , 2000 .

[65]  L. Siever,et al.  D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects. , 1997, American journal of human genetics.

[66]  J. Swanson,et al.  Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. , 1996, Molecular psychiatry.

[67]  S. Smalley Genetic influences in childhood-onset psychiatric disorders: autism and attention-deficit/hyperactivity disorder. , 1997, American journal of human genetics.