Probst-Schendzielorz Kristina, Scholl Catharina, Efimkina Olga, Ersfeld Eva, Viviani Roberto, Serretti Alessandro, Fabbri Chiara, Gurwitz David, Lucae Susanne, Ising Marcus, Paul Anna Maria, Lehmann Marie-Louise, Steffens Michael, Crisafulli Concetta, Calabrò Marco, Holsboer Florian, Stingl Julia
3Medical Faculty, Faculty Centre for Translational Medicine, University Bonn, Bonn, Germany.
7Max Planck Institute of Psychiatry, Munich, Germany.
Pharmacogenomics. 2015;16(7):689-701. doi: 10.2217/pgs.15.31. Epub 2015 May 6.
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.
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.
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.
鉴定抑郁症中抗抑郁药物(ADs)反应生物标志物具有高度临床重要性。我们探究了CHL1和ITGB3的表达作为初步反应生物标志物。
在58例抑郁症患者的淋巴母细胞系(LCLs)中测量了对ADs的体外敏感性以及候选基因CHL1、ITGB3和SLC6A4的基因表达和遗传变异。
发现抑郁症的临床缓解与CHL1和ITGB3的基础表达之间存在关联。其LCLs表达较高水平CHL1或ITGB3的个体在接受AD治疗后缓解情况明显更好。此外,CHL1 rs1516338 TT基因型个体在接受5周AD治疗后的缓解情况明显优于携带CC基因型的个体。未检测到LCLs对AD的体外敏感性与临床缓解之间存在关联。
患者来源的LCLs中CHL1表达与临床结果相关。因此,它可能是预测抗抑郁治疗成功的有效生物标志物。原始稿件于2014年12月8日提交;修订稿件于2015年3月2日提交。