CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study

Kristina Probst-Schendzielorz; Catharina Scholl; Olga Efimkina; Eva Ersfeld; Roberto Viviani; Alessandro Serretti; Chiara Fabbri; David Gurwitz; Susanne Lucae; Marcus Ising; Anna Maria Paul; Marie Louise Lehmann; Michael Steffens; Concetta Crisafulli; Marco Calabrò; Florian Holsboer; Julia Stingl

doi:10.2217/pgs.15.31

CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study

Kristina Probst-Schendzielorz, Catharina Scholl^*, Olga Efimkina, Eva Ersfeld, Roberto Viviani, Alessandro Serretti, Chiara Fabbri, David Gurwitz, Susanne Lucae, Marcus Ising, Anna Maria Paul, Marie Louise Lehmann, Michael Steffens, Concetta Crisafulli, Marco Calabrò, Florian Holsboer, Julia Stingl

^*Corresponding author for this work

Human Molecular Genetics Biochemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Aim: The identification of antidepressant drugs (ADs) response biomarkers in depression is of high clinical importance. We explored CHL1 and ITGB3 expression as tentative response biomarkers. Materials & methods: In vitro sensitivity to ADs, as well as gene expression and genetic variants of the candidate genes CHL1, ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58 depressed patients. Results: An association between the clinical remission of depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT genotype showed a significantly better remission after 5 weeks AD treatment than those carrying a CC genotype. No association between the in vitro sensitivity of LCLs toward AD and the clinical remission could be detected. Conclusion: CHL1 expression in patient-derived LCLs correlated with the clinical outcome. Thus, it could be a valid biomarker to predict the success of an antidepressant therapy. Original submitted 8 December 2014; Revision submitted 2 March 201.

Original language	English
Pages (from-to)	689-701
Number of pages	13
Journal	Pharmacogenomics
Volume	16
Issue number	7
DOIs	https://doi.org/10.2217/pgs.15.31
State	Published - 1 May 2015

Keywords

CHL1
ITGB3
MARS
Munich Antidepressant Response Signature Project
depression
gene expression
imipramine
lymphoblastoid cell line
mirtazapine
paroxetine
response biomarker

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Probst-Schendzielorz, K., Scholl, C., Efimkina, O., Ersfeld, E., Viviani, R., Serretti, A., Fabbri, C., Gurwitz, D., Lucae, S., Ising, M., Paul, A. M., Lehmann, M. L., Steffens, M., Crisafulli, C., Calabrò, M., Holsboer, F., & Stingl, J. (2015). CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study. Pharmacogenomics, 16(7), 689-701. https://doi.org/10.2217/pgs.15.31

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title = "CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study",

abstract = "Aim: The identification of antidepressant drugs (ADs) response biomarkers in depression is of high clinical importance. We explored CHL1 and ITGB3 expression as tentative response biomarkers. Materials & methods: In vitro sensitivity to ADs, as well as gene expression and genetic variants of the candidate genes CHL1, ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58 depressed patients. Results: An association between the clinical remission of depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT genotype showed a significantly better remission after 5 weeks AD treatment than those carrying a CC genotype. No association between the in vitro sensitivity of LCLs toward AD and the clinical remission could be detected. Conclusion: CHL1 expression in patient-derived LCLs correlated with the clinical outcome. Thus, it could be a valid biomarker to predict the success of an antidepressant therapy. Original submitted 8 December 2014; Revision submitted 2 March 201.",

keywords = "CHL1, ITGB3, MARS, Munich Antidepressant Response Signature Project, depression, gene expression, imipramine, lymphoblastoid cell line, mirtazapine, paroxetine, response biomarker",

author = "Kristina Probst-Schendzielorz and Catharina Scholl and Olga Efimkina and Eva Ersfeld and Roberto Viviani and Alessandro Serretti and Chiara Fabbri and David Gurwitz and Susanne Lucae and Marcus Ising and Paul, {Anna Maria} and Lehmann, {Marie Louise} and Michael Steffens and Concetta Crisafulli and Marco Calabr{\`o} and Florian Holsboer and Julia Stingl",

note = "Publisher Copyright: {\textcopyright} 2015 Future Medicine Ltd.",

year = "2015",

month = may,

day = "1",

doi = "10.2217/pgs.15.31",

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volume = "16",

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Probst-Schendzielorz, K, Scholl, C, Efimkina, O, Ersfeld, E, Viviani, R, Serretti, A, Fabbri, C, Gurwitz, D, Lucae, S, Ising, M, Paul, AM, Lehmann, ML, Steffens, M, Crisafulli, C, Calabrò, M, Holsboer, F & Stingl, J 2015, 'CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study', Pharmacogenomics, vol. 16, no. 7, pp. 689-701. https://doi.org/10.2217/pgs.15.31

TY - JOUR

T1 - CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response

T2 - Results from the Munich Antidepressant Response Signature (MARS) study

AU - Probst-Schendzielorz, Kristina

AU - Scholl, Catharina

AU - Efimkina, Olga

AU - Ersfeld, Eva

AU - Viviani, Roberto

AU - Serretti, Alessandro

AU - Fabbri, Chiara

AU - Gurwitz, David

AU - Lucae, Susanne

AU - Ising, Marcus

AU - Paul, Anna Maria

AU - Lehmann, Marie Louise

AU - Steffens, Michael

AU - Crisafulli, Concetta

AU - Calabrò, Marco

AU - Holsboer, Florian

AU - Stingl, Julia

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Aim: The identification of antidepressant drugs (ADs) response biomarkers in depression is of high clinical importance. We explored CHL1 and ITGB3 expression as tentative response biomarkers. Materials & methods: In vitro sensitivity to ADs, as well as gene expression and genetic variants of the candidate genes CHL1, ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58 depressed patients. Results: An association between the clinical remission of depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT genotype showed a significantly better remission after 5 weeks AD treatment than those carrying a CC genotype. No association between the in vitro sensitivity of LCLs toward AD and the clinical remission could be detected. Conclusion: CHL1 expression in patient-derived LCLs correlated with the clinical outcome. Thus, it could be a valid biomarker to predict the success of an antidepressant therapy. Original submitted 8 December 2014; Revision submitted 2 March 201.

AB - Aim: The identification of antidepressant drugs (ADs) response biomarkers in depression is of high clinical importance. We explored CHL1 and ITGB3 expression as tentative response biomarkers. Materials & methods: In vitro sensitivity to ADs, as well as gene expression and genetic variants of the candidate genes CHL1, ITGB3 and SLC6A4 were measured in lymphoblastoid cell lines (LCLs) of 58 depressed patients. Results: An association between the clinical remission of depression and the basal expression of CHL1 and ITGB3 was discovered. Individuals whose LCLs expressed higher levels of CHL1 or ITGB3 showed a significantly better remission upon AD treatment. In addition individuals with the CHL1 rs1516338 TT genotype showed a significantly better remission after 5 weeks AD treatment than those carrying a CC genotype. No association between the in vitro sensitivity of LCLs toward AD and the clinical remission could be detected. Conclusion: CHL1 expression in patient-derived LCLs correlated with the clinical outcome. Thus, it could be a valid biomarker to predict the success of an antidepressant therapy. Original submitted 8 December 2014; Revision submitted 2 March 201.

KW - CHL1

KW - ITGB3

KW - MARS

KW - Munich Antidepressant Response Signature Project

KW - depression

KW - gene expression

KW - imipramine

KW - lymphoblastoid cell line

KW - mirtazapine

KW - paroxetine

KW - response biomarker

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SN - 1462-2416

VL - 16

SP - 689

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JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 7

ER -

CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: Results from the Munich Antidepressant Response Signature (MARS) study

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Keywords

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