DRD4 Genotype Research Articles

Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder

Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes. We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P=0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P=0.027 and 0.006, respectively). We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct.

Additive effects of the dopamine D2 receptor and dopamine transporter genes on the error‐related negativity in young children

The error-related negativity (ERN) is a negative deflection in the event-related potential that occurs approximately 50 ms following the commission of an error at fronto-central electrode sites. Previous models suggest dopamine plays a role in the generation of the ERN. We recorded event-related potentials (ERPs) while 279 children aged 5-7 years completed a simple Go/No-Go task; the ERN was examined in relation to the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes. Results suggest an additive effect of the DRD2 and DAT1 genotype on ERN magnitude such that children with at least one DRD2 A1 allele and children with at least one DAT1 9 allele have an increased (i.e. more negative) ERN. These results provide further support for the involvement of dopamine in the generation of the ERN.

Effects of the DRD4 genotype on neural networks associated with executive functions in children and adolescents

Genetic variants within the dopamine D4 receptor gene (DRD4) are among the strongest and most consistently replicated molecular genetic findings in attentional functioning as well as attention deficit hyperactivity disorder (ADHD). Functionally, the 7-repeat allele of the DRD4-48 base pair repeat gene leads to a sub-sensitive postsynaptic D4 receptor, which is expressed at a particularly high density in the frontal lobes. We used fMRI to investigate the influence of the 7-repeat allele on BOLD (Blood Oxygen Level Dependency) responses in 26 healthy children and adolescents while they performed a combined stimulus-response Incompatibility Task (IC) and a Time Discrimination Task (TT). 7-repeat non-carriers exhibited increased neural activation of the left middle and inferior frontal gyrus (IFG) in the IC and greater cerebellar activation in the TT. Furthermore, the 7-repeat non-carriers exhibited a stronger coupling in haemodynamic responses between left IFG and the anterior cingulate cortex (ACC) during the IC and between cerebellar activation and brain regions that have high DRD4 density, including the IFG and the ACC during the TT. Our results indicate that the 7-repeat allele influences both regional brain activation patterns as well as connectivity patterns between neural networks of incompatibility and temporal processing.

DRD4 VNTR polymorphism and age at onset of severe mental illnesses

A large number of studies has investigated the hypothesis that DRD4 48bp variable number of tandem repeat (VNTR) polymorphism is involved in the etiology of schizophrenia and bipolar disorder. However, the results are inconsistent likely due to genetic and phenotypic heterogeneity. Age at onset (AAO) is considered an important alternate phenotype for genetic investigations of psychiatric disorders. In the present study, the DRD4 VNTR 7 repeat allele (7R) was examined in 477 patients with major psychoses. Age at onset was defined as the age of first psychotic episode for schizophrenia and the age at appearance of first clinically recognized symptoms for the bipolar sample. Our results showed an interaction between sex and DRD4 genotypes among schizophrenia patients (n=203, β=.213, p=.017). On comparing AAO between carriers and non-carriers of the 7R, we observed that females with 7R present had later onset (p=.021). The effect was not observed for males. In the sample with bipolar disorder, we observed significant association between DRD4 7R-genotype and AAO (n=274, β=−.148, p=.012). No interaction was observed between sex and genotypic groups of the bipolar sample. The 7R was associated with early onset of the bipolar illness (p=.028). In summary, our results suggest that the 7R is associated with AAO in both schizophrenia and bipolar disorders. The effect was observed across both sexes in bipolar disorder, but specifically in females for schizophrenia.

Polymorphic variation in the dopamine D4 receptor predicts delay discounting as a function of childhood socioeconomic status: evidence for differential susceptibility

Inconsistent or null findings among studies associating behaviors on the externalizing spectrum--addictions, impulsivity, risk-taking, novelty-seeking traits--with presence of the 7-repeat allele of a common length polymorphism in the gene encoding the dopamine D4 receptor (DRD4) may stem from individuals' variable exposures to prominent environmental moderators (gene × environment interaction). Here, we report that relative preference for immediate, smaller rewards over larger rewards delayed in time (delay discounting), a behavioral endophenotype of impulsive decision-making, varied by interaction of DRD4 genotype with childhood socioeconomic status (SES) among 546 mid-life community volunteers. Independent of age, sex, adulthood SES and IQ, participants who were both raised in families of distinctly low SES (low parental education and occupational grade) and carried the DRD4 7-repeat allele discounted future rewards more steeply than like-reared counterparts of alternate DRD4 genotype. In the absence of childhood socioeconomic disadvantage, however, participants carrying the 7-repeat allele discounted future rewards less steeply. This bidirectional association of DRD4 genotype with temporal discounting, conditioned by participants' early life circumstances, accords with a recently proposed developmental model of gene × environment interaction ('differential susceptibility') that posits genetically modulated sensitivity to both adverse and salubrious environmental influences.

Gene-environment interaction in problematic substance use: interaction betweenDRD4and insecure attachments

To investigate the combined effect of an exon III variable number tandem repeat in the dopamine receptor gene (DRD4) and insecure attachment style on risk for tobacco, cannabis and alcohol use problems in young adulthood. It was hypothesized that (1) individuals with 5, 6, 7 or 8 repeats (labelled 7R+) would be at increased risk for problematic drug use, and (2) risk for drug use would be further increased in individuals with 7R+ repeats who also have a history of insecure parent-child attachment relations. Data were drawn from the Victorian Adolescent Health Cohort Study, an eight-wave longitudinal study of adolescent and young adult development. DRD4 genotypes were available for 839 participants. Risk attributable to the combined effects of 7R+ genotype and insecure attachments was evaluated within a sufficient causes framework under the assumptions of additive interaction using a two-by-four table format with a common reference group. 7R+ alleles were associated with higher tobacco, cannabis and alcohol use (binging). Insecure attachments were associated with higher tobacco and cannabis use but lower alcohol use. For tobacco, there was evidence of interaction for anxious but not avoidant attachments. For cannabis, there was evidence of interaction for both anxious and avoidant attachments, although the interaction for anxious attachments was more substantial. There is no evidence of interaction for binge drinking. Results are consistent with a generic reward deficit hypothesis of drug addiction for which the 7R+ disposition may play a role. Interaction between 7R+ alleles and attachment insecurity may intensify risk for problematic tobacco and cannabis use.

The dopamine D2 receptor gene, perceived parental support, and adolescent loneliness: longitudinal evidence for gene-environment interactions

Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine-related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Associations among the DRD2, sex, parental support, and loneliness were examined in a longitudinal study spanning five annual waves (N = 307). Using Latent Growth Curve Modeling, DRD2 genotype was not directly related to loneliness. Interactions were found between parental support and DRD2 genotype, showing that adolescents with the A2A2 genotype who perceived little support from their parents had the highest baseline levels of loneliness. Adolescents with an A1 allele were not susceptible to the rewarding effect of parental support. The present study is the first to examine the role of the DRD2 genotype in loneliness. Our results contribute to a further understanding of the environmental and genetic basis of loneliness in adolescence.

Resting posterior minus frontal EEG slow oscillations is associated with extraversion and DRD2 genotype

The agency facet of extraversion has been hypothesized to be based on individual differences in dopamine activity. Recent work suggests that resting posterior minus frontal electroencephalographic (EEG) slow oscillations (delta, theta) is both consistently associated with extraversion and sensitive to dopamine D2 receptor antagonist-induced changes in dopaminergic activity. Here we examine for the first time the interrelations between polymorphisms of the dopamine D2 receptor (DRD2) gene (rs1800497 [previously termed TAQ1A], rs1076560, rs1799732 [−141C Ins/Del]), extraversion and resting posterior minus frontal (Pz–Fz) slow oscillations. As predicted, we found an association between DRD2 and resting Pz–Fz slow oscillations in a sample of 141 individuals participating in an eyes-closed resting EEG session. Moreover, we replicated the association between extraversion and Pz–Fz slow oscillations. Our findings strongly suggest that the posterior–frontal distribution of slow oscillations constitutes a useful brain-based intermediate phenotype for investigating the dopaminergic basis of extraversion.

Best friends and alcohol use in adolescence: the role of the dopamine D4 receptor gene

The influence of friends and peers is theoretically one of the most consistent and important factors explaining adolescent alcohol use. However, not all adolescents are equally likely to be influenced by their friends' drinking behaviors. Genetic factors may underlie these inter-individual differences in susceptibility to the drinking behavior of friends. Because the long allele (≥ 7 repeats) of the dopamine D4 receptor (DRD4) gene has been associated with susceptibility to alcohol and alcohol-related cues, we tested whether associations between best friend's and adolescent's alcohol use differed for DRD4 genotypes. A Dutch nationwide sample of 308 adolescents (age 13 at baseline) participated in a prospective, community-based study with five annual waves. A cross-lagged path analysis was carried out in Mplus to examine bi-directional relations between friends' and adolescents' weekly alcohol use (number of drinks). A multi-group approach was applied to test for moderation effects of a 48-base pair variable number of tandem repeats polymorphism in exon 3 of the DRD4 gene. Additionally, with latent growth curve models, it was examined whether the interaction between friends' drinking and DRD4 genotype predicted the development of adolescents' alcohol use. Results showed that both cross-sectionally and longitudinally higher levels of friends' alcohol use resulted in higher levels of adolescents' alcohol consumption over time (and vice versa). No significant moderation of DRD4 genotype was found: Associations between adolescents' and friends' drinking did not differ for adolescent carriers of the DRD4 long allele, when compared with adolescents without the DRD4 long allele. Because this is the first study to examine DRD4 × friends' drinking effects prospectively, replication is essential. Future longitudinal studies, possibly with observational or diary designs, are needed to increase our understanding of the interplay between genetic and environmental risk factors for adolescent alcohol use.

L-DRD4 genotype not associated with sensation seeking, gambling performance and startle reactivity in adolescents: The TRAILS study

The purpose of the present study was to investigate whether a length polymorphism in the dopamine receptor D4 gene (DRD4) was associated with approach related traits in adolescents. Data were used from TRAILS (TRacking Adolescents’ Individual Lives Survey), a population based cohort of Dutch adolescents. Sensation seeking, assessed with personality questionnaires from the participants themselves and their biological father and mother (n=1282) was not associated with DRD4 genotype. Gambling performance (n=591) and startle reactivity (n=432) were not associated with DRD4 genotype either. Explanations for the dissociation might be sought in differences in development of the limbic system and the prefrontal cortex, both with high dopamine receptor D4 densities and both involved in approach related behaviours.

Risky Alcohol Use in Adolescence: The Role of Genetics (DRD2, SLC6A4) and Coping Motives

Drinking to cope (i.e., drinking to forget or alleviate negative feelings) has been found to be associated with adolescents' heavy drinking and alcohol-related problems. Additionally, it is widely accepted that genetic factors are involved in alcohol use and dependence. Studies are only beginning to reveal, however, which specific genotypes are related to drinking behaviors, and it is unknown whether they may interact with coping motives in predicting adolescents' risky drinking. The aim of this study was to examine relationships between the dopamine D2 receptor gene (DRD2) Taq1A polymorphism (rs1800497), a serotonin transporter gene (SLC6A4) polymorphism (5-HTTLPR), coping motives, and adolescents' binge drinking and alcohol-related problems. Participants in this cross-sectional study were 282 Dutch adolescents (mean age 17.4, 47% men) who had consumed alcohol at least once in their life. Coping motives were positively related to both binge drinking and alcohol-related problems, while DRD2 and SLC6A4 genotypes were not. DRD2, but not the SLC6A4 genotype, interacted with coping motives. The link between coping motives and alcohol outcomes was stronger among those carrying the DRD2 risk (A1) allele. This study extends the present literature by providing additional insight into the etiological factors of adolescent drinking behavior. An interaction between a vulnerability gene (DRD2) and a cognitive factor (coping drinking) was found to be related to adolescents' binge drinking and alcohol-related problems.

D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans

ObjectivePre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [123I] FP-CIT SPECT. MethodsFifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [123I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. ResultsSubjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. InterpretationThe present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease.

Differential susceptibility to parenting among African American youths: Testing the DRD4 hypothesis.

To test the differential susceptibility to parenting hypothesis, a 4-wave, randomized prevention design was used to examine the impact of the Strong African American Families program on past-month substance use across 29 months as a function of DRD4 genotype. Youths (N = 337; M age = 11.65 years) were assigned randomly to treatment condition. Those carrying a 7-repeat allele showed greater differential response to intervention vs. control than those with two 4-repeat alleles. Control youths but not treatment youths with a 7-repeat allele reported increases in past-month substance use across the 29-month study period, but this pattern did not emerge for those with the 4-repeat allele. Supporting the differential susceptibility to parenting hypothesis, the results suggest a greater preventive effect for youths carrying a 7-repeat allele, a role for DRD4 in the escalation of substance use during adolescence, and potential for an enhanced understanding of early-onset substance use.

Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder

The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N=66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (ηp(2) ) was used to gauge the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate and >0.14=large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (ηp(2)=0.10) and teachers' (ηp(2)=0.06) ratings than noncarriers, but the latter was marginally significant (P=0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (ηp(2)=0.07) and obsessions-compulsions (ηp(2)=0.08). Findings for maternal ratings of separation anxiety were marginally significant (P=0.08, ηp(2) =0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P=0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples.

The dopamine receptor D4 gene (DRD4) moderates family environmental effects on ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prime candidate for exploration of gene-by-environment interaction (i.e., G x E), particularly in relation to dopamine system genes, due to strong evidence that dopamine systems are dysregulated in the disorder. Using a G x E design, we examined whether the DRD4 promoter 120-bp tandem repeat polymorphism, previously associated with ADHD, moderated the effects of inconsistent parenting and marital conflict on ADHD or Oppositional-Defiant Disorder (ODD). Participants were 548 children with ADHD and non-ADHD comparison children and their parents. Homozygosity for the DRD4 promoter 120-bp tandem repeat insertion allele increased vulnerability for ADHD and ODD only in the presence of inconsistent parenting and appeared to increase susceptibility to the influence of increased child self-blame for marital conflict on ADHD inattention. DRD4 genotypes may interact with these proximal family environmental risk factors by increasing the individual's responsivity to environmental contingencies.

Parent–child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder

The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent–child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother–child (MC) and father–child (FC) dyads. Mothers completed a validated DSM-IV-referenced rating scale. Partial eta-squared (ηp 2) was used to determine the magnitude of group differences: 0.01–0.06 = small, 0.06–0.14 = moderate, and > 0.14 = large. Analyses indicated that children in MC dyads with matched genotypes had the least (7−/7−) and most (7+/7+) severe mother-rated oppositional-defiant (ηp 2 = 0.11) and separation anxiety (ηp 2 = 0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7−/7−) and most (7+/7+) severe obsessive-compulsive behaviors (ηp 2 = 0.19) and tics (ηp 2 = 0.18). Youths whose parents were both noncarriers had less severe tics than peers with at least one parental carrier, and the effect size was large (ηp 2 = 0.16). There was little evidence that noncarrier children were rated more severely by mothers who were carriers versus noncarriers. Transmission Disequilibrium Test analyses provided preliminary evidence for undertransmission of the 2-repeat allele in youths with more severe tics ( p = 0.02). Parent genotype may be helpful in constructing prognostic biomarkers for behavioral disturbances in ASD; however, findings are tentative pending replication with larger, independent samples.

Monitoring antisaccades: inter-individual differences in cognitive control and the influence of COMT and DRD4 genotype variations

Conscious monitoring of behavior is an essential control function for adaptation and learning. Antisaccade performance was investigated in a large sample of young healthy men in two tasks, one that required conscious error monitoring and one that did not. Conscious error monitoring did not lead to changes in error rate between the two tasks, while other antisaccade parameters were significantly modulated. Application of signal detection theory showed a large inter-individual variability in error detection sensitivity: the majority of individuals were unable to monitor antisaccade errors (chance error detection group), while a minority that successfully monitored their errors (non-chance error detection group) were worse in antisaccade performance in both tasks. These results were explained by the hypothesis of two modes of antisaccade processing favored by each one of the two groups: a mode of conscious cortical cognitive control leading to error monitoring, worse performance and no post-error adaptation and a mode of non-conscious subcortical control leading to chance error monitoring, post-error slowing and better performance of the antisaccade task. This hypothesis was corroborated by the results of the genotype analysis. Error-monitoring sensitivity in the non-chance error detection group was modulated by COMT genotype variations that in turn did not have an effect on error rate. On the other hand, DRD4 genotype variations were related to differences in antisaccade error rate while not affecting error-monitoring sensitivity.

A Season-of-Birth/DRD4 Interaction Predicts Maximal Body Mass Index in Women with Bulimia Nervosa

We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene-environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season x DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring-birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall-birth/7R+ group exhibited the highest BMI values (N=17: mean maximal BMI=28.2 kg/m(2) (SE 0.9) vs 25.2 kg/ m(2) (SE 0.3) for all other probands combined (N=171); p=0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs 'other' group (29.9 vs 8.8%, respectively, p=0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.

Dopamine receptor 3(DRD3) polymorphism and risk for migraine

Dopamine has been implicated in the pathogenesis of migraine. We investigated the possible association between the polymorphism 312G>A (rs6280) in the DRD3 gene(essential tremor 1-ETM1- locus, chromosome 3q13) and the risk for migraine and for triggering migraine attacks by alcohol. We studied the frequency of the DRD3 genotypes and allelic variants in 197 patients with migraine and 282 healthy controls using a polymerase chain reaction and MlsI-restriction fragment length polymorphisms method. The frequencies of the DRD3 genotypes and DRD3Gly9 were similar in patients with migraine and controls and were unrelated to the age of onset of migraine, gender, family history of migraine and triggering of migraine attacks by alcohol. The frequency of the genotype DRD3Gly9Gly9 was significantly higher in patients with migraine with aura when compared with patients with migraine without aura, but not with controls. DRD3 genotype and allelic variants were not related to the risk for migraine in Caucasian Spanish people.

Interaction between serotonin 5-HT2A receptor gene and dopamine transporter (DAT1) gene polymorphisms influences personality trait of persistence in Austrian Caucasians

We examined 89 normal volunteers using Cloninger's Temperament and Character Inventory (TCI). Genotyping the 102T/C polymorphism of the serotonin 5HT2A receptor gene and the ser9gly polymorphism in exon 1 of the dopamine D3 receptor (DRD3) gene was performed using PCR-RFLP, whereas the dopamine transporter (DAT1) gene variable number of tandem repeats (VNTR) polymorphism was investigated using PCR amplification followed by electrophoresis in an 8% acrylamide gel with a set of size markers. We found a nominally significant association between gender and harm avoidance (P=0.017; women showing higher scores). There was no association of either DAT1, DRD3 or 5HT2A alleles or genotypes with any dimension of the TCI applying Kruskal–Wallis rank-sum tests. Comparing homozygote and heterozygote DAT1 genotypes, we found higher novelty seeking scores in homozygotes (P=0.054). We further found a nominally significant interaction between DAT1 and 5HT2A homo-/heterozygous gene variants (P=0.0071; DAT1 and 5HT2A genotypes P value of 0.05), performing multivariate analysis of variance (MANOVA). Examining the temperamental TCI subscales, this interaction was associated with persistence (genotypes: P=0.004; homo-/heterozygous gene variants: P=0.0004). We conclude that an interaction between DAT1 and 5HT2A genes might influence the temperamental personality trait persistence.