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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.

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.

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., (Copyright 2001 Wiley-Liss, Inc.)

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., (Copyright Wiley-Liss. Inc.)

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.

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.

Objective: There is considerable evidence supporting a genetic component in the etiology of attention-deficit/hyperactivity disorder (ADHD). Because stimulant medications act primarily on the dopaminergic system, dopamine system genes are prime candidates for genetic susceptibility factors for ADHD. Previous studies by several groups have observed a significant association of ADHD and an allele with 7 copies of the 48 base pair repeat in the third exon of the dopamine D4 receptor., Method: The authors sought to replicate these previous findings by collecting an independent sample of families from Toronto, Ontario, Canada, and confirming this finding in an expanded sample of ADHD families collected from Irvine, California. Using the transmission disequilibrium test (TDT), the authors tested for biased transmission of the 7-repeat allele at the exon III polymorphism of the dopamine D4 receptor locus in these samples of ADHD subjects., Results: Biased transmission of the 7-repeat allele from parents to ADHD probands and their affected siblings was observed in the 2 new samples of families collected in Toronto and Irvine (TDT chi2 = 2.711, 1 df, one-sided p value = .050) and for these samples combined with the 52 families previously reported from Irvine (TDT chi2 = 6.426, 1 df, one-sided p value = .006)., Conclusions: The results of this study further support the possibility of a role of the dopamine D4 receptor locus in ADHD.

A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels. The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Using the transmission disequilibrium test (TDT), the current study assesses for linkage disequilibrium between polymorphisms in the serotonin HTR2A receptor gene and ADHD. One hundred and fifteen families with a total of 143 children diagnosed with ADHD (DSM-IV) were genotyped for the His452 Tyr and the T102C polymorphisms in the serotonin HTR2A receptor gene. TDT analysis revealed a preferential transmission of the 452Tyr allele to the affected offspring (P = 0.03), suggesting linkage disequilibrium of this polymorphism with ADHD. This may open a new door in ADHD molecular genetics research, expanding the existing view of a catecholaminergic hypothesis to include a serotonergic hypothesis and should help elucidate the complex interplay among the neurotransmitter systems in the etiology of ADHD.

Objective: To compare children with comorbid anxiety disorders (ANX) and attention-deficit hyperactivity disorder (ADHD) with children with either pure disorder and normal controls on 2 cognitive measures to elucidate the cognitive basis of this comorbidity., Method: Four groups of children aged 8 to 12 years (n = 64 total) were assessed: ANX, ADHD, both conditions (comorbid group), and neither condition (normal control group). Groups were compared on 2 cognitive measures: a measure of auditory emotional perception (dichotic listening task) and a measure of response inhibition (stop task), chosen for their relative specificity for ANX and ADHD, respectively, in previous studies., Results: Multivariate analyses of variance revealed significant group differences on the dichotic listening task (p < .05), with the comorbid group differing from the control group on emotion targets (p < .01) and the ADHD group differing from the control group on word targets (p < .05). On the stop task, the ADHD group appeared slower than the other diagnostic groups on both go and stop-signal reaction times, but differences were not significant., Conclusions: In this study, children with comorbid ANX and ADHD showed reduced auditory emotion recognition relative to controls but did not show response inhibition deficits. Thus they appeared cognitively distinct from children with either pure disorder.

A recent study has suggested a possible association of a polymorphism near the dopamine D5 receptor gene (DRD5) and attention-deficit hyperactivity disorder. The polymorphism studied was a (CA)n repeat located in the cosmid containing the D5 receptor gene2 and the allele that was reported to be associated with attention-deficit hyperactivity disorder (ADHD) was the 148-bp allele. In this study we sought to replicate this finding by testing for biased transmission of the alleles at this same polymorphism in a sample of 92 families with an ADHD proband. We did not observe significant evidence for biased transmission of the 148-bp allele, however we did observe biased transmission of two other alleles, the 136-bp allele and the 146-bp allele. For these two alleles the bias was for these two alleles not to be transmitted to the ADHD children. The number of informative transmissions for these two alleles was small, therefore it would be premature to make any conclusions from our study concerning the role of DRD5 in ADHD.

An epidemiological study of Attention Deficit/Hyperactivity Disorder (ADHD) suggests that the prevalence may be two to three times higher than the figure of 3-5% often cited. In addition, the data suggest that both underdiagnosis and overdiagnosis occur frequently. Rodent animal models of ADHD, like the Spontaneously Hypertensive Rat (SHR) and other rat models such as those with chemical and radiation-induced brain lesions and cerebellar stunting, and the Coloboma mouse model exhibit clear similarities with several aspects of the human disorder and should prove useful in studying specific traits. Operant behavioral tasks that model learning, short-term memory and simple discriminations are sensitive to ADHD and methylphenidate has been shown to normalize ADHD performance in a short-term memory task. Recent findings challenge not only the current postulate that response inhibition is a unique deficit in ADHD, but also the concepts of ADHD and its treatment, which presume intact perceptual abilities. Time perception deficits may account, in part, for the excessive variability in motor response times on speeded reaction time tasks, motor control problems and motor clumsiness associated with ADHD. The Multimodality Treatment Study of ADHD (MTA) provided data suggesting that pharmacological interventions that included systematic and frequent follow-up with parents and teachers, with or without psychosocial interventions, are superior to psychosocial interventions or standard community care alone. Additionally, the MTA was one of the first studies to demonstrate benefits of multimodal and pharmacological interventions lasting longer than 1 year. Imaging studies have demonstrated differences in brain areas in children with ADHD: anterior corpus callosum, right anterior white matter, and cerebellar volumes are all decreased in children with ADHD and there is less brain asymmetry in ADHD subjects. Additionally, functional imaging studies, coupled with pharmacological manipulations, suggest decreased blood flow and energy utilization in prefrontal cortex and striatum and the dysregulation of catecholamine systems in persons with ADHD.

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.

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.

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.

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.

Objective: To compare subtypes of attention-deficit/hyperactivity disorder (ADHD) (predominantly inattentive and combined types) and a comparison group on an objective measure of activity level (actigraphy)., Method: Actigraphs were worn by 64 children (49 boys, 15 girls) during a full-day clinical diagnostic assessment; 20 subjects had a diagnosis of ADHD predominantly inattentive type, 22 had ADHD combined type, and 22 were non-ADHD controls. Mean actigraph scores were calculated for two 2-hour intervals, comprising, respectively, a psychometric evaluation in the morning and the completion of a speech and language assessment and research measures in the afternoon., Results: There were no significant group differences in activity level in the morning session. During the afternoon session, children with ADHD were significantly more active than controls, but there were no differences between ADHD subtypes., Conclusions: These data partially support specifications in the DSM-IV regarding hyperactivity in ADHD; however, they also indicate that situational and/or temporal factors may affect the degree to which hyperactivity is expressed. Furthermore, the findings contradict specifications in the DSM-IV that suggest that children with ADHD combined type should be more hyperactive than children with ADHD predominantly inattentive type.

Objective: To test for the distinctiveness of attention-deficit hyperactivity disorder (ADHD) and reading disability (RD) and the independence of the cognitive domains, inhibition and phonological processing, which are proposed as central to ADHD and RD, respectively, using a classic double dissociation design., Method: A 2 (ADHD versus no ADHD) x 2 (RD versus no RD) model was used to examine the cognitive profile of 4 groups of children, aged 7 to 11 years. Two measures of inhibitory control and 3 phonological processing measures were used., Results: The 2 RD groups (RD, ADHD + RD) were significantly impaired relative to the 2 non-RD groups (controls, ADHD) on all phonological processing measures. The 2 ADHD groups were significantly impaired on simple go-task responding relative to the non-ADHD groups and in inhibition. Contrary to predictions, an RD effect on inhibitory control was found on one inhibition measure. The comorbid group (ADHD + RD) generally exhibited the deficits of both single groups in an additive fashion., Conclusions: These findings question the role of inhibitory control as a unique cognitive marker for ADHD and suggest true comorbidity for children with both ADHD and RD.

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., (Copyright 2000 Wiley-Liss, Inc.)

Attention-deficit hyperactivity disorder is the most common child psychiatric disorder with a prevalence rate in an Ontario study of 9% in boys and 3% in girls [Szatmari et al., 1989]. This disorder is characterized by problems in the areas of attention, overactivity, impulse control, and distractibility. Strong evidence for a genetic component has been provided from twin, family, and adoption studies [for review see Levy et al., 1998] and molecular genetic studies are in progress by several groups worldwide. The Catechol-O-Methyltransferase (COMT) gene is an interesting candidate for ADHD as it is involved in the breakdown of dopamine and norepinephrine, neurotransmitters strongly implicated in the etiology of ADHD. In addition, children with velo-cardio-facial syndrome, a deletion syndrome of the chromosomal region 22q11 where the COMT gene has been localized, often have symptoms of ADHD suggesting this gene may have an etiological role in ADHD. In this study, we have tested for linkage in ADHD families using the functional polymorphism at codon 158 that determines COMT activity [Lachman et al., 1996] and analyzed the data with the transmission disequilibrium test (TDT). A total of 77 nuclear families collected from Toronto were genotyped. We find no evidence for linkage of this polymorphism and ADHD in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:710-713, 1999., (Copyright 1999 Wiley-Liss, Inc.)

Complex inhibitory control, defined as the ability to inhibit a planned or ongoing action, was assessed in a sample of individuals with a history of mild head injury, case-matched with normal control subjects for age and gender. This central act of control was assessed using a modification of the stop-signal paradigm. The group with mild head injury took longer to inhibit their on going action and reported more accidents than the normal control subjects. The group that reported having had a mild head injury did not differ in terms of their go reaction time, number of correct responses, handedness, education level, or reported learning disabilities. Limitations of this design and directions for future research are discussed., (Copyright 1999 Academic Press.)

Although subtle linguistic deficits have been postulated for children identified with nonverbal learning disabilities (NLD), there is little empirical evidence to support this contention. Two experimental language inferencing measures that have been demonstrated to be problematic for individuals with right hemisphere brain damage (RHBD) and one norm-referenced inferencing task were examined in three groups of children aged 9-13: (1) children with NLD (n = 14), (2) children with verbal impairments (VI) (n = 14), and (3) children without learning disabilities who served as controls (n = 19). The NLD and VI groups did not differ from one another on any of the three measures, indicating a generalized language inferencing deficit in the NLD group. Relative to the control group, however, the NLD group experienced specific difficulties with spatial and emotional inferencing. The implications for right hemisphere involvement in the NLD profile are examined in relation to the effects of working memory on inferential abilities., (Copyright 1999 Academic Press.)

Objective: To determine the relationship of sleep problems to attention-deficit/hyperactivity disorder (ADHD), diagnostic subtype, comorbid disorders, and the effects of stimulant treatment., Method: On the basis of clinical diagnostic interviews, children aged 6 to 12 years were assigned to 4 groups: unmedicated ADHD (n = 79), medicated ADHD (n = 22), clinical comparison (n = 35), and healthy nonclinical comparison (n = 36). These groups were compared on 2 sleep questionnaires completed by the parents that assessed current sleep problems and factors associated with sleep difficulties (i.e., sleep routines, sleep practices, child and family sleep history)., Results: Factor analysis revealed 3 sleep problem categories: dyssomnias, parasomnias, and sleep-related involuntary movements. Linear regression analyses showed that (1) dyssomnias were related to confounding factors (i.e., comorbid oppositional defiant disorder and stimulant medication) rather than ADHD; (2) parasomnias were similar in clinical and nonclinical children; and (3) the DSM-IV combined subtype of ADHD was associated with sleep-related involuntary movements. However, sleep-related involuntary movements were more highly associated with separation anxiety., Conclusions: The results suggest that the relationship between sleep problems and ADHD is complex and depends on the type of sleep problem assessed as well as confounding factors such as comorbid clinical disorders and treatment with stimulant medication.

Objective: To determine whether comorbid anxiety alters response to methylphenidate (MPH) in children with attention-deficit hyperactivity disorder (ADHD)., Method: Ninety-one children with ADHD were assessed for anxiety. Children were randomly assigned to receive MPH or placebo, titrated to a dose of 0.7 mg/kg, while side effects were minimized. Measures of side effects and behavioral response were obtained from parents and teachers before treatment, after titration to optimal dose, and after 4 months of treatment. These measures, dose of drug, and rate of adherence to assigned medication assignment were compared for nonanxious (ADHD- ANX) and anxious ADHD children (ADHD+ ANX)., Results: Rates of adherence to original medication assignment did not differ between the groups. ADHD+ ANX on both MPH and placebo titrated to a lower dose at the end of titration, although the dose of drug did not differ among the groups after 4 months of treatment. No differential response to MPH between ADHD+ ANX and ADHD- ANX was noted at end-titration or at 4 months on any side effect or behavioral measures., Conclusions: Comorbid anxiety does not appear to influence development of side effects or behavioral response to MPH when dose is titrated as in standard clinical practice.

The stop-signal procedure was used to examine the development of inhibitory control. A group of 275 participants, 6 to 81 years of age, performed a visual choice reaction time (go) task and attempted to inhibit their responses to the go task when they heard a stop signal. Reaction times to the stop and go signals were used to assess performance in inhibition and response execution, respectively. Results indicated the speed of stopping becomes faster with increasing age throughout childhood, with limited evidence of slowing across adulthood. By contrast, strong evidence was obtained for age-related speeding of go-signal reaction time throughout childhood, followed by marked slowing throughout adulthood. Hierarchical regression confirmed that the age-related change in inhibitory control could not be explained by general speeding or slowing of responses. Findings are discussed in regard to the contrast between the development of inhibition and response execution and the utility of the stop-signal procedure.

Objective: To evaluate the relationship between sleep disturbances and attention-deficit/hyperactivity disorder (ADHD)., Method: Empirical research published since 1970 on sleep disturbances in children with ADHD was systematically reviewed. A "box-score" approach was used to examine consistency of findings across the studies, which used different outcome measures., Results: Although subjective accounts of sleep disturbances in ADHD were prevalent, objective verification of these disturbances was less robust. The only consistent objective findings were that children with ADHD displayed more movements during sleep but did not differ from normal controls in total sleep time. An additional finding was that stimulant medication led to changes in the children's sleep (e.g., prolonged sleep latency, increased length of onset to first rapid eye movement cycle), but these changes were believed to be nonpathological., Conclusions: The exact nature of the sleep problems in children with ADHD remains to be determined. Many of the relevant issues have not been adequately addressed. Factors such as poorly defined diagnostic groups, small sample sizes, few studies, and methodological and procedural limitations make it difficult to determine the relationship between ADHD and sleep problems.

Conceptual and technological advances in cognitive neuroscience and molecular genetics have the potential to identify the pathogenesis of psychiatric disorders. This article reviews the application of these technologies to the scientific study of attention deficit hyperactivity disorder. It begins with a summary of shifts in conceptualization and scientific study of this common condition. This is followed by a critical review of findings from recent cognitive, neuroimaging, and genetic studies. The available data do not yet permit an integration across these different levels of enquiry, but implicate problems in response inhibition, dysfunction of frontostriatal networks, and genetic factors in the pathogenesis of this complex behavioral phenotype. The review closes with suggestions for future interdisciplinary research.

Objective: To investigate whether the presence of comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) alters the correlates of attention-deficit hyperactivity disorder (ADHD)., Method: Three groups of children (33 "pure" ADHD, 46 ADHD + ODD, and 12 ADHD + CD) were compared on measures of ADHD, aggression, anxiety, parental psychopathology, self-esteem, school, and social-emotional functioning., Results: Findings indicated that the presence of comorbid oppositional or conduct problems in children with ADHD altered the correlates of ADHD across a number of areas, including greater ADHD symptom severity and social dysfunction. Nevertheless, some correlates were more closely linked with the comorbid condition of ADHD + CD (e.g., higher aggression, anxiety, and maternal pathology, as well as decreased self-esteem), while others appeared more closely linked with ADHD + ODD (e.g., social withdrawal, elevated academic achievement paired with higher perceived scholastic competence)., Conclusions: Findings support the distinctive profiles of the disruptive behavior disorder groups and emphasize the deleterious effects on the quality of life experienced by the comorbid conditions. The need for syndrome-specific interventions is stressed.

Objective: To determine the behavioral, situational, and temporal effects of 4 months of methylphenidate (MPH) treatment for attention-deficit hyperactivity disorder (ADHD)., Method: Ninety-one children with ADHD were randomly assigned to receive either MPH (titrated to a target dose of 0.7 mg/kg twice a day) or a placebo. Treatment effects were investigated with measures sensitive to various behaviors (core and associated symptoms), situations (home and school), time periods (morning and afternoon, after reaching the target dose, and after 4 months of treatment), and side effects., Results: MPH treatment improved symptoms of ADHD and oppositional behavior at school, both in the morning and afternoon, but not at home. Side effects (increase in physiological and effective symptoms, lack of weight gain) were significantly more frequent with MPH than with placebo treatment. Benefit was evident after titration, but the onset of some side effects was delayed. Side effects were reported by parents but not by teachers., Conclusions: Positive effects of MPH on behavior are evident in the classroom, but with MPH given twice daily, parents do not report that MPH improves behavior at home. Greater impact on home behavior may require three times daily MPH and combined treatments.

Research has demonstrated a high prevalence of language impairments (LI) and reading disabilities (RD) in children with attention deficit hyperactivity disorder (ADHD). Since RD is also associated with LI, it is unclear whether the language impairments are specific to ADHD or associated with comorbid RD. The language abilities of ADHD children with and without RD were investigated in a task requiring recall of a lengthy narrative, and in tests assessing knowledge of the semantic aspects of language. The study was conducted with 50 boys--14 ADHD, 14 ADHD + RD, 8 RD, and 14 normal controls, aged 7 to 11. Children with ADHD (ADHD-only, ADHD + RD) exhibited difficulties in organizing and monitoring their story retelling. Children with RD (RD-only, ADHD + RD) demonstrated deficits in receptive and expressive semantic language abilities on the language processing tests. The comorbid group (ADHD + RD) exhibited the deficits of both ADHD and RD children. The deficiencies of ADHD children are consistent with higher-order executive function deficits while the deficits of RD children are consistent with deficits in the basic semantics of language processing.

To compare the performance of children with anxiety disorders with that of children with attention-deficit hyperactivity disorder (ADHD) and normal controls in the processing of emotional information. A total of 57 children ages 8 to 11 years (18 anxious, 20 ADHD, 19 normal control) were administered a dichotic listening task for the detection of words and emotions. Comparisons of overall performance, false alarms, and a sensitivity index (which took false alarms into account) were done using repeated measures analyses of variance. Anxious children made fewer false alarms for emotion targets compared to both ADHD children and normal controls, and fewer false alarms for words compared to normal controls. When controlling for false alarms, their performance exceeded that of both ADHD children and normal controls. There were no group differences in correct responses. Performance on a dichotic listening task differentiates anxious, ADHD, and normal children, particularly when listening for emotional targets. Further studies using this task may therefore elucidate differences in the processing of words and emotions between these three groups of children.

The purpose of this study was to examine two executive control processes--response inhibition and re-engagement of responses after inhibition in children with attention deficit hyperactivity disorder (ADHD). Thirty-three children with ADHD and 22 normal control children of similar age (7 to 11 years) and mean IQ (107) were tested with the change paradigm. ADHD subgroups were defined by the context in which the ADHD symptoms predominated (in the home only; at school only; and in both, i.e., pervasive ADHD). Children with marked oppositional defiant or conduct disorder were excluded. Children with ADHD exhibited deficits in inhibitory control and in response re-engagement. Deficits were greatest in pervasive ADHD and, to a lesser extent, in those with ADHD limited to the school context. ADHD limited to the home context showed the least deficit. These results replicate an earlier study that found deficient inhibitory control in pervasive ADHD and demonstrate that the deficit in ADHD involves a second aspect of executive control.

Objective: To examine the effects of methylphenidate (MPH) on working memory and behavior in anxious and nonanxious children with attention-deficit hyperactivity disorder (ADHD)., Method: A total of 40 ADHD children (22 nonanxious, 18 anxious) completed a randomized, double-blind, placebo-controlled, crossover trial with three doses (0.3, 0.6, 0.9 mg/kg) of MPH. A serial addition task was used to assess working memory; direct observation of motor activity indexed behavior., Results: MPH improved working memory in the nonanxious ADHD group but not in the comorbidity anxious group. By contrast, MPH reduced activity level in both groups. The presence of concurrent learning disabilities did not influence stimulant response., Conclusions: The presence of comorbid anxiety in children with ADHD predicts a less robust response to stimulant treatment and suggests that ADHD with anxiety may constitute a distinct and clinically meaningful subtype of ADHD.

Objective: To study the basis of the comorbidity of two common psychiatric disorders of childhood: attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD)., Method: Subjects were 45 boys (aged 7 to 11 years) with either ADHD, CD, or ADHD + CD and 16 normal control children (NC) studied by means of a 2 (ADHD versus no ADHD) x 2 (CD versus no CD) design. We (1) tested whether similar or different patterns of cognitive, developmental risk, and psychosocial factors characterize the "pure" forms of the two disorders (i.e., ADHD and CD), and (2) compared the profile of the comorbid group (ADHD + CD) with those of the two pure groups., Results: The ADHD group was significantly impaired on cognitive measures (inhibitory control and response alteration) and had greater delay in development and greater reading problems compared with CD and NC children; the CD group was exposed to significantly greater environmental adversity and had more severe problems in arithmetic than the ADHD and NC groups. The ADHD+CD group was similar to the ADHD group on cognitive, developmental, and reading measures and similar to the CD group on psychosocial and arithmetic measures., Conclusions: These results support the distinctiveness of ADHD and CD and the hypothesis that the comorbid condition of ADHD + CD is a hybrid of pure ADHD and pure CD.

A randomized, double-blind, placebo-controlled trial was conducted to assess the acute effects of placebo and three doses of methylphenidate (MPH) (0.3, 0.6, 0.9 mg/kg) on cognitive flexibility and overt behavior in 28 children with a confirmed diagnosis of attention deficit-hyperactivity disorder. Two underlying cognitive processes (response inhibition and response reengagement) were assessed by measuring the probability and speed with which subjects could inhibit responses to a primary task (forced-choice letter discrimination) and immediately execute a response to a secondary task (simple reaction time) when given a signal to do so. Results indicated that MPH enhanced cognitive flexibility, although the high dose was less effective than lower doses in enhancing response inhibition. Dissociations of dose effects on cognitive function and behavior were demonstrated: Dose-response functions for changes in behavior were linear, whereas the function for response inhibition was U-shaped. Findings argue against the typical clinical practice of determining the response to stimulant treatment from a single measure such as parent report of child behavior.

Twenty preschool-age children with developmental delays and language impairment participated in this study, which compared fathers' and mothers' directiveness and parental stress. Similarities between fathers and mothers were found for turntaking control, response referents, and responses to the child's participation. However, fathers differed from mothers in two of the dimensions of directiveness examined: fathers used more response control and topic control than mothers. Both parents reported similarly low levels of child-related and parenting stress, but mothers perceived more stress than fathers related to the responsibilities associated with parenting a child with a handicap. Correlations between directiveness, child characteristics, and stress revealed that fathers used greater turntaking control and topic control with children who were developmentally less mature, whereas mothers used greater topic control with children who were less involved in interaction. Both fathers' and mothers' use of response control was positively related to stress. Implications for involving fathers in parent-focused intervention include screening father-child interactions before intervention, interpreting parent-child interaction styles in terms of their role in enhancing the child's social participation, and acknowledging the role of familial factors (such as stress) on interaction styles.

ABSTRACT Clinical trials with a treatment duration of at least 3 months were reviewed to determine the effect of psychostimulants on the core symptoms of attention-deficit hyperactivity disorder (ADHD) and on its commonly associated features. Eighteen studies were identified: 17 were studies of methylphenidate, 1 was a study of dextroamphetamine, and none involved pemoline or slow-release stimulants. Eleven of these studies were randomized controlled trials, whereas seven employed quasi-experimental designs without randomization. The results of randomized controlled trials showed that psychostimulants provided greater benefit than did the nonrandomized trials, suggesting that the efficacy of extended treatment may have been underestimated because more seriously disturbed children were assigned to medication treatment than to control treatments in nonrandomized trials. Evidence from the more definitive randomized controlled trials indicates that stimulants are more effective in ameliorating the core behavioral symptoms of ADHD (restlessness, inattentiveness, impulsiveness) than placebos, nonpharmacological therapies, or no treatment-at least in 3-7-month trials. During extended psychostimulant treatment, few children become symptom-free, clinical effects may diminish with time, and improvement dissipates rapidly upon discontinuation of medication. There is minimal evidence that extended stimulant treatment improves cognitive deficits or associated problems such as conduct disturbance, low self-esteem, poor peer relationships, or academic underachievement. The belief that stimulants do not improve the long-term prognosis of children with ADHD may be based on weakly designed studies that focus on associated rather than core symptoms. A failure to assign patients of similar clinical severity to different treatment conditions may also have contributed to obscuring the efficacy of extended psychostimulant treatments.

A story retelling task was used to assess narrative abilities in 30 boys with attention deficit hyperactivity disorder (ADHD) and 30 normally developing boys, matched on age and IQ. Each boy listened to two stories and retold them for another child. Results indicated that the two groups did not differ in their ability to comprehend and extract the main ideas from the stories, but did differ in the production of narratives. Boys with ADHD provided less information overall, and their stories were more poorly organized and less cohesive and contained more inaccuracies. As a result, their stories were often confused and hard to follow. Organization and monitoring of information are functions of executive control. Thus the observed deficits in narrative production in children with ADHD may reflect underlying deficits in executive processes.

Effects of methylphenidate on cognitive flexibility were investigated in 26 children with Attention Deficit Hyperactivity Disorder (ADHD), by assessing perseverative errors on the Wisconsin Card Sorting Test (WCST) and the emergence of clinical symptoms indicative of cognitive perseveration. A double-blind, placebo-control, randomized crossover design was used in which each child was assessed twice in each drug condition (placebo, 0.3 and 1.0 mg/kg). Results indicated that methylphenidate increased perseverative errors on the first assessment but decreased them on the second; clinical symptoms of perseveration occurred at both assessments. Findings suggest that MPH may reduce cognitive flexibility temporarily in some ADHD children.

The interactive model of language intervention instructs parents to use techniques that promote reciprocal social interactions and facilitate the development of communication and language abilities. In this evaluation study, 32 mothers and their preschool-age children with developmental delays were randomly assigned to treatment and control (delayed treatment) groups. Consistent with the interactive model, mothers in the treatment group became more responsive, less directive, and provided clearer linguistic models. Furthermore, these changes were maintained for at least 4 months after intervention, and involvement in the parent-centered intervention program did not increase maternal stress. More important, these changes were accompanied by concomitant increases in children's use of vocal turns. Contrary to predictions, developmental improvements in children's communicative and linguistic abilities were comparable in both groups. Findings suggest that an interactive model may afford a useful adjunct to other intervention approaches by instructing parents on how to promote children's use of existing abilities, but an interactive model may have no effect on language acquisition of at least some children with developmental delays.

This study investigated the effects of methylphenidate (MPH) on inhibitory control in hyperactive children. A double-blind, placebo-control, within-subject (crossover) design was used in which 12 children, between 6 and 11 years of age, were each tested four times in each drug condition: 0.3 mg/kg and 1.0 mg/kg of methylphenidate, and placebo. Dependent measures included (a) the probability of inhibiting responses to a primary choice reaction time task given a stop signal, on the Stopping Task, and (b) response latency and errors on the Matching Familiar Figures Test (MFFT). MPH improved the efficiency of the central inhibitory mechanism by speeding the inhibitory process, thereby affording the children greater control over their actions and enabling them to increase the probability with which they inhibited responses given a stop signal. MPH increased response latency but did not reduce errors on the MFFT, and observation of the children's task performance highlighted the interpretive problems associated with this task. Performance on both tasks was better at a dosage of 1.0 mg/kg than at 0.3 mg/kg.

This article discusses scan access to microcomputers and describes a scanning keyboard designed to allow children who are severely physically disabled to access microcomputers for writing, playing, and engaging in educational activities. Two case examples are presented to illustrate potential applications of this keyboard.

A dichotic digits task with selective listening and attention-switching instructions, was administered to 10 mentally retarded individuals with Down's Syndrome between the ages of 10 and 37 years. Attention was focused on one ear for 20 trials before switching attention to the opposite ear after a 5-minute interval. A majority displayed a right ear-left hemisphere advantage for correct responses, although this advantage failed to reach significance. Comparison of left and right ear intrusion errors when each ear was attended first showed significantly more intrusions from the unattended right ear. No priming effects were found. The results do not support the hemispheric reversed specialization hypothesis. Rather, it is suggested that while Down's Syndrome individuals do possess an inherent left hemisphere advantage for language, such individuals may suffer from a left hemisphere information processing disorder that can produce functional reversals in dichotic listening.

In the present study, the effects of 0.3 mg/kg and 1.0 mg/kg of methylphenidate on the overt behavior and academic functioning of 12 children with an established diagnosis of attention deficit disorder with hyperactivity were evaluated. A double-blind, placebo-control, within-subject (crossover) design was used, in which each child was tested four times in each drug condition. Drug conditions were alternated on a bidaily basis and each child received two different drug conditions each day. The academic tasks were designed for evaluation of the relationship between task complexity and dose. Whereas overt behavior improved with increasing dose, academic functioning was improved with methylphenidate, but did not vary with either dose or task complexity. Also, investigated were potential carryover effects of a morning dose of methylphenidate on performance in the afternoon. Behavioral and academic improvements produced by a dose of 0.3 mg/kg in the morning were no longer evident in the afternoon, but a morning dose of 1.0 mg/kg produced behavioral improvements that were clinically and statistically discernible in the afternoon, although the academic improvements had dissipated.

Preschool-aged children (11 with and 11 without Down syndrome), individually matched for communicative ability, mental age, and demographic variables, were videotaped while interacting with their mothers during 15-minutes of free play in a simulated playroom. Maternal responsiveness and three components of maternal directiveness were examined in the context of the child's interactional behavior. Both groups of mothers used a high frequency of controls, but used them primarily to support and encourage the child's participation in interaction. Although mothers of children with Down syndrome exerted greater control in most of the aspects of directiveness, they were not less responsive. Mothers of children without Down syndrome were more likely to silently watch their children who, in turn, were more likely to initiate topics than were the children with the syndrome.