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PubMed2004

No evidence of linkage or association between the norepinephrine transporter (NET) gene MnlI polymorphism and adult ADHD.

Attention deficit hyperactivity disorder (ADHD) is a prevalent psychiatric condition in children and follow-up studies have indicated that one to two thirds of patients continue to suffer from ADHD during late adolescence and adulthood. The mechanism of action of the new selective noradrenergic reuptake inhibitor, atomoxetine, efficacious in the treatment of ADHD symptoms, suggests that the norepinephrine transporter (NET) may be involved in ADHD. The aim of this study was to investigate for the presence of linkage disequilibrium between the MnlI RFLP in the NET gene and adult ADHD in a sample of nuclear families. The MnlI polymorphism was typed in 128 trios and analyzed using the transmission disequilibrium test (TDT). There was no preferential transmission of either allele (chi(2) = 0.209, df = 1, P = 0.647).

Adolescent↗

PubMed2004

Adrenergic alpha 2C receptor genomic organization: association study in adult ADHD.

Attention deficit hyperactivity disorder (ADHD) is a chronic psychiatric condition in children and follow up studies have indicated that one to two thirds of patients continue to suffer from ADHD during late adolescence and adulthood. Pharmacological interventions, such as the new selective noradrenergic reuptake inhibitor, atomoxetine, suggest the adrenergic system as candidate in ADHD. We examined for the presence of linkage disequilibrium between the alpha 2C adrenergic receptor (ADRA2C) microsatellite polymorphism upstream of the ADRA2C gene and adult ADHD in a sample of nuclear families. We also present new information on the genomic organization of the ADRA2C locus. The microsatellite polymorphism was typed in 128 small families and analyzed using the Transmission Disequilibrium Test (TDT). There was no preferential transmission of any allele. These findings exclude a strong effect of this ADRA2C marker on risk for ADHD in our sample of adult proband families.

Adolescent↗

PubMed2005

The serotonin transporter gene as a QTL for ADHD.

Molecular studies of attention deficit hyperactivity disorder (ADHD) have identified susceptibility genes for the categorically diagnosed disorder using operational diagnostic criteria. Here, we take a QTL approach to mapping genes for ADHD using a composite continuous index of ADHD behavior in a large epidemiological sample. Previous studies of clinical ADHD suggest that two functional polymorphisms in the serotonin transporter gene (SLC6A4), one in the 5'-regulatory region of the gene (5-HTTLPR) and the other a VNTR (5-HTTVNTR) in the second intron, as well as a single nucleotide polymorphism in the 3'-untranslated region (3'-UTR SNP), may be associated with the disorder. Here, we investigate these polymorphisms as well as an additional ten SNPs spread across the gene. We found significant association with the long (L) allele of the 5-HTTLPR; P = 0.019, but neither the 5-HTTVNTR nor the 3'-UTR SNP were significantly associated. Significant associations (P < 0.05) were found for a further 5 the 10 other markers tested. We found evidence for two haplotype blocks spanning the region. We found strong evidence for association with the first haplotype block (comprised of four markers), with the significance of a combined primary and secondary test of association reaching an empirical P value = 0.0054 for the global test and an empirical P value = 0.00081 for the largest local test. Thus, we show here that SLC6A4, which has a major influence on brain serotonin availability, may be a QTL for ADHD.

Adolescent↗

PubMed2005

Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children.

Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B) degrade biogenic amines such as dopamine and serotonin and thereby control the levels of these neurotransmitters in the central nervous system. We examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (chi2 = 5.1, P = 0.03, OR = 1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, P = 0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.

Adult↗

PubMed2005

Sequence variation in the 3'-untranslated region of the dopamine transporter gene and attention-deficit hyperactivity disorder (ADHD).

The dopamine transporter gene (DAT1) has been reported to be associated with attention-deficit hyperactivity disorder (ADHD) in a number of studies [Cook et al. (1995): Am J Human Genet 56(4):9993-998; Gill et al. (1997): Mol Psychiatry 2(4):311-313; Waldman et al. (1998): Am J Human Genet 63(6):1767-1776; Barr et al. (2001): Biol Psychiatry 49(4):333-339; Curran et al. (2001): Mol Psychiatry 6(4):425-428; Chen et al. (2003): Mol Psychiatry 8(4):393-396]. Specifically, the 10-repeat allele of the 40-bp variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region (UTR) of the gene has been found to be associated with ADHD. There is evidence from in vitro studies indicating that variability in the repeat number, and sequence variation in the 3'-UTR of the DAT1 gene may influence the level of the dopamine transporter protein [Fuke et al. (2001): Pharmacogenomics J 1(2):152-156; Miller and Madras (2002): Mol Psychiatry 7(1):44-55]. In this study, we investigated whether DNA variation in the DAT1 3'UTR contributed to ADHD by genotyping DNA variants around the VNTR region in a sample of 178 ADHD families. These included a MspI polymorphism (rs27072), a DraI DNA change (T/C) reported to influence DAT1 expression levels, and a BstUI polymorphism (rs3863145) in addition to the VNTR. We also screened the VNTR region by direct resequencing to determine if there was sequence variation within the repeat units that could account for the association. Our results indicate that DAT1 is associated with ADHD in our sample but not with alleles of the VNTR polymorphism. We did not find any variation in the sequence for either the 10- or 9-repeat alleles in the probands screened nor did we observe the reported DraI (T/C) variation. Our results therefore refute the possibility of the reported DraI variation or alleles of the VNTR as the functional variants contributing to the disorder.

3' Untranslated Regions↗

PubMed2006

An examination of the behavioral and neuropsychological correlates of three ADHD candidate gene polymorphisms (DRD4 7+, DBH TaqI A2, and DAT1 40 bp VNTR) in hyperactive and normal children followed to adulthood.

Several candidate gene polymorphisms have been implicated in attention deficit hyperactivity disorder (ADHD), including DAT1 40bp VNTR, DRD4 7+, and DBH TaqI A2 alleles. We used the Milwaukee longitudinal study of hyperactive (n = 122) and normal (n = 67) children to compare participants with and without these respective polymorphisms on ADHD-related behavioral ratings at childhood, 8 years later in adolescence, and 13+ years later into young adulthood. Neuropsychological tests were given at the adolescent and young adulthood follow-up. No differences were found between the DRD4-7+ and 7- repeat polymorphism. The DBH TaqI A2 allele, when homozygous, was associated with being more hyperactive in childhood, having more pervasive behavior problems at adolescence, and earning less money on a card playing task in adulthood. At adolescence, poorer test scores were also found only in the hyperactive group with homozygous for this allele. The DAT1 40bp VNTR heterozygous 9/10 repeat, however, differed from the 10/10 repeat pair in many respects, having greater ADHD and externalizing symptoms at all three follow-ups, more cross-situational behavioral problems at both childhood and adolescence, poorer mother-teen relations at adolescence, and lower class rankings in high school. Participants with the 9/10 pair in the control group also had lower work performance, a lower grade point average in high school, greater teacher rated externalizing symptoms at adolescence, and greater omission errors on a continuous performance test in adulthood. The DAT1 40bp VNTR 9/10 polymorphism pairing appears to be reliably associated with greater symptoms of ADHD and externalizing behavior from childhood to adulthood, and with family, educational, and occupational impairments. We also present a contrary view on the appropriate endophenotypes for use in behavioral genetic research on ADHD.

Adolescent↗

PubMed2007

Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): an update.

Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431-434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder.

Adolescent↗

PubMed2005

Career choices and workplace challenges for individuals with ADHD.

Attention deficit hyperactivity disorder (ADHD) in adults is increasingly recognized as a common disorder that can significantly impact workplace functioning, yet few clinicians or career consultants have training in how to help adults select careers or jobs within a chosen career that are a good match for their strengths, weaknesses, ADHD tendencies, and coexisting conditions. Straightforward career counseling is inadequate to meet the needs of adults who have ADHD, and significant follow-up, brain-based counseling or therapy is often necessary to help these adults implement the recommendations generated by an ADHD career assessment. This article guides the clinician through the multiple steps of clinical interview, assessment, and intervention when working with adults who have ADHD who face challenges in the workplace.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome.

Hyperkinetic disorders may involve excess excitatory output from thalamus to cerebral cortex. Case-control, neurophysiological studies in persons with Tourette Syndrome (TS), Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD) support this model. To compare the strength of association between motor cortex inhibition and tic, ADHD, and OCD severity in TS, we used transcranial magnetic stimulation to measure motor cortex inhibition in 36 children and adults with TS. Current symptom severity was assessed with standard clinical rating scales and compared with neurophysiological measures using correlational and multivariate regression analyses. Severity of ADHD symptoms and motor tics were associated significantly and independently with short interval intracortical inhibition (SICI) (r(2) = 0.50; F[2,27] = 13.7; P < 0.001), particularly in subjects not taking neuroleptics (r(2) = 0.68; F[2,17] = 17.8; P < 0.0001). The correlation of cortical disinhibition was greater with ADHD symptoms severity (r = 0.53; P = 0.003) than with tic severity (r = 0.42; P = 0.02), suggesting that in TS, the association between SICI and ADHD symptoms may be more consistent or direct than the association between SICI and tics.

Adolescent↗

PubMed2002

Factorial validity, reliability of assessments and prevalence of ADHD behavioural symptoms in day and residential treatment centres for children with behavioural problems.

This study uses the attention deficit/hyperactivity disorder (ADHD) symptom ratings of professional care workers to estimate the prevalence of ADHD symptoms among children in day treatment centres (N = 162) and residential treatment centres (N = 195) in Holland. Although further research is needed, the study supports the suggestion that such ratings can add to reliable diagnostic outcomes when assessing the behavioural symptoms of ADHD in children in the centres. It is estimated that nearly a fifth of the children in such centres exhibit the symptoms of ADHD in the judgement of professional care workers. Model testing using confirmatory factor analysis favours a dimensional behavioural model that comprises all the three constitutional symptom dimensions of ADHD (inattention, hyperactivity and impulsivity) instead of the two-factor model as used in the DSM-IV (inattention and hyperactivity/impulsivity). However, the differences of fit between both models were only small and the hyperactivity and impulsivity factors were highly correlated. This suggests that, in practice, a two-factor model can also be appropriate. The issue of whether a two-factor or a three-factor model is more appropriate thus remains unsolved in this study.

Adolescent↗

PubMed2005

ADHD: strategies to unravel its genetic architecture.

Attention deficit/hyperactivity disorder (ADHD) is a common and impairing neuropsychiatric disorder with onset at preschool age and strong persistence over time. Its validity as a psychiatric disorder has been established according to Robins and Guze criteria. Genetic factors predominate in the etiology of ADHD. This paper summarizes the current status of genetic research into ADHD, and describes eight factors that complicate research into genetically complex disorders as ADHD. These factors are that multiple genes of small main effects are involved rather than main genes, the relevant phenotype is unknown, presence of clinical heterogeneity, presence of genetic heterogeneity, gene-environment correlation, gene-environment interaction, importance of endophenotypes, and importance of developmental factors. The further unraveling of the genetic architecture of ADHD will depend to a large extent on how well these complicating factors are handled or even used.

Attention Deficit Disorder with Hyperactivity↗

PubMed1990

Comorbidity of ADHD and reading disability among clinic-referred children.

Of a consecutive series of 115 boys diagnosed in a university outpatient clinic as ADHD, 39% also demonstrated a specific reading disability. Pure ADHD patients were compared with mixed ADHD + RD and normal controls on a battery of cognitive and attentional measures. The aim was to determine whether a distinct pattern of deficits would distinguish the groups. Both ADHD subgroups performed significantly worse than controls on measures of sequential memory and attentional tasks involving impulse control and planful organization. Only ADHD + RD boys differed from controls on measures or rapid word naming and vocabulary. The results are discussed within the framework of an automatic versus effortful information-processing model.

Achievement↗

PubMed1996

What they want and what they get: the social goals of boys with ADHD and comparison boys.

Twenty-seven boys diagnosed with attention-deficit hyperactivity disorder (ADHD) and 18 comparison boys participated in a competitive tetradic interaction task. Boys were individually interviewed before the game about their goals for the interaction, and adult observers inferred boys' social goals from videotapes of the interaction. Social acceptance was determined by combining positive and negative sociometric nominations collected through individual interviews at the end of the summer research program in which the interaction was held. In their self-reports, ADHD-high aggressive boys prioritized trouble-seeking and fun at the expense of rules to a greater extent than did both ADHD-low aggressive and comparison boys. Observers judged ADHD-high aggressive boys to seek attention more strongly and seek fairness less strongly than of the other two groups. Self-reported goals of defiance and cooperation predicted boys' end-of-program social standing, even with interactional behaviors and subgroup status controlled statistically. Observer-inferred goals were differentially associated with social acceptance for ADHD and comparison boys, suggesting discontinuities in peer interaction processes. Differentiation of goals from behavior and the integral role of children's goals in peer acceptance are discussed.

Aggression↗

PubMed1995

No confirmation of Geschwind's hypothesis of associations between reading disability, immune disorders, and motor preference in ADHD.

Geschwind and colleagues have proposed an association among reading disability, immune disorder, and motor preference. Although reading disability commonly overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been previously examined in studies evaluating Geschwind's hypothesis. In this paper we evaluate whether ADHD is associated with either asthma or left motor preference and whether asthma and left motor preference are associated with each other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). Information on reading disability, asthma, and motor preference was obtained in a standardized manner blind to the proband's clinical status. Neither ADHD nor reading disability was associated with either asthma or left motor preference nor was asthma and left motor preference associated with one another. Our results are not consistent with Geschwind's hypothesis linking reading disability, immune disorder, and left motor preference.

Adolescent↗

PubMed2003

Parental explanatory models of ADHD: gender and cultural variations.

BACKGROUND: This study describes parents' explanatory models of Attention Deficit Hyperactivity Disorder (ADHD) and examines model variation by child characteristics. METHOD: Children with ADHD (N = 182) were identified from a school district population of elementary school students. A reliable coding system was developed for parental responses obtained in ethnographic interviews in order to convert qualitative into numerical data for quantitative analysis. RESULTS: African-American parents were less likely to connect the school system to ADHD problem identification, expressed fewer worries about ADHD-related school problems, and voiced fewer preferences for school interventions than Caucasian parents, pointing to a potential disconnect with the school system. CONCLUSIONS: More African-American than Caucasian parents were unsure about potential causes of and treatments for ADHD, indicating a need for culturally appropriate parent education approaches.

Adult↗

PubMed2006

Improving antisaccade performance in adolescents with attention-deficit/hyperactivity disorder (ADHD).

The goal of the study was to examine the effects of task manipulations on antisaccade accuracy and response times (RTs) of adolescents with attention-deficit/hyperactivity disorder (ADHD), age-matched controls, 10-year-olds and young adults. Order effects were tested by administering the task at the beginning and end of the session. Other manipulations involved a visual landmark to reduce demands on working memory and internal generation of saccades; spatially specific and non-specific cues at three intervals; and central engagement of attention through perceptual and cognitive means at three intervals. As expected, adolescents with ADHD were impaired relative to age-matched controls in terms of accuracy and saccadic RT on the first administration of the task. Although their accuracy improved with most of the manipulations, it did not improve disproportionately compared to age-matched controls. Nevertheless, with most of the manipulations, they could achieve the same level of accuracy as unaided controls on the first administration of the task. In contrast, the saccadic RTs of the ADHD group came close to normal under several conditions, indicating that elevated antisaccade RTs in this disorder may be related to attentional factors. The ADHD group made more premature saccades and fewer corrective saccades than both the age-matched and younger groups, suggesting difficulties with impulsivity and goal neglect. The findings suggest that cognitive scaffolds can ameliorate at least some of the inhibition deficits in adolescents with ADHD.

Adolescent↗

PubMed2006

Sleep quality in adult patients with attention deficit hyperactivity disorder (ADHD).

Sleep disorders are common in adults with attention deficit/hyperactivity disorder (ADHD). Two sleep questionnaires; the Brown ADD Scale, the Symptom-Checklist-90-R, and a self-developed symptom questionnaire were administered in this study. In a sample of 61 patients without comorbidity, current substance abuse and medication intake, sleep problems were reported more often than in healthy controls. A lack of being refreshed in the morning was very closely associated with ADHD symptomatology whereas insomnia was related to the presence of comorbidity and depressive symptoms. In the total sample (N = 120), medication intake (mainly stimulants) was not related to any of the sleep parameters. It seems important to screen adult patients with ADHD for the presence of sleep disorders, especially insomnia, restless legs syndrome, and sleep-related breathing disorders (the last in conjunction with the body mass index). Since primary sleep disorders are associated with cognitive impairment, one might expect that ADHD symptomatology may improve if comorbid sleep disorders are adequately treated in addition to the specific ADHD treatment.

Adolescent↗

PubMed2006

Differential diagnosis and comorbidity of attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) in adults.

Attention-deficit/hyperactivity disorder (ADHD) in adults and borderline personality Disorder (BPD) share some similar clinical features (e. g. impulsivity, emotional dysregulation, cognitive impairment). ADHD in childhood has been reported to be highly associated with the diagnosis of BPD in adulthood and adult ADHD often co-occurs with BPD. Treatment studies revealed an efficacy of dialectical behavioral therapy (DBT) and DBT-based psychotherapy, respectively, in BPD and adult ADHD as well as neuroimaging and psychopharmacological studies showed some evidence for a potential common neurobiological dysfunction suggesting the hypothesis that ADHD and BPD may not be two distinct disorders, but represent at least in a subgroup of patients two dimensions of one disorder.

Adult↗