Abstract
The long forms of the dopamine D4 receptor (DRD4) exon III repeat polymorphism (L-DRD4) have been linked in some studies to the adult personality trait of novelty seeking (NS), as well as to infant personality traits related to interest and activity. The current investigation extends the results of our previous longitudinal study on 1- to 5-month-old neonates assessed by the Early and Revised Infancy Temperament Questionnaire (EITQ/RITQ), in which we found a significant correlation between the DRD4 polymorphism and the adaptability trait at 1 month of age. In this study, we examined the relationship between children′s behavior at 3 years of age, measured with the Toddler Temperament Scale (TTS), and DRD4 exon III repeat polymorphism. We found a significant association between the behavioral dimension of intensity of reaction and DRD4 genotypes. Current data failed to confirm the association with the adaptability trait. None of the extraversion and/or exploratory behavior measures was related to the L-DRD4 allele, as expected. In contrast, children with 4/7 genotypes showed worse response to new stimuli compared with 4/4 genotypes. This study corroborates only in part previous results on the link between the DRD4 gene and human temperament.
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Plomin R, Owen MJ, McGuffin P (1994) The genetic basis of complex human behaviors. Science 264:1733–1739
Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH (1996) Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat Genet 12:81–84.
Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M, Belmaker RH (1996) Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 12:78–80
Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65:1157–1165
Cloninger R (1987) A systematic method for clinical description and classification of personality variants. A proposal. Arch Gen Psychiatry 44:573–588
Jovanovic V, Guan HC, Van Tol HH (1999) Comparative pharmacological and functional analysis of the human dopamine D4.2 and D4.10 receptor variants. Pharmacogenetics 9:561–568
Meador-Woodruff JH, Grandy DK, Van Tol HH, Damask SP, Little KY, Civelli O, Watson SJ Jr (1994) Dopamine receptor gene expression in the human medial temporal lobe. Neuropsychopharmacology 10:239–248
Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Zhang G, Fang Y, Larson JL, McDougall JA, Chester JA, Saez C, Pugsley TA, Gershanik O, Low MJ, Grandy DK (1997) Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine. Cell 90:991–1001
Ritz MC, George FR (1993) Cocaine-induced seizures and lethality appear to be associated with distinct central nervous system binding sites. J Pharmacol Exp Ther 264:1333–1343
Menza MA, Golbe LI, Cody RA, Forman NE (1993) Dopamine-related personality traits in Parkinson's disease. Neurology 43:505–508
Noble EP, Ozkaragoz TZ, Ritchie TL, Zhang X, Belin TR, Sparkes RS (1998) D2 and D4 dopamine receptor polymorphisms and personality. Am J Med Genet 81:257–267
Strobel A, Wehr A, Michel A, Brocke B (1999) Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty Seeking in a German population. Mol Psychiatry 4:378–384
Tomitaka M, Tomitaka S, Otuka Y, Kim K, Matuki H, Sakamoto K, Tanaka A (1999) Association between novelty seeking and dopamine receptor D4 (DRD4) exon III polymorphism in Japanese subjects. Am J Med Genet 88:469–471
Gelernter J, Kranzler H, Coccaro E, Siever L, New A, Mulgrew CL (1997) D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects. Am J Hum Genet 61:1144–1152
Sullivan PF, Fifield WJ, Kennedy MA, Mulder RT, Sellman JD, Joyce PR (1998) No association between novelty seeking and the type 4 dopamine receptor gene (DRD4) in two New Zealand samples. Am J Psychiatry 155:98–101
Kluger AN, Siegfried Z, Ebstein RP (2002) A meta-analysis of the association between DRD4 polymorphism and novelty seeking. Mol Psychiatry 7:712–717
Loehlin J (1992) Genes and environment in personality development. Sage, Newbury Park
Auerbach JG, Faroy M, Ebstein R, Kahana M, Levine J (2001) The association of the dopamine D4 receptor gene (DRD4) and the serotonin transporter promoter gene (5-HTTLPR) with temperament in 12-month-old infants. J Child Psychol Psychiatry 42:777–783
Ebstein RP, Levine J, Geller V, Auerbach J, Gritsenko I, Belmaker RH (1998) Dopamine D4 receptor and serotonin transporter promoter in the determination of neonatal temperament. Mol Psychiatry 3:238–246
Auerbach J, Geller V, Lezer S, Shinwell E, Belmaker RH, Levine J, Ebstein R (1999) Dopamine D4 receptor (D4DR) and serotonin transporter promoter (5- HTTLPR) polymorphisms in the determination of temperament in 2-month-old infants. Mol Psychiatry 4:369–373
Medoff-Cooper B, Carey WB, McDevitt SC (1993) The Early Infancy Temperament Questionnaire. J Dev Behav Pediatr 14:230–235
Carey WB, McDevitt SC (1978) Revision of the Infant Temperament Questionnaire. Pediatrics 61:735–739
Fullard W, McDevitt SC, Carey WB (1984) Assessing temperament in one- to three-year-old children. J Pediatr Psychol 9:205–217
McDevitt SC, Carey WB (1978) The measurement of temperament in 3–7 year old children. J Child Psychol Psychiatry 19:245–253
Hegvik RL, McDevitt SC, Carey WB (1982) The middle childhood temperament questionnaire. J Dev Behav Pediatr 3:197–200
De Luca A, Rizzardi M, Torrente I, Alessandroni R, Salvioli GP, Filograsso N, Dallapiccola B, Novelli G (2001) Dopamine D4 receptor (DRD4) polymorphism and adaptability trait during infancy: a longitudinal study in 1- to 5-month-old neonates. Neurogenetics 3:79–82
Axia G BA (1995) Questionari per la misurazione del temperamento da 1 a 36 mesi. Dipartimento di Psicologia dello Sviluppo e della Socializzazione, Padova
Goldsmith H RM (1996) The Laboratory Temperament Assessment Battery (Locomotor version). Department of Psychology, University of Wisconsin, Madison
McNeil TF, Persson-Blennow I (1982) Temperament questionnaires in clinical research. Ciba Found Symp 89:20–35
Bates J (1980) The concept of difficult temperament. Merril-Palmer Quarterly 26:299–319
Gelernter J, Kennedy JL, Tol HH van, Civelli O, Kidd KK (1992) The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS. Genomics 13:208–210
Okuyama Y, Ishiguro H, Nankai M, Shibuya H, Watanabe A, Arinami T (2000) Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait. Mol Psychiatry 5:64–69
Ekelund J, Lichtermann D, Jarvelin MR, Peltonen L (1999) Association between novelty seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample. Am J Psychiatry 156:1453–1455
Eysenck H (1967) The biological basis of personality. Thomas, Springfield, Ill.
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This work was supported by a grant from the Italian Ministry of Health.
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De Luca, A., Rizzardi, M., Buccino, A. et al. Association of dopamine D4 receptor (DRD4) exon III repeat polymorphism with temperament in 3-year-old infants. Neurogenetics 4, 207–212 (2003). https://doi.org/10.1007/s10048-003-0146-z
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DOI: https://doi.org/10.1007/s10048-003-0146-z