Refining the attention deficit hyperactivity disorder phenotype for molecular genetic studies

It is well established that attention deficit hyperactivity disorder (ADHD) is a familial and highly heritable disorder. Consequently, much effort is being directed towards searching for specific susceptibility genes. There is a growing trend, across the field of complex disease genetics, towards undertaking secondary analyses based on refined phenotypic definitions and in testing whether specific susceptibility genes modify the phenotypic presentation of the disorder in question. It is crucial that good, empirically derived arguments are made before undertaking multiple analyses on different phenotype refinements. In this review article, we consider the evidence from genetic epidemiological studies as well as key clinical studies that provide guidance on examining the ADHD phenotype for the purpose of molecular genetic studies. Specifically, findings on categorical versus dimensional conceptualisations of ADHD, reporter effects, comorbidity, ADHD subtypes and persistence are reviewed. Current evidence suggests that for the purpose of identifying susceptibility genes for ADHD, parent and teachers should be used as informants and that focusing on the clinical diagnosis of ADHD is useful. There is also good empirical support in favour of examining antisocial behaviour in ADHD. Genetic studies of dimensional ADHD are useful for other complementary purposes.     

Analysis of methylphenidate's efficacy using the abbreviated version Conners' questionnaire in attention deficit hyperactivity disorder

The attention deficit/hyperactivity disorder (ADHD) is a complex diagnosis. Its installation is precocious, with chronic evolution that impacts on the subject's performance in several contexts. Three to 5% of the school aged children present this disorder. The Conners' questionnaire has been used as an instrument of epidemiological survey for ADHD children. OBJECTIVE: This study aimed to investigate if this instrument could be an useful tool for the analysis of the methylphenidate's treatment efficacy in ADHD's children. METHOD: Twenty-one male children were selected, with ADHD combined type, chronological ages ranging from seven to 10 years and 11 months and all were treated with methylphenidate. The Conners' questionnaire abbreviated version for parents and teachers was applied in two moments, one without medication and another between six to eight months after the beginning of the methylphenidate. RESULTS: Results pointed to a reduction in punctuation in Conners' questionnaire in all children with ADHD concomitant to clinical improvement. CONCLUSION: Conners' questionnaire revealed to be useful not only for diagnosis, but also as an instrument to evaluate the effectiveness of the treatment of ADHD.     

Genes and attention deficit hyperactivity disorder

The initial molecular genetic studies of attention deficit hyperactivity disorder (ADHD) evaluated two candidate genes (DAT and DRD4) suggested by dopamine theories of this common disorder and its treatment with stimulant medication. The initial reports of weak associations with ADHD have been replicated by many (but not all) investigators, as is expected for genes with small effects. This literature is reviewed, along with emerging literature generated by active research groups investigating additional genes that might contribute to the genetic basis of this complex disorder.     

Gait in attention deficit hyperactivity disorder

Abstract Background Cognitive function and the loading of attention presumably play an important role in gait as well as in fall risk, but previous work has not demonstrated this in any cause-and-effect way. Objectives To gain insight into the relationship between gait and cognitive function, we sought: (1) To compare the gait rhythmicity (stride time variability) of children with attention deficit hyperactivity disorder (ADHD) to controls, (2) To test the hypothesis that dual tasking leads to increased stride-to-stride variability in ADHD, and (3) To test whether pharmacological treatment that relieves ADHD symptoms reduces stride-to-stride variability. Patients and Methods Gait was quantified in children with ADHD and in age-matched healthy controls under single task and dual task conditions on three occasions: off medications (both groups) and, in the ADHD group, after double blinded, randomized administration of methylphenidate (MPH) or placebo. Results At baseline, children with ADHD tended to walk with increased stride-to-stride variability compared to the controls during the single task condition (p = 0.09). During dual task walking, stride time variability was significantly reduced in the children with ADHD (p < 0.004), but not in the controls. In the children with ADHD, the placebo did not significantly affect stride-to-stride variability or the dual tasking response. In contrast, stride time variability was significantly reduced on MPH (p < 0.001) such that dual tasking no longer affected variability. Conclusions The present findings demonstrate alterations in the gait of children with ADHD, support a cause and effect link between cognitive function and gait, and suggest that enhancement of attention abilities may, in certain populations, improve gait rhythmicity.     

Neurobiology of attention deficit hyperactivity disorder

This article addresses the current understanding of the neurobiological bases of attention deficit hyperactivity disorder (ADHD), focusing on empiric research findings that connect genetic and environmental factors to structural and functional brain abnormalities, ultimately leading to a set of age-dependent behavioral manifestations. Section one presents evidence for genetic risk factors for ADHD and discusses the role of potential environmental factors in the etiology of the disorder. Section two focuses on brain imaging studies and how they have helped generate different hypotheses regarding the pathophysiology of ADHD. Finally, the article addresses the longitudinal course of symptoms in ADHD from infancy to adulthood in an attempt to place biological findings for this complex brain disorder in the context of maturation and development.     

Genetics of attention deficit hyperactivity disorder

Results of behavioral genetic and molecular genetic studies have converged to suggest that both genetic and nongenetic factors contribute to the development of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies provide compelling evidence that genes play a strong role in mediating susceptibility to ADHD. In contrast to a handful of genome-wide scans conducted thus far, many candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder. Yet, even these associations are small and consistent with the idea that the genetic vulnerability to ADHD is mediated by many genes of small effects. These small effects emphasize the need for future candidate gene studies to implement strategies that will provide enough statistical power to detect such small effects.     

Multicomponent attention deficits in attention deficit hyperactivity disorder

The aim of this study was to examine the specific aspects of attention, such as selective attention, sustained attention, and short-term memory in children with attention deficit hyperactivity disorder, combined subtype (ADHD-C). A total of 40 children with a diagnosis of ADHD from the 4th edition of the Diagnostic and Statistical Manual, aged 6-11 years old were compared with 40 controls matched for age and gender on a battery of tests. Short-term memory span and attention was measured by Visual Aural Digit Span Test-Revised. Stroop test and the Turkish version of Cancellation Test were used to assess selective and sustained attention, respectively. In order to check for factor structure in two groups on the test scores, principal component analysis was conducted for both groups separately. Relative to the comparison children, children with ADHD showed significant deficits on tests that are related to different aspects of attention. The results are consistent with the theories explaining the biological basis of ADHD by scattered attention networks in the brain, which have reciprocal dynamic interactions. Further comparative studies are needed to elucidate whether the cognitive processes that are known to be assessed by these tests are specific to ADHD.     

Dexmethylphenidate extended-release capsules for attention deficit hyperactivity disorder

Medications for attention deficit hyperactivity disorder (ADHD) currently represent the ninth largest segment of the CNS market by sales, with 2.4 billion USD spent annually on this condition and 40% annual growth. Stimulant medications remain the most effective ADHD therapies and provide robust improvement in ADHD symptoms in both youth and adults. Current prescribing practices favor extended release preparations due to increased convenience, compliance and tolerability with once-daily dosing. Dexmethylphenidate extended release is a long-acting preparation of the ADHD medication Focalin (dexmethylphenidate immediate release) and was approved for marketing by the US Food and Drug administration in June 2005. Dexmethylphenidate consists of the single dextro-isomer form of d,l-methylphenidate commonly marketed as Ritalin. Dexmethylphenidate extended release utilizes spheroidal oral drug absorption system technology to achieve a 50% immediate medication delivery and 50% delayed release of dexmethylphenidate approximately 4 h after ingestion. Placebo-controlled, clinical trials in children and adults with ADHD have demonstrated efficacy for behavioral and academic ratings, with an analog classroom study showing medication effects up to 12 h after dosing. Dexmethylphenidate extended release was generally well tolerated with a side-effect profile similar to other stimulants. The most common reported side effects include diminished appetite and insomnia. Given its duration of effect, favorable tolerability and flexibility in dosing, dexmethylphenidate extended release is likely to gain considerable use as an ADHD treatment.     

Frontiers between attention deficit hyperactivity disorder and bipolar disorder

The co-occurrence of attention deficit hyperactivity disorder (ADHD) and bipolar disorder has received much recent attention in the literature. The authors review the literature examining associations between ADHD and bipolar disorder in children, and data concerning severe irritability in youth with ADHD. This article focuses on (1) population-based studies examining ADHD and bipolar disorder or ADHD and co-occurring irritability, (2) the co-occurrence and prospective relationships of ADHD and bipolar disorder in clinical samples, (3) phenomenology and assessment of bipolar disorder and ADHD, (4) treatment of comorbid ADHD and bipolar disorder, (5) family and genetic studies of ADHD and bipolar disorder, and (6) pathophysiologic comparisons between children with ADHD and irritability and bipolar disorder. We draw on the research to make clinical recommendations and highlight important directions for future research.     

Screening and diagnostic utility of self-report attention deficit hyperactivity disorder scales in adults

Attention deficit hyperactivity disorder (ADHD) in adults is associated with significant social, legal, occupational, and psychiatric difficulties. The estimated prevalence of ADHD in the adult population is between 0.3% and 5%. Recent interest in the condition in adults has been accompanied by the appearance of a number of readily available scales for screening adults and aiding in the diagnosis of ADHD in this age group. However, there are few published data on the validity and reliability of such measures. We examined the diagnostic and screening utility of three ADHD scales (Adult Rating Scale [ARS], Attention-Deficit Scales for Adults [ADSA], and Symptom Inventory for ADHD) in 82 adults presenting for ADHD evaluation. All three instruments were sensitive to the presence of symptoms in adults with ADHD (correctly identifying 78% to 92% of patients with ADHD), but a high proportion of individuals with non-ADHD diagnoses screened positive (incorrectly identifying between 36% and 67% of non-ADHD patients). Our results suggest that the use of such measures for screening and as an aid in diagnosis should be approached with considerable caution.     

Sustained attention in sensory modulation disorder and attention deficit/hyperactivity disorder

BackgroundThere are high comorbidity rates between sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD). Knowledge regarding the objective neuropsychological differentiation between them is scarce.AimThis study examines the effects of SMD and ADHD on a sustained attention task with and without aversive auditory conditions.MethodSixty six young adult females were tested on the Conjunctive - Continuous Performance Task-Visual (CCPT-V) measuring sustained attention, under two conditions: 1) aversive condition (with the three most aversive sounds chosen by the participant), and 2) non-aversive condition (without sounds).ResultsBoth the SMD and ADHD factors exhibited performance deficits in the sustained attention task. All study participants performed worse on both sustained attention and speed of processing when aversive sounds were present.ConclusionWe conclude that impaired sustained attention cannot differentiate between SMD and ADHD. Hence, these results should be taken under consideration in the assessment process of ADHD vs. SMD.     

Atypical outcome in attention deficit hyperactivity disorder

This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.     

Genetic influences on attention deficit hyperactivity disorder

In this article we review behavioral and molecular genetics studies of attention deficit hyperactivity disorder (ADHD). Family, twin, and adoption studies, along with segregation analyses and molecular genetic studies, all support the hypothesis that both genetic and environmental factors contribute to the etiology of ADHD. Despite this strong evidence for the familial transmission of ADHD, the mode of transmission requires further clarification. In addition, because ADHD appears to be genetically heterogeneous, more work is needed to delineate genetically homogeneous subtypes and describe the range of expression of their underlying genotypes.     

Psychosocial interventions in attention deficit hyperactivity disorder

This brief overview of psychosocial treatment approaches to attention deficit hyperactivity disorder (ADHD) concentrates on the two that receive the greatest research support, parent training in child behavior management and teacher training in classroom management. Cognitive-behavioral training of children who have ADHD has little evidence of efficacy and group social skills training has mixed or limited evidence of effectiveness. Research should focus on more theoretically driven psychosocial treatment approaches, on potential side effects or adverse events associated with this form of intervention, and on the complex pathways that affect impairment in major life activities that could guide subsequent treatment design for such impairments.     

Raising attention to attention deficit hyperactivity disorder in schizophrenia

Schizophrenia and attention deficit hyperactivity disorder (ADHD) are two psychiatric disorders with a negative impact on quality of life of individuals affected. Although they are classified into distinct disorders categories, attentional dysfunction is considered as a core feature in both conditions, either at the clinical then pathophysiological level. Beyond the obvious clinical overlap between these disorders, the Research Domain Criteria approach might offer an interesting perspective for disentangling common circuits underpinning both disorders. Hence, we review evidences regarding the overlap between schizophrenia and ADHD, at the clinical level, and at the level of underlying brain mechanisms. The evidence regarding the influence of environmental risk factors in the emergence of both disorders, and their developmental trajectories is also reviewed. Among these, we will try to elucidate the complex relationship between stimulants use and psychotic symptoms, discussing the potential role of ADHD medication in inducing psychosis or in exacerbating it. We aim that, taken together, these findings may promote further investigation with important implications both for clinicians and research. In fact, considering the amounting evidence on the overlap between schizophrenia and ADHD, the delineation of their boundaries might help in the decision for diagnosis and treatment. Moreover, it may help to promote interventions focused on the prevention of both schizophrenia and ADHD, by the reduction of recognized environmental risk factors.     

Neuroendocrine aspects of attention deficit hyperactivity disorder

This article summarizes the existing neuroendocrine literature and reports the growth hormone response to stimulation with L-dopa and clonidine in male children and adolescents with attention deficit hyperactivity disorder. Because growth hormone secretion is regulated by monoamine neurotransmitters, hyposecretion of growth hormone may reflect generalized changes in the neurochemical substrate of this disorder. With refinement, these neuroendocrine challenge tests may become unique biologic markers in identifying attention deficit hyperactivity disorder in children and adolescents.