Etiology Of Attention Deficit Hyperactivity Disorder Research Articles

Identification of DNA variants in the SNAP-25 gene and linkage study of these polymorphisms and attention-deficit hyperactivity disorder.

The gene for the synaptic vesicle docking fusion protein, synaptosomal-associated protein of 25 kDa (SNAP-25), has been implicated in the etiology of attention-deficit hyperactivity disorder (ADHD) based on the mouse mutant strain coloboma. This neutron-irradiation induced mouse strain is hemizygous for the deletion of the SNAP-25 gene and displays spontaneous hyperactivity that is responsive to dextroamphetamine. Because of these characteristics, this strain has been suggested to be a mouse model for ADHD. We identified using single stranded conformational polymorphism analysis (SSCP) four DNA sequence variants in the 3' untranslated region of the human SNAP-25 gene. We searched for polymorphisms in the 3' untranslated region because the intron/exon structure of this gene has not yet been determined. We tested for linkage of this gene and ADHD using two of the identified polymorphisms that change a restriction enzyme recognition site. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test in a sample of 97 small nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We observed biased transmission of the haplotypes of the alleles of these two polymorphisms. Our findings are suggestive of a role of this gene in ADHD.

Parallels between attention deficit hyperactivity disorder and behavioral deficits produced by neurotoxic exposure in monkeys.

Attention deficit hyperactivity disorder (ADHD) is a disability that affects between 3 and 7% of children, with a significant number of individuals continuing to be affected into adolescence and adulthood. ADHD is characterized in part by an inability to organize complex sequences of behavior, to persist in the face of distracting stimuli, and to respond appropriately to the consequences of past behavior. There are some parallels between the features of ADHD and the behavior of monkeys exposed developmentally to lead or polychlorinated biphenyls (PCBs), as evidenced by research from our laboratory. Both lead and PCB exposure produce deficits on discrimination reversal and spatial delayed alternation performance; treated monkeys exhibit deficits in their ability to change an already established response strategy and inhibit inappropriate responses. Monkeys exposed developmentally to lead or PCBs also perform differently from control monkeys on a fixed interval schedule of reinforcement, which requires the temporal organization of behavior using only internal cues. Whereas the etiology of ADHD is multifactorial, the possibility that neurotoxic agents in the environment contribute to the incidence of ADHD warrants attention.

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.

Adult attention deficit hyperactivity disorder and the dopamine D4 receptor gene.

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow up studies have indicated that 22-33% of patients continue to suffer from ADHD during late adolescence and adulthood. Convincing evidence supports the contribution of genetic factors in the etiology of ADHD, and the interaction of the psychostimulants with the dopamine system suggests that dopamine is involved in the pathophysiology. The 7-repeat allele of the 48 base pair repeat of the dopamine D4 receptor gene (DRD4) has been reported, with several replications, to be associated with ADHD in children. We tested for the presence of association between the DRD4 48 base repeat and adult ADHD in two independent samples: one comprised of cases and ethnically matched controls, and the second made up of nuclear families. Each case was assessed using a battery of adult ADHD assessment instruments. The analysis of the 66 cases and 66 controls showed a significantly higher presence of the 7-repeat in the adult ADHD patients vs. controls (chi(2) = 5.65; df = 1; P = 0.01). In the analysis of transmission of DRD4 alleles in 44 nuclear families with the transmission disequilibrium test, a trend was observed toward a increased transmission of the 7-repeat from the heterozygous parents to the affected offspring (chi(2) = 2.00; df = 1; P = 0.15). When the two samples were combined, the overall significance was stronger (N = 110; z = 2.68; P = 0.003). The results of our study suggest a role of the 7-repeat allele in adult subjects suffering from ADHD. This finding is an important continuation of the group of studies that together strongly suggest the involvement of DRD4 in ADHD.

Unravelling sleep problems in treated and untreated children with ADHD.

This study investigated parental perception of sleep problems in stimulant treated and untreated children with Attention Deficit Hyperactivity Disorder (ADHD). Parents of 135 psychiatric clinic referred children and 83 pediatric outpatients completed a sleep questionnaire and the Child Behavior Checklist. Moderate to severe "sleep problems" reportedly occurred at least once a week in 19.3% of children with ADHD, 13.3% of the psychiatric controls, and 6.2% of the pediatric controls. Children with ADHD treated with stimulants were reported to display a higher prevalence of nightly "severe" sleep problems than did untreated children with ADHD. Almost a third (29%) of stimulant treated ADHD children were reported to display increased sleep latency or insomnia every night versus 10% of untreated children with ADHD. Despite the high prevalence of sleep related problems in ADHD, the significance of the association between delayed sleep onset and ADHD with regard to etiology and management of ADHD is still poorly understood.

Comorbidity in ADHD: Implications for Research, Practice, and DSM-V

Since the introduction of DSM-III/III-R, clinicians and investigators have shown increasing interest in the study of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity patterns is needed to guide treatment, research and future classification approaches. The ADHD literature from the past 15 years was reviewed to (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the correlates and longitudinal predictors of comorbidity; and (3) determine the extent to which comorbid patterns convey unique information concerning ADHD etiology, treatment and outcomes. To identify potential new syndromes, the authors examined comorbid patterns based on eight validational criteria. The largest available body of literature concerned the comorbidity with ADHD and conduct disorder/aggression, with a substantially smaller amount of data concerning other comorbid conditions. In many areas the literature was sparse, and pertinent questions concerning comorbidity patterns remain unexplored. Nonetheless available data warrant the delineation of two new subclassifications of ADHD: (1) ADHD aggressive subtype, and (2) ADHD, anxious subtype. Additional studies of the frequency of comorbidity and associated factors are greatly needed to include studies of differential effects of treatment of children with various comorbid ADHD disorders, as well as of ADHD children who differ on etiological factors.

Attention Deficit Hyperactivity Disorder (ADHD): Selected review of causes, comorbidity and treatment

A limited review of the causes, comorbidity, diagnosis and treatment is offered to emphasize the difficulties in diagnosing and treating Attention Deficit Hyperactivity Disorder and Hyperkinetic Disorder. Some of the difficulties include controversies about the existence of a separate disorder, the changes in symptoms with age, the short-lived improvement on medication and the claims of unsubstantiated treatments. This selected review should help the reader to consider recent findings in the aetiology, diagnosis and treatment of ADHD.

Is Season of Birth a Risk Factor for Attention-Deficit Hyperactivity Disorder?

To investigate seasonal variations in the birth patterns of children with attention-deficit hyperactivity disorder (ADHD) in reference to a group of normal control children, attending to issues of comorbidity, familiality, and learning disability. Subjects were boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). The ADHD children were stratified by the presence of comorbid psychiatric disorders, learning disability, and family history of ADHD, and logistic regression was used to estimate relative risks. No statistically major effect for season of birth was observed in the comparison of ADHD and control children. However, significant effects were found for September births for ADHD children with learning disability (odds ratio = 5.4) and for ADHD children without psychiatric comorbidity (odds ratio = 4.5). A trend was also noted for winter births in ADHD children with learning disabilities, no psychiatric comorbidity, and positive family history for ADHD. These preliminary results suggest that there may be a seasonal pattern of birth for subtypes of ADHD. If season of birth serves as a proxy for the timing of seasonally mediated viral infections, it may lead to a greater understanding of the etiology and pathophysiology of ADHD.

Relationship between ADHD and Central Auditory Processing Disorder

It is increasingly apparent that differential diagnosis of children with Attention-deficit Hyperactivity Disorder (ADHD) is, at best, difficult, with a majority of children identified as ADHD also diagnosed with co-occurring developmental learning disorders. Most notably, children with ADHD have been found to have a high prevalence of language problems. Research has further indicated that children with ADHD demonstrate significant difficulty on tasks used to assess central auditory processing skills and that these difficulties are ameliorated by the use of stimulant medication. Early findings raised the question of whether ADHD and Central Auditory Processing Disorder (CAPD) can be differentiated, or if they represent a singular disorder. Literature highlignting the similarity of psychoeducational and behavioral sequelae of children with CAPD and those with ADHD are presented. Studies of central auditory processing abilities in children diagnosed as having ADHD as well as a more recent study investigating the prevalence of ADHD in children diagnosed as CAPD are reviewed as well. Given the overlap in etiology and symptomatology of ADHD and auditory/linguistic disorders such as CAPD, the need for a collaborative effort on the part of professionals who work with these children (school psychologists, speech-language pathologists, audiologists) in diagnosis and intervention planning as well as other implications of this research are presented.

Behavioral variability in SHR and WKY rats as a function of rearing environment and reinforcement contingency.

The spontaneously hypertensive rat (SHR) may model aspects of human attention deficit hyperactivity disorder (ADHD). For example, just as responses by children with ADHD tend to be variable, so too SHRs often respond more variably than do Wistar-Kyoto (WKY) control rats. The present study asked whether behavioral variability in the SHR strain is influenced by rearing environment, a question related to hypotheses concerning the etiology of human ADHD. Some rats from each strain were reared in an enriched environment (housed socially), and others were reared in an impoverished environment (housed in isolation). Four groups--enriched SHR, impoverished SHR, enriched WKY, and impoverished WKY--were studied under two reinforcement contingencies, one in which reinforcement was independent of response variability and the other in which reinforcement depended upon high variability. The main finding was that rearing environment did not influence response variability (enriched and impoverished subjects responded similarly throughout). However, rearing environment affected body weight (enriched subjects weighted more than impoverished subjects) and response rate (impoverished subjects generally responded faster than enriched subjects). In addition, SHRs tended to respond variably throughout the experiment, whereas WKYs were more sensitive to the variability contingencies. Thus, behavioral variability was affected by genetic strain and by reinforcement contingency but not by the environment in which the subjects were reared.

ADHD in Adults: A Clinical Guide

Originally published in Contemporary Psychology: APA Review of Books, 1996, Vol 41(10), 1026–1027. The author of this text (see record 1995-98003-000) is recognized as one of the first clinical researchers to understand attention deficit hyperactivity disorder (ADHD) as a neurobiological disorder and as an adult disorder. His pioneering research has encompassed issues of etiology, diagnosis, assessment, and treatment of ADHD. In this book, Wender has focused on work demonstrating that in a substantial number of individuals the disabling impairments of ADHD that appear in childhood do in fact continue into adulthood. In the first section of the book, Wender provides excellent descriptions of the cardinal symptoms of ADHD and how they are manifest in adults. They are followed by a comprehensive review of the epidemiology of ADHD and its prevalence in the adult population. Those with clinical interests will find valuable the subsequent presentation of information on diagnostic criteria and assessment tools. Likewise, clinicians will find useful his discussion of the multimodal use of medical, educational, and psychological treatments in assisting patients. The reviewer suggests that this book is a fine resource for anyone with a serious interest in ADHD in adults or in research on the topic. Readers will be informed by the comprehensive exposition of information about this complex but common psychiatric disorder. (PsycINFO Database Record (c) 2006 APA, all rights reserved)

Genetics of Attention-Deficit Hyperactivity Disorder

The authors review family, twin, adoption, and segregation analysis studies of attention-deficit hyperactivity disorder (ADHD) and show that these studies support the hypothesis that both genetic and environmental factors are relevant to the etiology of ADHD.

Comorbidity of Diagnosis in Attention-Deficit Hyperactivity Disorder

Attention-deficit hyperactivity disorder (ADHD) is increasingly recognized as a heterogeneous disorder with considerable comorbidity not only with conduct disorder but also with depressive and anxiety disorders. Current research findings suggest that subgroups of children with ADHD might be delineated based on the presence of comorbidity. These subgroups may have differing risk factors, clinical course, and pharmacologic responses. Thus, their proper identification may lead to refinements in preventive and treatment strategies. Investigation of these issues should help to clarify the etiology, course, and outcome of ADHD.