Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.
Attention Deficit Disorder with Hyperactivity ; diagnostic imaging ; genetics ; pathology ; Brain ; diagnostic imaging ; Cerebellum ; diagnostic imaging ; Child ; Corpus Striatum ; diagnostic imaging ; Female ; Frontal Lobe ; diagnostic imaging ; Genotype ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Minisatellite Repeats ; genetics ; Neural Pathways ; diagnostic imaging ; Oxygen ; blood ; Receptors, Dopamine D4 ; genetics ; metabolism ; Rest

OBJECTIVETo assess the association of cognitive functions with gender, age, education and polymorphism of dopamine receptor D4 (DRD4) gene in healthy adults.

METHODSFour hundred and fifty-five healthy participants have completed 3 cognitive function tests including Tower of Hanoi (TOH), Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT). Peripheral blood samples were collected from all participants, and genomic DNA was extracted according to a standard phenol-chloroform procedure. Rs3758653 in the promoter region of the DRD4 gene was genotyped using Illumina GoldenGate genotyping assay.

RESULTSMales have performed better than females in terms of TOH executive time and TOH total score, but did worse in TOH planning time. Most of the measured cognitive domains were affected by age and education. Cognitive ability has decreased along with increased age and decline of educational years. The polymorphism of rs3758653 has mainly correlated with the TOH executive time. Compared with A allele carriers, G allele carriers did worse in TOH executive time.

CONCLUSIONGender, age, education and the rs3758653 polymorphism of the DRD4 gene play an important role in cognitive functions in healthy adults.

Adolescent ; Adult ; Age Factors ; Cognition ; Education ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D4 ; genetics ; Sex Factors ; Young Adult

OBJECTIVETo investigate the relationship between 5-HTTLPR and/or DRD4 gene polymorphisms and the accident tendentiousness of drivers.

METHODSA case-control study, including 42 patients and 46 controls, were performed using type-A behavior questionnaire and EPQ scale. 5-HTTLPR and DRD4 gene -521 C/T were detected by the PCR-RFLP technique.

RESULTSThe scores of type-A behavior questionnaires, such as TH and TH + CH in exposure group were significantly higher than those in control group (P < 0.05). P and N scores of EPQ questionnaires in exposure group were significantly higher than those in control group, and L score in exposure group was significantly lower than that in control group (P < 0.05 or P < 0.01). There were significant differences in the frequencies of the genotypes and alleles of 5-HTTLPR gene between the cases and the controls (P < 0.05), but there were no significant differences in the frequencies of the genotypes and alleles of DRD4 gene between the two groups (P > 0.05). In the drivers with the accident tendentiousness, P scores in the cases with homozygous genotypes of the S/S in 5-HTTLPR gene were significantly higher than those in the cases with the genotypes of S/L and L/L in 5-HTTLPR gene (P > 0.05). E scores in subjects with homozygous genotypes of the T/T in DRD4 gene were significantly higher than those in subjects with genotypes of the T/C+C/C in DRD4 gene (P > 0.05).

CONCLUSIONThe driver accident tendentiousness may be associated with 5-HTTLPR gene, but not associated with DRD4 gene. The two genes are associated with the type-A behavior and personality characteristics of drivers with accident tendentiousness. However, 5-HTTLPR and DRD4 gene may not have synergism in these behaviors and personality.

Accidents, Traffic ; statistics & numerical data ; Adult ; Automobile Driving ; Case-Control Studies ; Genotype ; Humans ; Male ; Personality ; genetics ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics

OBJECTIVEAttention deficit hyperactivity disorder (ADHD) is one of the most common behavior disorders in childhood and adolescent. The etiology of ADHD is unknown. The aim of this study was to investigate the relationship between each of the 14 polymorphisms in the five candidate genes and ADHD, and between the combination of some polymorphisms in those genes and ADHD, in attempting to examine whether combinations of genotypes would confer a significant susceptibility to ADHD.

METHODSOne hundred and thirty-nine children with ADHD and one hundred and nineteen normal children were enrolled. Eight single nucleotide polymorphisms (SNP) of three candidate genes were examined with PCR and RFLP techniques. 48 bp VNTR in DRD4 gene was examined with PCR, nondenaturing polyacrylamide gel electrophoresis and silver staining. Five microsatellites (MS) of three candidate genes were examined with genotyping. The relationship between the combinations of 12 polymorphisms and ADHD was examined with logistic regression analysis.

RESULTS1.The frequency of 1065T/1065T genotype and the 1065T allele were significantly higher in ADHD children than that in normal controls (P<0.05). The frequency of -48G/-48G genotype of the A-48G polymorphism of DRD1 gene was significantly lower in ADHD children than that in normal controls (P<0.05). 2. A specific combination of three polymorphisms in the two genes showing an association with ADHD gave a prediction level of 77.5%.

CONCLUSIONSThe T1065G polymorphism in the SNAP-25 may be associated with ADHD. The 1065T/1065T genotype and the 1065T allele may be a risk factor for ADHD. The A-48G polymorphism of DRDI may be associated with ADHD. The -48G/-48G genotype may be a protective factor for ADHD. The specific combination of three sites of SNP in SNAP-25 gene and DRDI gene is found and shows an association with ADHD in 12 polymorphisms of the five candidate genes on glutamatergic/dopaminergic pathway.

Adolescent ; Attention Deficit Disorder with Hyperactivity ; genetics ; Child ; Female ; Humans ; Logistic Models ; Male ; Minisatellite Repeats ; Polymorphism, Single Nucleotide ; Receptors, Dopamine D3 ; genetics ; Receptors, Dopamine D4 ; genetics ; Receptors, Dopamine D5 ; genetics ; Receptors, N-Methyl-D-Aspartate ; genetics ; Synaptosomal-Associated Protein 25 ; genetics

OBJECTIVETo study polymorphisms of dopamine D4 receptor (DRD4) in children with primary nocturnal enuresis (PNE) and explore the relationship between DRD4 gene polymorphisms and PNE.

METHODSGenomic DNA was isolated from leukocytes in 86 unrelated children with PNE and in 100 healthy unrelated children (controls). Polymorphisms of DRD4-1240L/S, -616C/G and -521C/T were genotyped by allele-specific primer PCR.

RESULTSThere were significant differences in allele frequencies (x2=8.13, P<0.05) and genotypes frequencies (x2=6.23, P<0.05) of DRD4-616C/G between PNE patients and healthy controls. The frequency of haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T in PNE patients was statistically higher than that in healthy controls (x2=5.88, P<0.05).

CONCLUSIONSThe change of C to G of DRD4-616 may affect the induction and transcription of DRD4 gene. The haplotype LCT consisting of 3 function polymorphic sites DRD4-1240L/S, -616C/G and -521C/T may synergistically inhibit the transcription activity of DRD4 gene. This might lead to a reduction of DRD4 protein expression and cause nocturnal enuresis.

Adolescent ; Child ; Female ; Genotype ; Haplotypes ; Humans ; Male ; Nocturnal Enuresis ; genetics ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.
Temperament ; Receptors, Dopamine D4/*genetics ; *Polymorphism, Genetic ; Personality/*genetics ; Male ; Korea ; Humans ; Female ; Dopamine Plasma Membrane Transport Proteins/*genetics ; Adult

OBJECTIVETo study a possible association between the three functional polymorphisms in the promoter region of dopamine D4 receptor (DRD4) gene and chronic tic disorder.

METHODSGenomic DNA was isolated from the venous blood leukocytes of 84 unrelated patients with chronic tic disorder (Study group) and 100 healthy unrelated individuals (Control group). Polymorphisms of DRD4, 1240L/S, 616C/G and 521C/T, were genotyped by the allele-specific primer (ASP) PCR. Genotype, allele and haplotype frequencies were analysed by SHEsis online.

RESULTSThere were significant differences in both allele and genotype frequencies (chi(2) = 8.419, P < 0.01; chi(2) = 7.860, P < 0.05 respectively) of DRD4-616C/G between the Study and the Control groups. Haplotypic frequencies of LCT (1240L/S, 616C/G, 521C/T) in the Study group were noticeably higher than in the Control group (chi(2) = 6.371, P < 0.05).

CONCLUSIONSThere is an association between the DRD4-616C/G polymorphism and chronic tic disorder. The individuals with haplotype LCT (1240L/S, 616C/G, 521C/T) are susceptible to this disorder.

Adolescent ; Child ; Chronic Disease ; Female ; Gene Frequency ; Genotype ; Haplotypes ; Humans ; Male ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Receptors, Dopamine D4 ; genetics ; Tic Disorders ; genetics

OBJECTIVETo investigate the distribution of genotype and allele frequencies of the dopamine D4 receptor(DRD4) gene exon 3 48 bp variable number of tandem repeats polymorphism in Hunan Han population.

METHODSThe genotype and alleles of 304 healthy persons were examined with polymerase chain reaction, denaturing polyacrylamide gel electrophoresis and silver staining.

RESULTSSeven alleles and twelve genotypes were found. The most common allele was allele 5 with a frequency of 70.6%. There was statistically significant difference in allele distribution between the Hunan Han population and the Han population of other regions such as Shanghai, Beijing and Sichuan in China (P< 0.05). Different allele frequency distributions were observed when compared to other ethnic populations such as Japanese, American, Mexican, and Italian (P< 0.05).

CONCLUSIONThe distributions of allele of DRD4 gene exhibit regional and ethnic heterogeneity.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Minisatellite Repeats ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, Dopamine D4 ; genetics

OBJECTIVETo investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine.

METHODSOne hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA).

RESULTSNo association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03).

CONCLUSIONThe results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.

Adolescent ; Adult ; Catechol O-Methyltransferase ; genetics ; Female ; Humans ; Male ; Monoamine Oxidase ; genetics ; Obsessive-Compulsive Disorder ; drug therapy ; genetics ; Pharmacogenetics ; methods ; Receptor, Serotonin, 5-HT2A ; genetics ; Receptors, Dopamine D2 ; genetics ; Receptors, Dopamine D4 ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo assess the associations between schizophrenia and six functional genes: dopamine D2 receptor gene (DRD2), dopamine D4 receptor gene (DRD4), 5-hydroxytryptamine 2A receptor gene (5-HT2A), 5-HT6 receptor gene (5-HT6), catechol-O-methyltransferase gene (COMT) and dopamine transporter gene (DAT1).

METHODSWith the techniques of Amp-RFLP and Amp-FLP, association analysis was made between schizophrenia and the six genes in 67 schizophrenic patients from Chinese Han population.

RESULTS(1) Neither genotypes nor alleles of DRD2, 5-HT2A, 5-HT6 and COMT gene showed significant differences between patients and controls (P>0.05). (2) Six repeats (6R) in DRD4 gene, the allele of 480 bp and the genotype of 480/520 in DAT1 gene were found to be of significant differences between the two groups (P<0.05). (3) Only one negative association was observed between the 480 bp allele of DAT1 gene and schizophrenia (OR=0.441, 95% CI:0.202-0.963, Z=2.05, P<0.05).

CONCLUSIONThe 480 bp allele of DAT1 gene is negatively associated with schizophrenia in Chinese Han population, which stands for the dopamine hypothesis of schizophrenia.

Adult ; Alleles ; Catechol O-Methyltransferase ; genetics ; DNA ; genetics ; Dopamine Plasma Membrane Transport Proteins ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Membrane Glycoproteins ; Membrane Transport Proteins ; genetics ; Middle Aged ; Nerve Tissue Proteins ; Polymorphism, Restriction Fragment Length ; Receptor, Serotonin, 5-HT2A ; Receptors, Dopamine D2 ; genetics ; Receptors, Dopamine D4 ; Receptors, Serotonin ; genetics ; Schizophrenia ; genetics