Influence of methylenetetrahydrofolate reductase genetic polymorphisms on antidepressant response

Abstract

Objective: To assess influence of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene on response to antidepressant treatment. Methods: Two hundred and eight one Chinese Han patients have received single antidepressant drugs for at least 6 weeks, among whom 275 were followed up for 8 weeks. Hamilton depression scale-17 (HAMD-17) was used to evaluate the severity of depressive symptoms and therapeutic effects. Single nucleotide polymorphisms (SNPs) of the MTHFR gene was determined using gene chips. Associations of single loci and haplotypes with response to treatment were analyzed using an Unphased 3.0.13 software. Results: No significant difference of gender, age, year of education, family history, episode times, and antidepressant agents was found between responders and non-responders (all P>0.05), while the baseline scores of HAMD-17 was significantly different (t=2.891, P=0.004). There were also no significant difference between age, years of education, family history, baseline scores of HAMD-17 and antidepressant agents between remitters and non-remitters (both P>0.05), while proportion of male patients was significantly higher in non-remission group than remission group (t=2.381, P=0.018), and episode times in non-remission group was significantly higher (t=-1.983, P=0.049). Single locus association analysis has found no significant association between SNPs rs1801131 and rs1801133 in the MTHFR gene with antidepressant response (P>0.05). On the other hand, haplotype (A-C) in MTHFR gene (rs1801131 and rs1801133) was significantly associated with antidepressant response in total group (χ2=11.39, P=0.0007), male subgroup (χ2=8.767, P=0.003) and serotonin-noradrenaline reuptake inhibitors (SNRIs) subgroup (χ2= 10.51, P=0.001). Conclusion: Particular haplotype of MTHFR gene may be related with antidepressant effect, in which the haplotype (rs1801131-rs1801133) A-C type may be associated with better antidepressant efficacy, particularly in males and patients receiving SNRIs drugs.