Variation in GNB3 predicts response and adverse reactions to antidepressants
There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine recept...
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| creator | Keers, Robert Bonvicini, Cristian Scassellati, Catia Uher, Rudolf Placentino, Anna Giovannini, Caterina Rietschel, Marcella Henigsberg, Neven Kozel, Dejan Mors, Ole Maier, Wolfgang Hauser, Joanna Souery, Daniel Mendlewicz, Julien Schmäl, Christine Zobel, Astrid Larsen, Erik R Szczepankiewicz, Aleksandra Kovacic, Zrnka Elkin, Amanda Craig, Ian McGuffin, Peter Farmer, Anne E Aitchison, Katherine J Gennarelli, Massimo |
| description | There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response. |
| doi_str_mv | 10.1177/0269881110376683 |
| format | Article |
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GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response.</description><identifier>ISSN: 0269-8811</identifier><identifier>EISSN: 1461-7285</identifier><identifier>DOI: 10.1177/0269881110376683</identifier><identifier>PMID: 20826553</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Activation ; Adult ; Adult and adolescent clinical studies ; Antidepressants ; Antidepressive Agents - adverse effects ; Antidepressive Agents - therapeutic use ; Appetite ; Biological and medical sciences ; Citalopram ; Citalopram - adverse effects ; Citalopram - therapeutic use ; Data processing ; Depression ; Depressive Disorder, Major - diagnosis ; Depressive Disorder, Major - drug therapy ; Depressive Disorder, Major - genetics ; Europe ; Female ; Functional anatomy ; Gene Frequency ; Gene polymorphism ; Genes ; Guanine nucleotide-binding protein ; Haplotypes ; Heterotrimeric GTP-Binding Proteins - genetics ; Humans ; Insomnia ; Linkage Disequilibrium ; Male ; Medical sciences ; Mental depression ; Middle Aged ; Mood ; Mood disorders ; Neuropharmacology ; Nortriptyline - adverse effects ; Nortriptyline - therapeutic use ; Pharmacogenetics ; Pharmacogenomics ; Pharmacology. Drug treatments ; Polymorphism, Single Nucleotide ; Psychiatric Status Rating Scales ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer ; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Receptor mechanisms ; Risk Assessment ; Risk Factors ; Side effects ; Single-nucleotide polymorphism ; Sleep disorders ; Sleep Initiation and Maintenance Disorders - chemically induced ; Time Factors ; Transcription ; Treatment Outcome ; Weight Gain - drug effects</subject><ispartof>Journal of psychopharmacology (Oxford), 2011-07, Vol.25 (7), p.867-874</ispartof><rights>The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-c6f190c8a163eb98b240a5588e9ef848fba94bce10757f19abf81be302361d973</citedby><cites>FETCH-LOGICAL-c426t-c6f190c8a163eb98b240a5588e9ef848fba94bce10757f19abf81be302361d973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0269881110376683$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0269881110376683$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24315118$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20826553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Keers, Robert</creatorcontrib><creatorcontrib>Bonvicini, Cristian</creatorcontrib><creatorcontrib>Scassellati, Catia</creatorcontrib><creatorcontrib>Uher, Rudolf</creatorcontrib><creatorcontrib>Placentino, Anna</creatorcontrib><creatorcontrib>Giovannini, Caterina</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Henigsberg, Neven</creatorcontrib><creatorcontrib>Kozel, Dejan</creatorcontrib><creatorcontrib>Mors, Ole</creatorcontrib><creatorcontrib>Maier, Wolfgang</creatorcontrib><creatorcontrib>Hauser, Joanna</creatorcontrib><creatorcontrib>Souery, Daniel</creatorcontrib><creatorcontrib>Mendlewicz, Julien</creatorcontrib><creatorcontrib>Schmäl, Christine</creatorcontrib><creatorcontrib>Zobel, Astrid</creatorcontrib><creatorcontrib>Larsen, Erik R</creatorcontrib><creatorcontrib>Szczepankiewicz, Aleksandra</creatorcontrib><creatorcontrib>Kovacic, Zrnka</creatorcontrib><creatorcontrib>Elkin, Amanda</creatorcontrib><creatorcontrib>Craig, Ian</creatorcontrib><creatorcontrib>McGuffin, Peter</creatorcontrib><creatorcontrib>Farmer, Anne E</creatorcontrib><creatorcontrib>Aitchison, Katherine J</creatorcontrib><creatorcontrib>Gennarelli, Massimo</creatorcontrib><title>Variation in GNB3 predicts response and adverse reactions to antidepressants</title><title>Journal of psychopharmacology (Oxford)</title><addtitle>J Psychopharmacol</addtitle><description>There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response.</description><subject>Activation</subject><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Antidepressants</subject><subject>Antidepressive Agents - adverse effects</subject><subject>Antidepressive Agents - therapeutic use</subject><subject>Appetite</subject><subject>Biological and medical sciences</subject><subject>Citalopram</subject><subject>Citalopram - adverse effects</subject><subject>Citalopram - therapeutic use</subject><subject>Data processing</subject><subject>Depression</subject><subject>Depressive Disorder, Major - diagnosis</subject><subject>Depressive Disorder, Major - drug therapy</subject><subject>Depressive Disorder, Major - genetics</subject><subject>Europe</subject><subject>Female</subject><subject>Functional anatomy</subject><subject>Gene Frequency</subject><subject>Gene polymorphism</subject><subject>Genes</subject><subject>Guanine nucleotide-binding protein</subject><subject>Haplotypes</subject><subject>Heterotrimeric GTP-Binding Proteins - genetics</subject><subject>Humans</subject><subject>Insomnia</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mental depression</subject><subject>Middle Aged</subject><subject>Mood</subject><subject>Mood disorders</subject><subject>Neuropharmacology</subject><subject>Nortriptyline - adverse effects</subject><subject>Nortriptyline - therapeutic use</subject><subject>Pharmacogenetics</subject><subject>Pharmacogenomics</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</subject><subject>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Receptor mechanisms</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Side effects</subject><subject>Single-nucleotide polymorphism</subject><subject>Sleep disorders</subject><subject>Sleep Initiation and Maintenance Disorders - chemically induced</subject><subject>Time Factors</subject><subject>Transcription</subject><subject>Treatment Outcome</subject><subject>Weight Gain - drug effects</subject><issn>0269-8811</issn><issn>1461-7285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0UtLxDAQAOAgiq6PuycpiHiqZpomnR5VdBUWvajXkqZTqey2a6Yr-O9N2fXBgnjKwHzzCCPEIcgzgCw7l4nJEQFAqswYVBtiBKmBOEtQb4rRkI6H_I7YZX6VEkxq9LbYSSQmRms1EpNn6xvbN10bNW00vr9U0dxT1bieI08871qmyLZVZKt38iH2ZN3AOeq7kOibikIBcwh5X2zVdsp0sHr3xNPN9ePVbTx5GN9dXUxilyamj52pIZcOLRhFZY5lkkqrNSLlVGOKdWnztHQEMtNZoLasEUpSMlEGqjxTe-J02Xfuu7cFcV_MGnY0ndqWugUXiEoqian8X2YYZNgmyOM1-dotfBu-UYS0HkbDoORSOd8xe6qLuW9m1n8UIIvhJMX6SULJ0arxopxR9V3wdYMATlbAsrPT2tvWNfzjUgUaAIOLl47tC_3a7q_Bn4-Pnlo</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Keers, Robert</creator><creator>Bonvicini, Cristian</creator><creator>Scassellati, Catia</creator><creator>Uher, Rudolf</creator><creator>Placentino, Anna</creator><creator>Giovannini, Caterina</creator><creator>Rietschel, Marcella</creator><creator>Henigsberg, Neven</creator><creator>Kozel, Dejan</creator><creator>Mors, Ole</creator><creator>Maier, Wolfgang</creator><creator>Hauser, Joanna</creator><creator>Souery, Daniel</creator><creator>Mendlewicz, Julien</creator><creator>Schmäl, Christine</creator><creator>Zobel, Astrid</creator><creator>Larsen, Erik R</creator><creator>Szczepankiewicz, Aleksandra</creator><creator>Kovacic, Zrnka</creator><creator>Elkin, Amanda</creator><creator>Craig, Ian</creator><creator>McGuffin, Peter</creator><creator>Farmer, Anne E</creator><creator>Aitchison, Katherine J</creator><creator>Gennarelli, Massimo</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</general><scope>IQODW</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>7TK</scope><scope>7X8</scope></search><sort><creationdate>20110701</creationdate><title>Variation in GNB3 predicts response and adverse reactions to antidepressants</title><author>Keers, Robert ; Bonvicini, Cristian ; Scassellati, Catia ; Uher, Rudolf ; Placentino, Anna ; Giovannini, Caterina ; Rietschel, Marcella ; Henigsberg, Neven ; Kozel, Dejan ; Mors, Ole ; Maier, Wolfgang ; Hauser, Joanna ; Souery, Daniel ; Mendlewicz, Julien ; Schmäl, Christine ; Zobel, Astrid ; Larsen, Erik R ; Szczepankiewicz, Aleksandra ; Kovacic, Zrnka ; Elkin, Amanda ; Craig, Ian ; McGuffin, Peter ; Farmer, Anne E ; Aitchison, Katherine J ; Gennarelli, Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-c6f190c8a163eb98b240a5588e9ef848fba94bce10757f19abf81be302361d973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Activation</topic><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Antidepressants</topic><topic>Antidepressive Agents - adverse effects</topic><topic>Antidepressive Agents - therapeutic use</topic><topic>Appetite</topic><topic>Biological and medical sciences</topic><topic>Citalopram</topic><topic>Citalopram - adverse effects</topic><topic>Citalopram - therapeutic use</topic><topic>Data processing</topic><topic>Depression</topic><topic>Depressive Disorder, Major - diagnosis</topic><topic>Depressive Disorder, Major - drug therapy</topic><topic>Depressive Disorder, Major - genetics</topic><topic>Europe</topic><topic>Female</topic><topic>Functional anatomy</topic><topic>Gene Frequency</topic><topic>Gene polymorphism</topic><topic>Genes</topic><topic>Guanine nucleotide-binding protein</topic><topic>Haplotypes</topic><topic>Heterotrimeric GTP-Binding Proteins - genetics</topic><topic>Humans</topic><topic>Insomnia</topic><topic>Linkage Disequilibrium</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mental depression</topic><topic>Middle Aged</topic><topic>Mood</topic><topic>Mood disorders</topic><topic>Neuropharmacology</topic><topic>Nortriptyline - adverse effects</topic><topic>Nortriptyline - therapeutic use</topic><topic>Pharmacogenetics</topic><topic>Pharmacogenomics</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer</topic><topic>Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Receptor mechanisms</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Side effects</topic><topic>Single-nucleotide polymorphism</topic><topic>Sleep disorders</topic><topic>Sleep Initiation and Maintenance Disorders - chemically induced</topic><topic>Time Factors</topic><topic>Transcription</topic><topic>Treatment Outcome</topic><topic>Weight Gain - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Keers, Robert</creatorcontrib><creatorcontrib>Bonvicini, Cristian</creatorcontrib><creatorcontrib>Scassellati, Catia</creatorcontrib><creatorcontrib>Uher, Rudolf</creatorcontrib><creatorcontrib>Placentino, Anna</creatorcontrib><creatorcontrib>Giovannini, Caterina</creatorcontrib><creatorcontrib>Rietschel, Marcella</creatorcontrib><creatorcontrib>Henigsberg, Neven</creatorcontrib><creatorcontrib>Kozel, Dejan</creatorcontrib><creatorcontrib>Mors, Ole</creatorcontrib><creatorcontrib>Maier, Wolfgang</creatorcontrib><creatorcontrib>Hauser, Joanna</creatorcontrib><creatorcontrib>Souery, Daniel</creatorcontrib><creatorcontrib>Mendlewicz, Julien</creatorcontrib><creatorcontrib>Schmäl, Christine</creatorcontrib><creatorcontrib>Zobel, Astrid</creatorcontrib><creatorcontrib>Larsen, Erik R</creatorcontrib><creatorcontrib>Szczepankiewicz, Aleksandra</creatorcontrib><creatorcontrib>Kovacic, Zrnka</creatorcontrib><creatorcontrib>Elkin, Amanda</creatorcontrib><creatorcontrib>Craig, Ian</creatorcontrib><creatorcontrib>McGuffin, Peter</creatorcontrib><creatorcontrib>Farmer, Anne E</creatorcontrib><creatorcontrib>Aitchison, Katherine J</creatorcontrib><creatorcontrib>Gennarelli, Massimo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of psychopharmacology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Keers, Robert</au><au>Bonvicini, Cristian</au><au>Scassellati, Catia</au><au>Uher, Rudolf</au><au>Placentino, Anna</au><au>Giovannini, Caterina</au><au>Rietschel, Marcella</au><au>Henigsberg, Neven</au><au>Kozel, Dejan</au><au>Mors, Ole</au><au>Maier, Wolfgang</au><au>Hauser, Joanna</au><au>Souery, Daniel</au><au>Mendlewicz, Julien</au><au>Schmäl, Christine</au><au>Zobel, Astrid</au><au>Larsen, Erik R</au><au>Szczepankiewicz, Aleksandra</au><au>Kovacic, Zrnka</au><au>Elkin, Amanda</au><au>Craig, Ian</au><au>McGuffin, Peter</au><au>Farmer, Anne E</au><au>Aitchison, Katherine J</au><au>Gennarelli, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variation in GNB3 predicts response and adverse reactions to antidepressants</atitle><jtitle>Journal of psychopharmacology (Oxford)</jtitle><addtitle>J Psychopharmacol</addtitle><date>2011-07-01</date><risdate>2011</risdate><volume>25</volume><issue>7</issue><spage>867</spage><epage>874</epage><pages>867-874</pages><issn>0269-8811</issn><eissn>1461-7285</eissn><abstract>There is substantial inter-individual variation in response and adverse reactions to antidepressants, and genetic variation may, in part, explain these differences. GNB3 encodes the β3 subunit of the G protein complex, which is involved in the downstream signalling cascade following monoamine receptor activation. A functional polymorphism in this gene (C825T) has been associated with response to antidepressants. Several lines of evidence suggest that GNB3 moderates improvement in the neurovegetative symptoms of depression (such as sleep and appetite) and related adverse reactions independently of change in core mood symptoms. We here report analysis of data from GENDEP, a part-randomized pharmacogenomic trial, on the outcome of 811 subjects with major depression undergoing treatment with either escitalopram or nortriptyline in which the C825T SNP and three further SNPs in GNB3 were genotyped. The TT genotype was significantly associated with a superior response to nortriptyline and these effects were specific to improvements in neurovegetative symptoms. In addition, the same genotype predicted fewer incidents of treatment-emergent insomnia and greater weight gain on the same drug. Our results are consistent with previous associations with GNB3 and emphasize the importance of signalling genes in antidepressant response.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>20826553</pmid><doi>10.1177/0269881110376683</doi><tpages>8</tpages></addata></record> |
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| subjects | Activation Adult Adult and adolescent clinical studies Antidepressants Antidepressive Agents - adverse effects Antidepressive Agents - therapeutic use Appetite Biological and medical sciences Citalopram Citalopram - adverse effects Citalopram - therapeutic use Data processing Depression Depressive Disorder, Major - diagnosis Depressive Disorder, Major - drug therapy Depressive Disorder, Major - genetics Europe Female Functional anatomy Gene Frequency Gene polymorphism Genes Guanine nucleotide-binding protein Haplotypes Heterotrimeric GTP-Binding Proteins - genetics Humans Insomnia Linkage Disequilibrium Male Medical sciences Mental depression Middle Aged Mood Mood disorders Neuropharmacology Nortriptyline - adverse effects Nortriptyline - therapeutic use Pharmacogenetics Pharmacogenomics Pharmacology. Drug treatments Polymorphism, Single Nucleotide Psychiatric Status Rating Scales Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Receptor mechanisms Risk Assessment Risk Factors Side effects Single-nucleotide polymorphism Sleep disorders Sleep Initiation and Maintenance Disorders - chemically induced Time Factors Transcription Treatment Outcome Weight Gain - drug effects |
| title | Variation in GNB3 predicts response and adverse reactions to antidepressants |
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