Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder

ABSTRACT: BACKGROUND: Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 genes and attentional performance before and after medication in children with ADHD. METHODS: Fifty-three medication-naive children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. RESULTS: There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p= 0.005) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p= 0.004) than those with the A/A genotypes CONCLUSIONS: Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.     

Possible association of norepinephrine transporter -3081(A/T) polymorphism with methylphenidate response in attention deficit hyperactivity disorder

Background  

Attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Methylphenidate (MPH) has been shown to block the norepinephrine transporter (NET), and genetic investigations have demonstrated that the norepinephrine transporter gene (SLC6A2) is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 -3081(A/T) and G1287A polymorphisms with MPH response in ADHD.     

Analysis of Association between Norepinephrine Transporter Gene Polymorphisms and Personality Traits of NEO-FFI in a Japanese Population

Objective

Norepinephrine is an important chemical messenger that is involved in mood and stress in humans, and is reabsorbed by the norepinephrine transporter (NET). According to Cloninger''s theory, the noradrenergic system mediates the personality trait of reward dependence. Thus far, although association studies on NET gene polymorphisms and Cloninger''s personality traits have been reported, they yielded inconsistent results. Therefore, in the present study we investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of the NET gene (SLC6A2) are associated with reward dependence-related traits, as assessed by the five-factor model.

Methods

After written informed consent was obtained from participants, the three NET gene polymorphisms were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and personality was assessed by the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) in 270 Japanese university students.

Results

A significant relation was found between the -3081A/T functional promoter polymorphism and NEO-FFI scores: those with the T allele exhibited a lower extraversion (E) score than those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However, there was no correlation between the other NET gene polymorphisms and E score, and no association with other dimensions and these three polymorphisms.

Conclusion

We conclude that the -3081A/T functional polymorphism in the NET gene may affect the extraversion of reward dependence-related traits, as measured by NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study. Further investigations are necessary using the full version of self-rating personality questionnaires.     

Association Study between Norepinephrine Transporter Gene Polymorphism and Schizophrenia in a Korean Population

Objective

We aimed to investigate possible associations between three norepinephrine transporter gene (SLC6A2) single nucleotide polymorphisms (T182C, A3081T, and G1287A) and schizophrenia. Also, we investigated the relationships of those polymorphisms with clinical severity and characteristics of schizophrenia.

Methods

Participants were 220 schizophrenia patients in the acute phase and 167 healthy controls. The genotype, allele frequency, and haplotype of each group were analyzed for T182C, A3081T, and G1287A polymorphisms. Of the 220 schizophrenia patients, 163 patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) and the Korean version of the Calgary depression scale for schizophrenia (K-CDSS) at baseline.

Results

We found no significant differences between the schizophrenia patient group and the control group in genotype distribution or allele frequency of the three tested polymorphisms. Likewise, we could not find any significant differences in genotype or allele frequency by analyzing according to gender. In the haplotype study, no significant association emerged between specific haplotype combinations and schizophrenia. We also found no association between clinical scales (PANSS and K-CDSS) and the studied polymorphisms.

Conclusion

Our results suggest that the investigated polymorphisms of the NET gene are not associated with susceptibility to schizophrenia or its clinical features in a Korean population. However, this study remains significant because it is the first haplotype study to investigate associations between NET gene (SLC6A2) single nucleotide polymorphisms and schizophrenia in a Korean population. Future research with a larger sample size and more genetic markers is needed to replicate our results.     

Biogenetic temperament and character and attention deficit hyperactivity disorder in Korean children

BACKGROUND: The objective of this study was to evaluate the relationship between symptoms of attention deficit hyperactivity disorder (ADHD) and biogenetic temperament, as assessed by the Junior Temperament and Character Inventory (JTCI) in Korean elementary school children. SAMPLING AND METHODS: Five hundred and sixteen elementary school students (254 boys and 262 girls; age range 9-14 years, mean age 11.0 +/- 1.0 years) were studied. The Junior Temperament and Character Inventory, both the self-rating and parent rating scales, the DuPaul ADHD rating scale (ARS-IV) for parents and teachers and the Child Behavior Checklist have been completed by study subjects. Children with high ARS-IV scores (the upper 10th percentile, n = 52) were defined to have ADHD. Fifty-two age- and sex-matched non-ADHD control subjects were selected randomly from a pool of 464 subjects. RESULTS: Inattention and hyperactivity/impulsivity symptoms correlated positively with Novelty Seeking in both children and parent ratings. These symptoms correlated negatively with Persistence, Self-Directedness and Cooperativeness. Novelty Seeking also had significant correlations with attention problems, delinquent behavior, aggressive behavior, externalizing problems and social problems in the Child Behavior Checklist. The ADHD group (n = 52) had higher scores of Novelty Seeking and lower scores of Self-Directedness and Cooperativeness, compared with the control group. CONCLUSIONS: There were significant correlations between ADHD symptoms and Novelty Seeking. Current findings suggest that Novelty Seeking and ADHD share biogenetic backgrounds.     

Correlation of a set of gene variants, life events and personality features on adult ADHD severity

Increasing evidence suggests that symptoms of attention deficit hyperactivity disorder (ADHD) could persist into adult life in a substantial proportion of cases. The aim of the present study was to investigate the impact of (1) adverse events, (2) personality traits and (3) genetic variants chosen on the basis of previous findings and (4) their possible interactions on adult ADHD severity. One hundred and ten individuals diagnosed with adult ADHD were evaluated for occurrence of adverse events in childhood and adulthood, and personality traits by the Temperament and Character Inventory (TCI). Common polymorphisms within a set of nine important candidate genes (SLC6A3, DBH, DRD4, DRD5, HTR2A, CHRNA7, BDNF, PRKG1 and TAAR9) were genotyped for each subject. Life events, personality traits and genetic variations were analyzed in relationship to severity of current symptoms, according to the Brown Attention Deficit Disorder Scale (BADDS). Genetic variations were not significantly associated with severity of ADHD symptoms. Life stressors displayed only a minor effect as compared to personality traits. Indeed, symptoms’ severity was significantly correlated with the temperamental trait of Harm avoidance and the character trait of Self directedness. The results of the present work are in line with previous evidence of a significant correlation between some personality traits and adult ADHD. However, several limitations such as the small sample size and the exclusion of patients with other severe comorbid psychiatric disorders could have influenced the significance of present findings.     

Interactions between child and parent temperament and child behavior problems

OBJECTIVE: Few studies of temperament have tested goodness-of-fit theories of child behavior problems. In this study, we test the hypothesis that interactions between child and parent temperament dimensions predict levels of child psychopathology after controlling for the effects of these dimensions individually. METHODS: Temperament and psychopathology were assessed in a total of 175 children (97 boys, 78 girls; mean age, 10.99 years; SD, 3.66 years) using composite scores from multiple informants of the Junior Temperament and Character Inventory and the Achenbach System of Empirically Based Assessment. Parent temperament was assessed using the adult version of the Temperament and Character Inventory. Statistical analyses included multiple regression procedures to assess the contribution of child-parent temperament interactions after controlling for demographic variables, other types of child psychopathology, and the individual Temperament and Character Inventory and Junior Temperament and Character Inventory dimensions. RESULTS: Interactions between child and parent temperament dimensions predicted higher levels of externalizing, internalizing, and attention problems over and above the effects of these dimensions alone. Among others, the combination of high child novelty seeking with high maternal novelty was associated with child attention problems, whereas the combination of high child harm avoidance and high father harm avoidance was associated with increased child internalizing problems. Many child temperament dimensions also exerted significant effects independently. CONCLUSIONS: The association between a child temperament trait and psychopathology can be dependent upon the temperament of parents. These data lend support to previous theories of the importance of goodness-of-fit.     

Patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder

Aims:  The purpose of the present study was to assess patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder (ADHD) and to investigate the relationship between patterns of temperament and character and the severity of ADHD symptoms.
Methods:  Fifty-one children who met DSM-IV criteria for ADHD and 51 age- and sex-matched healthy comparison subjects completed the Junior Temperament and Character Inventory (JTCI) and the DuPaul's ADHD Rating Scale (ARS-IV).
Results:  Children with ADHD had significantly higher scores of Novelty Seeking and lower scores of Self-directedness in both parents' rating and children's self-rating. In addition, low Self-directedness scores predicted higher total scores of ARS-IV.
Conclusions:  In a clinical sample of Korean children with ADHD, a distinct pattern of temperament and character was found. The current findings suggest that low Self-directedness may be related to the severity of ADHD symptoms.     

Temperament and character factors in a prepubertal and early adolescent bipolar disorder phenotype compared to attention deficit hyperactive and normal controls

OBJECTIVE: To compare temperament and character (T/C) factors in a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP), attention deficit hyperactivity disorder (ADHD), and normal community controls (NC). METHODS: Subjects in PEA-BP (n = 101), ADHD (n = 68), and NC (n = 94) groups were diagnostically assessed with the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia given separately to mothers about their children and to children about themselves. Diagnosis of PEA-BP was defined as Diagnostic and Statistical Manual of Mental Disorders, fourth edition, bipolar disorder (manic or mixed phase) with at least one cardinal symptom of mania (i.e., elation and/or grandiosity) to avoid diagnosing mania by symptoms that overlapped with those for ADHD. The Junior Temperament and Character Inventory (JTCI) was used to measure T/C factors. Separate JTCI data were obtained from mothers about their children and from children about themselves. RESULTS: Parent- and child-reported novelty seeking were significantly higher in PEA-BP than in NC subjects. Novelty seeking was significantly higher in the ADHD group than in the NC group only by parent report. Parent and/or child report showed PEA-BP and ADHD subjects to be significantly less reward-dependent, persistent, self-directed, and cooperative than NC subjects. Parent-reported cooperativeness was significantly lower in PEA-BP than in ADHD subjects. CONCLUSION: These findings are consistent with studies of novelty seeking in adults who had either BP or ADHD and are discussed in relationship to genetic studies of dopamine receptors and novelty seeking.     

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

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

The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits

Arias B, Aguilera M, Moya J, Sáiz PA, Villa H, Ibáñez MI, García‐Portillo MP, Bobes J, Ortet G, Fañanás L. The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety‐related traits. Objective: The aims of this study were to test the individual association of the serotonin transporter gene (SLC6A4), the brain‐derived neurotrophic factor gene (BDNF) and the GABA_Aα₆ receptor subunit gene (GABRA6) with anxiety‐related traits and to explore putative gene–gene interactions in a Spanish healthy sample. Method: A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5‐HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene). Results: Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers (F = 2.96, P = 0.019). In addition, there was a significant gene–gene interaction on HA between the 5‐HTTLPR and Val66Met polymorphisms (F = 3.4, P = 0.009). Conclusion: GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene–gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety‐related traits.     

The role of dopamine transporter (SLC6A3) and dopamine D2 receptor/ankyrin repeat and kinase domain containing 1 (DRD2/ANKK1) gene polymorphisms in personality traits

Variations in personality traits are caused by interactions between multiple genes of small effect and environmental factors. To date, gender- and ethnicity-specific variations in personality have been established. In the present study, we aimed to test: 1) the effects of four polymorphisms of dopamine system genes: ANKK1/DRD2 Taq1A, DRD2 rs6275, SLC6A3 40-bp VNTR and rs27072, on personality traits; 2) whether these effects differ between men and women and between Russians and Tatars. A sample of 652 healthy individuals (222 men and 430 women) of Caucasian origin (233 Russians and 419 Tatars) from Russia was subjected to personality traits assessment with Eysenck Personality Inventory (EPI) and Temperament and Character Inventory-125 (TCI-125). The associations between each personality trait and polymorphisms were assessed with regression models adjusted for gender and ethnicity. There were significant effects of ANKK1/DRD2 Taq1A on Neuroticism (p = 0.016) and of SLC6A3 rs27072 on Persistence (p = 0.021) in both genders. The association between ANKK1/DRD2 Taq1A A2/A2-genotype and higher Novelty Seeking and lower Reward Dependence was shown in men only (p for gender interaction = 0.018). In women only, there was a significant association between SLC6A3 10R*G-haplotype and higher Persistence (p = 0.002). Our findings provide evidence for a modifying effect of gender on the associations between dopamine system genes and approach-related traits (in men) and Persistence (in women).     

The 5-HT2A -1438 A/G and 5-HTTLPR polymorphisms and personality dimensions in adolescent anorexia nervosa: association study

Disturbances of serotonergic neurotransmission and temperamental vulnerability have both been implicated in the pathogenesis of anorexia nervosa (AN). We genotyped the -1438 A/G polymorphism in the 5-HT2A receptor gene and serotonin transporter linked-polymorphic region (5-HTTLPR) in 132 adolescent subjects with AN and in 93 healthy controls. Personality dimensions in AN patients were assessed with the Temperament and Character Inventory. In a case-control model, we tested the hypothesis that these genetic variants confer susceptibility to AN. We also analyzed whether two polymorphisms show association with temperamental and character traits. No significant difference was found in the 5-HTTLPR frequency between AN patients and controls; however, there was a statistical trend towards a higher frequency of the A allele of the -1438 A/G polymorphism in patients than in controls (64.9 vs. 56.7%, chi2 test, p=0.08). We also found a significant association between the A allele of this polymorphism and two temperamental traits. Patients homozygous for the A allele showed lower reward dependence than G/G homozygotes, and A/A homozygotes showed lower harm avoidance than heterozygotes. Low reward dependence and harm avoidance were more characteristic of the restrictive-type AN than of other subtypes of the disorder. No association of 5-HTTLPR with personality dimensions in AN patients was observed. Our results may suggest that the A allele of the -1438 A/G polymorphism confers some genetic risk for adolescent AN patients, especially in those with personality traits, which are typical of the restrictive-type AN.     

Association study between reward dependence temperament and a polymorphism in the phenylethanolamine N-methyltransferase gene in a Japanese female population

Cloninger's theory is that specific dimensions of temperament are associated with single neurotransmitter systems, and it is based on neurophysiologic and genetic approaches to the human traits. It suggests that overexpression of temperament could cause psychiatric illness. Based on this theory, we examined the correlation between reward dependence (RD) trait, measured with the Temperament and Character Inventory, and 5 polymorphisms in genes of norepinephrine pathways, ADRB1, COMT, PNMT, SLC18A1, and SLC6A2, in 85 Japanese female nursing students. We found that rs3764351 in PNMT was significantly associated with RD on Fisher's exact test (P = .029, P_corr = .236). When haplotype analysis was performed for rs3764351 and rs876493 polymorphisms in the 5′ flanking region of PNMT, 3 haplotypes were identified. Rs3764351 itself appeared to be correlated with RD in the present study of a specific population, although we could not demonstrate an association between RD and any of the haplotypes. Our findings have implications for the understanding of temperament using neurophysiologic approaches.     

Temperament in the developmental course: a longitudinal comparison of New York Longitudinal Study-derived dimensions with the Junior Temperament and Character Inventory

OBJECTIVE: Despite theoretical discrepancies between different concepts of temperament, some core dimensions are thought to be common to the various models. We compared temperamental traits derived from the New York Longitudinal Study (NYLS) model and the Cloninger dimensions in the developmental course and investigated the associations of temperament with sex as well as with obstetric risks or psychosocial risks present at birth. METHODS: Participants were 151 boys and 157 girls born at differing degrees of obstetric and psychosocial risk from a longitudinal study on a high-risk community sample. In infancy and childhood, NYLS-derived temperamental characteristics were assessed by a highly structured parent interview and standardized behavioral observations. At age 15 years, the Junior Temperament and Character Inventory/12-18 was administered. RESULTS: Moderate correlations were found between Junior Temperament and Character Inventory scales in adolescence and NYLS-derived factors in childhood. The psychosocial risk load seemed to influence the expression of novelty seeking or corresponding NYLS-derived factors, whereas the obstetric risks did not contribute to variation in temperament. Our findings further support highly sex-specific gene x environment interactions on temperament in the developmental course. CONCLUSION: The content of our NYLS-derived factors and the specific type of association across different temperament constructs fit into the increasing consensus regarding a small number of higher-order temperamental traits.     

The reliability and validity of the junior temperament and character inventory

The purpose of this study was to evaluate the reliability and validity of the Junior Temperament and Character Inventory (Junior TCI), a child and adolescent version of the Adult Temperament and Character Inventory (TCI), which is based on Cloninger’s biosocial model of personality. The Junior TCI was translated into Korean and administered to 663 Korean middle school students (male/female, 360/303; age, 13.3 ± 1.0 years) and their parents (mother/father, 444/84). Internal consistency was calculated by Cronbach α. A test-retest study of the Junior TCI was conducted across a 3-month interval with 97 subjects. Factor analyses for the temperament and character dimensions were performed using principal component analysis, rotating factors by Promax. Cronbach α values of the Junior TCI scales ranged from .48 to .80 for the temperament scales and from .64 to .68 for the character scales. Test-retest correlations ranged from .62 to .85 for the temperament scales and from .76 to .79 for the character scales. Principal component factor analyses showed three factors out of four temperament scales (Harm Avoidance 1 to 4; Novelty Seeking 1 to 4; Persistence; and Reward Dependence 1, 3, 4) and three factors out of three character scales (Self-Directedness 1 to 5; Cooperativeness 1 to 5; and Self-Transcendence 1 to 3) that were similar to factor structures of adult versions of the TCI. Explorative factor analysis with a condition of eigenvalue greater than 1 produced six factors, as compared to seven factors extracted in Cloninger’s original report of the adult TCI. In conclusion, this was the first study to tests and report detailed psychometric properties of the Junior TCI. The current study confirms that the Junior TCI has satisfactory psychometric properties for the use in child and adolescent populations and reflects Cloninger’s biosocial model of personality.     

Do the dimensions of the temperament and character inventory map a simple genetic architecture? Evidence from molecular genetics and factor analysis

OBJECTIVE: It has been reported that the human temperament dimensions of novelty seeking and harm avoidance are associated with polymorphisms in the D(4) dopamine receptor gene (D4DR) and the serotonin-transporter-linked promoter region (5-HTTLPR), respectively. Although these findings are consistent with Cloninger's hypothesized psychobiological model of temperament and character, many studies failed to replicate these findings. In the present study the authors tested whether the psychobiological model taps the genetic architecture of personality by exploring associations between these candidate genes and the dimensions of the Temperament and Character Inventory and by examining its phenotypic structure. METHOD: Of the 946 male and female participants in the Baltimore Longitudinal Study of Aging to whom the Temperament and Character Inventory was administered, 587 were genotyped for a polymorphism with a 48-base-pair repeat in the D4DR gene and 425 were genotyped for a 44-base-pair insertion or deletion in the 5-HTTLPR polymorphism. RESULTS: There was no significant association between D4DR polymorphisms and novelty seeking. The authors also failed to find an association between 5-HTTLPR polymorphisms and harm avoidance. The factor structure of the Temperament and Character Inventory did not reveal the hypothesized phenotypic structure. CONCLUSIONS: This investigation produced no support for the temperament-character model at either the biological or psychological level.     

No evidence for an association between the T102C and 1438 G/A polymorphisms of the serotonin 2A receptor gene in attention deficit/hyperactivity disorder in a Turkish population

Disturbances in the serotonergic neurotransmission system have been implicated in the etiology of attention deficit/hyperactivity disorder (ADHD). As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We previously demonstrated that the polymorphisms of the serotonin transporter gene promoter and regions of variable number of tandem repeats were involved in the pathogenesis of ADHD. The purpose of this study was to examine the relationship between ADHD and two polymorphisms (T102C and 1438 G/A) in the 5-HT2A gene in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 70 patients with ADHD and in 100 healthy controls. There was no significant difference between the frequencies of the T, C, G and A alleles of both groups. No association was found between the studied polymorphisms of the 5-HT2A gene and ADHD in this sample consisting of Turkish children. Overall, our results suggest that the investigated 5-HT2A polymorphisms are not major susceptibility factors in the etiology of ADHD.     

Psychotherapy as a treatment modality for psychiatric disorders: Perceptions of general public of Karachi, Pakistan

Background

Attention deficit hyperactivity disorder (ADHD) is a complex neurobehavioral disorder. The dopamine transporter gene (DAT1/SLC6A3) has been considered a good candidate for ADHD. Most association studies with ADHD have investigated the 40-base-pair variable number of tandem repeat (VNTR) polymorphism in the 3'-untranslated region of DAT1. Only few studies have reported association between promoter polymorphisms of the gene and ADHD.

Methods

To investigate the association between the polymorphisms -67A/T (rs2975226) and -839C/T (rs2652511) in promoter region of DAT1 in ADHD, two samples of ADHD patients from the UK (n = 197) and Taiwan (n = 212) were genotyped, and analysed using within-family transmission disequilibrium test (TDT).

Results

A significant association was found between the T allele of promoter polymorphism -67A/T and ADHD in the Taiwanese population (P = 0.001). There was also evidence of preferential transmission of the T allele of -67A/T polymorphism in combined samples from the UK and Taiwan (P = 0.003). No association was detected between the -839C/T polymorphism and ADHD in either of the two populations.

Conclusion

The finding suggests that genetic variation in the promoter region of DAT1 may be a risk factor in the development of ADHD.