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Association Between the Type 4 Dopamine Receptor Gene Polymorphism and Novelty Seeking

From the Department of Psychology (L.K.-J., M.E., M.K.), University of Helsinki, Helsinki, Finland; Finnish Institute of Occupational Health (M.K.), Helsinki; Institute of Public Health Department of Molecular Medicine (D.L., J.E., L.P.), National Public Health Institute, Helsinki; Department of Psychiatry, University of Bonn (D.L.), Bonn, Germany; and Department of Human Genetics (L.P.), University of California, Los Angeles.

Address reprint requests to: Liisa Keltikangas-Järvinen, Department of Psychology, University of Helsinki, PO Box 13, FIN 00014 University of Helsinki, Finland. Email: liisa.keltikangas-jarvinen{at}helsinki.fi

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: Mixed results have been reported on the association between the type 4 dopamine receptor gene (DRD4) and the temperament dimension of novelty seeking. We tested this association by specifying the analysis to components of novelty seeking.

METHODS: Participants were 150 high and low novelty-seeking scorers (the highest and lowest 10%) from a randomized, population-based sample of Finnish citizens in six age cohorts. We genotyped a 48-bp repeat polymorphism in the DRD4 gene. Novelty seeking was assessed by the Temperament and Character Inventory.

RESULTS: No difference in overall novelty seeking between individuals with no seven-repeat allele (short) and any seven-repeat allele (long), between the 4,4 and 4,7 genotype groups, and between long (l/l and s/l) and short (s/s) polymorphism groups were found. The odds ratio for high overall novelty seeking in the presence of any two- or five-repeated alleles vs. none was 2.41 (95% CI, 1.11–5.20). Corresponding odds ratios were significant for exploratory excitability (2.94; 95% CI, 1.32–6.59) and impulsiveness (2.74; 95% CI, 1.23–6.11) but not for other components of novelty seeking. No interactions with age or gender were detected.

CONCLUSIONS: The present study confirmed previous findings on the association between the type 4 dopamine receptor gene and novelty seeking, in particular exploratory excitability and impulsiveness. The tendency to avoid or approach a novel situation is a core concept of several temperamental theories. The present findings support the hypothesis that this tendency is associated with DRD4 and might concern temperament psychology in general, not only the concept of novelty seeking.

Key Words: DRD4, • novelty seeking, • exploratory excitability, • temperament, • genetic.

Abbreviations: CI = confidence interval;; CRYF = Cardiovascular Risk in Young Finns study;; DRD4 = dopamine 4 receptor gene;; OR = odds ratio;; TCI = Temperament and Character Inventory.

	INTRODUCTION

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According to Cloninger and others (1, 2), temperament is largely heritable and relates to brain systems involved in individual differences in response to environmental stimuli such as novelty, danger, or punishment and reward (ie, the amygdala, hypothalamus, striatum, and other parts of the limbic system). However, systematic research on the associations between genetics and temperament has only begun to emerge.

Cloninger’s original (1) model included three primary dimensions of temperament, each of which identified a specific stimulus-response sensitivity, the particular modes of behavior that resulted, and the specific neurotransmitters involved. These are as follows: 1) novelty seeking, associated with variation in dopamine levels, represents a tendency toward frequent exploratory activity and intense excitement in response to novel stimuli and active avoidance of monotony; 2) harm avoidance, associated with individual variation in serotonin levels, is a tendency to respond intensely to aversive stimuli and to learn to avoid punishment, novelty, and frustrating nonreward; and 3) reward dependency, associated with individual variation in norepinephrine levels, refers to a tendency to respond intensely to signals of reward, in particular to signals of social approval and succor, and to maintain or resist the extinction of behavior that has previously been associated with rewards or relief of punishment. Thus, novelty seeking relates to approaching, harm avoidance to avoiding, and reward dependency to maintaining. In later revisions of this model, Cloninger has treated one of the subscales of reward dependence, ie, persistence (a tendency to persevere despite frustration and fatigue) as an independent dimension (2).

Research on the genetic background of Cloninger’s temperament model has been most active in relation to novelty seeking. It has been suggested that polymorphism in the dopamine 4 receptor (DRD4) influences the function of the receptor and also an individual’s need for novelty (3). The potential linking mechanism between DRD4 and novelty seeking is that the number of repeats in DRD4 can affect the binding of ligands to the receptor and that dopamine mediates the exploratory behavior in experimental animals (4). Furthermore novelty seeking has been shown to be low in dopamine-deficient patients with Parkinson’s disease (2). Indeed, a significant association between novelty seeking and the seven-repeat allele (long form) of the 16-amino acid polymorphism of the D4 dopamine receptor gene DRD4 was reported in 1996 (4, 5) and later replicated (6, 7). However, failures to replicate this association (8–10) have also been reported. A study by Ekelund et al. (11) in Finnish men and women who were born in 1966 suggested that the two- and five-repeat alleles, rather than the seven-repeat allele, were significantly associated with high novelty-seeking scores. An American study by Herbst et al. (8), however, failed to replicate this finding.

In the present study we attempted to replicate or refute the finding of an association between the 48-bp repeat polymorphism in DRD4 and novelty seeking. According to the model of Cloninger and colleagues (12), novelty seeking includes dimensions of exploratory excitability, impulsiveness, extravagance, and disorderliness. We also examined which of these dimensions, if any, are associated with DRD4 polymorphism. We statistically controlled the analysis for such demographic variables as age, gender, and education level, and we also attempted to determine whether the association between genotype and novelty-seeking scores was modified by those factors.

	METHODS

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Selection Procedure and Participants
The participants were from the ongoing population-based study of Cardiovascular Risk in Young Finns (CRYF) (13). In this prospective, epidemiological study, a randomized sample of 3600 healthy Finnish children and adolescents in age cohorts of 3, 6, 9, 12, 15, and 18 years have been followed since 1980. During the fifth follow-up of the CRYF (17 years after the baseline), the subjects completed the Temperament and Character Inventory (TCI) (2). The complete data were obtained from 1265 women and 884 men, a total of 2149 subjects. In this sample the original factor structure of the TCI (2) was replicated. Cronbach’s reliabilities were 0.86, 0.92, and 0.80 for novelty seeking, harm avoidance, and reward dependence, respectively, slightly higher than reported in the original study (0.78, 0.87, and 0.76, respectively) (2). The mean score of novelty seeking for the CRYF sample was 20.6 (SD, 4.0).

From this sample persons with extremely high or extremely low novelty-seeking scores (the highest and lowest 10%) were invited to participate in the genetic part of the study. A total of 154 subjects (77 men and 77 women) agreed to participate, and they gave blood samples. (In accordance with the Helsinki Declaration, written informed consent was obtained after a written and verbal description of the study was given to the subjects.) The subjects belonged to the highest 9% or lowest 8% of the novelty-seeking scale. Their age groups and corresponding frequencies were as follows: 20 years, 13.6%; 23 years, 21.4%; 26 years, 13.1%; 29 years, 16.2%; 32 years, 19.5%; and 35 years, 16.2%. Fifty-two percent of the participants had at least upper secondary education, 20% had vocational school, and 29% had comprehensive school as their highest education. Parental educational level was higher than comprehensive school for 42% of the participants (information based on the parent with a higher educational level).

DRD4 Polymorphism Genotyping
Polymerase chain reaction was performed as described by Lichter et al. (14), with slight modifications. One primer was fluorescently labeled with Cy5 for size separations on an automated DNA sequencer (ALF Express, Pharmacia Biotech AB). Genotyping was done through use of the Allelinks software (Pharmacia Biotech AB). Alleles were not identifiable for four participants. They were therefore excluded from the sample.

Statistical Analysis
We followed the procedure used by Herbst et al. (8) and defined the short and long DRD4 groups as follows. The first approach defined short polymorphism by the absence of the exon III seven-repeat allele and long polymorphism by the presence of any seven-repeat allele. Because four- and seven-repeated alleles are the most common alleles in the population, a second approach compared the 4,4 genotype to the 4,7 genotype. A third approach defined short polymorphism as two copies of two to five repeats (s/s genotype) and long polymorphism as one or two copies of six to eight repeats (s/l and l/l genotypes). A fourth approach was to compare those with any two- or five-repeat alleles with others.

Associations between genotype group and scores of novelty seeking were assessed with logistic regression analysis and were expressed as odds ratios (OR) and 95% confidence intervals (CI). This is a more illustrative way to compare associations of genotypes with various novelty-seeking subscales than simple chi-square testing. We repeated the analysis while controlling for age and gender. We also tested whether the association between novelty seeking and DRD4 is dependent on demographic factors, such as age, gender, education, and parental education, by adding a cross-product term in the models, as recommended by Cohen and Cohen (15).

	RESULTS

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The frequencies of the DRD4 polymorphism alleles in the final sample were as follows: allele 2, 8.3%; allele 3, 7.7%; allele 4, 63.7%; allele 5, 4.3%; allele 6, 0%; and allele 7, 15.7%. One participant had an eight-repeat allele. These distributions corresponded with those reported in previous studies (8, 11).

The predicted difference in scores on the overall scale for novelty seeking between individuals with no seven-repeat allele (short) and any seven-repeat allele (long) was not found. An analysis comparing the scores for novelty seeking of the 4,4 and 4,7 genotype groups was also not significant. Comparison of the groups with long (l/l and s/l) and short (s/s) polymorphism also resulted in no significant differences in novelty seeking. However, when participants with the presence of any two- or five-repeat alleles were compared with those without these alleles, a significant effect on the overall novelty-seeking score was obtained. The odds ratio of any two- or five-repeat alleles for high novelty-seeking scores was 2.4 (Table 1).

	DISCUSSION

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We used the same method of sample selection as Ekelund et al. (11), ie, the subjects with extreme scores on novelty seeking were derived from a population-based sample. However, instead of selecting patients from one age cohort, we selected participants from six different age cohorts. This increases the generalizability of Ekelund and others’ findings and excludes validity problems due to focusing on individuals from only one age cohort.

Is Exploratory Excitability the Core of the Inherited Component of Novelty Seeking?
We carried out 20 different tests on the association between genotype and novelty seeking. The main finding of this study was the importance of using the four subscales of novelty seeking (ie, exploratory excitability, impulsiveness, extravagance, and disorderliness) rather than a global score. We showed that only exploratory excitability and impulsiveness were associated with the DRD4 gene, exploratory excitability reaching the highest level of significance.

Previous genetic research has mostly treated novelty seeking as a global score, only two studies having subdivided it. Ono and coworkers (6) found an association of the DRD4 genotype with exploratory excitability; and Strobel et al. (19) found an association with exploratory excitability and extravagance but not with other subscales. Thus, in agreement with our findings, the previous studies of the TCI subscales have come to the same conclusion: If the studied polymorphism affects novelty-seeking scores, it is most likely to be associated with the excitability component. The present results, combined with other findings from the Finnish as well as other populations, also support the claim that in different populations, different variants in the DRD4 gene are associated with novelty seeking.

With respect to the other subscales, an association with impulsiveness was found only in the present study, and an association with extravagance was found only in the study by Strobel et al. (19). Inconsistencies in these results may be explained by cultural differences. Impulsiveness is conceptually close to excitability. It measures a tendency to follow intuition in making decisions instead of considering things in all details. Extravagance seems to be rather far from other subscales. Although other subscales indicate a person’s strategies and ways to behave in various situations, extravagance concerns excess, usually in relation to tastes or expenses. Here the cultural variance should not be ignored. An old Finnish principle, still existing among older generations, is that a civilized person does not speak about money. Even a person’s annual income is an intimate matter, sometimes to the degree that measuring it using self-reports creates validity problems. Consequently items associated with this quality may have different meanings in different cultures.

Measurement of novelty seeking and sample limitations might offer at least a partial explanation for negative findings in some earlier studies of DRD4 and novelty seeking. Jönsson et al. (20) assessed novelty seeking with the Karolinska Scales of Personality (21). This instrument includes two subscales, monotony avoidance and impulsiveness, that, according to the authors, encompass traits similar to novelty seeking. Those subscales might, however, be of secondary importance, at least in this particular context. Jönsson et al.’s concept of novelty seeking is not the same as that in studies that replicated Ebstein’s original finding (4).

Herbst et al. (8) reported a deviant factor structure for TCI (ie, the original factors were not replicated) with a lower reliability for novelty seeking than that reported by Cloninger et al. (2). Problems of construct validity in the study of Herbst et al. may have resulted from the high average age of the participants (62 and 55 years for men and women, respectively). Although age is not an issue in genotyping, it may play a significant role in the assessment of novelty seeking. In a Finnish population-based sample, the level of novelty seeking decreased with age (unpublished data, available from the first author). Opportunities to observe associations with novelty seeking are limited among older individuals if variation in novelty seeking decreases with age.

Corresponding sample limitations are also possible in studies focusing on alcohol-dependent subjects (9, 22) and subjects with depressive or personality disorders (10, 23). It has been found that alcohol-dependent subjects have an exceptional distribution of novelty seeking (24) and that their subscale profile is significantly different from that of control subjects (unpublished data, available from the first author). It is important to note that the final test of heritability always requires a family-based design. However, observed associations between genotypes and novelty seeking suggest that DRD4 influences temperament.

Implication for Temperament Theories
In our sample most of the evidence for association between DRD4 and novelty seeking came from the exploratory excitability subscale. It might be that the association does not cover the whole novelty-seeking concept but is actually restricted to exploratory excitability. This characteristic refers to a person’s way of responding to novel things and new events. It is assessed with items such as "I like to try new things just for fun; I like doing things in new and improved ways; I like to explore new places; I am slower than most people to get excited about new ideas and activities" inversely coded). This is very close to Gray’s concept of behavioral activation (25) and Kagan et al.’s concept of "uninhibited temperament" (26). Gray has proposed a temperamental model in which inherited tendencies, ie, BIS (behavioral inhibition system) and BAS (behavioral activation system), are responsible for a person’s way of reacting to novel, challenging, frustrating, or rewarding situations. Kagan, in turn, has suggested that about 15% to 20% of all white children are born with a physiology that predisposes them to become behaviorally inhibited in their second year when confronted with unfamiliar people, places, or events, whereas another 30% to 35% are born with a physiology that predisposes them to approach that which is unfamiliar (26). Thus the association reported here is to a temperamental dimension that is comparable to the core of several temperament concepts, actually close to the very core of temperament psychology in general, ie, a person’s tendency to avoid or approach strange, novel, and unexpected situations.

Recently novelty seeking has been associated with several behavioral outcomes, most of them negative, such as substance and drug use (27, 28), alcoholism (29, 30), antisocial behavior (30), and eating disorders (31, 32) among others. This is surprising because related concepts, such as uninhibited behavior and the behavioral activation system, are systematically related to "positive" consequences, such as social adaptability and social activity (33) and resilience (34). This, indeed, points to a need for a deeper understanding of the concept of novelty seeking. For example, if the same genetic basis is likely to lead to opposite behavioral and psychological outcomes, what is the role of the environment in these different developmental processes?

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION CONCLUSIONS ACKNOWLEDGMENTS REFERENCES

 
The present study confirmed previous findings on the association of the type 4 dopamine receptor gene to novelty seeking. In different genetic populations different variants in the DRD4 gene seem to be responsible for the high and low novelty-seeking scores. We also showed that exploratory excitability and impulsiveness, in particular, were associated with DRD4, excitability reaching the highest level of significance. Considering all of the evidence on genetic factors and novelty seeking, it seems possible that excitability is associated with different gene variants in different populations and that the same gene variants could be associated with different novelty-seeking subscales depending on cultural and other factors. In general terms the tendency to avoid or approach novel situations, as reflected in exploratory excitability, may be a core concept of several temperamental theories.

This finding should be replicated by other studies by analyzing the subscales of novelty seeking in relation to DRD4.

	ACKNOWLEDGMENTS

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The study was supported by the Academy of Finland (Projects 50907 and 44968).

Received for publication January 14, 2002.

	REFERENCES

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1. Cloninger CR. A systematic method for clinical description and classification of personality variants: a proposal. Arch Gen Psychiatry 1987; 44: 573–88.[Abstract]
2. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry 1993; 50: 975–90.[Abstract]
3. Comings DE, Flanagan SD, Dietz G, Muhleman D, Knell E, Gysin R. The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol 1999; 50: 176–85.
4. Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D, Bennett ER, Nemanov L, Katz M, Belmaker RH. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of novelty seeking. Nat Genet 1996; 12: 78–80.[CrossRef][Medline]
5. Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH. Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 1996; 12: 81–4.[CrossRef][Medline]
6. Ono Y, Manki H, Yoshimura K, Muramatsu T, Mizushima H, Higuchi S, Yagi G, Kanba S, Asai M. Association between dopamine D4 receptor (D4DR) exon III polymorphism and novelty seeking in Japanese subjects. Am J Med Genet 1997; 74: 501–3.[CrossRef][Medline]
7. Noble EP, Ozkaragoz TZ, Ritchie TL, Zhang X, Belin TR, Sparkes RS. D2 and D4 dopamine receptor polymorphisms and personality. Am J Med Genet 1998; 81: 257–67.[CrossRef][Medline]
8. Herbst JH, Zonderman AB, McCrae RR, Costa PT Jr. Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis. Am J Psychiatry 2000; 157: 1285–90.[Abstract/Free Full Text]
9. Malhotra AK, Virkkunen M, Rooney W, Eggert M, Linnoila M, Goldman D. The association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Mol Psychiatry 1996; 1: 388–91.[Medline]
10. Gelernter J, Kranzler H, Coccaro E, Siever L, New A, Mulgrew CL. D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects. Am J Hum Genet 1997; 61: 1144–52.[CrossRef][Medline]
11. Ekelund J, Lichtermann D, Järvelin M-R, Peltonen L. Association between novelty seeking and the type 4 dopamine receptor gene in a large Finnish cohort sample. Am J Psychiatry 1999; 156: 1453–5.[Abstract/Free Full Text]
12. Cloninger CR, Adolfsson R, Svrakic D. Mapping genes for human personality. Nat Genet 1996; 12: 3–4.[CrossRef][Medline]
13. Åkerblom HK, Uhari M, Pesonen E, Dahl M, Kaprio EA, Nuutinen EM, Pietikäinen M, Salo MK, Aromaa A, Kannas L, Keltikangas-Jãrvinen L, Kuusela V, Rãsãnen L, Rõnnemaa T, Knip M, Telama R, Vãlimãk I, Pyõrãlã K, Viikari J. Cardiovascular risk in young Finns. Ann Med 1991; 23: 35–9.[Medline]
14. Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum Mol Genet 1993; 2: 767–73.[Abstract/Free Full Text]
15. Cohen J, Cohen P. Applied multiple regression/correlation analysis for the behavioral sciences. 2nd ed. Hillsdale (NY): Erlbaum; 1983.
16. Ekelund J, Suhonen J, Jarvelin MR, Peltonen L, Lichterman D. No association of the -521 C/T polymorphism in the promoter of DRD4 with novelty seeking. Mol Psychiatry 2001; 6: 618–9.[CrossRef][Medline]
17. Okuyama Y, Ishiguro H, Nankai M, Shibuya H, Watanabe A, Arinami T. Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait. Mol Psychiatry 2000; 5: 64–9.[CrossRef][Medline]
18. Sirota LA, Greenberg BD, Murphy DL, Hamer DH. Non-linear associations between the serotonin transporter promoter polymorphism and neuroticism: a caution against using extreme samples to identify quantitative trait loci. Psychiatr Genet 1999; 9: 35–8.[Medline]
19. Strobel A, Wehr A, Michel A, Brocke B. Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of novelty seeking in a German population. Mol Psychiatry 1999; 4: 378–84.[CrossRef][Medline]
20. Jönsson EG, Nöthen MM, Gustavsson JP, Neidt H, Brene S, Tylec A, Propping P, Sedvall GC. Lack of evidence for allelic association between personality traits and the dopamine D4 receptor gene polymorphisms. Am J Psychiatry 1997; 154: 697–9.[Abstract]
21. Schalling D, Åsberg M, Edman G, Oreland L. Markers for vulnerability to psychopathology: temperament traits associated with platelet MAO activity. Acta Psychiatr Scand 1987; 76: 172–82.[Medline]
22. Sander T, Harms H, Dufeu P, Kuhn S, Rommelspacher H, Schmidt LG. Dopamine D4 receptor exon III alleles and variation of novelty seeking in alcoholics. Am J Med Genet 1997; 74: 483–7.[CrossRef][Medline]
23. Sullivan PF, Fifield WJ, Kennedy MA, Mulder RT, Sellman JD, Joyce PR. No association between novelty seeking and the type 4 dopamine receptor gene (DRD4) in two New Zealand samples. Am J Psychiatry 1998; 155: 98–101.[Abstract/Free Full Text]
24. Ravaja N, Keltikangas-Järvinen L. Cloninger’s temperament and character dimensions in young adulthood and their relation to characteristics of parental alcohol use and smoking. J Stud Alcohol 2001; 62: 98–104.[Medline]
25. Gray JA. The neuropsychology of anxiety. New York: Oxford University Press; 1982.
26. Kagan J, Snidman N, Arcus DM. Initial reactions to unfamiliarity. Curr Dir Psychol Sci 1992; 1: 171–4.[CrossRef]
27. Wills TA, Sandy JM, Yaeger A. Temperament and adolescent substance use: an epigenetic approach to risk and protection. J Pers 2000; 68: 1127–51.[CrossRef][Medline]
28. Krebs H, Weyers P, Janke W. Validation of the German version of Cloninger’s TPQ: replication and correlations with stress coping, mood measures and drug use. Pers Individual Differ 1998; 24: 805–14.[CrossRef]
29. Zaninelli RM, Porjesz B, Begleiter H. The tridimensional personality questionnaire in males at high and low risk for alcoholism. Alcohol Clin Exp Res 1992; 16: 68–70.[CrossRef][Medline]
30. Hesselbrock MN, Hesselbrock VM. Relationship of family history, antisocial personality disorder and personality traits in young men at risk for alcoholism. J Stud Alcohol 1992; 53: 619–25.[Medline]
31. Brewerton TD, Hand LD, Bishop ER Jr. The tridimensional personality questionnaire in eating disorder patients. Int J Eat Disord 1993; 14: 213–8.[Medline]
32. Bulik CM, Sullivan PF, Weltzin TE, Kaye WH. Temperament in eating disorders. Int J Eat Disord 1995; 17: 251–61.[Medline]
33. Kagan J. Temperamental contributions to social behavior. Am Psychol 1989; 44: 668–74.[CrossRef]
34. Calkins SD, Fox NA. The relations among infant temperament, security of attachment, and behavioral inhibition at twenty-four months. Child Dev 1992; 63: 1456–72.[CrossRef][Medline]

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