Aribert Rothenberger

European clinical guidelines for hyperkinetic disorder -- first upgrade.

AbstractBackgroundThe validity of clinical guidelines changes over time, because new evidencebased knowledge and experience develop.ObjectiveHence, the European clinical guidelines on hyperkinetic disorder from 1998 had to be evaluated and modified.MethodDiscussions at the European Network for Hyperkinetic Disorders (EUNETHYDIS) and iterative critique of each clinical analysis. Guided by evidence-based information and based on evaluation (rather than metaanalysis) of the scientific evidence a group of child psychiatrists and psychologists from several European countries updated the guidelines of 1998. When reliable information is lacking the group gives a clinical consensus when it could be found among themselves.ResultsThe group presents here a set of recommendations for the conceptualisation and management of hyperkinetic disorder and attention deficit/hyperactivity disorder (ADHD).ConclusionA general scheme for practice in Europe could be provided, on behalf of the European Society for Child and Adolescent Psychiatry (ESCAP).

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder : association signals in DRD4, DAT1 and 16 other genes

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Multicultural assessment of child and adolescent psychopathology with ASEBA and SDQ instruments: research findings, applications, and future directions.

Around the world, cultural blending and conflict pose challenges for assessment and understanding of psychopathology. Economical, evidence-based, culturally robust assessment is needed for research, for answering public health questions, and for evaluating immigrant, refugee, and minority children. This article applies multicultural perspectives to behavioral, emotional, and social problems assessed on dimensions describing childrens functioning, as rated by parents, teachers, children, and others. The development of Achenbach System of Empirically Based Assessment (ASEBA) and Strengths and Difficulties Questionnaire (SDQ) forms and their applications to multicultural research are presented. A primary aim of both questionnaires is to identify children at high risk of psychiatric disorders and who therefore warrant further assessment. The forms are self-administered or administered by lay interviewers. ASEBA problem items are scored on 6 DSM-oriented scales and 3 broader band scales, plus 8 syndromes derived statistically as taxonomic constructs and supported by uniform confirmatory factor analyses of samples from many populations. Comparisons of ASEBA scale scores, psychometrics, and correlates are available for diverse populations. SDQ forms are scored on one broad-band scale and 5 a priori behavioral dimensions supported by data from various populations. For both instruments, factor analyses, psychometrics, and correlates are available for diverse populations. The willingness and ability of hundreds of thousands of respondents from diverse groups to complete ASEBA and SDQ forms support this approach to multicultural assessment. Although particular items and scales may have differential relevance among groups and additional assessment procedures are needed, comparable results are found in many populations. Scale scores vary more within than between populations, and distributions of scores overlap greatly among different populations. Ratings of childrens problems thus indicate more heterogeneity within populations than distinctiveness between populations. Norms from multiple populations can be used to compare childrens scores with relevant peer groups. Multicultural dimensional research can advance knowledge by diversifying normative data; by comparing immigrant children with nonimmigrant compatriots and with host country children; by identifying outlier findings for elucidation by emic research; and by fostering efforts to dimensionalize DSM-V diagnostic criteria.

Long-acting medications for the hyperkinetic disorders : A systematic review and European treatment guideline

A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.

Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist.

Abstract The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4–16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes.

Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder

OBJECTIVE Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. As prior genome-wide association studies (GWAS) have not yielded significant results, we conducted a meta-analysis of existing studies to boost statistical power. METHOD We used data from four projects: a) the Childrens Hospital of Philadelphia (CHOP); b) phase I of the International Multicenter ADHD Genetics project (IMAGE); c) phase II of IMAGE (IMAGE II); and d) the Pfizer-funded study from the University of California, Los Angeles, Washington University, and Massachusetts General Hospital (PUWMa). The final sample size consisted of 2,064 trios, 896 cases, and 2,455 controls. For each study, we imputed HapMap single nucleotide polymorphisms, computed association test statistics and transformed them to z-scores, and then combined weighted z-scores in a meta-analysis. RESULTS No genome-wide significant associations were found, although an analysis of candidate genes suggests that they may be involved in the disorder. CONCLUSIONS Given that ADHD is a highly heritable disorder, our negative results suggest that the effects of common ADHD risk variants must, individually, be very small or that other types of variants, e.g., rare ones, account for much of the disorders heritability.

Co-existing disorders in ADHD - implications for diagnosis and intervention

Abstract.BackgroundIt is only recently that “comorbidity” in ADHD has come to the forefront as one of the most important aspects of the disorder. It is agreed that, often, these problems are at least as important as ADHD in contributing to the longer term outcome in the individual child.ObjectiveTo provide the reader with basic information about clinics and treatment of “comorbidity” in ADHD.MethodReview of the empirically based literature.ResultsADHD exists in a surprisingly high frequency together with a broad range of child neuropsychiatric disorders. This is accompanied with many still unresolved treatment problems.ConclusionIt would not be appropriate to develop ADHD–services where clinicians would only have expertise in ADHD as such. Anyone working with children, adolescents and adults with ADHD would need to have training in general neuropsychiatry. Further research in this field is urgently needed.

Genome-Wide Association Scan of Quantitative Traits for Attention Deficit Hyperactivity Disorder Identifies Novel Associations and Confirms Candidate Gene Associations

Attention deficit hyperactivity disorder (ADHD) is a complex condition with environmental and genetic etiologies. Up to this point, research has identified genetic associations with candidate genes from known biological pathways. In order to identify novel ADHD susceptibility genes, 600,000 SNPs were genotyped in 958 ADHD proband‐parent trios. After applying data cleaning procedures we examined 429,981 autosomal SNPs in 909 family trios. We generated six quantitative phenotypes from 18 ADHD symptoms to be used in genome‐wide association analyses. With the PBAT screening algorithm, we identified 2 SNPs, rs6565113 and rs552655 that met the criteria for significance within a specified phenotype. These SNPs are located in intronic regions of genes CDH13 and GFOD1, respectively. CDH13 has been implicated previously in substance use disorders. We also evaluated the association of SNPs from a list of 37 ADHD candidate genes that was specified a priori. These findings, along with association P‐values with a magnitude less than 10−5, are discussed in this manuscript. Seventeen of these candidate genes had association P‐values lower then 0.01: SLC6A1, SLC9A9, HES1, ADRB2, HTR1E, DDC, ADRA1A, DBH, DRD2, BDNF, TPH2, HTR2A, SLC6A2, PER1, CHRNA4, SNAP25, and COMT. Among the candidate genes, SLC9A9 had the strongest overall associations with 58 association test P‐values lower than 0.01 and multiple association P‐values at a magnitude of 10−5 in this gene. In sum, these findings identify novel genetic associations at viable ADHD candidate genes and provide confirmatory evidence for associations at previous candidate genes. Replication of these results is necessary in order to confirm the proposed genetic variants for ADHD.

European guidelines on managing adverse effects of medication for ADHD

The safety of ADHD medications is not fully known. Concerns have arisen about both a lack of contemporary-standard information about medications first licensed several decades ago, and signals of possible harm arising from more recently developed medications. These relate to both relatively minor adverse effects and extremely serious issues such as sudden cardiac death and suicidality. A guidelines group of the European Network for Hyperkinetic Disorders (EUNETHYDIS) has therefore reviewed the literature, recruited renowned clinical subspecialists and consulted as a group to examine these concerns. Some of the effects examined appeared to be minimal in impact or difficult to distinguish from risk to untreated populations. However, several areas require further study to allow a more precise understanding of these risks.

The quality of life of children with attention deficit/ hyperactivity disorder: a systematic review

Quality of life (QoL) describes an individual’s subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents’ perspective. QoL outcomes should be included as a matter of course in future treatment studies.