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Objective: Studies to reduce the heterogeneity of attention-deficit/hyperactivity disorder (ADHD) have increased interest in the concept of sluggish cognitive tempo (SCT). The aim of this study was to investigate if the prevalence of two variable-number tandem repeats (VNTRs) located within the 3′-untranslated region of the DAT1 gene and in exon 3 of the dopamine D4 receptor (DRD4) gene differ among four groups (31 subjects with SCT but no ADHD, 146 individuals with ADHD but no SCT, 67 subjects with SCT + ADHD, and 92 healthy controls). Methods: We compared the sociodemographic profiles, neurocognitive domains, and prevalence of two VNTRs in SCT and ADHD subjects versus typically developing (TD) controls. Results: The SCT without ADHD group had a higher proportion of females and lower parental educational attainment. Subjects in this group performed worse on neuropsychological tests, except for psychomotor speed and commission errors, compared to controls. However, the ADHD without SCT group performed significantly worse on all neuropsychological domains than controls. We found that 4R homozygosity for the DRD4 gene was most prevalent in the ADHD without SCT group. The SCT without ADHD group had the highest 7R allele frequency, differing significantly from the ADHD without SCT group. Conclusion: The 7R allele of DRD4 gene was found to be significantly more prevalent in SCT cases than in ADHD cases. No substantial neuropsychological differences were found between SCT and ADHD subjects.
Subject(s)
Humans , Female , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/genetics , Cognition , Minisatellite Repeats/genetics , Receptors, Dopamine D4/genetics , GenotypeABSTRACT
Objective: To explore the relationship between aggressive behavior, dopamine receptor D4 (DRD4) exon III 48 bp variable number tandem repeat (VNTR) and personality characteristics in patients with bipolar disorder. Methods: From January 2015 to December 2018, 173 patients with bipolar disorder were selected from Shanghai Changning Mental Health Center, Shanghai Jing'an Mental Health Center, Shanghai Xuhui Mental Health Center, and Shanghai Jiading Central Hospital. According to the score of Modified Overt Aggression scale (MOAS), 173 patients were divided into aggressive behavior group (research group) and non-aggressive behavior group (control group). General survey and the temperament and personality questionnaire (Temperature and Character Inventory, TCI) were carried out, respectively. The polymorphism of DRD4 gene were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. Genetic equilibrium test of genotype Hardy-Weinberg and the difference of genotype frequency between the two groups were analyzed by using SHEsis software. The relationship between aggression behavior and DRD4 gene polymorphism and personality traits in bipolar disorder patients was analyzed by χ2 test and t test. Results: There was no significant difference in the general data between research group and control group (P>0.05). Six alleles and nine genotypes of DRD4 exon III 48 bp VNTR were detected. The most common alleles in the two groups were four repeat alleles. There were statistical differences in the frequency distribution of genotypes and alleles of DRD4 exon III 48 bp VNTR between the two groups (P=0.040, P=0.018). The scores of novelty seeking and harm avoidance in the research group were higher than those in the control group (P=0.026, P=0.000), while the scores of cooperativeness and self-directedness were lower than those in the control group (both P=0.000). Patients with long repeat alleles had significantly higher scores in novelty seeking and harm avoidance, and lower scores in cooperativeness, compared with patients with short repeat alleles (P=0.000, P=0.006, P=0.038). Conclusion: Aggressive behavior in patients with bipolar disorder may be associated with DRD4 exon III 48 bp VNTR. In bipolar disorder, patients with aggressive behavior have unique personality characteristics in impulsiving, novelty-seeking, exploring, being afraid of uncertainty, revengeful, behaving himself and so on. Patients with long repeat alleles have more significant personality abnormalities.
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Objective To investigate the correlation of methylation status in DA T1 and DRD4 genes and severity of clinical manifestations in ADHD patients.Methods One hundrd eleven DSM-Ⅳ defined ADHD patients were enrolled in this study and the demographic data were collected.Clinical symptoms were also assessed by Attention Deficit Hyperactivity Disorder Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) and self-developed Oppositional Defiant Disorder (ODD) rating scale.Bisulfite genomic sequencing (BGS) was used to detect the methylation status of every CpG site in DA T1 and DRD4 promoter CpG island in peripheral venous blood.Results The DNA methylation level in total CpG island for DA T1 was higher in individuals without depression,anxiety or ADHD family history compared to individuals with above family histories (P＜0.05).The differences on methylation levels for DA T1 and DRD4 were not significant between high and low ADHD-RS-Ⅳ total score (≤30 vs.＞30),ADHD-RS-Ⅳ inattention score (≤ 17 vs.＞17),and ADHD-RS-Ⅳ hyperactivity/impulsivity score (≤13 vs.＞13) subgroups (all P＜0.05).The methylation levels in total CpG island in DA T1 was higher in individuals whose ODD score were ＜9 compared to those whose ODD score were ≥9 (P＜0.05).Conclusions Methylation status of CpG island in DAT1 may influence the severity of oppositional defiant symptom in ADHD patients,which is correlated with depression,anxiety and ADHD family histories.
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Objective To explore the difference of methylation status of CpG island in promoter re?gion of DAT1 and DRD4 genes between children with attention deficit hyperactivity disorder ( ADHD) and normal controls,and further understand the pathogenesis of ADHD from a epigenetics point of view. Methods 111 ADHD patients and 118 normal controls were enrolled in the present study. The demographic data and peripheral venous blood were collected from both groups. Bisulfite genomic sequencing ( BGS) was used to confirm the methylation status of every CpG site in promoter region of DAT1 and DRD4 genes. Results No significant differences were found between ADHD patients and normal controls on percentage of methylated CpG sites in total CpG islands for both DAT1 and DRD4 (P>0.05) . However,the percentage of methylation in No. 17 CpG site for DAT1 and No. 8 CpG site for DRD4 was higher in ADHD patients ( 23. 42% and 64.86% respectively)compared with that in normal controls(11.86% and 47.46% respectively)(P<0.05).In all samples,the percentage of methylated CpG site in total CpG island for DAT1 was higher in males com?pared with that in females(P<0.05),whereas that for DRD4 was higher in females compared with that in males (P<0.05);the same gender difference on methylation level for DAT1 was also found in ADHD patients and for DRD4 in normal controls(P<0.05) . In all samples and in ADHD patients,percentage of methylated CpG site in total CpG island for DAT1 was higher in individuals over 7 years old compared with that in indi?viduals younger than or equal to 7 years old(P<0.05). Conclusions Methylation status of CpG island in DAT1 and DRD4 genes promoter region might correlate with ADHD susceptibility.Methylation status of CpG island in DAT1 and DRD4 genes show differences in different age span and sex.
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0.05). After dividing the patients into early-onset and late-onset subgroups, there were significant differences of DRD4 genotype and allele frequency between early-onset patients and controls (P0.05). Conclusion The results suggested that the polymorphism of DRD4 receptor gene may be associated with early-onset OCD. The 3/4 genetype may be the risk factor of early-onset OCD. Early-onset and late-onset OCD may have different etiology.
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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.
Subject(s)
Male , Humans , Female , Adult , Temperament , Receptors, Dopamine D4/genetics , Polymorphism, Genetic , Personality/genetics , Korea , Dopamine Plasma Membrane Transport Proteins/geneticsABSTRACT
OBJECTIVE: The definite causes of obsessive-compulsive disorder (OCD) are still unknown. Evidences from familial, twin and segregation studies support the role of a genetic component in the etiology of OCD. There are growing evidences that OCD has specific neurochemical and neuroanatomical basis. It has been shown that serotonergic neurons play the predominant pathophysiological role in OCD. Recently, it has also been proposed that neurotransmitters other than serotonin play a role in the pathophysiology of OCD, and a series of studies have provided evidence that dopamine is involved in some OCD patients. Therefore, the aims of this study were to investigate the association between dopamine receptor D4 (DRD4) and OCD. METHODS: One hundred and fifteen OCD patients and 160 normal controls participated in this study. Genomic DNA was extracted from their blood. The genotypes and allele frequencies of the DRD4 polymorphism between OCD group and control group were compared. OCD patients were classified into early onset group (age of onset or =17) according to their onset age and the genotype and allele frequency were compared between two groups. Using principal component analysis, we had already derived 4 factors from 13 main contents of YBOCS checklist in the previous study and in this study, we investigated the association between these three factors and DRD4 genotypes. RESULTS: In this case-control study, we could find that the L-genotype frequencies of DRD4 were significantly higher in OCD than in normal control groups (chi2 test, p=0.04). There were no difference in genotype frequencies between early onset OCD group and late onset OCD group. In OCD group, patients with L-genotype had higher scores for the religious/somatic factor than the other groups (t test, p=0.009). CONCLUSIONS: The L-genotype of DRD4 may have negative effects on the development of OCD and religious/somatic factor of the obsessive-compulsive symptoms.