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1.  Adherence to Psychostimulant Medication in Children with Attention-Deficit/Hyperactivity Disorder: The Role of Attitudes 
Objective:
To investigate how attitudes towards psychostimulant medication influence the adherence to psychostimulant treatment in children with Attention-Deficit/Hyperactivity Disorder (ADHD).
Method:
Thirty-three children with ADHD were prospectively recruited to take part in this study. The children and their parents filled questionnaires at both baseline and at a three-month follow-up to assess the severity of ADHD symptoms in the child and attitudes towards psychostimulant medication. Adherence to medication was assessed through standardized interviews of parents.
Results:
Parental perceived psychosocial benefits of psychostimulant medication at the three-month follow-up were found to be positive predictors of adherence to medication. Parental perceived psychosocial benefits of medication at the three-month follow-up was in turn predicted by parental medication acceptability at three months and child’s perceived psychosocial benefits of medication at three-months.
Conclusion:
Improving parents’ awareness of psychosocial benefits of psychostimulant medication may increase adherence to psychostimulant medication in children with ADHD. Age of the child and severity of symptoms did not significantly affect medication adherence.
PMCID: PMC3825473  PMID: 24223052
Attention-Deficit/Hyperactivity Disorder (ADHD); medication adherence; psychostimulants; attitudes; trouble de déficit de l’attention avec hyperactivité (TDAH); observance des médicaments; psychostimulants; attitudes
2.  Sensitivity of Scales to Evaluate Change in Symptomatology with Psychostimulants in Different ADHD Subtypes 
Objective:
To assess the sensitivity of scales (Conners’ Global Index Parent and Teacher form [CGI-P, CGI-T], Clinical Global Impression Scale [CGI], Continuous Performance Test [CPT], and Restricted Academic Situation Scale [RASS]) in evaluating improvement in symptomatology with methylphenidate in different Attention Deficit Hyperactivity Disorder (ADHD) subtypes.
Method:
Four hundred and ninety children (309 with ADHD Combined/Hyperactive [ADHD-CH] and 181 with ADHD Inattentive subtype [ADHD-I]) participated in a two week double-blind placebo-controlled crossover methylphenidate trial.
Results:
CGI-P showed small effect size for ADHD-I and medium effect size for the ADHD-CH subtype. CGI-T showed medium effect size for ADHD-I and large effect size for ADHD-CH subtype. CGI and RASS showed large effect size while CPT showed medium effect size for both subtypes.
Conclusion:
Acute behavioural assessments by clinicians (CGI, RASS) are better at detecting improvement with medication in all subtypes than parent or teacher reports (CGI-P, CGI-T). CGI-T is better than CGI-P for ADHD-I in detecting change in symptomatology as there is a greater demand for attention at school.
PMCID: PMC3647632  PMID: 23667362
Attention Deficit Hyperactivity Disorder; ADHD; Conners’ scales; RASS; CGI; CPT; scales; ADHD subtypes; inattention; hyperactivity; trouble de déficit de l’attention avec hyperactivité; TDAH; échelles de Conners; RASS; CGI; CPT; échelles; sous-types du TDAH; inattention; hyperactivité
3.  Body Weight and ADHD: Examining the Role of Self-Regulation 
PLoS ONE  2013;8(1):e55351.
Objective
Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.
Methods
284 ADHD children were stratified by weight status/BMI according to WHO classification and compared with regard to their neurocognitive characteristics, motivational style, and motor profile as assessed by a comprehensive battery of tests. All comparisons were adjusted for demographic characteristics of relevance including, socioeconomic status (SES).
Results
Both Obese and overweight ADHD children exhibited significantly lower SES compared to normal weight ADHD children. No significant differences were observed between the three groups with regards to their neurocognitive, emotional and motor profile.
Conclusions
Our findings provide evidence that differences in weight/BMI are not accounted for by cognitive, motivational and motor profiles. Socio-economic characteristics are strongly associated with overweight and obesity in ADHD children and may inform strategies aimed at promoting healthier weight.
doi:10.1371/journal.pone.0055351
PMCID: PMC3558419  PMID: 23383165
4.  Comprehensive Phenotype/Genotype Analyses of the Norepinephrine Transporter Gene (SLC6A2) in ADHD: Relation to Maternal Smoking during Pregnancy 
PLoS ONE  2012;7(11):e49616.
Objective
Despite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD.
Methods
Children (6–12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial. Family-based association tests (FBAT), including categorical and quantitative trait analyses, were conducted in 377 nuclear families.
Results
A highly significant association was observed with rs36021 (and linked SNPs) in the group where mothers smoked during pregnancy. Association was noted with categorical DSM-IV ADHD diagnosis (Z = 3.74, P = 0.0002), behavioral assessments by parents (CBCL, P = 0.00008), as well as restless-impulsive subscale scores on Conners’-teachers (P = 0.006) and parents (P = 0.006). In this subgroup, significant association was also observed with cognitive deficits, more specifically sustained attention, spatial working memory, planning, and response inhibition. The risk allele was associated with significant improvement of behavior as measured by research staff (Z = 3.28, P = 0.001), parents (Z = 2.62, P = 0.009), as well as evaluation in the simulated academic environment (Z = 3.58, P = 0.0003).
Conclusions
By using maternal smoking during pregnancy to index a putatively more homogeneous group of ADHD, highly significant associations were observed between tag SNPs within SLC6A2 and ADHD diagnosis, behavioral and cognitive measures relevant to ADHD and response to MPH. This comprehensive phenotype/genotype analysis may help to further understand this complex disorder and improve its treatment. Clinical trial registration information – Clinical and Pharmacogenetic Study of Attention Deficit with Hyperactivity Disorder (ADHD); www.clinicaltrials.gov; NCT00483106.
doi:10.1371/journal.pone.0049616
PMCID: PMC3502190  PMID: 23185385
5.  Efficacy of Methylphenidate in ADHD Children across the Normal and the Gifted Intellectual Spectrum 
Objective:
This study evaluates whether attention-deficit/hyperactivity disorder (ADHD) children with a borderline intelligence quotient (IQ) (70≤FSIQ<80), normal IQ (80≤FSIQ<120) and high IQ (FSIQ≥120) respond differently to psychostimulant treatment.
Method:
502 children, aged 6 to 12 years, with an IQ range from 70 to 150 participated in a two-week, double-blind, placebo-controlled, crossover methylphenidate (MPH) trial.
Results:
In addition to differences in socioeconomic background and parental education, higher IQ children were found to present with less severe symptoms. No significant differences were found with regards to treatment response.
Conclusion:
ADHD children within the normal and high levels of intellectual functioning all respond equally to psychostimulant treatment, and that proper medication management is necessary for all children with the disorder.
PMCID: PMC3490529  PMID: 23133462
ADHD; IQ; methylphenidate response; TDAH; QI; réponse au méthylphénidate
6.  Differential association between the norepinephrine transporter gene and ADHD: role of sex and subtype 
Background
Pharmacologic and animal studies have strongly implicated the norepinephrine transporter (NET) in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We conducted a family-based study, with stratification based on sex and subtype, to test the association between 30 tag single-nucleotide polymorphisms (SNPs) within the gene encoding NET (SLC6A2) and ADHD.
Methods
Family-based association tests were conducted with the categorical diagnosis of ADHD, as well as quantitative phenotypes of clinical relevance (Conners Global Index for Teachers and Parents, and Child Behavior Checklist measures). Sliding window haplotype analysis was conducted with screening based on conditional power using PBAT.
Results
A previously reported association with rs3785143 was confirmed in this study. Further, extensive association was observed with haplotype blocks, with a differential pattern observed based on sex and subtype. The 5′ region of the gene (encompassing haplotype block 1 and including a functional promoter SNP, rs28386840) showed an association with ADHD in girls (irrespective of subtype). A different region of the gene (distributed around haplotype block 2) was associated with distinct behavioural phenotypes in boys. These findings are correlated with previously reported functional studies of gene variants in SLC6A2.
Limitations
The most important limitation of the study is the small size of the groups resulting from the stratification based on sex followed by subtype.
Conclusion
The results obtained in this family-based study suggest that haplotype blocks within different regions of SLC6A2 show differential association with the disorder based on sex and subtype. These associations may have been masked in previous studies when tests were conducted with pooled samples.
doi:10.1503/jpn.110073
PMCID: PMC3297073  PMID: 22297068
7.  Maternal Stress during Pregnancy, ADHD Symptomatology in Children and Genotype: Gene-Environment Interaction 
Objective
Case control studies suggest a relationship between maternal stress during pregnancy and childhood ADHD. However, maternal smoking, parenting style and parental psychiatric disorder are possible confounding factors. Our objective was to control for these factors by using an intra-familial design, and investigate gene-environment interactions.
Methods
One hundred forty two children, ages 6 to 12, (71 with ADHD, and their 71 non-ADHD siblings) participated in the intra-familial study design. A larger sample of ADHD children (N=305) was genotyped for DAT1 and DRD4 to examine gene-environment interactions. Symptom severity was evaluated using the Child Behavior Checklist (CBCL) and the Conners’ Global Index for Parents (CGI-P). The Kinney Medical and Gynecological Questionnaire was used to report stressful events during pregnancies.
Results
Logistic regression indicated that mothers were more likely to have experienced high stress during pregnancy of their ADHD child compared to that of the unaffected sibling (OR: 6.3, p=.01). In the larger sample, DRD4 7/7 genotype was associated with increased symptom severity in the high stress pregnancy (p=.01).
Conclusions
Maternal stress during pregnancy was associated with the development of ADHD symptomatology after controlling for family history of ADHD and other environmental factors. This association could partly be mediated through the DRD4 genotype.
PMCID: PMC3269259  PMID: 22299010
ADHD; prenatal stress; pregnancy; DRD4; TDAH; stress prénatal; grossesse; DRD4
8.  Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD 
BMC Psychiatry  2011;11:70.
Background
The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations.
Methods
One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS).
Results
The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers.
Conclusion
The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.
doi:10.1186/1471-244X-11-70
PMCID: PMC3095543  PMID: 21510895
9.  The 5-HTTLPR polymorphism of the serotonin transporter gene and short term behavioral response to methylphenidate in children with ADHD 
BMC Psychiatry  2010;10:50.
Background
Animal models of ADHD suggest that the paradoxical calming effect of methylphenidate on motor activity could be mediated through its action on serotonin transmission. In this study, we have investigated the relationship between the 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4) and the response of ADHD relevant behaviors with methylphenidate treatment.
Methods
Patients between ages 6-12 (n = 157) were assessed with regard to their behavioral response to methylphenidate (0.5 mg/kg/day) using a 2-week prospective within-subject, placebo-controlled (crossover) trial. The children were then genotyped with regard to the triallelic 5-HTTLPR polymorphism in the SLC6A4 gene. Main outcome measure: Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) at baseline and at the end of each week of treatment with placebo and methylphenidate. For both outcome measurements, we used a mixed model analysis of variance to determine gene, treatment and gene × treatment interaction effects.
Results
Mixed model analysis of variance revealed a gene × treatment interaction for CGI-Parents but not for CGI-Teachers. Children homozygous for the lower expressing alleles (s+lG = s') responded well to placebo and did not derive additional improvement with methylphenidate compared to children carrying a higher expressing allele (lA). No genotype main effects on either CGI-Parents or CGI-teachers were observed.
Conclusions
A double blind placebo-controlled design was used to assess the behavioral effects of methylphenidate in relation to the triallelic 5-HTTLPR polymorphism of the SLC6A4 gene in children with ADHD. This polymorphism appears to modulate the behavioral response to methylphenidate in children with ADHD as assessed in the home environment by parents. Further investigation is needed to assess the clinical implications of this finding.
Trial Registration
ClinicalTrials.gov NCT00483106
doi:10.1186/1471-244X-10-50
PMCID: PMC2905344  PMID: 20569447
10.  COMT Val108/158Met polymorphism modulates task-oriented behaviour in children with ADHD 
Context
It has been suggested that the symptoms of ADHD (inattention and/or hyperactivity/impulsivity), translate into deficits in task-oriented behaviour or problem-focussed activity. The fronto-subcortical dopamine and norepinephrine pathways have been implicated in ADHD, and one of the key modulators of these neurotransmitters in the prefrontal cortex is catechol-O-methyltransferase (COMT).
Objective
To examine the association of the COMT Val108/158Met polymorphism with (1) task-oriented behaviour in children with ADHD, and (2) response of this phenotype to methylphenidate treatment.
Design, Setting, Participants
Children diagnosed with ADHD (n=212), were assessed using the Restricted Academic Situation Scale (RASS). The RASS uses a simulated academic environment within the research clinic, to assess the child's ability for independent, sustained orientation to a task of math problems.
Interventions
Each child was administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. On day 3 of the respective treatment week, the child was administered placebo/ methylphenidate in the clinic, and the acute change in behaviour (before and 1 hour after treatment) was evaluated on the RASS.
Main Outcome Measure
The main outcome measure was the RASS score (number of behavioural events measured during a 15-minute time period), measured at four time points: before and after placebo/methylphenidate treatment. Analysis was carried out using mixed model analysis of variance.
Results
Significant main effects of COMT genotype [F2,206 = 4.78, p = 0.009] and treatment [F1,206 = 45.22, p < 0.0001] on task-oriented behaviour were observed. The Met-Met and Val-Met genotype groups had fewer behavioural events, and were more engaged in the math task, compared to the Val-Val group. No genotype by treatment interaction was observed.
Conclusion
These results suggest that the COMT Val108/158Met polymorphism modulates task-oriented behaviour, but it does not modulate the response of this behaviour to MPH treatment.
doi:10.1038/npp.2008.85
PMCID: PMC2885152  PMID: 18580877
COMT; task-oriented behaviour; methylphenidate; ADHD
11.  Dopamine Transporter Genotype and Stimulant Side Effect Factors in Youth Diagnosed with Attention-Deficit/Hyperactivity Disorder 
Abstract
The dopamine transporter locus (DAT1) has been studied as a risk factor for attention-deficit/hyperactivity disorder (ADHD) and in pharmacogenetic studies of stimulant response. Several prospective studies have reported an association between the homozygous 9 repeat allele of the DAT1 3′ untranslated region (UTR) variable number tandem repeat (VNTR) (DAT1 3′) and decreased efficacy of methylphenidate (MPH). We hypothesized that children with the 9/9 genotype would display higher rates of specific stimulant side effects. Data on adverse events and DAT1 3′ genotypes were combined from two, double-blind, placebo-controlled, crossover studies of MPH conducted in child psychiatric outpatient clinics in Montreal and Washington, D.C. There were 177 participants, 5–16 years old (mean age = 8.99, standard deviation [SD] = 2), with ADHD. Parents completed the Stimulant Side Effect Scale (SERS) after a week of placebo and a week of MPH treatment. Principal components analysis of the SERS resulted in three factors: Emotionality, Somatic Complaints, and Over-focused. Children with the 9/9 genotype displayed higher scores on the Emotionality factor during placebo than children with the 9/10 and the 10/10 genotype, and their Emotionality scores increased further during MPH treatment (F[2,151] = 3.24, p < 0.05). Children with the 10/10 genotype displayed a significant increase in Somatic Complaint factor scores during MPH treatment relative to the other genotype groups (F[2,150] = 3.4, p < 0.05). These data provide suggestive evidence that DAT1 variants are differentially associated with specific stimulant side effects. Children with the 9/10 genotype displayed less severe stimulant side-effect ratings than either of the homozygous groups, who each displayed increased susceptibility to different types of adverse events. Preliminary evidence suggests that pharmacogenetic analysis using DAT1 variants shows promise for identifying individuals at increased or decreased risk for poor tolerability.
doi:10.1089/cap.2008.0133
PMCID: PMC2856973  PMID: 19519258
12.  Dopamine transporter 3'UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD 
BMC Psychiatry  2008;8:45.
Background
Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder.
Methods
To investigate the relationship between the dopamine transporter gene (SLC6A3) 3'-UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning.
Results
Taking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009) and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III) Freedom From Distractibility Index (F = 7.125, p = 0.008), as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026) and WISC-III Digit Span performance (F = 6.28, p = 0.023). Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected.
Conclusion
Results are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD.
doi:10.1186/1471-244X-8-45
PMCID: PMC2443797  PMID: 18559107
13.  Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD 
Objective
There is considerable evidence that maternal stress is associated with behavioural disturbances in offspring. The objective of this study was to examine whether there is an association between the severity of maternal stress during pregnancy and the severity of symptoms of attention-deficit hyperactivity disorder (ADHD). A second objective was to examine whether there is an association between maternal stress and children's response to methylphenidate (MPH).
Methods
Using the Kinney Medical and Gynecological Questionnaire, we assessed 203 children with ADHD, aged between 6 and 12 years, regarding maternal stress during pregnancy. We assessed symptom severity with the Child Behavior Checklist (CBCL) and Conners' Global Index for Parents (CGI-P) and Teachers (CGI-T). Subjects were recruited from the ADHD clinic and the day-treatment program of the Child Psychiatry Department of the Douglas Hospital, Montréal, Quebec. The quality of their therapeutic response was assessed in a double-blind, placebo-controlled randomized 2-week crossover trial of MPH.
Results
The most severe symptoms as assessed by the CBCL were found in the moderate stressor group, (p < 0.002), whereas, according to the CGI-P (emotional liability), the most severe symptoms were found in the severe stressor group (p < 0.029). There was no statistically significant difference between degree of response to MPH and level of maternal stress.
Conclusion
Children with ADHD whose mothers were exposed to moderate and severe stress during pregnancy tend to develop more severe symptoms than children with ADHD whose mothers were not exposed to prenatal stress. It is therefore important to minimize stress in pregnant women.
PMCID: PMC2186370  PMID: 18197267
attention deficit disorder with hyperactivity; methylphenidate; stress; pregnancy
14.  Efficacy of methylphenidate in children with attention-deficit hyperactivity disorder and learning disabilities: a randomized crossover trial 
Objective: To determine whether children with attention-deficit hyperactivity disorder (ADHD) and learning disabilities respond differently to methylphenidate (MPH) compared with children with ADHD only. Methods: We conducted a prospective, double-blind, placebo-controlled, randomized, 2-week crossover trial of MPH, during which response to MPH was assessed. Learning ability was appraised using the Wide Range Achievement Test, Revised (WRAT-R), for English-speaking students and the Test de rendement pour francophones for French-speaking students. The study was conducted at the Douglas Hospital, a McGill University–affiliated teaching hospital in Montréal. Ninety-five children, aged 6–12 years, who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria for ADHD participated in the study, which ran from 2001 to 2004. The outcome measure used was the Consensus Clinical Response, an indicator of the degree of clinical improvement shown when taking MPH. Results: The proportion of children with learning disabilities who responded to MPH (55%) was significantly smaller (χ21 = 4.5, p = 0.034) than the proportion of children without learning disabilities who responded adequately to MPH (75%). This difference was mainly because of children with mathematics disability being particularly unresponsive to MPH (χ21 = 4.5, p = 0.034). Children with reading disability did not show this pattern of poor response (χ21 = 1.0, p = 0.33). Conclusion: Children with ADHD and comorbid learning disability tended to respond more poorly to MPH. In particular, children with disability in mathematics responded less to MPH than those without disability in mathematics. Additional therapy may be indicated for this group of patients.
PMCID: PMC1325066  PMID: 16496035
attention deficit disorder with hyperactivity; learning disorders; methylphenidate
15.  Perinatal complications in children with attention-deficit hyperactivity disorder and their unaffected siblings  
Objectives
Genetic and nonshared environmental factors (experienced by 1 family member to the exclusion of the others) have been strongly implicated in the causes of attention-deficit hyperactivity disorder (ADHD). Pregnancy, labour/delivery and neonatal complications (PLDNC) have often been associated with ADHD; however, no investigations aimed at delineating the shared or nonshared nature of these factors have been reported. We aimed to identify those elements of the PLDNC that are more likely to be of a nonshared nature.
Methods
We used an intrafamily study design, comparing the history of PLDNC between children diagnosed with ADHD, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), and their unaffected siblings. Children with ADHD were recruited from the outpatient, day-treatment program of the Child Psychiatry Department, Douglas Hospital, Montréal. The unaffected sibling closest in age to the child with ADHD was used as a control. The history of PLDNC was assessed using the Kinney Medical and Gynecological Questionnaire and the McNeil–Sjöstrom Scale for both children with ADHD and their siblings. Seventy children with ADHD along with 50 of their unaffected siblings agreed to participate in the study. Child Behavior Checklist (CBCL), Continuous Performance Test (CPT) and Restricted Academic Situation Scale (RASS) scores were also used as measures of ADHD symptoms in children with ADHD.
Results
The children with ADHD had significantly higher rates of neonatal complications compared with their unaffected siblings (F4,196 = 3.67, p < 0.006). Furthermore, neonatal complications in the children with ADHD were associated with worse CBCL total and externalizing scores and with poorer performance on the CPT.
Conclusions
These results suggest that neonatal complications are probably a nonshared environmental risk factor that may be pathogenic in children with ADHD.
PMCID: PMC551167  PMID: 15798787
attention deficit disorder with hyperactivity; child; perinatal care; pregnancy complications; siblings
16.  Catechol-O-Methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD 
BMC Medical Genetics  2004;5:30.
Background
An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children.
Methods
The Val108/158 Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance.
Results
ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F2,97 = 0.67; p > 0.05], TOL standardized scores [F2,99 = 0.97; p > 0.05], and SOPT error scores [F2,108 = 0.62; p > 0.05].
Conclusions
Contrary to the observed association between WCST performance and the Val108/158 Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD.
doi:10.1186/1471-2350-5-30
PMCID: PMC544598  PMID: 15613245
17.  Sensitivity of Tests to Assess Improvement In ADHD Symptomatology 
Objective
To assess which measurements best predict improvement on ADHD symptomatology after medication is given.
Methods
147 children aged 6 to 12 years, diagnosed with ADHD, participated in a double-blind placebo controlled twoweek crossover trial of methylphenidate.
Results
There were statistically significant differences on all measures between placebo and medication. Effect size for the overall group was 0.33 (CGI-P), 0.80 (CGI-T), 1.33 (CGI), 0.56 (CPT), 0.82 (RASS).
Conclusions
Acute behavioural response measures, where children are observed by clinicians (RASS and CGI), were overall more reliable than parent reports in detecting improvement on ADHD symptomatology. Teacher reports were also very important, especially in the 9 to 12 year old group.
PMCID: PMC2538631  PMID: 19030484
Attention Deficit Hyperactive Disorder; medication response; methylphenidate; trouble déficitaire de l’attention avec hyperactivité; réponse à la médication; méthylphénidate

Results 1-17 (17)