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


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.


CONCLUSIONS
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.
Kristina
K
Probst-Schendzielorz
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
Catharina
C
Scholl
Olga
O
Efimkina
Eva
E
Ersfeld
Roberto
R
Viviani
Alessandro
A
Serretti
Chiara
C
Fabbri
David
D
Gurwitz
7Max Planck Institute of Psychiatry, Munich, Germany.
Susanne
S
Lucae
7Max Planck Institute of Psychiatry, Munich, Germany.
Marcus
M
Ising
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
Anna Maria
AM
Paul
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
Marie-Louise
ML
Lehmann
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
Michael
M
Steffens
Concetta
C
Crisafulli
Marco
M
Calabrò
7Max Planck Institute of Psychiatry, Munich, Germany.
Florian
F
Holsboer
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
Julia
J
Stingl
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D039661:Integrin beta3 / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D013557:Switzerland / Q000453:epidemiology; D016896:Treatment Outcome
D000928:Antidepressive Agents; D054316:Biomarkers, Pharmacological; C490650:CHL1 protein, human; D015815:Cell Adhesion Molecules; C061248:ITGB3 protein, human; D039661:Integrin beta3; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
CHL1; ITGB3; MARS; Munich Antidepressant Response Signature Project; depression; gene expression; imipramine; lymphoblastoid cell line; mirtazapine; paroxetine; response biomarker