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A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
Poor parent and teacher awareness for attention-deficit/hyperactivity disorder (ADHD) and the scepticism of many clinicians on the prevalence of the disorder, make Italy an interesting environment in which to verify neuropsychological constructs generated in a predominantly Northern American cultural contest. The aim of the study was to verify, by factor confirmatory analysis, the empirical validity of the DSM constructs underlying the diagnostic criteria for developmental disruptive behaviour disorders in Italian school-age children.
Scores for DSM-IV inattention and hyperactivity/impulsivity, for oppositional defiant disorder (ODD) and for conduct disorder (CD) symptoms in 6–12 years old Italian children were analysed from 1575 parent and 1085 teacher forms of the disruptive behaviour disorders questionnaires collected in four different Italian regions.
Reliability indicates high internal consistencies for both parent and teacher rating of inattention, hyperactivity/impulsivity, and oppositionality, but not for conduct problems. In accordance with the literature, a relatively low inter-rater convergent and discriminant validity correlation was observed comparing measures obtained by between parents and teachers. Confirmatory factor analysis of both parent and teacher data showed a better fit for a four-factor model, indicating a factor structure in accordance with the DSM-IV taxonomy. When completed by parents and teachers of clinically assessed ADHD, dyslexic or normal children, the disruptive behavioural disorder questionnaires showed a significant predictive diagnostic value.
Although an informant variance higher that dimensional (trait) variance was observed, the study provides support for DSM-IV taxonomy for developmental disruptive disorders, showing construct validity of ADHD. ODD and CD could also be distinguished from each other.
Attention-deficit hyperactivity disorder (ADHD) is linked to increased risk for substance use disorders and nicotine dependence.
To examine the effects of stimulant treatment on subsequent risk for substance use disorder and nicotine dependence in a prospective longitudinal ADHD case–control study.
At baseline we assessed ADHD, conduct disorder and oppositional defiant disorder. Substance use disorders, nicotine dependence and stimulant treatment were assessed retrospectively after a mean follow-up of 4.4 years, at a mean age of 16.4 years.
Stimulant treatment of ADHD was linked to a reduced risk for substance use disorders compared with no stimulant treatment, even after controlling for conduct disorder and oppositional defiant disorder (hazard ratio (HR) = 1.91, 95% Cl 1.10−3.36), but not to nicotine dependence (HR = 1.12, 95% Cl 0.45−2.96). Within the stimulant-treated group, a protective effect of age at first stimulant use on substance use disorder development was found, which diminished with age, and seemed to reverse around the age of 18.
Stimulant treatment appears to lower the risk of developing substance use disorders and does not have an impact on the development of nicotine dependence in adolescents with ADHD.
Regulatory decisions regarding attention deficit hyperactivity disorder drug licensing and labelling, along with recent statements from professional associations, raise questions of practice regarding the evaluation and treatment of patients with attention deficit hyperactivity disorder. To address these issues for the European community, the European Network for Hyperkinetic Disorders, through its European Attention Deficit Hyperactivity Disorder Guidelines Group, organised a meeting between attention deficit hyperactivity disorder specialists, paediatric cardiovascular specialists, and representatives of the major market authorisation holders for attention deficit hyperactivity disorder medications. This manuscript represents their consensus on cardiovascular aspects of attention deficit hyperactivity disorder medications. Although sudden death has been identified in multiple young individuals on attention deficit hyperactivity disorder medication causing regulatory concern, when analysed for exposure using currently available data, sudden death does not appear to exceed that of the general population. There is no current evidence to suggest an incremental benefit to electrocardiography assessment of the general attention deficit hyperactivity disorder patient. Congenital heart disease patients have an increased prevalence of attention deficit hyperactivity disorder, and can benefit from attention deficit hyperactivity disorder therapies, including medication. The attention deficit hyperactivity disorder specialist is the appropriate individual to evaluate benefit and risk and recommend therapy in all patients, although discussion with a heart specialist is reasonable for congenital heart disease patients. For attention deficit hyperactivity disorder patients with suspected heart disease or risk factor/s for sudden death, assessment by a heart specialist is recommended, as would also be the case for a non-attention deficit hyperactivity disorder patient. The identification of risk factors for sudden death should not automatically exclude the use of attention deficit hyperactivity disorder medication.
“A dynamic developmental theory of attention-deficit/hyperactivity disorder (ADHD) predominantly hyperactive/impulsive and combined subtypes” is a major contribution linking comparative psychology with clinical developmental neuropsychopathology. In this commentary, I place some critical remarks concerning the theory’s explanation of sleep problems, inhibition, error monitoring, and motor control.
Background. Several theoretical explanations of ADHD in children have focused on executive functioning as the main explanatory neuropsychological domain for the disorder. In order to establish if these theoretical accounts are supported by research data for adults with ADHD, we compared neuropsychological executive functioning and non-executive functioning between adults with ADHD and normal controls in a meta-analytic design.
Method. We compared 13 studies that (1) included at least one executive functioning measure, (2) compared the performance of an adult ADHD group with that of an adult normal control group, (3) provided sufficient information for calculation of effect sizes, and (4) used DSM-III-R or DSM-IV criteria to diagnose ADHD.
Results. We found medium effect sizes both in executive functioning areas [verbal fluency (d=0·62), inhibition (d=0·64 and d=0·89), and set shifting (d=0·65)] and in non-executive functioning domains [consistency of response (d=0·57), word reading (d=0·60) and color naming (d=0·62)].
Conclusions. Neuropsychological difficulties in adult ADHD may not be confined to executive functioning. The field is in urgent need of better-designed executive functioning tests, methodological improvements, and direct comparisons with multiple clinical groups to answer questions of specificity.
The main aims of this study were to investigate if children with
high-functioning autism (HFA) and children with Tourette syndrome (TS) can
be differentiated in their executive functioning (EF) profile compared to
normal controls (NCs) and compared to each other and to investigate
whether children with HFA or children with TS and a comorbid group of
children with both disorders are distinct conditions in terms of EF. Four
groups of children participated in this study: HFA, TS, comorbid HFA + TS,
and a NC group. All children were in the age range of 6 to 13 years. The
groups were compared on five major domains of EF: inhibition, visual
working memory, planning, cognitive flexibility, and verbal fluency.
Children with HFA scored lower than NC children on all the EFs measured.
Children with TS and NC children showed the same EF profile. The HFA group
scored lower than the TS group for inhibition of a prepotent response and
cognitive flexibility. Children with HFA performed poorer than children
with comorbid HFA + TS on all functions, with the exception of inhibiting
an ongoing response, interference control, and verbal fluency. Children
with TS and children with comorbid HFA + TS could not be differentiated
from one another in terms of EF. This study indicates that EF deficits are
highly characteristic of children with HFA in comparison to children with
TS and NC. The results suggest that for the comparison between HFA and TS
groups, it is important to take into account comorbidity. A reevaluation
of the EF hypothesis in children with TS is suggested.We thank the children and parents without whose participation
this research would not have been possible.
The use of DSM-IV based questionnaires in child psychopathology is on the increase. The internal construct validity of a DSM-IV based model of ADHD, CD, ODD, Generalised Anxiety, and Depression was investigated in 11 samples by confirmatory factor analysis. The factorial structure of these syndrome dimensions was supported by the data. However, the model did not meet absolute standards of good model fit. Two sources of error are discussed in detail: multidimensionality of syndrome scales, and the presence of many symptoms that are diagnostically ambiguous with regard to the targeted syndrome dimension. It is argued that measurement precision may be increased by more careful operationalisation of the symptoms in the questionnaire. Additional approaches towards improved conceptualisation of DSM-IV are briefly discussed. A sharper DSM-IV model may improve the accuracy of inferences based on scale scores and provide more precise research findings with regard to relations with variables external to the taxonomy.
This study was aimed at (a) replicating findings of slow and variable response execution and slow response inhibition in Attention Deficit/Hyperactivity Disorder (AD/HD), (b) investigating whether these deficits are specifically related to AD/HD or may also be observed in Oppositional Defiant Disorder (ODD), and children comorbid for AD/HD+ODD, and (c) examining the role of activation level in task performance of children with AD/HD. To meet these aims, the stop paradigm was administered at three levels of activation, using a slow, medium, and fast presentation rate of stimuli, to 4 groups of children: 24 AD/HD children, 21 children with ODD, 27 children with comorbid AD/HD+ODD, and 41 normal controls. As hypothesized, children with AD/HD exhibited a slow response execution process with considerable variability in the speed of responding compared to normal controls. Slow response execution was also observed in the comorbid AD/HD+ODD group but not in the pure ODD group. Larger variability in the speed of responding was common to all disruptive groups compared with controls. In contrast to our hypothesis, no group differences emerged for inhibitory functioning. Finally, the slow event rate condition caused a further deterioration in the speed of the response execution process in both the AD/HD group and ODD group.
The construct representation of the cross-informant model of the Child Behavior Checklist
(CBCL) and the Teacher Report Form (TRF) was evaluated using confirmatory factor
analysis. Samples were collected in seven different countries. The results are based on 13,226
parent ratings and 8893 teacher ratings. The adequacy of fit for the cross-informant model
was established on the basis of three approaches: conventional rules of fit, simulation, and
comparison with other models. The results indicated that the cross-informant model fits
these data poorly. These results were consistent across countries, informants, and both
clinical and population samples. Since inadequate empirical support for the cross-informant
syndromes and their differentiation was found, the construct validity of these syndrome
dimensions is questioned.
The aim of this study was to investigate whether impaired
response inhibition is uniquely
related to AD/HD or whether deficits in response inhibition are also
evident in other
psychopathological disorders. Furthermore, the suggestion was examined
disorders are associated with abnormally high levels of response inhibition.
presents the results of a meta-analysis of eight studies in which response
assessed with the so-called stop task in five groups of children: children
deficit/hyperactivity disorder (AD/HD), children with conduct disorder
children with AD/HD+CD, children with anxiety disorders, and control
children. A total of 456 children participated in the 8 studies. All children
were in the age range 6–12 years. Consistent and
robust evidence was found for a response inhibition deficit in AD/HD.
inhibition deficits did not distinguish children with AD/HD from children
with CD, nor
from children with comorbid AD/HD+CD. Contrary to predictions, anxious
not demonstrate enhanced levels of response inhibition.
Abnormal EEGs have been reported in XYY and XXY men located in psychiatric hospitals and prisons. In general, persons resident in institutions are more likely to exhibit EEG abnormalities than ‘normal’ population, and this bias of ascertainment has complicated the interpretation of these results.
The present study was conducted in Denmark. Chromosome determinations were made on 4,140 men selected from a birth cohort of 31,438 men. Twelve XYY and 16 XXY men were detected. Appropriate XY control groups were selected from the same population. The XYY men were found to have a significantly lower average frequency of the occipital alpha activity than their controls. The XYY and XXY men showed significantly more theta activity than the controls.
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