Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

Katherine Tansey; J. J H Rucker; D. H. Kavanagh; M. Guipponi; N. Perroud; G. Bondolfi; E. Domenici; Darren M Evans; Jon C Hauser; N. Henigsberg; B. Jerman; W. Maier; O. Mors; M. O'Donovan; Tim J Peters; A. Placentino; M. Rietschel; D. Souery; K. J. Aitchison; I. Craig; A. Farmer; J. R. Wendland; A. Malafosse; Geoffrey W Lewis; S. Kapur; P. McGuffin; R. Uher

doi:10.1038/tpj.2013.51

Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

Katherine Tansey^*, J. J H Rucker, D. H. Kavanagh, M. Guipponi, N. Perroud, G. Bondolfi, E. Domenici, Darren M Evans, Jon C Hauser, N. Henigsberg, B. Jerman, W. Maier, O. Mors, M. O'Donovan, Tim J Peters, A. Placentino, M. Rietschel, D. Souery, K. J. Aitchison, I. CraigA. Farmer, J. R. Wendland, A. Malafosse, Geoffrey W Lewis, S. Kapur, P. McGuffin, R. Uher

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

Original language	English
Pages (from-to)	395-399
Number of pages	5
Journal	Pharmacogenomics Journal
Volume	14
Issue number	4
Early online date	21 Jan 2014
DOIs	https://doi.org/10.1038/tpj.2013.51
Publication status	Published - Aug 2014

Keywords

15q13.3
antidepressant
copy number variants
major depressive disorder
psychiatry
treatment response

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Tansey, K., Rucker, J. J. H., Kavanagh, D. H., Guipponi, M., Perroud, N., Bondolfi, G., Domenici, E., Evans, D. M., Hauser, J. C., Henigsberg, N., Jerman, B., Maier, W., Mors, O., O'Donovan, M., Peters, T. J., Placentino, A., Rietschel, M., Souery, D., Aitchison, K. J., ... Uher, R. (2014). Copy number variants and therapeutic response to antidepressant medication in major depressive disorder. Pharmacogenomics Journal, 14(4), 395-399. https://doi.org/10.1038/tpj.2013.51

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title = "Copy number variants and therapeutic response to antidepressant medication in major depressive disorder",

abstract = "It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant. ",

keywords = "15q13.3, antidepressant, copy number variants, major depressive disorder, psychiatry, treatment response",

author = "Katherine Tansey and Rucker, \{J. J H\} and Kavanagh, \{D. H.\} and M. Guipponi and N. Perroud and G. Bondolfi and E. Domenici and Evans, \{Darren M\} and Hauser, \{Jon C\} and N. Henigsberg and B. Jerman and W. Maier and O. Mors and M. O'Donovan and Peters, \{Tim J\} and A. Placentino and M. Rietschel and D. Souery and Aitchison, \{K. J.\} and I. Craig and A. Farmer and Wendland, \{J. R.\} and A. Malafosse and Lewis, \{Geoffrey W\} and S. Kapur and P. McGuffin and R. Uher",

year = "2014",

month = aug,

doi = "10.1038/tpj.2013.51",

language = "English",

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Tansey, K, Rucker, JJH, Kavanagh, DH, Guipponi, M, Perroud, N, Bondolfi, G, Domenici, E, Evans, DM, Hauser, JC, Henigsberg, N, Jerman, B, Maier, W, Mors, O, O'Donovan, M, Peters, TJ, Placentino, A, Rietschel, M, Souery, D, Aitchison, KJ, Craig, I, Farmer, A, Wendland, JR, Malafosse, A, Lewis, GW, Kapur, S, McGuffin, P & Uher, R 2014, 'Copy number variants and therapeutic response to antidepressant medication in major depressive disorder', Pharmacogenomics Journal, vol. 14, no. 4, pp. 395-399. https://doi.org/10.1038/tpj.2013.51

TY - JOUR

T1 - Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

AU - Tansey, Katherine

AU - Rucker, J. J H

AU - Kavanagh, D. H.

AU - Guipponi, M.

AU - Perroud, N.

AU - Bondolfi, G.

AU - Domenici, E.

AU - Evans, Darren M

AU - Hauser, Jon C

AU - Henigsberg, N.

AU - Jerman, B.

AU - Maier, W.

AU - Mors, O.

AU - O'Donovan, M.

AU - Peters, Tim J

AU - Placentino, A.

AU - Rietschel, M.

AU - Souery, D.

AU - Aitchison, K. J.

AU - Craig, I.

AU - Farmer, A.

AU - Wendland, J. R.

AU - Malafosse, A.

AU - Lewis, Geoffrey W

AU - Kapur, S.

AU - McGuffin, P.

AU - Uher, R.

PY - 2014/8

Y1 - 2014/8

N2 - It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

AB - It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

KW - 15q13.3

KW - antidepressant

KW - copy number variants

KW - major depressive disorder

KW - psychiatry

KW - treatment response

UR - https://www.scopus.com/pages/publications/84904960520

U2 - 10.1038/tpj.2013.51

DO - 10.1038/tpj.2013.51

M3 - Article (Academic Journal)

C2 - 24445990

AN - SCOPUS:84904960520

SN - 1470-269X

VL - 14

SP - 395

EP - 399

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 4

ER -

Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

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GENETIC CLINICAL AND ENDOCRINE PREDICTORS OF TREATMENT OUTCOME IN DEPRESSION

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Copy number variants and therapeutic response to antidepressant medication in major depressive disorder

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GENETIC CLINICAL AND ENDOCRINE PREDICTORS OF TREATMENT OUTCOME IN DEPRESSION

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