1. CHL1, ITGB3 and SLC6A4 gene expression and antidepressant drug response: results from the Munich Antidepressant Response Signature (MARS) study
- Author
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Anna Maria Paul, Alessandro Serretti, Olga Efimkina, Julia C. Stingl, Michael Steffens, David Gurwitz, Chiara Fabbri, Eva Ersfeld, Marcus Ising, Susanne Lucae, Catharina Scholl, Concetta Crisafulli, Kristina Probst-Schendzielorz, Roberto Viviani, Marco Calabrò, Marie-Louise Lehmann, Florian Holsboer, Probst-Schendzielorz, Kristina, Scholl, Catharina, Efimkina, Olga, Ersfeld, Eva, Viviani, Roberto, Serretti, Alessandro, Fabbri, Chiara, Gurwitz, David, Lucae, Susanne, Ising, Marcu, Paul, Anna Maria, Lehmann, Marie-Louise, Steffens, Michael, Crisafulli, Concetta, Calabrò, Marco, Holsboer, Florian, and Stingl, Julia
- Subjects
Male ,Candidate gene ,Imipramine ,Biomarkers, Pharmacological ,Basal (phylogenetics) ,CHL1 ,depression ,gene expression ,imipramine ,ITGB3 ,lymphoblastoid cell line ,MARS ,mirtazapine ,Munich Antidepressant Response Signature Project ,paroxetine ,response biomarker ,Adult ,Antidepressive Agents ,Cell Adhesion Molecules ,Depressive Disorder, Major ,Dose-Response Relationship, Drug ,Female ,Gene Expression Regulation ,Germany ,Humans ,Integrin beta3 ,Middle Aged ,Polymorphism, Single Nucleotide ,Serotonin Plasma Membrane Transport Proteins ,Switzerland ,Treatment Outcome ,Molecular Medicine ,Genetics ,Pharmacology ,Genotype ,Gene expression ,Medicine ,Single Nucleotide ,Paroxetine ,Antidepressive Agent ,Antidepressant ,Drug ,Serotonin Plasma Membrane Transport Protein ,Human ,medicine.drug ,Mirtazapine ,Dose-Response Relationship ,Genetic ,Polymorphism ,Depressive Disorder ,business.industry ,Pharmacological ,Major ,Cell Adhesion Molecule ,Immunology ,business ,Biomarkers - 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 2015
- Published
- 2015
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