The Clinical Manifestation, Executive Dysfunction, and Caregiver Strain in Subthreshold Attention-Deficit/Hyperactivity Disorder

Objective@#Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a “morbid condition” which also needs medical attention. @*Methods@#The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire. @*Results@#For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC. @*Conclusion@#Our present findings supported the suggestion of subthreshold ADHD as “morbid condition,” which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent

Objective@#Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. @*Methods@#The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. @*Results@#The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. @*Conclusion@#The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

A review of family and parenting interventions in children with attention-deficit/hyperactivity disorder / 中国心理卫生杂志

Family environment plays an important part of the occurrence,development and outcome of attention-deficit/hyperactivity disorder (ADHD).Family and parenting interventions focus on the inter environment,aiming at forming an effective behavioral management,a better communication strategy,which will be conductive for child's symptoms as well as functions.Parents'emotion and self-efficacy as well as family functioning will be affected also.Common family and parenting skills include parent training and systematic family therapy,which respectively focus on behavior management and the whole family in view of system.The Multimodal Treatment Study of Children with ADHD (MTA) may have potential effects compared with single medical treatment and behavioral treatment.In China,parent training and structural family therapy have been proved to be effective.However,further consideration and experiments are necessary,especially on the long-time ending and individual management.

Characteristics of attention during visual search in adults with attention-deficit/hyperactivity disorder / 中国心理卫生杂志

Objective:To explore the characteristics of attention during visual search tasks in adults with attention-deficit/hyperactivity disorder (ADHD).Methods:Totally 45 adult patients with ADHD who met the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-IV) and 44 healthy controls matched with age,gender and IQ were selected.The reaction time and accuracy rate of two groups were compared under visual search tasks of low and high visual working memory load.Results:The reaction time was longer in patients with ADHD than in the healthy controls in both low-load task [(823 ± 144) ms vs.(754 ± 123) ms,P ＜ 0.01] and highload task [(912 ± 163) ms vs.(851 ± 162) ms,P ＜ 0.01].Compared with the performance in low load task,the search reaction time was longer in high load task [ADHD group:(823 ± 144) ms vs.(912 ± 163) ms,P ＜ 0.01;control group:(754 ± 123) ms vs.(851 ± 162) ms,P ＜0.01] and the accuracy rate was lower during high load task than low load task[ADHD group:(95.9 ±4.3)％ vs.(91.2 ± 14.29)％;control group:(95.8 ± 4.2)％ vs.(94.4 ±4.9) ％,P ＜ 0.01] in both ADHD and control groups.Conclusion:The results suggest impairment in top-down attentional control in ADHD adults.When the visual working memory load is increasing,ADHD patients allocate more working memory resources on storing the target representation and less resources on visual attention,so the search efficiency may be influenced.

Executive function performances in adults with attention deficit hyperactivity disorder / 中国神经精神疾病杂志

Objective To explore the executive function profiles in adults with attention deficit hyperactivity disorder(ADHD)in a Chinese sample population. Methods We identified 68 outpatients fulfilling the diagnostic criteria for ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-IV(DSM-IV)and 74 normal adults.All subjects completed clinical interview, Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Cambridge Neuropsychological Test Automated Battery (CANTAB). Results ADHD group had higher scores in all factors of BRIEF-A questionnaire compared with normal control (P<0.01). ADHD group had a higher score in SWM strategy score [(30.84±5.58)vs.(28.80±5.85), t=2.056,P=0.042]compared with control group. Compared with control group, ADHD group had a lower score in RVP total hits [37(33,41.75) vs.3(37,48), Z=-3.184,P<0.01]. Total correct rejections[(508(497.5,518)vs. 516(503,529.5),Z=-2.229,P=0.0260)]were significantly lower,while RVP total misses were significantly higher [(17 (12.25,21)vs.12(7,20),Z=2.293,P=0.022)].ADHD-RS-IV attention deficit score was positively correlated with SWM strategy while RVP total misses were negatively correlated with RVP total hits and RVP correct rejections.Working memory score in BRIEF-A was significantly correlated with the SWM strategy,RVP total hits, RVP total correct rejections and RVP probable of hit as well as RVP total misses. Conclusion Adults with ADHD have executive functioning deficits which is correlated with ADHD core symptoms.

The role of CLOCK gene and sleep problems on inhibition in male children with attention-deficit/hyperac-tivity disorder / 中国神经精神疾病杂志

Objective To explore the correlation between circadian clock gene clock circadian regulator (CLOCK) and attention-deficit/hyperactivity disorder (ADHD) and the role of CLOCK and sleep problems on inhibition in male children with ADHD. Methods Two single nucleotide polymorphisms (SNPs) of CLOCK were genotyped in 854 male ADHD children and 320 male controls. Sleep problems were assessed using parent symptom questionnaire. In ADHD cases, the main effects and interaction of CLOCK SNPs and sleep problems on inhibition assessed by using Stroop Color and Word Test, were analyzed using the analysis of covariance (ANCOVA). Results No significant differences of allele and genotype frequencies were found for rs6832769 and rs11932595 in all case-control groups (P>0.05). In ADHD cas?es, the main effects of rs6832769 and rs11932595 genotypes and sleep problems on inhibition were not significant (P>0.05). However, the interaction of rs6832769 genotype and sleep problems was significant (F=6.71, P=0.01). When ac?companied with sleep problems, ADHD cases carrying the AA&AG genotype showed the longest time of word interfer? ence (F=6.63, P=0.01). Conclusions Inhibition of male ADHD children can be modulated by the interaction of CLOCK rs6832769 and sleep problems.

Association between LPHN3 and attention-deficit/hyperactivity disorder in Chinese Han subjects / 中国心理卫生杂志

Objective:To investigate the association between LPHN3 andattention-deficit/hyperactivity disor-der(ADHD)in Chinese Han children.Methods:Based on the Diagnostic and Statistical Manual of Mental Disor-ders,Fourth Edition (DSM-IV)diagnosis criteria,921 normal controls and 1052 ADHD children were included in the study.The Clinical Diagnostic Interview Scale (CDIS )was used to assess symptoms and ADHD sub-types.ADHD was divided into three subtypes,namely ADHD inattentive type (ADHD-I),ADHD hyperactive-im-pulsive type (ADHD-HI),and ADHD combined type (ADHD-C).The ADHD rating-scale was used to assess ADHD symptoms.Including inattentive symptoms,hyperactive symptoms,impulsive symptoms and ADHD total symptoms.Three single nucleotide polymorphisms (SNPs)of LPHN3 were genotyped.Case-control studies were conducted to investigate the association of each SNP with the ADHD and the subgroups using chi-square test.Results:rs11131347 was associated with ADHD P <0.05,OR =0.86(0.76 -0.98)],but the difference didn't survive significance after corrections,The frequency of minor allele C in cases and control was0.409 vs.0.445.For different genders,rs11131347 was significantly associated with ADHD boys [P <0.05,OR =0.82(0.71 -0.96)], The frequency of minor allele C in cases and control was0.402 vs.0.449.For different subtypes,rs11131347 was associated with ADHD-C [P <0.05,OR =0.85(0.74 -0.98)]and ADHD-C boys[P <0.05,OR =0.82(0.70 -0.97)],but none of the difference survived significance after corrections,The frequencies of minor allele C in cases and control were respectively 0.407 vs.0.445 and 0.401 vs.0.449.Genotypes distribution analysis indicated that rs11131347 was associated with ADHD in general (recessive model,P <0.05),ADHD boys (additive model,P <0.05;dominant model,P <0.05;recessive model,P <0.05),ADHD-C(recessive model,P <0.05)and ADHD-C boys (dominant model,P <0.05 ),however,none of the difference survived significance after correc-tions.rs11131347 was nominal associated with impulsive scores(P <0.05).Conclusion:These findings suggest that the polymorphism of LPHN3 is probably involved in the pathological mechanisms of ADHD and its core symptoms of impulsivity.

An exploratory clinical study of attention deficit hyperactivity disorder in young adulthood / 中国神经精神疾病杂志

Objective The exploratory study aimed to characterize the clinical features and the patterns of comorbidity and psychosocial functioning of adult attention deficit hyperactivity disorder (ADHD). Methods The study initially recruited 88 children who diagnosed with ADHD at age 6～16 years. They were reevaluated and administered structured psychiatric interviews for DSM-IV when they were at least 18 years old. A total of 59 adults with ADHD and 29 controls with GAF>70 were included in the study. Results Fifty-one(86.4%)of the adult ADHD were diagnosed as predominantly inattentive subtype of ADHD. The most common adult ADHD symptoms included "often has difficulty organizing tasks and activities (98.3%); often avoiding doing work projects where effort at thinking a lot is required (96.6%); often has trouble paying close attention to details (94.9%); often has problems following through on instructions and finishing job tasks (96.6%); often has difficulty sustaining attention (88.1%); often is distracted easily by extraneous stimuli (72.9%)". The majority (66.1%) of the adult ADHD had one or more psychiatric axis-I/axis-II comorbidity. Among them, 39.0% had psychiatric axis-I comorbidity and 49.2% had personality axis-II comorbidity. The average GAF score was significant lower in adult ADHD than in controls ( t =12.96, P <0.001). The majority (74.6%) of the adult ADHD had mild or moderate impairment or distress of overall functioning. Conclusions The main feature of adult ADHD is attention deficit. Patients with adult ADHD usually have comorbid conditions such as other psychiatric disorders and personality disorders and their psychosocial functioning is relatively poor.

Comorbidity of attention deficit hyperactivity disorder in different age group / 北京大学学报(医学版)

Objective:To study age distribution of attention deficit hyperactivity disorder(ADHD) comorbidities in a relatively large sample,and exam the hypothesis of bad prognosis for ADHD.Methods:Using semi-structured clinical diagnosis interview scale,we investigated comorbidities of 1 002 ADHD children and adolescents from psychiatric out-patient clinic,and compared comorbidity frequency in 4 age groups.Results:The comorbidity frequencies of disruptive behavior disorder(DBD),mood disorder,tics disorder and learning disorder(LD) in different age groups of ADHD patients differed significantly(P

Association analysis of dopamine D4 receptor gene polymorphism and attention deficit hyperactivity disorder with/without disruptive behavior disorder / 北京大学学报(医学版)

Objective:To examine the role of dopamine D4 receptor gene(DRD4) in attention deficit hyperactivity disorder(ADHD) with/without disruptive behavior disorder(DBD) by focusing on a-521C/T SNP within the promoter region of this gene.Methods:A total of 401 DSM-Ⅳ ADHD children(including 284 trios) of Chinese Han descent were genotyped.Chi-square test and the transmission disequilibrium test(TDT) were used to test for associations in ADHD with and without DBD respectively.Results:In the comparison of ADHD with(n= 143) and without(n= 258) DBD,the-521T allele(?2 = 6.778,P= 0.009,OR= 1.485) and the TT genotype(?2 = 6.292,P= 0.012,OR= 1.729) showed higher frequency in children with ADHD and DBD simultaneously.For family based analysis,T allele of the-521C/T polymorphism was preferentially transmitted to ADHD children with comorbid DBD(n= 100,?2 = 3.868,P= 0.049),whereas no significant distortion was found in the transmission of the tested variant for ADHD without DBD(n= 184,?2 = 0.223,P= 0.637).Conclusion:Our findings suggest that the-521C/T SNP of DRD4 may contribute to the predisposition to ADHD with comorbid DBD.This study supports for the hypothesis that ADHD with comorbid DBD may be influenced by greater genetic effect compared to ADHD alone.

Adult's outcome of attention deficit hyperactivity disorder and its predictive factors(review) / 北京大学学报(医学版)

The prognosis of attention deficit hyperactivity disorder(ADHD)is poor,and approximately two third patients still have obvious symptoms when they grow up into adults,thus interfering with their social functions including work,study,family and interpersonal relation etc,and even causing the mental disorders and/or antisocial personality disorder.The predictive factors of adult outcome of ADHD include genetic,environmental and clinical factors.This review deals with the adult outcome and its predictive factors,and explores the severes harmfulness against individual,family and society brought by ADHD and its underlying mechanisms so as to facilitate the clinical intervention and research.

Association studies of dopamine D_4 receptor gene and dopamine transporter gene polymorphisms in Han Chinese patients with attention deficit hyperactivity disorder / 北京大学学报(医学版)

Objective: To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the D 4 receptor gene ( DRD4 ) exon 3 and 40 bp VNTR polymorphism in the dopamine transporter gene ( DAT1 ) 3′ untranslated region with attention deficit hyperactivity disorder (ADHD) in Han Chinese children. Methods: The study samples were comprised of 340 ADHD children, 226 unrelated controls and 202 integrated ADHD trios (included proband and biological parents). The polymorphisms consisted of 48 bp VNTR in exon 3 of DRD4 , and 40 bp VNTR in the 3′ untranslated region of DAT1 . Associations of polymorphisms with ADHD and its subtypes were examined by: (i) comparing cases and controls; and (ii) using family based association study in an extension of exact transmission disequilibrium test (ETDT) and haplotype based haplotype relative risk (HHRR). Results: The repeat numbers at the DRD4 48 bp locus ranged from 2—6 repeats in the Han Chinese controls, with the most common being the 4 repeat (77%) and 2 repeat (19.4%) alleles. Neither the 7 repeat allele nor longer repeats were found. For the DAT1 , the repeat numbers at the 40 bp locus ranged from 6—7 repeats and 9—11 repeats. The 10 repeat allele was the most frequent (90.7%). The long repeat alleles of DRD4 (ranging from 4—6 repeats) and DAT1 (ranging from 11—12 repeats), were present more frequently in ADHD probands than in controls. Our primary analyses failed to replicate the associations between ADHD and 7 repeat allele of DRD4 and the 10 repeat allele of DAT1 . Conclusion: The long repeat alleles of DRD4 (after a stratification by gender) and DAT1 may increase the risk for ADHD in Han Chinese children.