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      주의력결핍과잉행동장애에서 Alpha-2A-Adrenergic 수용체 유전자와 Methylphenidate 반응과의 연관성에 대한 연구 = No Evidence of Association of the Alpha-2A-Adrenergic Receptor Gene with Methylphenidate Response in Attention Deficit Hyperactivity Disorder

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      https://www.riss.kr/link?id=A103913755

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      Objectives The aim of this study was to examine the association of the ADRA2A MspI and DraI polymorphisms with methylphenidate (MPH) response in Korean children with ADHD.
      Methods The present study included 112 children and adolescents with ADHD (mean age= 9.1±2.1 years), consisting of 92 boys (82.1%) and 20 girls (17.9%). ADHD was diagnosed based on the DSM-IV criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). For the clinical evaluation of the ADHD subjects, the ADHD Rating Scale-IV (ADHD-RS) and Clinical Global Impression (CGI) were administered at baseline and 8 weeks after MPH treatment. ADRA2A MspI and DraI polymorphisms were genotyped. The χ2 test was used to evaluate the relationship between the ADRA2A genotype and the response to MPH. The correlation between the genotype of ADRA2A and the change in the ADHD-RS scores after MPH treatment was assessed using the analysis of variance test and t-test. The significance level was set at p=0.01.
      Results No significant association was found between the genotypes of the ADRA2A MspI or DraI polymorphisms and MPH treatment response according to the CGI-improvement score (p>0.05). Comparing the changes in ARS scores after MPH treatment according to the genotypes of the MspI or DraI polymorphisms, we found no significant differences between subjects with different genotypes (p>0.05).
      Conclusion Our results do not support the significant association between the MspI genotype and MPH response in Korean ADHD subjects, which was previously reported. In addition, we document no evidence of association between the DraI polymorphism and MPH treatment response in the Korean ADHD population.
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      Objectives The aim of this study was to examine the association of the ADRA2A MspI and DraI polymorphisms with methylphenidate (MPH) response in Korean children with ADHD. Methods The present study included 112 children and adolescents with ADHD (mea...

      Objectives The aim of this study was to examine the association of the ADRA2A MspI and DraI polymorphisms with methylphenidate (MPH) response in Korean children with ADHD.
      Methods The present study included 112 children and adolescents with ADHD (mean age= 9.1±2.1 years), consisting of 92 boys (82.1%) and 20 girls (17.9%). ADHD was diagnosed based on the DSM-IV criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). For the clinical evaluation of the ADHD subjects, the ADHD Rating Scale-IV (ADHD-RS) and Clinical Global Impression (CGI) were administered at baseline and 8 weeks after MPH treatment. ADRA2A MspI and DraI polymorphisms were genotyped. The χ2 test was used to evaluate the relationship between the ADRA2A genotype and the response to MPH. The correlation between the genotype of ADRA2A and the change in the ADHD-RS scores after MPH treatment was assessed using the analysis of variance test and t-test. The significance level was set at p=0.01.
      Results No significant association was found between the genotypes of the ADRA2A MspI or DraI polymorphisms and MPH treatment response according to the CGI-improvement score (p>0.05). Comparing the changes in ARS scores after MPH treatment according to the genotypes of the MspI or DraI polymorphisms, we found no significant differences between subjects with different genotypes (p>0.05).
      Conclusion Our results do not support the significant association between the MspI genotype and MPH response in Korean ADHD subjects, which was previously reported. In addition, we document no evidence of association between the DraI polymorphism and MPH treatment response in the Korean ADHD population.

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      참고문헌 (Reference)

      1 소유경, "한국어판 부모, 교사 ADHD 평가 척도의 신뢰도와 타당도 연구" 대한신경정신의학회 41 (41): 2002

      2 Polanczyk G, "The worldwide prevalence of ADHD: a systematic review and metaregression analysis" 164 : 942-948, 2007

      3 Madras BK, "The dopamine transporter and attention-deficit/hyperactivity disorder" 57 : 1397-1409, 2005

      4 Arnsten AF, "The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder" 53 : 448-455, 1996

      5 김영신, "The Reliability and Validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version (K-SADS-PL-K)" 연세대학교의과대학 45 (45): 81-89, 2004

      6 Arnsten AF, "Stimulants: Therapeutic actions in ADHD" 31 : 2376-2383, 2006

      7 Ma CL, "Selective deficit in no-go performance induced by blockade of prefrontal cortical alpha 2-adrenoceptors in monkeys" 14 : 1013-1016, 2003

      8 Cho SC, "Possible association of the alpha-2A-adrenergic receptor gene with response time variability in attention deficit hyperactivity disorder" WILEY-LISS 147B : 957-963, 2008

      9 Spencer T, "Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle" 35 : 409-432, 1996

      10 Polanczyk G, "Pharmacogenetic approach for a better drug treatment in children" 16 : 2462-2473, 2010

      1 소유경, "한국어판 부모, 교사 ADHD 평가 척도의 신뢰도와 타당도 연구" 대한신경정신의학회 41 (41): 2002

      2 Polanczyk G, "The worldwide prevalence of ADHD: a systematic review and metaregression analysis" 164 : 942-948, 2007

      3 Madras BK, "The dopamine transporter and attention-deficit/hyperactivity disorder" 57 : 1397-1409, 2005

      4 Arnsten AF, "The contribution of alpha 2-noradrenergic mechanisms of prefrontal cortical cognitive function. Potential significance for attention-deficit hyperactivity disorder" 53 : 448-455, 1996

      5 김영신, "The Reliability and Validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version (K-SADS-PL-K)" 연세대학교의과대학 45 (45): 81-89, 2004

      6 Arnsten AF, "Stimulants: Therapeutic actions in ADHD" 31 : 2376-2383, 2006

      7 Ma CL, "Selective deficit in no-go performance induced by blockade of prefrontal cortical alpha 2-adrenoceptors in monkeys" 14 : 1013-1016, 2003

      8 Cho SC, "Possible association of the alpha-2A-adrenergic receptor gene with response time variability in attention deficit hyperactivity disorder" WILEY-LISS 147B : 957-963, 2008

      9 Spencer T, "Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle" 35 : 409-432, 1996

      10 Polanczyk G, "Pharmacogenetic approach for a better drug treatment in children" 16 : 2462-2473, 2010

      11 DuPaul GJ, "Parent and teacher ratings of ADHD symptoms: psychometric properties in a community-based sample" 20 : 245-253, 1991

      12 Lario S, "MspI identifies a biallelic polymorphism in the promoter region of the alpha 2Aadrenergic receptor gene" 51 : 129-130, 1997

      13 Berridge CW, "Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function" 60 : 1111-1120, 2006

      14 Andrews GD, "Methylphenidate increases cortical excitability via activation of alpha-2 noradrenergic receptors" 31 : 594-601, 2006

      15 Arnsten AF, "Methylphenidate improves prefrontal cortical cognitive function through alpha2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder" 1 : 2-, 2005

      16 Ma CL, "Locomotor hyperactivity induced by blockade of prefrontal cortical alpha2-adrenoceptors in monkeys" 57 : 192-195, 2005

      17 Weinshilboum R, "Inheritance and drug response" 348 : 529-537, 2003

      18 Jäkälä P, "Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans" 20 : 119-130, 1999

      19 Wilens TE, "Effects of methylphenidate on the catecholaminergic system in attention-deficit/hyperactivity disorder" 28 : 46-53, 2008

      20 Hoehe MR, "Dra I identifies a two allele DNA polymorphism in the human alpha 2-adrenergic receptor gene (ADRAR), using a 5.5 kb probe (p ADRAR)" 16 : 9070-, 1988

      21 Engert V, "Dopaminergic and noradrenergic contributions to functionality in ADHD: the role of methylphenidate" 6 : 322-328, 2008

      22 Arnsten AF, "Catecholamine modulation of prefrontal cortical cognitive function" 2 : 436-447, 1998

      23 Gizer IR, "Candidate gene studies of ADHD: a meta-analytic review" 126 : 51-90, 2009

      24 National Institute of Mental Health, "CGI, Clinical Global Impressions. In Manual of the ECDEU Assessment Battery, revised edition" Chevy Chase, Maryland: National Institute of Mental Health 1970

      25 McGough JJ, "Attention-deficit/hyperactivity disorder pharmacogenomics" 57 : 1367-1373, 2005

      26 Polanczyk G, "Association of the adrenergic alpha2A receptor gene with methylphenidate improvement of inattentive symptoms in children and adolescents with attention-deficit/hyperactivity disorder" 64 : 218-224, 2007

      27 Cheon KA, "Association Between Homozygosity of a G Allele of the Alpha-2a-Adrenergic Receptor Gene and Methylphenidate Response in Korean Children and Adolescents with Attention-Deficit/Hyperactivity Disorder" 65 (65): 564-570, 2009

      28 Lowe N, "An overview of the Pharmacogenetics and Molecular Genetics of ADHD" 4 : 231-243, 2006

      29 Contini V, "Adrenergic α2A receptor gene is not associated with methylphenidate response in adults with ADHD" 261 : 205-211, 2011

      30 da Silva TL, "Adrenergic alpha2A receptor gene and response to methylphenidate in attention-deficit/hyperactivity disorder-predominantly inattentive type" 115 : 341-345, 2008

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