Variation in GNB3 predicts response and adverse reactions to antidepressants

Robert Keers; Cristian Bonvicini; Catia Scassellati; Rudolf Uher; Anna Placentino; Caterina Giovannini; Marcella Rietschel; Neven Henigsberg; Dejan Kozel; Ole Mors; Wolfgang Maier; Joanna Hauser; Daniel Souery; Julien Mendlewicz; Christine Schmäl; Astrid Zobel; Erik R. Larsen; Aleksandra Szczepankiewicz; Zrnka Kovacic; Amanda Elkin; Ian Craig; Peter McGuffin; Anne E. Farmer; Katherine J. Aitchison; Massimo Gennarelli

doi:10.1177/0269881110376683

Variation in GNB3 predicts response and adverse reactions to antidepressants

Robert Keers, Cristian Bonvicini, Catia Scassellati, Rudolf Uher, Anna Placentino, Caterina Giovannini, Marcella Rietschel, Neven Henigsberg, Dejan Kozel, Ole Mors, Wolfgang Maier, Joanna Hauser, Daniel Souery, Julien Mendlewicz, Christine Schmäl, Astrid Zobel, Erik R. Larsen, Aleksandra Szczepankiewicz, Zrnka Kovacic, Amanda ElkinIan Craig, Peter McGuffin, Anne E. Farmer, Katherine J. Aitchison, Massimo Gennarelli

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

44 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	867-874
Número de páginas	8
Publicación	Journal of Psychopharmacology
Volumen	25
N.º	7
DOI	https://doi.org/10.1177/0269881110376683
Estado	Published - jul. 2011
Publicado de forma externa	Sí

Nota bibliográfica

Funding Information:
The GENDEP clinical trial was funded as part of an Integrated Project by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for GENDEP. GlaxoSmithKline, the Medical Research Council, and the Biomedical Research Centre for Mental Health at the Institute of Psychiatry and South London and Maudsley NHS Foundation Trust (funded by the United Kingdom National Institute for Health Research of the Department of Health) latterly contributed to the funding of the sample collection at the Institute of Psychiatry, London, through add-on projects or staff funding. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing of the report.

ASJC Scopus Subject Areas

Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Acceder al documento

10.1177/0269881110376683

Otros archivos y enlaces

Citar esto

Keers, R., Bonvicini, C., Scassellati, C., Uher, R., Placentino, A., Giovannini, C., Rietschel, M., Henigsberg, N., Kozel, D., Mors, O., Maier, W., Hauser, J., Souery, D., Mendlewicz, J., Schmäl, C., Zobel, A., Larsen, E. R., Szczepankiewicz, A., Kovacic, Z., ... Gennarelli, M. (2011). Variation in GNB3 predicts response and adverse reactions to antidepressants. Journal of Psychopharmacology, 25(7), 867-874. https://doi.org/10.1177/0269881110376683

Keers, R, Bonvicini, C, Scassellati, C, Uher, R, Placentino, A, Giovannini, C, Rietschel, M, Henigsberg, N, Kozel, D, Mors, O, Maier, W, Hauser, J, Souery, D, Mendlewicz, J, Schmäl, C, Zobel, A, Larsen, ER, Szczepankiewicz, A, Kovacic, Z, Elkin, A, Craig, I, McGuffin, P, Farmer, AE, Aitchison, KJ & Gennarelli, M 2011, 'Variation in GNB3 predicts response and adverse reactions to antidepressants', Journal of Psychopharmacology, vol. 25, n.º 7, pp. 867-874. https://doi.org/10.1177/0269881110376683

@article{b21244ac0ad9492abb7e236c93d7bc86,

title = "Variation in GNB3 predicts response and adverse reactions to antidepressants",

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.",

author = "Robert Keers and Cristian Bonvicini and Catia Scassellati and Rudolf Uher and Anna Placentino and Caterina Giovannini and Marcella Rietschel and Neven Henigsberg and Dejan Kozel and Ole Mors and Wolfgang Maier and Joanna Hauser and Daniel Souery and Julien Mendlewicz and Christine Schm{\"a}l and Astrid Zobel and Larsen, {Erik R.} and Aleksandra Szczepankiewicz and Zrnka Kovacic and Amanda Elkin and Ian Craig and Peter McGuffin and Farmer, {Anne E.} and Aitchison, {Katherine J.} and Massimo Gennarelli",

note = "Funding Information: The GENDEP clinical trial was funded as part of an Integrated Project by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for GENDEP. GlaxoSmithKline, the Medical Research Council, and the Biomedical Research Centre for Mental Health at the Institute of Psychiatry and South London and Maudsley NHS Foundation Trust (funded by the United Kingdom National Institute for Health Research of the Department of Health) latterly contributed to the funding of the sample collection at the Institute of Psychiatry, London, through add-on projects or staff funding. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing of the report. ",

year = "2011",

month = jul,

doi = "10.1177/0269881110376683",

language = "English",

volume = "25",

pages = "867--874",

journal = "Journal of Psychopharmacology",

issn = "0269-8811",

publisher = "SAGE Publications Ltd",

number = "7",

}

TY - JOUR

T1 - Variation in GNB3 predicts response and adverse reactions to antidepressants

AU - Keers, Robert

AU - Bonvicini, Cristian

AU - Scassellati, Catia

AU - Uher, Rudolf

AU - Placentino, Anna

AU - Giovannini, Caterina

AU - Rietschel, Marcella

AU - Henigsberg, Neven

AU - Kozel, Dejan

AU - Mors, Ole

AU - Maier, Wolfgang

AU - Hauser, Joanna

AU - Souery, Daniel

AU - Mendlewicz, Julien

AU - Schmäl, Christine

AU - Zobel, Astrid

AU - Larsen, Erik R.

AU - Szczepankiewicz, Aleksandra

AU - Kovacic, Zrnka

AU - Elkin, Amanda

AU - Craig, Ian

AU - McGuffin, Peter

AU - Farmer, Anne E.

AU - Aitchison, Katherine J.

AU - Gennarelli, Massimo

N1 - Funding Information: The GENDEP clinical trial was funded as part of an Integrated Project by a European Commission Framework 6 grant, EC Contract Ref.: LSHB-CT-2003-503428. Lundbeck provided both nortriptyline and escitalopram free of charge for GENDEP. GlaxoSmithKline, the Medical Research Council, and the Biomedical Research Centre for Mental Health at the Institute of Psychiatry and South London and Maudsley NHS Foundation Trust (funded by the United Kingdom National Institute for Health Research of the Department of Health) latterly contributed to the funding of the sample collection at the Institute of Psychiatry, London, through add-on projects or staff funding. The sponsors had no role in the design and conduct of the study, in data collection, analysis, interpretation or writing of the report.

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052002492&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052002492&partnerID=8YFLogxK

U2 - 10.1177/0269881110376683

DO - 10.1177/0269881110376683

M3 - Article

C2 - 20826553

AN - SCOPUS:80052002492

SN - 0269-8811

VL - 25

SP - 867

EP - 874

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

IS - 7

ER -

Variation in GNB3 predicts response and adverse reactions to antidepressants

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

ODS de las Naciones Unidas

Acceder al documento

Otros archivos y enlaces

Huella

Citar esto