Biomedical subjects

R Tannock

Publications and source records attributed to R Tannock.

At least 19 recordsLinked to original sources

PubMed2003

The serotonin 5-HT1B receptor gene and attention deficit hyperactivity disorder.

Recent research has suggested that serotonin, in addition to dopamine, may be involved in the development of attention deficit hyperactivity disorder (ADHD). Serotonin regulates dopaminergic neurotransmission in some areas of the brain via several 5-HT receptors including 5-HT1B. Animal studies have suggested the involvement of the 5-HT1B receptors in locomotor behaviour. For these reasons, we hypothesized that the 5-HT1B receptor gene may be a good candidate for genetic studies of ADHD. We tested for linkage disequilibrium between the 5-HT1B G861C polymorphism and ADHD in 115 families using the transmission disequilibrium test (TDT). We found evidence for a trend towards excess transmission of the 861G allele (chi(2) = 2.91, P = 0.09) that when further analysed for parental allele transmissions exhibited significantly greater paternal transmission of the G allele (chi(2) = 4.80, P = 0.03) to the affected child. Although preliminary, results from this study provide additional evidence that serotonin genes may be important risk factors for the development of ADHD.

Adolescent↗

PubMed2003

Time perception deficits in attention-deficit/ hyperactivity disorder and comorbid reading difficulties in child and adolescent samples.

BACKGROUND: Our objective was to investigate time perception in Attention-Deficit/Hyperactivity Disorder (ADHD) with and without comorbid reading difficulties (RD) in child and adolescent participants. METHOD: In study 1, 50 children with ADHD (31 ADHD, 19 ADHD+RD) and age-matched healthy controls (n = 50) completed three psychophysical tasks: duration discrimination (target duration of 400 ms versus a foil duration), frequency discrimination (a control condition to evaluate general perceptual ability), and a duration estimation task using the method of reproduction for intervals of 400 ms, 2000 ms, and 6000 ms. Study 2 used the same tasks with an adolescent sample (35 ADHD, 24 ADHD+RD, 39 controls). RESULTS: In both studies, children and adolescents with ADHD and ADHD+RD displayed some impairments in duration discrimination and the precision with which they reproduced the intervals on the estimation task, particularly the shorter 400 ms interval. The most severe impairments tended to occur in the comorbid ADHD+RD group. No impairments were found on the frequency discrimination task. ADHD participants also displayed significant intra-individual variability in their performance on the estimation task. Finally, short-term and working memory, estimated full-scale IQ, and teacher report of hyperactivity/impulsivity were found to differentially predict performance on the time perception measures in the adolescent clinical sample. CONCLUSIONS: Deficits in duration discrimination, duration estimation, and intra-individual performance variability may have cascaded effects on the temporal organisation of behaviour in children and adolescents with ADHD and ADHD+RD.

Adolescent↗

PubMed2003

The attributions of children with Attention-Deficit/ Hyperactivity Disorder for their problem behaviors.

This study investigated the attributions children with ADHD make about their most problematic symptoms. Children were interviewed to determine the degree to which they felt their behavior was controllable, stable, global, and stigmatizing; and about the locus of the cause of their behavior. Participants were 16 children with ADHD (10 boys, 6 girls), and 16 children without ADHD (9 boys, 7 girls), ages 7 to 13. The present study demonstrated that children with ADHD viewed their most problematic behaviors as less within their control and more global across situations than children without ADHD. Children with ADHD were more likely than children without ADHD to view their most problematic behavior as always having been present, but were no more likely to view their most problematic behavior as persisting into the future. No significant group differences emerged on the locus of causality dimension. With regards to stigmatization, girls without ADHD reported that their behaviors can bother their teachers, parents, and peers, whereas girls and boys with ADHD did not perceive their behavior as bothersome.

Adolescent↗

PubMed2002

Validity of the Brown ADD scales: an investigation in a predominantly inattentive ADHD adolescent sample with and without reading disabilities.

The Brown ADD Scale for Adolescents is widely used in clinical settings, yet, no published studies have investigated divergent and concurrent validity and specificity and sensitivity to inattentive ADHD symptomatology. Ninety-eight participants (13 to 16 years) were classified as ADHD/I and/or reading disabled (RD) using Kiddie Schedule for Affective Disorder and Schizophrenia (K-SADS), Conners' Rating Scales (CRS-R), and Ontario Child Health Study Scales (OCHSS), WRAT3, and WRMT-R. The results were: 29 ADHD/I; 12 RD, 16 ADHD/I with RD; and, 41 controls. The RD group was included to evaluate specificity. The Brown was administered but not used in classification. The ADHD groups scored higher on the Brown subscales compared with the other two groups. The recommended cutoffs resulted in high rates of false negatives but few false positives; this suggests good specificity but poor sensitivity. There were moderate correlations among the Brown, CRS-R, and OCHSS. The Brown can be useful in screening out ADHD; however, its low sensitivity precludes its usefulness in diagnosing ADHD.

Adolescent↗

PubMed2001

Actigraphy and parental ratings of sleep in children with attention-deficit/hyperactivity disorder (ADHD).

STUDY OBJECTIVES: To assess various sleep parameters in latency-aged children with ADHD and their normally developing peers through the use of multiple sleep measures. DESIGN: Six sleep parameters were evaluated for two groups of children, ADHD and normal comparison. Each group consisted of 25 children (20 males, 5 females) who ranged in age from 7 to 11 years. All children underwent rigorous diagnostic procedures and the ADHD subjects were selected only if they displayed pervasiveness in their symptomatology and were medication naive. Parents completed a retrospective questionnaire which evaluated sleep problems over the past six months. Additionally, each child wore an actigraph for seven consecutive nights, and the child's parents completed a sleep diary during this time period. SETTING: N/A. PATIENTS OR PARTICIPANTS: N/A. INTERVENTIONS: N/A. RESULTS: Based on the findings from the questionnaire, parents of children with ADHD reported significantly more sleep problems than parents of normally developing children. However, the majority of these sleep differences were not verified through actigraphy or sleep diary data, with the exception of longer sleep duration for children with ADHD and parent reports that describe increased bedtime resistence. It was also found that child-parent interactions during bedtime routines were more challenging in the ADHD group. CONCLUSIONS: Despite the possibility of intrinsic sleep problems such as longer sleep duration, results indicate that many of the sleep problems of children with ADHD may be due to challenging behaviours during bedtime routines. The reason for discrepancies among sleep studies employing objective measures as well as between retrospective and prospective measures are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Linkage study of polymorphisms in the gene for myelin oligodendrocyte glycoprotein located on chromosome 6p and attention deficit hyperactivity disorder.

Family and twin studies have shown that there is a substantial genetic contribution to both reading disabilities (RD) and attention deficit hyperactivity disorder (ADHD), and recent twin studies have suggested that the overlap between these phenotypes is largely due to common genetic influences. Studies using a linkage approach to search for genes for susceptibility to RD and ADHD have identified regions linked to each of these phenotypes separately, with recent studies suggesting that some chromosomal regions may contribute to both. Linkage to the human leukocyte antigen (HLA) region has been targeted in particular for RD and ADHD, as both of these disorders have been suggested to be autoimmune. Linkage to the HLA region of 6p for RD has now been reported by several groups. Alleles at two genes in the HLA (C4B and DRB1) have also been reported to be associated with ADHD, prompting one investigator to suggest a possible connection between the linkage of RD and ADHD to this region. The location of the gene for myelin oligodendrocyte glycoprotein (MOG), in the region of 6p with the strongest evidence for linkage to RD, and its proposed role as a minor component of myelin in the central nervous system suggest that it may be a factor in neuronal functioning and therefore a candidate for RD and ADHD. In this study, we tested the gene for linkage to ADHD by genotyping two polymorphisms in the MOG gene-a dinucleotide repeat located upstream from the MOG transcription start site and a Val145Ile substitution in exon 3-in a sample of 104 nuclear families identified through a proband with ADHD. We examined the transmission of the alleles of the Val145Ile and the dinucleotide repeat polymorphisms using the transmission disequilibrium test. We did not observe biased transmission of the alleles at either polymorphism to ADHD probands or siblings. Our findings using this sample do not support the role of the MOG gene in ADHD.

Amino Acid Substitution↗

PubMed2001

Linkage study of the alpha2A adrenergic receptor in attention-deficit hyperactivity disorder families.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder, characterized by marked and pervasive inattention, hyperactivity, and impulsiveness. An alteration in the expression or function of the adrenergic system has been suggested to be involved in ADHD based on animal models, pharmacological interventions, and the neural circuitry of attentional processes. The efficacy of clonidine in reducing disruptive behaviors in some children with ADHD argues for a causal role of the adrenergic system and more specifically for the alpha2A receptors as clonidine is an alpha2A agonist that inhibits release of noradrenaline into the synapse. In animal studies, alpha2A receptor agonists have also been shown to improve performance on working memory tasks under distracting conditions, indicating that these receptors function in the regulation of attention. We examined the possibility that the gene for the alpha2A adrenergic receptor (ADRA2A) is linked to ADHD by testing a polymorphism located in the promoter region of the ADRA2A gene in a sample of 94 nuclear families with an ADHD proband. We found no evidence for linkage of the ADRA2A gene with ADHD, using the transmission disequilibrium test in this set of families.

Adolescent↗

PubMed2001

Haplotype study of three polymorphisms at the dopamine transporter locus confirm linkage to attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is often treated using methylphenidate, a psychostimulant that inhibits the dopamine transporter. This led E.H. Cook and colleagues to consider the dopamine transporter locus (DAT1) as a primary candidate gene for ADHD. That group reported a significant association between ADHD and the 480-base pair (bp) allele of the variable number of tandem repeats (VNTR) polymorphism located in the 3' untranslated region of the DAT1 gene. This association was later replicated in additional studies. METHODS: The DAT1 gene has additional common polymorphisms in intron 9 and exon 9. We investigated the possibility of linkage of DAT1 and ADHD using the VNTR polymorphism and two additional common polymorphisms in 102 nuclear families with an ADHD proband. Using the transmission disequilibrium test, we examined the transmission of the alleles of each of these polymorphisms, as well as the haplotypes of the polymorphisms. RESULTS: We did not observe significant evidence for the biased transmission of the alleles of either the VNTR or the additional two polymorphisms when examined individually, although there was a trend for the biased transmission of the 480-bp allele of the VNTR. When we examined the haplotypes of the three polymorphisms we found significant evidence for biased transmission of one of the haplotypes containing the 480-bp VNTR allele. We also genotyped six additional DNA sequence variants of the DAT1 gene. However, these variants were not sufficiently polymorphic in our sample to be informative. Two of the DNA variants that result in an amino acid change, Ala559Val and Glu602Gly, were not observed in our sample. CONCLUSIONS: Our results support previous findings of an association between the DAT1 gene and ADHD.

Alleles↗

PubMed2001

5'-untranslated region of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Recently the molecular genetic basis of attention-deficit hyperactivity disorder (ADHD) has been the focus of a number of studies with the majority of these investigating the role of dopamine system genes. A great deal of attention has been focused on the possible involvement of the dopamine D4 receptor gene (DRD4) following a report of an association of ADHD with the allele containing seven copies of the 48-bp repeat in the third exon. In this paper we extended the search for the molecular explanation for the observed association by testing three polymorphisms in the region 5' to the dopamine receptor D4 gene transcription start site for linkage to ADHD. We specifically targeted polymorphisms in the region 5' to the start site of transcription as DNA variants in this region could alter the transcription level of the gene and hence the phenotype. We did not observe significant evidence for biased transmission of any of the alleles at these three polymorphisms to ADHD probands using the transmission disequilibrium test. We conclude that these three polymorphisms are not related to the ADHD phenotype.

5' Untranslated Regions↗

PubMed2001

Attention-deficit hyperactivity disorder and the adrenergic receptors alpha 1C and alpha 2C.

The adrenergic system has been hypothesized to be involved in the etiology of attention-deficit hyperactivity disorder (ADHD) based on pharmacological interventions and animal models. Noradrenergic neurons are implicated in the modulation of vigilance, improvement of visual attention, initiation of adaptive response, learning and memory. In this study we tested the genes for two adrenergic receptors, alpha 1C (ADRA1C) located on chromosome 8p11.2, and alpha 2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in ADHD. For the adrenergic receptor alpha 1C we used a C to T polymorphism that results in a change of Cys to Arg at codon 492 for the linkage study. For the adrenergic receptor alpha 2C gene we examined a dinucleotide repeat polymorphism located approximately 6 kb from the gene. We examined these polymorphisms in a sample of 103 families ascertained through an ADHD proband. Using the transmission disequilibrium test, we did not observe biased transmission of any of the alleles of these polymorphisms. We conclude that the alleles at the polymorphisms tested in these two genes are not linked to the ADHD phenotype in this sample of families.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Methylphenidate selectively improves story retelling in children with attention deficit hyperactivity disorder.

OBJECTIVES: The goal of this study was to determine stimulant effects on story grammar, comprehension, and errors in the narratives of children with attention deficit hyperactivity disorder (ADHD) with and without comorbid language impairment. Previous research has demonstrated impairments in the narrative abilities of children with ADHD, but the effect of the primary treatment modality (methylphenidate) is unknown. METHODS: Fifty children with ADHD (7 to 12 years of age) were stratified for language impairment that might influence performance. In an acute, randomized, placebo-controlled crossover trial with two single doses (10 and 20 mg) of methylphenidate, the children listened to an audiotaped story while viewing a wordless picture book of the study, then retold the story and answered comprehension questions. The narratives were transcribed and coded for story grammar, length, and errors. RESULTS: Methylphenidate only increased children's reporting of the story characters' internal responses and attempts. It had no effect on story length or responses to comprehension questions. Responses to the factual questions were significantly more accurate than the inferential questions, irrespective of medication dose. Comorbid language impairment had no effect on performance or stimulant response. CONCLUSION: Story grammar analysis was sensitive to drug effects, which were subtle but specific and clinically meaningful. Results provide evidence for the theoretical linkage between internal responses and attempts.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Psychiatric, psychosocial, and cognitive functioning of female adolescents with ADHD.

OBJECTIVE: To characterize the psychiatric, psychosocial, and cognitive functioning of female adolescents with attention-deficit/hyperactivity disorder (ADHD) in comparison with female controls and males with ADHD. Female controls were also compared with male controls to verify gender differences in a nonclinical sample. METHOD: One hundred seven adolescents from Southern Ontario aged 13 to 16 were included: 24 females with ADHD, 35 males with ADHD, 28 control females, and 20 control males. All were assessed with semistructured interviews, questionnaires, and tests of achievement and intellectual functioning. RESULTS: After controlling for parental education and estimated Full Scale IQ, females with ADHD were more impaired than control females in depression, anxiety, distress, teacher relationships, stress, attributional styles, and locus of control and on all cognitive and achievement measures. Females with ADHD were more impaired than males with ADHD in self-reported anxiety, distress, depression, locus of control, and vocabulary scores. These group differences were confirmed by higher ratings by parents and teachers in symptoms of psychopathology. Males with ADHD were more impaired in processing speed. Some gender differences (locus of control and vocabulary scores) were eliminated when controlling for ADHD severity. The absence of any differences between male and female controls indicates gender differences were specific to the clinical groups. CONCLUSION: Females with ADHD are at high risk for more psychological impairment than both males with ADHD and control females. The identified psychosocial problems point to areas for intervention.

Achievement↗

PubMed2001

DSM-IV internal construct validity: when a taxonomy meets data.

The use of DSM-IV based questionnaires in child psychopathology is on the increase. The internal construct validity of a DSM-IV based model of ADHD, CD, ODD, Generalised Anxiety, and Depression was investigated in 11 samples by confirmatory factor analysis. The factorial structure of these syndrome dimensions was supported by the data. However, the model did not meet absolute standards of good model fit. Two sources of error are discussed in detail: multidimensionality of syndrome scales, and the presence of many symptoms that are diagnostically ambiguous with regard to the targeted syndrome dimension. It is argued that measurement precision may be increased by more careful operationalisation of the symptoms in the questionnaire. Additional approaches towards improved conceptualisation of DSM-IV are briefly discussed. A sharper DSM-IV model may improve the accuracy of inferences based on scale scores and provide more precise research findings with regard to relations with variables external to the taxonomy.

Adolescent↗

PubMed2000

Further evidence from haplotype analysis for linkage of the dopamine D4 receptor gene and attention-deficit hyperactivity disorder.

Several studies have suggested a possible association of a polymorphism at the dopamine D4 receptor gene and attention-deficit hyperactivity disorder [LaHoste et al., 1996; Rowe et al., 1998; Smalley et al., 1998; Sunohara et al., submitted; Swanson et al., 1998]. The allele reported to be associated with attention-deficit hyperactivity disorder (ADHD) is the allele with seven copies of the 48 bp repeat in the third exon. We extend our study of the dopamine D4 gene and ADHD by testing for linkage using two additional polymorphisms in the dopamine D4 receptor gene and a polymorphism in the closely linked gene, tyrosine hydroxylase. We also searched for two previously reported deletions, a 13 bp and a 21 bp deletion in the first exon. We examined the haplotypes of three polymorphisms of the D4 receptor gene and observed biased transmission of two of these haplotypes. Our findings further support the role of the dopamine D4 gene in ADHD.

Adolescent↗

PubMed2000

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder.

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114-117, 2000.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Confirmation of an inhibitory control deficit in attention-deficit/hyperactivity disorder.

The objective of this study was to determine whether deficient inhibitory control distinguishes children with a diagnosis of attention-deficit/hyperactivity (ADHD) disorder, conduct disorder (CD), and comorbid ADHD + CD from normally developing children. Participants were rigorously diagnosed children (age 7 to 12 years) with ADHD (N = 72), CD (N = 13) or ADHD + CD (N = 47) and 33 control children (NC). We studied inhibitory control using the stop-signal paradigm, a laboratory task that assessed the ability to inhibit an ongoing action. The ADHD group had significantly impaired inhibitory control compared to NC, CD, and ADHD + CD children. These results indicate that children with ADHD have deficient inhibition as measured in the stop-signal paradigm and that ADHD occurring in the presence of ADHD + CD may represent a phenocopy of CD rather than a variant of ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

Naming speed performance and stimulant effects indicate effortful, semantic processing deficits in attention-deficit/hyperactivity disorder.

This study investigated rapid automatized naming and effects of stimulant medication in school-age children with attention-deficit/hyperactivity disorder (ADHD) with and without concurrent reading disorder (RD). Two ADHD groups (67 ADHD only; 21 ADHD + RD) and a control group of 27 healthy age-matched peers were compared on four variables: color naming speed, letter naming speed, phonologic decoding, and arithmetic computation. Discriminant function analysis (DFA) was conducted to predict group membership. The four variables loaded onto two discriminant functions with good specificity: phonologic decoding, letter naming speed, and arithmetic defined the first function; color naming speed defined the second function. Both ADHD groups were significantly slower in color naming than controls, but did not differ from one another. DFA correctly classified 96% of the control group, 91% of ADHD + RD, and 82% of ADHD only. A subset of children in the ADHD groups participated subsequently in an acute, randomized, placebo-controlled, crossover trial with three single doses (10, 25, 20 mg) of methylphenidate. Methylphenidate selectively improved color-naming speed but had no effect on the speed of naming letters or digits. These findings challenge the tenet that naming speed deficits are specific to RD and implicate naming speed deficits associated with effortful semantic processing in ADHD, which are improved but not normalized by stimulant medication.

Attention Deficit Disorder with Hyperactivity↗

PubMed2000

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.

Adolescent↗