Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response
ABT-925, a selective dopamine D 3 receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some a...
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| creator | Bhathena, A Wang, Y Kraft, J B Idler, K B Abel, S J Holley-Shanks, R R Robieson, W Z Spear, B Redden, L Katz, D A |
| description | ABT-925, a selective dopamine D
3
receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (
N
=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (
P
=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the
DRD3
G allele than in those who carried the
DRD3
SS genotype. |
| doi_str_mv | 10.1038/tp.2013.22 |
| format | Article |
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3
receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (
N
=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (
P
=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the
DRD3
G allele than in those who carried the
DRD3
SS genotype.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/tp.2013.22</identifier><identifier>PMID: 23571810</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/436/434 ; 692/699/476/1799 ; Adolescent ; Adult ; Aged ; Alleles ; Antipsychotic Agents - therapeutic use ; Behavioral Sciences ; Biological Psychology ; Catechol O-Methyltransferase - genetics ; Dopamine Antagonists - therapeutic use ; Dose-Response Relationship, Drug ; Double-Blind Method ; Female ; Genotype ; Humans ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Neurosciences ; Original ; original-article ; Pharmacotherapy ; Piperazines - therapeutic use ; Polymorphism, Single Nucleotide - genetics ; Psychiatric Status Rating Scales ; Psychiatry ; Pyrimidines - therapeutic use ; Receptors, Dopamine D3 - genetics ; Schizophrenia - drug therapy ; Schizophrenia - genetics ; Treatment Outcome ; Young Adult</subject><ispartof>Translational psychiatry, 2013-04, Vol.3 (4), p.e245-e245</ispartof><rights>The Author(s) 2013</rights><rights>Copyright Nature Publishing Group Apr 2013</rights><rights>Copyright © 2013 Macmillan Publishers Limited 2013 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-8b1ca65e18d625f59309b0a6bbd88ad35c762cd48bf67bef6db29ba9bf3e378b3</citedby><cites>FETCH-LOGICAL-c442t-8b1ca65e18d625f59309b0a6bbd88ad35c762cd48bf67bef6db29ba9bf3e378b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641409/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641409/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23571810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bhathena, A</creatorcontrib><creatorcontrib>Wang, Y</creatorcontrib><creatorcontrib>Kraft, J B</creatorcontrib><creatorcontrib>Idler, K B</creatorcontrib><creatorcontrib>Abel, S J</creatorcontrib><creatorcontrib>Holley-Shanks, R R</creatorcontrib><creatorcontrib>Robieson, W Z</creatorcontrib><creatorcontrib>Spear, B</creatorcontrib><creatorcontrib>Redden, L</creatorcontrib><creatorcontrib>Katz, D A</creatorcontrib><title>Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>Transl Psychiatry</addtitle><description>ABT-925, a selective dopamine D
3
receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (
N
=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (
P
=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the
DRD3
G allele than in those who carried the
DRD3
SS genotype.</description><subject>631/92/436/434</subject><subject>692/699/476/1799</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Alleles</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>Behavioral Sciences</subject><subject>Biological Psychology</subject><subject>Catechol O-Methyltransferase - genetics</subject><subject>Dopamine Antagonists - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Genotype</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neurosciences</subject><subject>Original</subject><subject>original-article</subject><subject>Pharmacotherapy</subject><subject>Piperazines - therapeutic use</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychiatry</subject><subject>Pyrimidines - therapeutic use</subject><subject>Receptors, Dopamine D3 - genetics</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenia - genetics</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>2158-3188</issn><issn>2158-3188</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkUtrGzEUhUVpqEOSTX9AEXTXMo4eMxrNpuC8A4FskrWQNHdcmbE0leRA_n1l7BqH3s29cD7OPXAQ-krJnBIuL_M0Z4TyOWOf0Cmjjaw4lfLz0T1DFymtSJmmlrSlX9CM8aalkpJT5BYpBet0dsHjMOA-THrtPFQRRp2hx0vwkJ3FY6FwDgcA33AcwcKUQ8TaZ70M3qWMF1cvVccabEfnndVjgdIUfIJzdDLoMcHFfp-h17vbl-uH6un5_vF68VTZuma5koZaLRqgshesGZqOk84QLYzppdQ9b2wrmO1raQbRGhhEb1hndGcGDryVhp-hXzvfaWPW0FvwOepRTdGtdXxXQTv1UfHut1qGN8VFTWvSFYPve4MY_mwgZbUKm-hLZkXbjvJOUCEL9WNH2RhSijAcPlCits2oPKltM4qxAn87znRA__VQgJ87IBXJLyEe_fzf7i-0XJkx</recordid><startdate>20130409</startdate><enddate>20130409</enddate><creator>Bhathena, A</creator><creator>Wang, Y</creator><creator>Kraft, J B</creator><creator>Idler, K B</creator><creator>Abel, S J</creator><creator>Holley-Shanks, R R</creator><creator>Robieson, W Z</creator><creator>Spear, B</creator><creator>Redden, L</creator><creator>Katz, D A</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20130409</creationdate><title>Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response</title><author>Bhathena, A ; Wang, Y ; Kraft, J B ; Idler, K B ; Abel, S J ; Holley-Shanks, R R ; Robieson, W Z ; Spear, B ; Redden, L ; Katz, D A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-8b1ca65e18d625f59309b0a6bbd88ad35c762cd48bf67bef6db29ba9bf3e378b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>631/92/436/434</topic><topic>692/699/476/1799</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>Behavioral Sciences</topic><topic>Biological Psychology</topic><topic>Catechol O-Methyltransferase - genetics</topic><topic>Dopamine Antagonists - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Genotype</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neurosciences</topic><topic>Original</topic><topic>original-article</topic><topic>Pharmacotherapy</topic><topic>Piperazines - therapeutic use</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Pyrimidines - therapeutic use</topic><topic>Receptors, Dopamine D3 - genetics</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenia - genetics</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bhathena, A</creatorcontrib><creatorcontrib>Wang, Y</creatorcontrib><creatorcontrib>Kraft, J B</creatorcontrib><creatorcontrib>Idler, K B</creatorcontrib><creatorcontrib>Abel, S J</creatorcontrib><creatorcontrib>Holley-Shanks, R R</creatorcontrib><creatorcontrib>Robieson, W Z</creatorcontrib><creatorcontrib>Spear, B</creatorcontrib><creatorcontrib>Redden, L</creatorcontrib><creatorcontrib>Katz, D A</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Translational psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bhathena, A</au><au>Wang, Y</au><au>Kraft, J B</au><au>Idler, K B</au><au>Abel, S J</au><au>Holley-Shanks, R R</au><au>Robieson, W Z</au><au>Spear, B</au><au>Redden, L</au><au>Katz, D A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response</atitle><jtitle>Translational psychiatry</jtitle><stitle>Transl Psychiatry</stitle><addtitle>Transl Psychiatry</addtitle><date>2013-04-09</date><risdate>2013</risdate><volume>3</volume><issue>4</issue><spage>e245</spage><epage>e245</epage><pages>e245-e245</pages><issn>2158-3188</issn><eissn>2158-3188</eissn><abstract>ABT-925, a selective dopamine D
3
receptor (DRD3) antagonist, was tested in schizophrenia. A DRD3 gene polymorphism results in an S9G amino-acid change that has been associated with lower risk of schizophrenia, higher affinity for dopamine and some antipsychotics, and differential response to some antipsychotics. The effect of S9G genotype on response to ABT-925 was examined. DNA samples (
N
=117) were collected in a proof-of-concept, double-blind, randomized, placebo-controlled study of ABT-925 (50 or 150 mg QD) in acute exacerbation of schizophrenia. A pre-specified analysis assessed impact of genotype (SS versus SG+GG) on change from baseline to final evaluation for the Positive and Negative Syndrome Scale (PANSS) total score using analysis of covariance with genotype, treatment and genotype-by-treatment interaction as factors, and baseline score as covariate. Significant genotype-by-treatment interaction (
P
=0.015) was observed for change from baseline to final evaluation for the PANSS total score. Within subgroup analyses showed significant improvement from placebo in the SG+GG group treated with ABT-925 150 mg. More favorable clinical outcomes were observed in patients treated with ABT-925 150 mg who carried the
DRD3
G allele than in those who carried the
DRD3
SS genotype.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23571810</pmid><doi>10.1038/tp.2013.22</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 631/92/436/434 692/699/476/1799 Adolescent Adult Aged Alleles Antipsychotic Agents - therapeutic use Behavioral Sciences Biological Psychology Catechol O-Methyltransferase - genetics Dopamine Antagonists - therapeutic use Dose-Response Relationship, Drug Double-Blind Method Female Genotype Humans Male Medicine Medicine & Public Health Middle Aged Neurosciences Original original-article Pharmacotherapy Piperazines - therapeutic use Polymorphism, Single Nucleotide - genetics Psychiatric Status Rating Scales Psychiatry Pyrimidines - therapeutic use Receptors, Dopamine D3 - genetics Schizophrenia - drug therapy Schizophrenia - genetics Treatment Outcome Young Adult |
| title | Association of dopamine-related genetic loci to dopamine D3 receptor antagonist ABT-925 clinical response |
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