CREB1 and BDNF gene polymorphisms are associated with early treatment response to escitalopram in panic disorder

Abstract

Objectives: Increasing evidence shows that the alternations under escitalopram treatment for Panic disorder (PD) patients are related to the cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF). We aimed to explore the single nucleotide polymorphisms (SNPs) of genes BDNF and CREB1 in the treatment response to escitalopram on PD.

Methods: There were 80 PD patients with DSM-5 diagnosis and 78 healthy controls. All PD patients have received escitalopram treatment for consecutive 8 weeks. The Chinese version of Panic Disorder Severity Scale (PDSS-CV) and the Hamilton Anxiety Scale (HAMA-14) were used to evaluate the severity of panic and anxious symptoms for PD patients at baseline, week-2, week-4, and week-8, respectively. Four SNPs (rs11904814, rs6740584, rs2253206, and rs2551941) in CREB1 gene and rs6265 in BDNF gene were genotyped using matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS). Quantitative and binary genetic associations between SNPs and escitalopram treatment response were performed.

Results: The comparisons of three genotypes in CREB1 SNPs rs11904814 and rs2551941 among the PDSS-CV responders showed significant differences at the end of week-2 (both p<0.05). The results remained significant after Bonferroni corrections. For candidate genes in our present study, the gene CREB1 SNP rs11904814 (p=0.007) was significantly associated with changes of PDSS-CV scores under escitalopram treatment for 12 weeks in PD patients. And the result was still significant after adjusting age and gender.

Conclusions: The findings provide preliminary evidence supporting the potential role of BDNF and CREB1 on a rapid response after escitalopram intervention in PD patients.

Keywords: BDNF; CREB1; Escitalopram; Panic disorder; SNP.