Noradrenergic Mechanisms in ADHD Children With and Without Reading Disabilities: A Replication and Extension

Halperin, Jeffrey M.; Newcorn, Jeffrey H.; Koda, Vivian H.; Pick, Lawrence H.; McKay, Kathleen E.; Knott, P. J.

doi:10.1097/00004583-199712000-00017

Cited by 56 publications

(46 citation statements)

References 43 publications

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“…Taken together, these data support the burgeoning research that suggests that RD and ADHD are two distinct disorders with separate cognitive profiles, and support the "etiological subtype" hypothesis over the "phenocopy" hypothesis (Purvis & Tannock, 2000;Willcutt et al, 2001). Moreover, it ties in with the research emerging on the biogenetic markers for ADHD and RD as separate disorders with separate cognitive manifestations (e.g., Davis et al, 2001;Halperin et al, 1997;Willcutt, Pennington, & DeFries, 2000).…”

Section: Discussionsupporting

confidence: 76%

Time Perception: Does It Distinguish ADHD and RD Children in a Clinical Sample?

McGee

Brodeur

Symons

et al. 2004

J Abnorm Child Psychol

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This study used a double-dissociation design to evaluate whether children with ADHD demonstrated specific deficits relative to children with Reading Disorders. Recent theory suggests that ADHD children have deficits in time perception and working memory, whereas RD children have deficits in phonological decoding. The performance of 113 clinic-referred children aged 6-11 was examined using measures of working memory, phonological processing, and time perception. Respondents completed two time production tasks in which they were to judge when 30-s had elapsed, and another in which they were asked to estimate the duration of the Conners' CPT (CCPT). Time Perception and phonological processing variables were submitted to a 2 × 2 ANCOVA (ADHD vs. RD), covarying for age, SES, IQ, and working memory. Children with ADHD were more likely to overestimate the time taken for the CCPT than children without ADHD, but no group differences were found on the 30-s estimation tasks. Children with RD did not display deficits in time estimation, but showed deficits in auditory phonological processing. The lack of interaction effects supported an "etiological subtype" over the "phenocopy" model of ADHD and RD. No group differences were detected using the CCPT. Although our previous studies did not find an order effect for the Conners' CPT in a 1-hr battery, a fatigue effect was evident with a 1.5-hr battery. The implications for Barkley's behavioral inhibition theories (R. Barkley, 1997) are discussed.

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Section: Discussionsupporting

confidence: 76%

Time Perception: Does It Distinguish ADHD and RD Children in a Clinical Sample?

McGee

Brodeur

Symons

et al. 2004

J Abnorm Child Psychol

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“…Children with ADHD þ RD had higher plasma levels of the noradrenaline metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) than children with ADHD. MPHG appeared to be inversely associated with academic achievement and verbal processing, but was not related to behavior ratings or measures of attention and impulsivity (Halperin et al 1997).…”

Section: Discussionmentioning

confidence: 71%

“…Atomoxetine affected executive functioning only in children with ADHD þ RD, which suggests that ADHD and ADHD þ RD are not only different subtypes of ADHD at a neuropsychological level (Purvis and Tannock 2000), but possibly also at the neurochemical level (Halperin et al 1997). Previous research suggests a difference in noradrenaline levels between children with ADHD and children with ADHD þ RD.…”

Section: Discussionmentioning

confidence: 91%

Differential Effects of Atomoxetine on Executive Functioning and Lexical Decision in Attention-Deficit/Hyperactivity Disorder and Reading Disorder

Jong

Voorde

Roeyers

et al. 2009

Journal of Child and Adolescent Psychopharmacology

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Objective: The effects of a promising pharmacological treatment for attention-deficit=hyperactivity disorder (ADHD), atomoxetine, were studied on executive functions in both ADHD and reading disorder (RD) because earlier research demonstrated an overlap in executive functioning deficits in both disorders. In addition, the effects of atomoxetine were explored on lexical decision. Methods: Sixteen children with ADHD, 20 children with ADHD þ RD, 21 children with RD, and 26 normal controls were enrolled in a randomized placebo-controlled crossover study. Children were measured on visuospatial working memory, inhibition, and lexical decision on the day of randomization and following two 28-day medication periods. Results: Children with ADHD þ RD showed improved visuospatial working memory performance and, to a lesser extent, improved inhibition following atomoxetine treatment compared to placebo. No differential effects of atomoxetine were found for lexical decision in comparison to placebo. In addition, no effects of atomoxetine were demonstrated in the ADHD and RD groups. Conclusion: Atomoxetine improved visuospatial working memory and to a lesser degree inhibition in children with ADHD þ RD, which suggests differential developmental pathways for co-morbid ADHD þ RD as compared to ADHD and RD alone. Clinical Trial Registry: B4Z-MC-LYCK, NCT00191906; http:==clinicaltrials.gov=ct2=show=NCT00191906

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“…Also these two genes may contribute to a particular part or subtype of the phenotype. As previously summarized, 13 some studies have reported children with ADHD to have higher levels in the serum or urine of the noradrenergic metabolite 3-methoxy-4-hydroxyphenyl glycol (MHPG), while others have reported lower MHPG levels compared to controls, suggesting that there may be subgroups of ADHD based on adrenergic function. One study suggested that this distinction may be related to comorbid reading disabilities in the ADHD subjects.…”

mentioning

confidence: 99%

“…One study suggested that this distinction may be related to comorbid reading disabilities in the ADHD subjects. 13 This finding suggests that perhaps adrenergic dysfunction is a factor in only a subset of ADHD children. Currently we have less than 20 subjects in our sample with comorbid reading disabilities and thus we lack sufficient power to subdivide our sample by comorbid disorders.…”

mentioning

confidence: 99%

Attention-deficit hyperactivity disorder and the adrenergic receptors α1C and α2C

et al. 2001

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Keywords: attention-deficit hyperactivity disorder; adrenergic receptor ␣1C; adrenergic receptor ␣2C; linkage; norepinephrineThe 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, ␣1C (ADRA1C) located on chromosome 8p11.2, and ␣2C (ADRA2C) located on chromosome 4p16, as genetic susceptibility factors in ADHD. For the adrenergic receptor ␣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 ␣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. Molecular Psychiatry (2001) 6, 334-337. While the recent investigation of the molecular genetics of ADHD has focused on the dopaminergic system, an extensive body of literature has implicated the involvement of the adrenergic system in ADHD. 1,2 The notion that the adrenergic system is involved in ADHD derives from several lines of research including the manipulation of the catecholamine system in animals and the pharmacological response to adrenergic agonists in humans. In rodents, norepinephrine depletion results in increased distractibility and motor hyperactivity and in non-human primates, stimulation of the noradrenergic system has been shown to improve cognitive function and distractibility. 3 The improvement in ADHD symptoms with tricyclic antidepressants has been attributed to the actions of these drugs in the reuptake of norepinephrine. 1 Noradrenergic receptors are divided into three major categories: alpha1, alpha2, and beta. Activation of alpha 1 receptors in rats promotes vigilance (sustained attention), decreases impulsivity, and influences working memory and behavioral activation while having only a minor role in the modulation of long-term memory. 4 The alpha adrenergic receptors have been classified as ␣1A, ␣1B, and ␣1D corresponding to their ligand binding properties. Four ␣ adrenoreceptors, ␣1a, ␣1b, ␣1c, and ␣1d, have been cloned 5 and the cloned ␣1c receptor 6 has been identified as the receptor corresponding to the alpha 1 A-ligand binding site. 5 The gene for the ␣1C receptor has been localized by somatic cell hybridization 7 and by multi-point linkage analysis to 8p11.2. 8 Thus far only a single polymorphism has been identified for this gene, a C to T change located in codon 492 resulting in a change of cysteine to argin...

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Noradrenergic Mechanisms in ADHD Children With and Without Reading Disabilities: A Replication and Extension

Cited by 56 publications

References 43 publications

Time Perception: Does It Distinguish ADHD and RD Children in a Clinical Sample?

Time Perception: Does It Distinguish ADHD and RD Children in a Clinical Sample?

Differential Effects of Atomoxetine on Executive Functioning and Lexical Decision in Attention-Deficit/Hyperactivity Disorder and Reading Disorder

Attention-deficit hyperactivity disorder and the adrenergic receptors α1C and α2C

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