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Objective To explore the factors affecting methylphenidate (MHP)efficacy in children with attention deficit hyperactivity disorder (ADHD). Methods One hunadard eleven DSM-Ⅳ defined ADHD patients were enrolled for 6 weeks systemic MHP titration treatmnet. ADHD Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) were applied as index of clinical efficacy, and Continuous Performance Task (CPT) as index of cognition efficacy. Determining potential influential factors was analyzed on MPH efficacy including demographic,baseline clinical symptoms and cognitive factors. Results Sixty-five (59.1%) were defined as responders and 45 (40.9%) as non-reponders to MHP, respectively. CPT which were conducted in 87 patient showed that 35 (40.2%) were defined as responders on commission errors, 31 (35.6%) on omission errors and 10 (11.5%) on reaction time. Logistic analysis revealed two potential influential factors that predicted better clinical efficacy (P<0.05): better parental relationship (OR=3.516, 95% CI: 1.087~11.375) and baseline ADHD-RS-Ⅳ score above 35 points (OR=3.075, 95%CI: 1.131~8.359). Higher IQ score was the potential influential factor that predicted better commission errors efficacy (OR=1.085, 95%CI: 1.013~1.162) and omission errors efficacy (OR=1.078, 95%CI: 1.008~1.153). Conclusion MHP efficacy may result in better outcomes in children with ADHD who have higher baseline ADHD-RS-Ⅳ score, poorer baseline CPT result, younger onset age, higher IQ and better parental relationship.
ABSTRACT
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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Objective To investigate the influence of hyperactivity, Stereotyped behaviors , self-injury and irritabili?ty on parenting stress and emotions of the caregivers for patients with pervasive developmental disorders (PDDs). Methods Abnormal behaviors during last month were assessed in 138 PDDs patients by using Aberrant Behavior Checklist (ABC) and Conners Index of Hyperactivity (CIH). The parenting stress and the emotional state of the patients’parents were evalu?ated by the Caregiver Strain Questionnaire (CGSQ) and Hospital Anxiety and Depression Scale (HAD), respectively. Re?sults Anxiety, depression and combination of anxiety and depression were present in 6.2%, 17.8%and 29.5%of PDDs caregivers, respectively. The partial correlation analysis showed that CGSQ score of patients’parents positively correlated with CIH score (r=0.201, P=0.023) and stereotyped act (r=0.189, P=0.033) of the patients, and negatively correlated with stereotyped speech (r=-0.219, P=0.013). The anxious mood of parents positively correlated with stereotyped act (r=0.206, P=0.021). Conclusions Anxiety and depression are common in caregivers of PDDs. Except for stereotyped speech, aber?rant behaviors of the PDDs increase parenting stress and worsen anxious mood of caregivers.
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Objective To investigate mRNA expression level changes of dopamine transporter gene (DAT1) and dopamine receptor gene(DRD4) in attention deficit hyperactivity disorder(ADHD) children's peripheral blood before and after methylphenidate treatment,and to explore associations between the mRNA expression level and symptom severity,as well as methylphenidate response.Methods Forty five ADHD children by DSM-Ⅳ diagnostic criteria,aged six to fifteen years old participated in a six-week drug titration treatment of metbylphenidate.ADHD-RS-Ⅳ Home Version, WCST and VCPT were used to evaluate the ADHD clinical symptoms and cognitive functions.RNA Simple Total RNA Kit was used to extract the total RNA.After reverse transcription, the obtained c-DNA was used in the following qRT-PCR to evaluate relative mRNA expression of the candidate genges before and after medication.Results The DRD4 mRNA relative expression level after taking methylphenidate was significantly higher than that before methylphenidate treatment (0.23 ± 0.23 vs 0.16± 0.18, P =0.041).There was no significant difference between DAT1 mRNA relative expression level before (0.43 ± 0.40) and after (0.43±0.40) methylphenidate treatment.No significant difference was found on eitber basal DAT1/DRD4 mRNA expression or fold change of DAT1/DRD4 mRNA expression before and after medication between methylphenidate treatment responders and non-responders groups.There was a positively significant correlation between baseline DRD4 mRNA relative expression level and erroneous T score of CPT(r=0.424, P=0.025) , however, no other statistically significant correlation was found between basal DRD4 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level, CPT missing T score, and CPT reaction T sco~ (all P＞0.05).There was also no statistical significant correlation between basal DAT1 mRNA relative expression level and ADHD-RS-Ⅳ total score,WCST conceptual level,and CPT T scores(all P＞0.05).Conclusion DRD4 gene function may be increased after methylphenidate treatment and play an important role in impulsivity behavior of ADHD.Therefore, DRD4 mRNA expression level might be a biomarker for ADHD diagnosis and a predicting indicator of drug efficacy.