Dopamine Transporter 3′-UTR VNTR Genotype and ADHD: a Pharmaco-Behavioural Genetic Study with Methylphenidate
We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the SLC6A3 gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 y...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2007-06, Vol.32 (6), p.1370-1376 |
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| creator | Joober, Ridha Grizenko, Natalie Sengupta, Sarojini Amor, Leila Ben Schmitz, Norbert Schwartz, George Karama, Sherif Lageix, Philippe Fathalli, Ferid Torkaman-Zehi, Adam Stepanian, Marina Ter |
| description | We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the
SLC6A3
gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of
SLC6A3,
as indicated by a significant (
p
=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH. |
| doi_str_mv | 10.1038/sj.npp.1301240 |
| format | Article |
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SLC6A3
gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of
SLC6A3,
as indicated by a significant (
p
=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/sj.npp.1301240</identifier><identifier>PMID: 17063150</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>3' Untranslated Regions - genetics ; Attention Deficit Disorder with Hyperactivity - drug therapy ; Attention Deficit Disorder with Hyperactivity - genetics ; Attention Deficit Disorder with Hyperactivity - psychology ; Attention deficit hyperactivity disorder ; Behavior ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Central Nervous System Stimulants - administration & dosage ; Central Nervous System Stimulants - therapeutic use ; Child ; Child & adolescent psychiatry ; Cross-Over Studies ; Dopamine ; Dopamine Plasma Membrane Transport Proteins - genetics ; Female ; Genotype ; Genotype & phenotype ; Humans ; Hypotheses ; Male ; Medical sciences ; Medicine ; Medicine & Public Health ; Methylphenidate - administration & dosage ; Methylphenidate - therapeutic use ; Minisatellite Repeats - genetics ; Neuropharmacology ; Neurosciences ; original-article ; Pharmacology. Drug treatments ; Pharmacotherapy ; Polymorphism ; Polymorphism, Genetic - genetics ; Prospective Studies ; Psychiatric Status Rating Scales ; Psychiatry ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopharmacology ; Research centers ; Schools</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2007-06, Vol.32 (6), p.1370-1376</ispartof><rights>American College of Neuropsychopharmacology 2007</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jun 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-970a698a821b375120055203c748ebeb323bc9478de472064181975d063c73533</citedby><cites>FETCH-LOGICAL-c412t-970a698a821b375120055203c748ebeb323bc9478de472064181975d063c73533</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.npp.1301240$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.npp.1301240$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18968886$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17063150$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Joober, Ridha</creatorcontrib><creatorcontrib>Grizenko, Natalie</creatorcontrib><creatorcontrib>Sengupta, Sarojini</creatorcontrib><creatorcontrib>Amor, Leila Ben</creatorcontrib><creatorcontrib>Schmitz, Norbert</creatorcontrib><creatorcontrib>Schwartz, George</creatorcontrib><creatorcontrib>Karama, Sherif</creatorcontrib><creatorcontrib>Lageix, Philippe</creatorcontrib><creatorcontrib>Fathalli, Ferid</creatorcontrib><creatorcontrib>Torkaman-Zehi, Adam</creatorcontrib><creatorcontrib>Stepanian, Marina Ter</creatorcontrib><title>Dopamine Transporter 3′-UTR VNTR Genotype and ADHD: a Pharmaco-Behavioural Genetic Study with Methylphenidate</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacol</addtitle><addtitle>Neuropsychopharmacology</addtitle><description>We sought to test the hypothesis that the variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region (3′-UTR) of the
SLC6A3
gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of
SLC6A3,
as indicated by a significant (
p
=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.</description><subject>3' Untranslated Regions - genetics</subject><subject>Attention Deficit Disorder with Hyperactivity - drug therapy</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>Attention Deficit Disorder with Hyperactivity - psychology</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Behavior</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Central Nervous System Stimulants - administration & dosage</subject><subject>Central Nervous System Stimulants - therapeutic use</subject><subject>Child</subject><subject>Child & adolescent psychiatry</subject><subject>Cross-Over Studies</subject><subject>Dopamine</subject><subject>Dopamine Plasma Membrane Transport Proteins - genetics</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methylphenidate - administration & dosage</subject><subject>Methylphenidate - therapeutic use</subject><subject>Minisatellite Repeats - genetics</subject><subject>Neuropharmacology</subject><subject>Neurosciences</subject><subject>original-article</subject><subject>Pharmacology. Drug treatments</subject><subject>Pharmacotherapy</subject><subject>Polymorphism</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Prospective Studies</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychiatry</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. 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Drug treatments</topic><topic>Pharmacotherapy</topic><topic>Polymorphism</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Prospective Studies</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. 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SLC6A3
gene modulates behavior in children with ADHD and/or behavioral response to methylphenidate (MPH). One hundred and fifty-nine children with AHDH (6–12 years) were assessed with regard to the Conners’ Global Index for parents (CGI-Parents) and teachers (CGI-Teachers) and the response of these behaviors to MPH (0.5 mg/kg/day) using a 2-week prospective within-subject (crossover) trial. Based on CGI-Parents, the profile of behavioral response to MPH as compared to placebo was not parallel in the three groups of children separated according to their genotype in the 3′-UTR VNTR polymorphism of
SLC6A3,
as indicated by a significant (
p
=0.017) genotype by treatment two-way interaction. Individuals having the 9/10 and 10/10 genotypes displayed a significant positive response to MPH as opposed to those homozygous for the 9-repeat allele. No genotype or genotype by treatment interaction was observed for CGI-Teachers. These findings support a role for the DAT gene 3′-UTR VNTR polymorphism in modulating the response of some behavioral dimensions to MPH in children with ADHD. They also suggest the presence of genetic heterogeneity that could be indexed by the quality of behavioral response to MPH.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>17063150</pmid><doi>10.1038/sj.npp.1301240</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0893-133X 1740-634X |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings |
| subjects | 3' Untranslated Regions - genetics Attention Deficit Disorder with Hyperactivity - drug therapy Attention Deficit Disorder with Hyperactivity - genetics Attention Deficit Disorder with Hyperactivity - psychology Attention deficit hyperactivity disorder Behavior Behavioral Sciences Biological and medical sciences Biological Psychology Central Nervous System Stimulants - administration & dosage Central Nervous System Stimulants - therapeutic use Child Child & adolescent psychiatry Cross-Over Studies Dopamine Dopamine Plasma Membrane Transport Proteins - genetics Female Genotype Genotype & phenotype Humans Hypotheses Male Medical sciences Medicine Medicine & Public Health Methylphenidate - administration & dosage Methylphenidate - therapeutic use Minisatellite Repeats - genetics Neuropharmacology Neurosciences original-article Pharmacology. Drug treatments Pharmacotherapy Polymorphism Polymorphism, Genetic - genetics Prospective Studies Psychiatric Status Rating Scales Psychiatry Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopharmacology Research centers Schools |
| title | Dopamine Transporter 3′-UTR VNTR Genotype and ADHD: a Pharmaco-Behavioural Genetic Study with Methylphenidate |
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