Methylphenidate improves reading performance in children with attention deficit hyperactivity disorder and comorbid dyslexia: An unblinded clinical trial

Keulers, Esther H. H.; Hendriksen, Jos G.M.; Feron, Frans; Wassenberg, Renske; Wuisman-Frerker, Mea G.F.; Jolles, Jelle; Vles, Johan S.H.

doi:10.1016/j.ejpn.2006.10.002

Cited by 46 publications

(44 citation statements)

References 42 publications

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“…A resposta ao tratamento com psicoestimulantes em crianças com a comorbidade TDAH-dislexia é semelhante àquela observada no grupo diagnosticado com TDAH apenas (Elia et al, 1993). O uso de psicoestimulantes em crianças com TDAH-dislexia, conforme demonstrado por Keulers et al (2006), aumenta o número de palavras corretamente lidas.…”

Section: Potenciais Conflitos De Interesseunclassified

Dificuldades no diagnóstico de TDAH em crianças

Souza

Serra-Pinheiro

Fortes

et al. 2007

J. bras. psiquiatr.

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RESUMOO transtorno do déficit de atenção e/ou hiperatividade (TDAH) é uma doença de alta prevalência em crianças em idade escolar. Erroneamente entendido anteriormente como um diagnóstico de baixa morbidade, o TDAH é reconhecido atualmente como uma condição importante, não só pelo forte impacto funcional e social como também pela alta prevalên-cia de comorbidades psiquiátricas. Déficits cognitivos globais e transtornos invasivos do desenvolvimento assim como transtornos do aprendizado são condições complexas que, quando estão associadas aos sintomas de TDAH, têm seus quadros agravados, requerendo maior atenção e estratégias de tratamento mais individualizadas. O objetivo deste artigo é uma discussão sobre esses diagnósticos diferenciais que representam um desafio na prá-tica clínica. ABSTRACT Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder among school age children. Once understood as a common and mild disorder restricted to childhood, ADHD is now recognized as an important condition because of its INTRODUÇÃODurante muito tempo, o transtorno do déficit de atenção (TDAH) foi entendido equivocadamente como um diagnóstico com poucas implicações na vida dos pacientes. Comumente, a criança era avaliada e tratada pelo não-especialista, que se baseava nas queixas de hiperatividade e impulsividade para fazer o diagnóstico, referidas pelos pais ou professores, permanecendo a crença de remissão da sintomatologia na puberdade. A crença de que se tratava de transtorno que acomete principalmente meninos com problemas comportamentais até hoje é bastante difundida. Nos últimos anos, porém, tanto a experiência clínica quanto as recentes pesquisas em genética, neuroimagem e neuropsicologia têm contribuído para uma drástica mudança na forma de entender o TDAH.Diversos estudos comprovam que mais de 50% dos pacientes mantêm sintomas na vida adulta, com significativo

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Section: Potenciais Conflitos De Interesseunclassified

Dificuldades no diagnóstico de TDAH em crianças

Souza

Serra-Pinheiro

Fortes

et al. 2007

J. bras. psiquiatr.

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“…Methylphenidate is known to increase extracellular dopamine and noradrenalin Segal 1997, 2002), but not serotonin (Kuczenski and Segal 1997) suggesting that therapeutic efficacy relates to alterations in dopamine and noradrenalin. Despite knowledge of these neurochemical effects, the mechanisms contributing to the effectiveness of methylphenidate are unclear (Safer and Allen 1989; National Institutes of Health Consensus Development Conference Statement 2000;Greenhill 2001).One clue to mechanisms of efficacy can be found at a behavioral level, where methylphenidate improves academic performance (Yang et al 2004;McGough et al 2006), working (Wright and White 2003) and visual (Rhodes et al 2004) memory, nonverbal (O'Toole et al 1997) and visuospatial (Bedard et al 2004) learning, and reading skills (Keulers et al 2007), which may explain why, in addition to its medicinal use, it is used illegally by healthy students to aid study (Teter et al 2006). Despite evidence of methylphenidate-induced changes in learning and memory, the mechanisms underlying these changes have received little focus and are commonly assumed to be a by-product of improved attention.…”

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confidence: 99%

“…One clue to mechanisms of efficacy can be found at a behavioral level, where methylphenidate improves academic performance (Yang et al 2004;McGough et al 2006), working (Wright and White 2003) and visual (Rhodes et al 2004) memory, nonverbal (O'Toole et al 1997) and visuospatial (Bedard et al 2004) learning, and reading skills (Keulers et al 2007), which may explain why, in addition to its medicinal use, it is used illegally by healthy students to aid study (Teter et al 2006). Despite evidence of methylphenidate-induced changes in learning and memory, the mechanisms underlying these changes have received little focus and are commonly assumed to be a by-product of improved attention.…”

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confidence: 99%

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Dommett¹,

Henderson²,

Westwell³

et al. 2008

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Methylphenidate treatment is used for Attention Deficit Hyperactivity Disorder and can improve learning and memory. Previously, improvements were considered a by-product of increased attention; however, we hypothesize that methylphenidate directly alters mechanisms underlying learning and memory, and therefore examined its effects on hippocampal long-term potentiation and long-term depression. Methylphenidate enhanced both mechanisms in the absence of presynaptic changes and in a noradrenalin ␤-receptor-dependent manner. These findings can explain both the improved learning and memory and decreased learning selectivity found with methylphenidate treatment and constitute the first demonstration of direct actions of methylphenidate on mechanisms implicated in cognition.Attention Deficit Hyperactivity Disorder (ADHD) affects 8%-12% of children (Biederman and Faraone 2005) and is characterized by inattention, hyperactivity, and impulsivity. Consequences of the disorder include poorer academic performance, employment records, social relationships, and a higher risk of drug abuse (Doggett 2004). While behavioral, cognitive, and psychosocial therapies exist for ADHD, they are often ineffective unless combined with pharmacological treatment , the most common of which is the psychostimulant, methylphenidate (Ritalin, Concerta). Methylphenidate is known to increase extracellular dopamine and noradrenalin Segal 1997, 2002), but not serotonin (Kuczenski and Segal 1997) suggesting that therapeutic efficacy relates to alterations in dopamine and noradrenalin. Despite knowledge of these neurochemical effects, the mechanisms contributing to the effectiveness of methylphenidate are unclear (Safer and Allen 1989; National Institutes of Health Consensus Development Conference Statement 2000;Greenhill 2001).One clue to mechanisms of efficacy can be found at a behavioral level, where methylphenidate improves academic performance (Yang et al. 2004;McGough et al. 2006), working (Wright and White 2003) and visual (Rhodes et al. 2004) memory, nonverbal (O'Toole et al. 1997) and visuospatial (Bedard et al. 2004) learning, and reading skills (Keulers et al. 2007), which may explain why, in addition to its medicinal use, it is used illegally by healthy students to aid study (Teter et al. 2006). Despite evidence of methylphenidate-induced changes in learning and memory, the mechanisms underlying these changes have received little focus and are commonly assumed to be a by-product of improved attention. However, we suggest that these findings are the result of direct actions of methylphenidate on learning and memory mechanisms.In support of this hypothesis, methylphenidate has been shown to increase hippocampal noradrenalin in vivo (Kuczenski and Segal 2002), and such changes are known to impact on plasticity such as long-term potentiation (LTP) and long-term depression (LTD) (Hopkins and Johnston 1984;Izumi et al. 1992;Sah and Bekkers 1996;Thomas et al. 1996;Izumi and Zorumski 1999;Schimanski et al. 2007;Lin et al. 2008), both of which a...

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“…improves academic performance (47,48), working (49) and visual (50) memory, nonverbal (51) and visuospatial (52) learning, and reading skills (53), which may explain why, in addition to its medicinal use, it is used illicitly by healthy students as a study aid (54). In addition to being a first-line treatment for ADHD, MPH has also been used as a tool to investigate its pathogenesis.…”

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confidence: 99%

Homer expression in the hippocampus of an animal model of attention-deficit/hyperactivity disorder

et al. 2011

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Abstract. Attention-deficit/hyperactivity disorder (ADHD) is a pervasive neurobehavioral disorder. We previously demonstrated differential expression of some isoforms of Homer, a family of scaffolding proteins localized to the postsynaptic density of glutamatergic excitatory synapses, in the spontaneous hypertensive rat (SHR), which is the most frequently used animal model of ADHD. Since these changes were observed in the prefrontal cortex (PFC), a critical structure in ADHD, it was hypothesized that these Homer isoforms may play a role in ADHD. The present study aimed to extend these findings to the hippocampus, which has direct connections to the PFC and subserves attention and cognition, two functions that are disturbed in ADHD. Hippocampal mRNA and protein expression of several Homer isoforms were investigated in both SHR and control Wistar-Kyoto (WKY) rats using reverse transcription-polymerase chain reaction and Western blotting, respectively. Both mRNA and protein for Homer 1a and Homer 2a/b, but not Homer 1b/c, were expressed at significantly lower levels in the hippocampus of SHR compared to WKY rats. The effects of methylphenidate (MPH) on spatial learning and memory in SHRs were also examined using the Morris water maze and on hippocampal expression of Homer isoforms. MPH improved spatial learning and memory and up-regulated hippocampal expression of Homer 1a and Homer 2a/b, but not Homer 1b/c, in SHRs. The animal model of ADHD may have altered expression of Homer 1a and Homer 2a/b in the hippocampus, in addition to the PFC. Future studies will focus on elucidating the specific mechanisms of Homer 1a and Homer 2a/b in

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Methylphenidate improves reading performance in children with attention deficit hyperactivity disorder and comorbid dyslexia: An unblinded clinical trial

Cited by 46 publications

References 42 publications

Dificuldades no diagnóstico de TDAH em crianças

Dificuldades no diagnóstico de TDAH em crianças

Methylphenidate amplifies long-term plasticity in the hippocampus via noradrenergic mechanisms

Homer expression in the hippocampus of an animal model of attention-deficit/hyperactivity disorder

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