Neuroscience Letters 468 (2010) 234–237

Contents lists available at ScienceDirect

Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet

Variation in DRD2 dopamine gene predicts Extraverted personality

Luke D. Smillie a,∗ , Andrew J. Cooper a , Petroula Proitsi b , John F. Powell b , Alan D. Pickering a
a
Goldsmiths, University of London, UK
b
Institute of Psychiatry, Kings College London, UK

a r t i c l e i n f o a b s t r a c t

Article history: Quantitative geneticists estimate the heritability of Extraverted personality to be around 40–60%. Theory
Received 11 September 2009 and research which links Extraversion with variation in dopaminergic function suggests that dopamin-
Received in revised form 28 October 2009 ergic genes should be a start-point for molecular genetic investigations of this trait. Recent endeavours
Accepted 30 October 2009
in this area have met with some encouragement but also setbacks. In this study, we investigate the rela-
tionship between Extraversion and the DRD2 TaqIA/ANKK1 polymorphism in 224 university students.
Keywords:
Presence of at least one copy of the A1 allele was associated with significantly higher Extraversion. The
Extraversion
robustness of this finding was confirmed through bootstrap analysis. Findings are discussed in relation
EPQ
Dopamine
to the broader literature, in particular, methodological issues which may have obscured this finding in
DRD2 previous research.
TaqIA Crown Copyright © 2009 Published by Elsevier Ireland Ltd. All rights reserved.
ANKK1

Extraversion – a personality descriptor reflecting variation general; in particular, the agency and approach motivation pro-
in sociability, positive affectivity, behavioural approach and cesses which characterise this trait [9,27,28]. Reward-reactivity
agency/dominance [41] – represents a major source of varia- has been linked with dopamine function in behavioural neuro-
tion in human personality. Over the last 20 years, large-scale science research [8,34,35] and with Extraversion in psychometric
twin studies have consistently indicated that approximately half [6], behavioural [26] and neuroimaging [5] research. Other com-
of the variation in scores on Extraversion questionnaires can ponents of Extraversion, such as positive affectivity, are thought
be attributed to genetic factors [10,17,19]. Similar estimates are to have no direct relationship with dopamine function [34,1] (and
also obtained when Extraversion scores are derived from peer as such the dopamine hypothesis is at best a partial explanation
ratings or from ratings by unacquainted judges of videotaped sub- of this trait [36]). Nevertheless, a dopamine model of Extraversion
jects [4]. However, very little is known about the specific genes appears biologically plausible and potentially powerful. It also
which underlie variation in Extraversion. This is firstly because provides strong guidance for candidate-gene approaches to the
relatively few molecular genetic investigations of individual dif- study of Extraversion; one would predict dopaminergic gene poly-
ferences have focused on non-clinical personality dimensions morphisms to influence scores on measures of trait Extraversion
such as Extraversion [42]. Furthermore, genetic variations which [36].
underlie complex, continuously distributed phenotypes such as This line of investigation has yielded encouraging findings,
personality traits almost certainly involve multiple and interacting but also met with challenges and setbacks. For example, two
gene effects which are difficult to specify theoretically and detect variants of the dopamine D4 receptor (DRD4) gene have been
empirically [29]. associated with questionnaire measures of Extraversion in several
Biologically oriented theories of personality may help studies [2,3,15]. On the other hand, a recent meta-analysis and
researchers to specify candidate-genes which may be asso- high-powered (N = 309 extreme high/low scorers on Extraversion
ciated with Extraversion (this strategy is in contrast to the from the Eysenck Personality Questionnaire; EPQ [11]) replica-
genome-wide association scan approach, which, though powerful, tion study has cast doubt on the reliability of these findings [24].
may risk capitalization on chance relationships [14]). Several More recently, variation in the dopamine transporter gene (DAT)
theories identify the mesolimbic dopamine system as the primary was shown to predict a potential animal analogue of Extraver-
mechanism underlying individual differences in Extraversion in sion, social dominance, in Cynomolgus Macaques [21]. However,
DAT variation differs greatly between humans and these mon-
keys, potentially limiting the implications of this finding for human
∗ Corresponding author at: Department of Psychology, Goldsmiths, University of personality. Finally, a polymorphism in the COMT gene, which
London, London, SE14 6NW, UK. Tel.: +44 0 207 919 7874; fax: +44 0 207 919 7873. influences metabolism of dopamine in the prefrontal cortex, has
E-mail address: [email protected] (L.D. Smillie). been associated with Extraversion and related traits, both alone

0304-3940/$ – see front matter. Crown Copyright © 2009 Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.neulet.2009.10.095
 L.D. Smillie et al. / Neuroscience Letters 468 (2010) 234–237 235

and in gene–gene interactions [30,31]. These effects, however, do Table 1

Means and standard deviations of trait measures and genotype frequencies.
not appear to have been replicated.
It is instructive to recall that the dopamine hypothesis of Mean SD ˛ A2/A2 A2/A1 A1/A1
Extraversion, in most articulations, specifically concerns the Extraversion 16.09 4.63 0.83 131 83 10
mesolimbic dopamine system [9]. This pathway projects from the Neuroticism 12.97 5.69 0.89
ventral tegmental area to the nucleus accumbens, and has been Psychoticism 8.69 4.28 0.75
primarily associated with the processing of rewards [34,35]. Con-
trastingly, the mesocortical dopamine system, projecting from the
ventral tegmental area to the prefrontal cortex, has been primar- noted for the behavioural content of its items (e.g., “Do you usu-
ily associated with executive processes such as working memory ally take the initiative in making new friends?”; “Are you rather
[20]. If Extraversion is primarily characterised by reward process- lively?”), in contrast with alternative measures (e.g., NEO-PI-R [7])
ing, and dopamine involvement in reward-processing is specific that tend to emphasise affective components, as has been noted
to particular brain pathways, then dopaminergic gene polymor- elsewhere [41]. EPQ Extraversion has 25 items and the internal
phisms may differ in their influence on Extraversion depending consistency in this sample was acceptable (˛ = 0.83). Genomic DNA
upon where they are expressed in the brain. This could potentially was extracted from self-administered cheek-swabs using standard
explain why genes such as DRD4, expressed primarily in prefrontal methods, as described elsewhere [13]. The genotypes for the DRD2
cortex [22], have not emerged as clear or consistent genetic markers TaqIA/ANKK1 (rs1800479) polymorphism was determined by an
for Extraverted personality. allelic discrimination assay based on fluorogenic 5 nuclease activ-
One gene which is primarily expressed in mesolimbic regions, ity: TaqMan Single Nucleotide Polymorphism (SNP) Genotyping
and does not appear to have been widely investigated in relation to Assay (Applied Biosystems INC). SNP-specific primers and probes
Extraversion, is the DRD2 gene. A restriction fragment length poly- were designed and assays were performed according to the man-
morphism (RFLP), known as the TaqIA polymorphism (rs1800479), ufacturer’s instructions. Participants were divided into two groups
has been associated with a 1/3 reduction in D2 receptor binding according to presence or absence of the A1 allele, as is the con-
sites [32,33,38]. (Although, as has recently been noted, this poly- vention in the literature due to the skewed distribution of this
morphism actually lies 10 kb downstream of the DRD2 gene within polymorphism (see Table 1). This grouping variable was then used
the encoding region of the ANKK1 gene [12].) As we have sug- to predict personality scores.
gested elsewhere [36,16], one might expect that a reduction in Descriptive statistics, including means for EPQ Extraversion
post-synaptic D2 sites results in increased dopamine release as (along with other EPQ scale scores) and allele frequencies are dis-
a result of receptor down regulation (i.e., the allele may reduce played in Table 1. The DRD2 TaqIA/ANKK1 genotype frequencies
postsynaptic inhibition of DA release). Therefore, if Extraversion were in Hardy–Weinberg-Equilibrium, 2 = 0.48, d.f. = 1, p > 0.05,
is associated with greater dopamine activity, Extraversion scores and allele frequencies for our planned comparison groups were
should be higher for subjects with at least one copy of the A1 similar to those observed in recent studies of DRD2 variation, with
allele of the DRD2 TaqIA/ANKK1 polymorphism. Some studies have 41.7% of participants having at least one copy of the A1 allele. Also,
found A1 carriers to report higher scores on personality measures ethnogeographic group was not significantly associated with A1
that have a conceptual overlap with Extraversion (e.g., “Reward- allele frequency in this sample (African: 42%; Asian: 43%; Euro-
Responsiveness” [18]). However, we are aware of only two studies pean: 34%; North American: 22%; South American: 33%; 2 = 6.02,
that report on this relationship using a bona fide Extraversion scale: d.f. = 4, p > 0.05).
The first, being in part an investigation of parental alcoholism, Three univariate ANOVAs were conducted to examine the influ-
found that children with one copy of the A1 allele reported higher ence of the A1 allele on EPQ Extraversion and, for divergent validity,
Extraversion scores than those without, however this effect only EPQ Neuroticism and Psychoticism. A Bonferroni correction was
held for children living in an alcoholic home [25]. The second, in applied to significance levels by multiplying obtained p-values
a sample of Caucasian German adults, failed to find any signifi- by the number of comparisons. As predicted, participants car-
cant relationship with Extraversion [40]. As such, there is some rying at least one copy of the A1 allele reported significantly
(qualified) support for our prediction, which, given the narrow sam- higher Extraversion on the EPQ, F(1,222) = 5.92, p = .048 (Bonfer-
ple characteristics of these previous studies, may warrant further roni corrected from p = .016). The effect size was typical for single
investigation. candidate-gene studies, with DRD2 variation explaining 2.5% of the
The aim of this study was to examine the association between variance in Extraversion; A1 carriers differed from their counter-
Extraversion and the DRD2 TaqIA/ANKK1 polymorphism in a demo- parts by 1.52 points (approximately 1/3 of a standard deviation) on
graphically diverse sample of healthy adults. Upon receiving ethical the Extraversion scale. Divergent validity was established through
approval from Goldsmiths, University of London, subjects were the lack of an association of DRD2 variation with either Neuroti-
recruited via web- and paper-based advertisements on the student cism, F < 1, ns, or Psychoticism, F(1,222) = 2.36, p = .378 (Bonferroni
intranet and campus notice boards around the Goldsmiths campus. corrected from p = .126). (The trend in the case of Psychoticism was
A total of 224 subjects participated (66% females; age M = 22.13, in the opposite direction to the effect for Extraversion; A1 carriers
SD = 5.39, range = 18–45), for which they received either course had slightly lower scores on Psychoticism.)1
credit or a small financial payment (£5). Recording of ethnographic In order to confirm that these findings were not attributable to
data is potentially important due to variance in frequency over sampling bias and/or violations of parametric test assumptions, a
ethnogeographic groups [23,37]. As such, participants were asked bootstrap resampling analysis was performed on 1000 data-sets
to indicate (a) ethnic identification, (b) place of birth of parent(s), (c)
place of birth of grandparent(s). This data was used to code ethno-
geographic group as follows: Europe (41.5%), Asia (13.4%), Africa 1
Although not a main focus of the present study, we also explored potential
(11.6%), North America (4.0%), and South America (2.7%). Addi- gene–gender interaction effects on our personality traits. No significant interac-
tionally, 26.8% of participants declined to provide ethnographic tions were found (all ps > 0.05), and again the only significant main effect was
information. that of the DRD2 TaqIA/ANKK1 polymorphism on Extraversion, F(1,220) = 6.39,
p = 0.036 (Bonferroni corrected from 0.012), 2 = 0.028. We were therefore unable
Extraversion scores were measured using the Revised EPQ to replicate a recently reported gender-dependent effect of the DRD2 TaqIA/ANKK1
[11], one of the most well-validated and widely used measures polymorphism on trait Neuroticism [40], but were able to demonstrate the gender-
of this trait. The EPQ conceptualisation of Extraversion has been independence of this gene’s association with Extraversion.
236 L.D. Smillie et al. / Neuroscience Letters 468 (2010) 234–237

resampled with replacement from the original data. For techni- of the self-report respondent [4]. Secondly, it is unclear to what
cal reasons it is preferred to bootstrap a t-statistic for the A1+ vs. extent present results using EPQ Extraversion will generalise to
A1− comparison, even though an F-test was reported above; this other Extraversion measures, and whether measures most strongly
is the same statistical test as F = t2 . The observed effect of genotype related to the agentic component of Extraversion will yield the
on Extraversion was shown to be robust, as the mean t-statistic strongest relationship (as some theories predict [9]). Future stud-
over 1000 bootstrap resamples was greater than zero (M = 2.45; 95% ies should therefore examine a wider range of traits and genetic
CIs = 0.51 and 4.39, assuming a t-distribution for the bootstrap dis- markers than was possible in the present study.
tribution). The bootstrapped 95th percentile confidence intervals Given the large number of candidate-gene studies assessing
(based on the bootstrap sample data without making any theoreti- personality in recent years, it is surprising that the relationship
cal assumptions about the bootstrap distribution) were very similar observed in this study has not been reported in healthy subjects
(CIs = 0.53 and 4.34). For Neuroticism, the mean t-statistic over before. There are at least three potential explanations for this
the 1000 bootstrap samples was not reliably different from zero state of affairs. First, as noted earlier, previous published studies
(M = 0.22; 95% CIs = −1.79 and 2.23). Similarly, the mean t-statistic that have assessed both Extraversion and the DRD2 TaqIA/ANKK1
for Psychoticism was also not reliably above zero (M = −1.56; 95% polymorphism have employed highly non-random samples with
CIs = −3.58 and 0.46). For all three traits, permutation resampling limited demographic variation. This potentially biases gene–trait
(in which all trait-allele data pairs were randomly re-paired with- relationships, and calls have been made in the recent literature
out replacement) was used to numerically estimate the p-values for more demographically diverse samples such as we present
for the F-statistics calculated from the actual data, and these were here [39]. Second, although often treated as interchangeable,
very close to those reported earlier based on the theoretical F dis- different measures of Extraversion may place unequal empha-
tributions. These bootstrap and permutation tests gives us further sis on the psychobehavioural features of this trait that relate to
confidence that the traditional statistics reported earlier are robust, dopamine function (as noted earlier). This is a problem that may
and are unlikely to reflect a type-1 error. also arise when Extraversion measures are translated into differ-
To our knowledge this is the first time a significant association ent languages, due to subtle changes in semantic meaning. For
between the DRD2 TaqIA/ANKK1 polymorphism and Extraverted instance, using German translations of alternative measures from
personality has been reported in a sample of healthy adults. The ours, Wacker et al. [40] could not find an effect of the DRD2
finding replicates a study of children in alcoholic families [25] and TaqIA/ANKK1 polymorphism on trait Extraversion, yet did find a
supports dopaminergic models of variation in Extraversion [9]. As gender-dependent effect on Neuroticism which could not be repli-
the A1 allele is associated with fewer D2 receptor binding sites, cated here. This underlines our recommendation for future studies
the positive association with Extraversion plausibly relates to a to provide more comprehensive personality assessment. Third, as
reduction in postsynaptic DA inhibition, resulting in increased DA- is the case with any gene association study, power constraints and
mediated behaviour (e.g., agency and reward-reactivity). Such an measurement error may have masked effects in previous work.
account chimes closely with recent findings in behavioural neu- Future psychogenomic investigations of personality should seek to
roscience. For instance, animal models of reward-sensitivity show replicate and extend the present research, perhaps by examining
that rat strains selected for anticipatory responding for rewards more thoroughly the role of demographic and also environmental
have lower D2 receptor availability [8]. Of course, this is not to variables on gene–personality relationships.
suggest that the A1 allele provides an equivalent model of reward-
reactivity, and further research is required to explicate mediating
brain processes. As several neurochemicals influence dopamine Acknowledgements
transmission (e.g., COMT, MAO, DAT), genomic imaging studies are
needed to assess variation in dopaminergic activity as a function The first author would like to acknowledge financial support
of the DRD2 TaqIA/ANKK1 polymorphism and in relation to trait from the British Academy (PDF/2006/291 and SG-44287) and the
Extraversion. Simple gene–trait associations such as we report here University of London Central Research Fund (AR/CRF/B).
are only first steps in this direction (although, given the high cost
of imaging technologies, they might be considered essential pre-
References
requisites).
Some limitations to this research should be noted and addressed [1] F.G. Ashby, A.M. Isen, A.U. Turken, A neuropsychological theory of positive affect
in future replications of these findings. Although our sample osten- and its influence on cognition, Psychol. Rev. 106 (1999) 529–550.
sibly consisted of healthy adults (i.e., first year psychology students) [2] J. Benjamin, L. Li, C. Patterson, B.D. Greenberg, D.L. Murphy, D.H. Hamer, Pop-
ulation and familial association between the D4 dopamine receptor gene and
this was not confirmed via clinical screening. Therefore, any influ- measures of Novelty Seeking, Nat. Genet. 12 (1996) 81–84.
ence of lifetime mental disorder on our findings could not be [3] E.B. Bookman, R.E. Taylor, L. Adams-Campbell, R.A. Kittles, DRD4 promoter SNPs
controlled for. Similarly, roughly 1/4 of our participants declined and gender effects on Extraversion in African Americans, Mol. Psychiatry 7
(2002) 786–789.
to provide ethnographic information, which limits the extent to [4] P. Borkenau, R. Reiman, A. Angleitner, F. Spinath, Genetic and environmental
which we could control for the potential influence of ethnographic influences on observed personality: evidence from the German observational
variation. However, both of these concerns – along with any other study of adult twins, J. Pers. Soc. Psychol. 80 (2001) 655–668.
[5] M.X. Cohen, J. Young, J.M. Baek, C. Kessler, C. Ranganath, Individual differences
concerns relating to sample heterogeneity – are greatly allevi- in extraversion and dopamine genetics predict neural reward responses, Brain
ated by the results of the bootstrap resampling analysis. This is Res. Cogn. Brain Res. 25 (2005) 851–861.
because the effect of the DRD2 TaqIA/ANKK1 polymorphism on trait [6] A.J. Cooper, L.D. Smillie, C.J. Jackson, A trait conceptualisation of Reward-
Reactivity: psychometric properties of the Appetitive Motivation Scale (AMS),
Extraversion was shown to be reliable over 1000 different data-sets
J. Individ. Dif. 29 (2008) 168–180.
sampled randomly (with replacement) from the original data. Also [7] P.T Costa, R.R. McRae, NEO-PI-R Professional Manual, Psychological Assessment
of potential concern is the measurement of Extraversion: Firstly, it Resources, Odessa, FL, 1992.
[8] J.W. Dalley, T.D. Fryer, L. Brichard, E.S. Robinson, D.E. Theobald, K. Lääne, Y. Peña,
would be ideal to have provided a measure of Extraversion that did
E.R. Murphy, Y. Shah, K. Probst, I. Abakumova, F.I. Aigbirhio, H.K. Richards, Y.
not rely on self-report. On the other hand, the field as a whole has Hong, J.C. Baron, B.J. Everitt, T.W. Robbins, Nucleus accumbens D2/3 recep-
gradually worn down the scepticism often directed toward self- tors predict trait impulsivity and cocaine reinforcement, Science 315 (2007)
report measures. For instance, it has been shown that self-report 1267–1270.
[9] R.A. Depue, P.F. Collins, Neurobiology of the structure of personality: dopamine,
measures of Extraversion strongly predict both peer-report mea- facilitation of incentive motivation, and extraversion, Behav. Brain Sci. 22
sures and ratings by non-acquainted judges viewing video footage (1999) 491–517.
 L.D. Smillie et al. / Neuroscience Letters 468 (2010) 234–237 237

[10] J.L. Eaves, H.J. Eysenck, N.G. Martin, Genes, Culture and Personality, Academic [27] A.D Pickering, J.A. Gray, Dopamine, appetitive reinforcement, and the neu-
Press, London, UK, 1989. ropsychology of human learning: An individual differences approach, in: A.
[11] H.J. Eysenck, S.B.G. Eysenck, The Eysenck Personality Questionnaire-revised, Eliasz, A. Angleitner (Eds.), Advances in Individual Differences Research, PABST
Hodder & Stoughton, Sevenoaks, UK, 1991. Science Publishers, Lengerich, Germany, 2001, pp. 113–149.
[12] J. Fossella, A.E. Green, J. Fan, Evaluation of a structural polymorphism in the [28] A.D. Pickering, L.D. Smillie, The behavioural activation system: challenges and
ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activa- opportunities, in: P.J. Corr (Ed.), The Reinforcement Sensitivity Theory of Per-
tion of executive attention networks, Cogn. Affect. Behav. Neurosci. 6 (2006) sonality, Cambridge University Press, UK, 2008, pp. 120–154.
71–78. [29] R. Plomin, J.C. DeFries, G.E. McClearn, P. McGuffin, Behavioural Genetics, 4th
[13] B. Freeman, N. Smith, C. Curtis, L. Huckett, J. Mill, I.W. Craig, DNA from buccal ed, Worth Publishers, NY, 2001, 449 pp.
swabs recruited by mail: evaluation of storage effects on long-term stability and [30] M. Reuter, J. Hennig, Association of the functional catechol-O-
suitability for multiplex polymerase chain reaction genotyping, Behav. Genet. methyltransferase VAL158MET polymorphism with the personality trait
33 (2003) 67–72. of extraversion Neuroreport 16 (2005) 1135–1138.
[14] D.B. Goldstein, K.R. Ahmadi, M.E. Weale, N.W. Wood, Genome scans and can- [31] M. Reuter, A. Schmitz, P. Corr, J. Hennig, Molecular genetics support Gray’s per-
didate gene approaches in the study of common diseases and variable drug sonality theory: the interaction of COMT and DRD2 polymorphisms predicts the
responses, Trends Genet. 19 (2003) 615–622. behavioural approach system, Int. J. Neuropsychopharmacol. 9 (2006) 155–166.
[15] V.E. Golimbet, M.V. Alfimova, I.K. Gritsenko, R.P. Ebstein, Relationship between [32] T. Ritchie, E.P. Noble, [3H]naloxone binding in the human brain: alcoholism
dopamine system genes and extraversion and novelty seeking, Neurosci. Behav. and the TaqI A D2 dopamine receptor polymorphism, Brain Res. 718 (1996)
Physiol. 37 (2007) 601–606. 193–197.
[16] N.S. Gray, A.D. Pickering, J.A. Gray, Psychoticism and dopamine D2 binding in [33] T. Ritchie, E.P. Noble, Association of seven polymorphisms of the D2 dopamine
the basal ganglia using SPET, Pers. Indiv. Differ. 17 (1994) 431–434. receptor gene with brain receptor-binding characteristics, Neurochem. Res. 28
[17] K.L. Jang, W.J. Livesley, P.A. Vernon, Heritability of the big five personality (2003) 73–78.
dimensions and their facets: a twin study, J. Pers. 64 (1996) 575–591. [34] S. Robinson, S.M. Sandstrom, V.H. Denenberg, R.D. Palmiter, Distinguishing
[18] S.H. Lee, B.J. Ham, Y.H. Cho, S.M. Lee, S.H. Shim, Association study of dopamine whether dopamine regulates liking, wanting, and/or learning about rewards,
receptor D2 TaqI A polymorphism and reward-related personality traits in Behav. Neurosci. 119 (2005) 5–15.
healthy Korean young females, Neuropsychobiology 56 (2007) 146–151. [35] W Shultz, Predictive reward signal of dopamine neurons, J. Neurophysiol. 80
[19] J.C. Loehlin, N.G. Martin, Age changes in personality traits and their heritabilities (1998) 1–27.
throughout the adult years. Evidence from Australian twin registry samples, [36] L.D. Smillie, What is reinforcement sensitivity? Neuroscience paradigms for
Pers. Indiv. Differ. 30 (2002) 1147–1160. approach-avoidance process theories of personality, Eur. J. Pers. 22 (2008)
[20] E.K. Miller, J.D. Cohen, An integrative theory of prefrontal cortex function, Annu. 359–384.
Rev Neurosci. 24 (2001) 167–202. [37] There is extensive data on allele frequency variation in different ethnogeo-
[21] C.M. Miller-Butterworth, J.R. Kaplan, J. Shaffer, B. Devlin, S.B. Manuck, R.E. Fer- graphic groups to be found at: http://alfred.med.yale.edu/alfred/mvograph.
rell, Sequence variation in the primate dopamine transporter gene and its asp?siteuid=SI000144J.
relationship to social dominance, Mol. Biol. Evol. 25 (2008) 18–28. [38] J. Thompson, N. Thomas, A. Singleton, M. Piggott, S. Lloyd, E.K. Perry, C.M. Mor-
[22] J. Mulcrone, R.W. Kerwin, The regional pattern of D4 gene expression in human ris, R.H. Perry, I.N. Ferrier, J.A. Court, D2 dopamine receptor gene (DRD2) Taq1 A
brain, Neurosci. Lett. 234 (1997) 147–150. polymorphism: reduced dopamine D2 receptor binding in the human striatum
[23] M.R. Munafò, Candidate gene studies in the 21st century: meta-analysis, medi- associated with the A1 allele, Pharmacogenetics 7 (1997) 479–484.
ation, moderation, Genes Brain Behav. 5 (Suppl. 1) (2006) 3–8. [39] T. Urata, N. Takahashi, Y. Hakamata, Y. Iijima, N. Kuwahara, N. Ozaki, Y. Ono,
[24] M.R. Munafò, B. Yalcin, S.A. Willis-Owen, J. Flint, Association of the dopamine D4 M. Amano, T. Inada, Gene-gene interaction analysis of personality traits in a
receptor (DRD4) gene and approach-related personality traits: meta-analysis Japanese population using an electrochemical DNA array chip analysis, Neu-
and new data, Biol. Psychiatry 63 (2007) 197–206. rosci. Lett. 414 (2007) 209–212.
[25] T. Ozkaragoz, E.P. Noble, Extraversion. Interaction between D2 dopamine [40] J. Wacker, M. Reuter, J. Hennig, G. Stemmler, Sexually dimorphic link between
receptor polymorphisms and parental alcoholism, Alcohol 22 (2000) dopamine D2 receptor gene and neuroticism-anxiety, Neuroreport 16 (2005)
139–146. 611–614.
[26] A.D. Pickering, The neuropsychology of impulsive antisocial sensation seeking [41] J. Wilt, W. Revelle, Extraversion, in: M. Leary, R. Hoyle (Eds.), Handbook of
personality traits: from dopamine to hippocampal function? in: R.M. Stelmack Individual Differences in Social Behaviour, Guilford, UK, 2009, pp. 27–45.
(Ed.), On the Psychobiology of Personality: Essays in Honour of Marvin Zuck- [42] M. Zuckerman, Psychobiology of Personality, 2nd ed., Cambridge University
erman, Elsevier, UK, 2009, pp. 455–478. Press, UK, 2005, 322 pp.