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PubMed1998

Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral problem afflicting 5-10% of children and adolescents and persisting into adulthood in 30-50% or more of cases. Family, twin, and adoption studies suggest genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and hyperactivity. Because stimulant intervention is effective in reducing ADHD symptoms in about 70-80% of cases, molecular genetic investigations of genes involved in dopamine regulation are currently underway by many groups. In a case control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and colleagues found an increase of a 7-repeat variant of a 48-bp VNTR in exon 3 among ADHD subjects compared to controls. Swanson and colleagues replicated this finding in a sample of 52 ADHD probands and their biological parents using a haplotype relative risk analysis. Here, we describe linkage investigations of the VNTR and ADHD in affected sibling pair (ASP) families and singleton families using both the transmission disequilibrium test (TDT) and a mean test of identity-by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is differentially transmitted to ADHD children (P = 0.03) while the mean test revealed no evidence of increased IBD sharing among ASPs. In the current sample, the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of the allele estimated under a model described by Risch and Merikangas.

Adult↗

PubMed2006

Attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a behavioral diagnosis based on the presence of developmentally inappropriate levels of impulsivity, overactivity, and inattentiveness. It is a familial condition with a complex pattern of inheritance. Variation of several genes involved in the regulation of dopamine, norepinephrine, and serotonin neurotransmission is associated with ADHD. We highlight the two most prominent findings with the dopamine D4 receptor (DRD4) gene and the dopamine transporter (DAT1) gene, and their implications for the understanding of the cellular and neurobiological basis for ADHD. Cognitive and functional studies using electrophysiology and brain imaging frequently indicate altered processing in ADHD during performance on cognitive tasks hypothesized to measure a "core" deficit, such as response inhibition. Yet, children with ADHD appear to suffer from a more general deficit, including impairment in attentional alerting, orienting, response preparation, and control. Reward processes are also altered and, further, a strong association emerges with intraindividual variability, with several causal hypotheses being proposed. Task performance correlates with underactivation of, especially, frontostriatal areas of the brain, but an extended network of brain regions is also implicated. Electroencephalography studies indicate abnormalities in ADHD in relation to slow-wave activity, linked to underarousal. These advances in the areas of genetics, cognitive function, neurophysiology, and neuroanatomy of ADHD give important leads for interdisciplinary research that aims to delineate the causal pathways. Such research is only at its beginning, but is illustrated by recent findings of an association between DAT1 and increased response variability in ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Preferential transmission of interleukin-1 receptor antagonist alleles in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, where family data support substantial heritability.(1) To date, association studies focussed mainly on genes regulating dopaminergic neurotransmission.(2)Interleukin-1 (IL-1) activity in the brain has been implicated with differentiation of dopaminergic neurons(3,4) and modulation of central monoaminergic reactivity.(5) We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) gene variable number tandem repeat (VNTR) polymorphism,(6) in a sample of 86 children with DSM-IV ADHD and their parents. Transmission disequilibrium analysis showed increased transmission of the IL-1Ra 4-repeat allele (chi(2) = 4.07, P = 0.04) and decreased transmission of the 2-repeat allele (chi(2) = 4.59, P = 0.03) to affected children. The 4-repeat allele was associated with a significantly increased risk for ADHD (chi(2) = 4.46, df 1, P = 0.035, RR = 1.292, 95% CI 1.01-1.66). The IL-1Ra 2-repeat allele was associated with a significantly decreased risk for ADHD (chi(2) = 4.65, df 1, P = 0.03, RR = 0.763, 95% CI 0.59-0.98). If replicated, this finding may point to a role for brain cytokine activity in the etiopathogenesis of ADHD.

Adolescent↗

PubMed2006

Oral health, dental anxiety, and behavior management problems in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common developmental disorder. The aim of this study was to investigate whether children with ADHD have a higher caries prevalence, a higher degree of dental anxiety, or more dental behavior management problems (BMP) than children of a control group. Twenty-five children with ADHD and a control group of 58 children, all aged 11 yr, were included in the study. The children underwent a clinical dental examination, and bitewing radiographs were taken. The parents completed the Dental Subscale of Children's Fear Survey Schedule (CFSS-DS). Dental records from the subjects were obtained, and data regarding notes on behavior management problems (BMP) of the children when between 3 and 10 yr of age were compiled. Compared with controls, children with ADHD had significantly higher decayed, missing or filled surfaces (DMFS) (2.0 +/- 3.0 vs. 1.0 +/- 1.5) and significantly higher decayed surfaces (DS) (1.7 +/- 3.6 vs. 0.5 +/- 0.9). Differences between the groups regarding CFSS-DS scores were non-significant. In the ADHD group, the prevalence of BMP increased when the children were between 7 and 9 yr of age. In conclusion, children with ADHD exhibited a higher caries prevalence, did not exhibit a higher degree of dental anxiety, and had more BMP than children of a control group.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

The neurological basis of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a serious disability with long-term consequences. At present the disorder is considered organic in pathology, particularly in regard to central nervous system functioning. This paper reviews research on ADHD. The role of neurochemical stimulation is discussed, and the signs of neurological deficits are explored. Nearly 600,000 young people in the United States receive medication daily for ADHD, and these drugs mimic brain neurotransmitters. The chemical action of these drugs and the cognitive, affective, and behavioral effects are discussed. Side effects and dosage levels are also examined. Basic behavior modification with ADHD children and how these techniques can be combined with effective drug treatment are elaborated.

Attention Deficit Disorder with Hyperactivity↗

PubMed1998

Current drug therapy recommendations for the treatment of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is characterised by symptoms of inattentiveness and/or hyperactivity-impulsivity which are not appropriate to the child's age. This disorder usually manifests by age 3 and affects up to 5% of school-age children. Although the aetiology is unknown, ADHD appears to have a strong genetic component and to involve dysregulation of the CNS dopaminergic system. Psychostimulants are the mainstay of therapy. The majority of patients will respond to an adequate trial of one of the 3 available stimulants, methylphenidate, dexamphetamine or pemoline. Use of the tricyclic antidepressants as second-line agents is supported by substantial literature. Third-line agents include amfebutamone (bupropion) and clonidine. Other modalities have been studied, but sufficient research is not available to recommend their use over the abovementioned treatments. Assessment of response is best achieved by objective rating scales which allow for input from various environments.

Antidepressive Agents, Tricyclic↗

PubMed2003

Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor-adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters and therefore has been suggested as a strong candidate gene for ADHD. Animal and human studies have implicated MAOA and 5-HT in impulsive and aggressive behavior. We therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. We have tested this hypothesis by genotyping two polymorphisms (the 30-bp VNTR in the promoter and the Fnu4HI 941T-->G) in MAOA that are associated with altered MAOA function. Our sample consisted of 171 British Caucasian children 6-16 years of age fulfilling DSM-III R, DSM-IV or ICD-10 criteria for ADHD/Hyperkinetic Disorder. Using case control analysis and then the TDT, no association was found between these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed an association with a subgroup of children with comorbid conduct problems (OR = 2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward association. Our findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined.

Adolescent↗

PubMed2002

Frontoorbital volume reductions in adult patients with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric disorder in childhood and adolescence and in a considerable number of patients it persists into adulthood. A network of brain regions have been shown to be abnormal in ADHD. In the present study we used magnetic resonance volumetry to investigate a possible role of the orbitofrontal cortex (OFC). Eight never medicated male patients fulfilling diagnostic criteria for ADHD and 17 male healthy controls were investigated. There was a significant reduction of the volume of the left OFC in patients with ADHD. It remains unknown whether small volumes are a primary deficit or a result of dysfunctional activation during childhood in terms of a residual deficit or a specific type of adult outcome of the disease.

Adult↗

PubMed2002

Specificity of quantitative EEG analysis in adults with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) in children and adolescents is characterised by excessive restlessness and an extremely poor concentration span, resulting in impulsive and disruptive behaviour. Clinical observation of ADHD in adults suggests that the early hyperactivity is diminished in terms of its impact on social and academic function, while impulsive-type behaviours remain unchanged. EEG studies in children and adolescents with ADHD have reported significantly more low-frequency power (predominantly theta) and less high-frequency power (predominantly beta) than in normal subjects. In normal children and adolescents, a decrease in theta power and an increase in beta power are found with increasing age, leading some researchers to interpret the EEG anomalies in ADHD as evidence of developmental delay. Studies of adults with ADHD compared with normal adult control subjects have found a reduction in the difference between the two groups, suggesting that the reduced beta activity apparent in ADHD children and adolescents changes with age. Adults with ADHD thus appear to have elevated low-frequency power as their predominant EEG difference from normal control subjects. The present study examined whether this EEG profile was specific to adult ADHD patients. Quantitative EEGs were recorded at rest in an eyes-open condition and used to compare 50 adult patients diagnosed with ADHD with 50 non-ADHD subjects (who presented for ADHD assessment but failed to meet the diagnostic criteria) and 50 control subjects. The ADHD group differed from both the non-ADHD and the control groups on the basis of elevated theta activity. The ADHD and control groups did not differ in beta activity, but relative theta was reduced and relative beta power was elevated in the non-ADHD group compared with both the ADHD and control groups. These results suggest that quantitative EEG may be used to differentiate ADHD adults from both normal adults and adults who display some of the symptoms of ADHD, but fail to meet the diagnostic criteria of ADHD.

Adult↗

PubMed1999

Circulatory levels of catecholamines, serotonin and lipids in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) may be associated with a dysregulation of the catecholaminergic and serotonergic systems. Furthermore, ADHD is frequently complicated by aggressive impulsive behaviour, which is suggested to be related to low serum cholesterol levels. We examined the relationship between blood serotonin, norepinephrine, dopa and lipid levels and the degree of hyperactivity, impulsiveness, lack of concentration, and aggressiveness in boys with ADHD of low and high severity as determined by a specially designed formulated scale based on the DSM-IV criteria for ADHD. No differences were noted between the groups in any of the peripheral biological parameters except blood serotonin, for which a tendency (P=0.08) towards lower levels was observed in the children with more severe disorder. We conclude that children with severe ADHD may have a different serotonin turnover compared to children with mild ADHD. These results may have implications for our understanding of the pathogenesis of ADHD, at least the more severe type.

Adolescent↗

PubMed2005

Identification and characterization of human NR4A2 polymorphisms in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable and common disorder thought to arise, in part, from alterations in dopamine function. NR4A2, or Nurr1, is an orphan nuclear receptor implicated in the development of dopaminergic cells of the ventral tegmental area (VTA) and the substantia nigra (SN). Dopaminergic cells of the VTA provide innervation to the prefrontal cortex, believed to be of major importance in the etiology of ADHD, suggesting that NR4A2 is a potential candidate gene for ADHD susceptibility. This study aimed to identify polymorphisms in NR4A2 and test their association to ADHD. Database analysis revealed a CA repeat polymorphism in the 3' UTR of NR4A2 that was confirmed by PCR. SSCP screening revealed a common DeltaC polymorphism, 254 bp 5' to the transcriptional start site. These polymorphisms were tested for an association with ADHD in both a case control study of individuals from the Milwaukee Longitudinal Study of ADHD (103 cases and 66 controls), and in 35 families composed of trios or affected sib pairs (ASP) with ADHD. Functional effects of the promoter polymorphism were tested in vitro. The non-deleted allele was significantly more active in undifferentiated SK-N-MC cells compared to differentiated SK-N-MC and HeLa cells while a trend for increased activity for the DeltaC allele was observed in undifferentiated SK-N-MC cells. Identification of these polymorphisms may aid future candidate gene studies in disorders with altered dopamine signaling, such as schizophrenia Parkinson's disease and ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

Teachers' perceptions of the incidence and management of attention-deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) continues to be a common diagnosis of school children, and according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV], American Psychiatric Association, 1994), it affects approximately 3%-5% of the population. Teachers are often the primary source of information regarding ADHD diagnoses in school children. A previous study by Glass and Wegar (2000) found that teachers were overidentifying children with ADHD and that medication was preferred as the primary treatment for these students. This study further examined teacher perceptions on the causes, incidence, and appropriate treatment methods of ADHD. In addition, this study also examined the prevalence of ADHD as determined by ADHD Rating Scale-IV (School Version; DuPaul et al., 1998) and examined differential identification rates by gender and ethnicity. Results showed that teachers were likely to identify children as having ADHD at rates higher than the expected prevalence rates specified in DSM-IV. Out of 121 rating scales analyzed, 23.97% of students were identified by teachers as meeting criteria for 1 of the 3 types of ADHD. Males had significantly higher scores than females and Whites had significantly higher scores than Hispanics. Class size was also associated with the likelihood that teachers would identify more than 5% of their students as having ADHD. Results suggest that, despite increasing evidence of a connection between biological factors and ADHD, environmental factors (i.e., class size and culture) may still influence teachers' perceptions about what students have the disorder.

Adult↗

PubMed2002

Dopamine transporter density in the basal ganglia assessed with [123I]IPT SPET in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder in childhood that is known to be associated with dopamine dysregulation. In this study, we investigated dopamine transporter (DAT) density in children with ADHD using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([(123)I]IPT) single-photon emission tomography (SPET) and postulated that an alteration in DAT density in the basal ganglia is responsible for dopaminergic dysfunction in children with ADHD. Nine drug-naive children with ADHD and six normal children were included in the study. We performed brain SPET 2 h after the intravenous administration of [(123)I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific DAT binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of ADHD symptoms in children with ADHD assessed with ADHD rating scale-IV and the specific/non-specific DAT binding ratio in the basal ganglia. Drug-naive children with ADHD showed a significantly increased specific/non-specific DAT binding ratio in the basal ganglia compared with normal children. However, no significant correlation was found between the severity scores of ADHD symptoms in children with ADHD and the specific/non-specific DAT binding ratio in the basal ganglia. Our findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

[Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2003

Increased levels of ethane, a non-invasive marker of n-3 fatty acid oxidation, in breath of children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.

Attention Deficit Disorder with Hyperactivity↗

PubMed2006

Effect of methylphenidate on Stroop Color-Word task performance in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome common in the pediatric population. It is associated with multiple nonspecific deficits on neuropsychological tests of executive function, and a beneficial response to pharmacotherapy with methylphenidate (MPH) and other psychostimulants. The Stroop Color-Word task is used empirically as an aid in diagnosis and treatment monitoring of ADHD; however, data on the sensitivity of the Stroop interference score to the effects of MPH are limited. To address this issue, we studied Stroop performance in a cohort of 18 MPH-treated prepubescent boys with ADHD and six healthy controls on and off MPH treatment conditions. MPH significantly improved performance in both groups, with the ADHD participants consistently displaying worse scores than those of controls both on and off MPH. These results suggest that though the diagnostic value of the Stroop task in ADHD remains controversial, it has heuristic value for monitoring clinical responses to MPH treatment. More research is needed to ascertain the clinical significance of our findings and to replicate this relatively small effect in a larger cohort, to determine whether MPH effects on Stroop performance are specific to ADHD symptoms or they generalize to other forms of symptomatology.

Adolescent↗

PubMedDate not supplied

The nursing student with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) in college-age students presents a complex challenge of coping with academic coursework, refining life skills, and addressing self-limitations. Behaviors that characterize ADHD are particularly problematic for nursing students, especially when the student has difficulty with behaviors that exemplify executive functioning. The authors discuss symptoms and treatments associated with the diagnosis of ADHD and evaluation and interventions for college students, based on guidelines from the Americans With Disabilities Act. Nursing faculty can facilitate academic success by recognizing the problem in nursing students and implementing strategies useful for self-management of ADHD.

Adaptation, Psychological↗

PubMed2005

The genetics of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable, disruptive, childhood-onset condition, the aetiology and pathogenesis of which is poorly understood. There have been relatively few genome-wide linkage studies, and no chromosomal region has yet been unequivocally implicated. In contrast, evidence from pharmacological, neuroimaging and animal studies has suggested the involvement of specific neurotransmitter systems, notably dopaminergic pathways, in ADHD and these aetiological clues have inspired a fruitful application of the candidate gene association approach. Meta-analyses or pooled data analyses have supported association between ADHD and polymorphisms in DRD4, DRD5 and SLC6A3 which encode dopamine D4 and D5 receptors and the dopamine transporter, respectively. A weaker, but nevertheless replicated, body of evidence also supports associations with SNAP-25 (synaptosomal-associated protein, 25 kDa) and SLC6A4 (serotonin transporter). There is increasing research interest in gene-phenotype links, clinical phenotypic markers of heterogeneity and gene--environment interaction, which are likely to be important in the next generation of genetic studies.

Attention Deficit Disorder with Hyperactivity↗