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Escitalopram Response in Panic Disorder

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Escitalopram Response in Panic Disorder essio epr n D an f d Wenhui et al., J Depress Anxiety 2017, S12 o A l a n n x r DOI: 10.4172/2167-1044.S12-006 i e u t y o J Journal of Depression and Anxiety ISSN: 2167-1044 Research Article Article OpenOpen Access Access Escitalopram Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients Wenhui C1, Qian L2, Suxia C2, Jianyue P2 and Hengfen L2* 1Department of Psychiatry, Shenyang Mental Health Center, Shenyang 110168, Liaoning Province, P. R. China 2Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450002, Henan Province, P. R. China Abstract Background: Prior studies have implicated 5-HT1A receptor gene (HTR1A) polymorphisms in the etiology of panic disorder (PD) as well as in the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). A functional HTR1A C-1019G polymorphism (rs6295) in the promoter region and two non-synonymous polymorphisms (rs10042486 and rs1364043) were previously found to be associated with SSRI pharmacogenetics. However, no studies have examined this relationship in Chinese-Han PD patients. Methods: Seventy-seven patients with PD according to DSM-IV criteria were recruited. All of them with a minimum score of 8 on the seven item Panic Disorder Severity Scale, Chinese version (PDSS-CV). In this study, we evaluated the association between three single nucleotide polymorphisms (SNPs) of HTR1A (rs6295, rs10042486, and rs1364043) and the clinical effects of escitalopram in Chinese-Han PD patients. Results: The C/C genotype of C-1019G carriers showed better responses to escitalopram compared to the C/G or G/G genotypes. However, after Bonferroni correction, the effect was not statistically significant. Similarly, no significant associations were noted between rs10042486 or rs1364043 and the escitalopram clinical response. Conclusion: Our results suggest that these three single nucleotide polymorphisms (SNPs) in 5-HT1A genes examined here may not influence the escitalopram response in Chinese-Han PD patients. Keywords: 5-HT1A receptor gene; Single nucleotide polymorphism; associated with SSRI pharmacogenetics. However, no association study Panic disorder; Escitalopram of HTR1A gene polymorphisms (rs6295, rs10042486, and rs1364043) and escitalopram clinical response in Chinese-Han PD patients has Introduction been reported. Panic disorder (PD) is a common anxiety disorder that affects up to Therefore, we conducted an association study with three HTR1A 5% of the population over their lifetime [1]. In addition, PD has been gene SNPs (rs6295, rs10042486, and rs1364043) to determine the best linked to increased cardiovascular morbidity and mortality, which predictive value for clinical responses in Chinese-Han PD patients. typically increases the burden of suffering as well as economic costs [2,3]. Therefore, it is valuable to determine its etiology and provide Methods targeted treatment methods for this disorder. Subjects Positron emission tomography (PET) analyses have found This study was performed at Shenyang Mental Health Center. The significantly reduced 5-HT1A radio ligand binding in the raphe Ethics Committee of Shenyang Mental Health Center approved this nuclei, orbitofrontal cortex, temporal cortex, and amygdala regions study, and each subject provided written informed consent before of PD patients compared to control subjects [4]. Moreover, genetic enrollment. Seventy-seven patients (24 males, 53 females) with PD studies suggest the involvement of the 5-HT1A receptor gene in panic according to DSM-IV criteria were recruited. disorder [5]. Animal studies have demonstrated that 5-HT1A receptor knockout mice show increased anxiety-like behavior [6]. Thus, based Only subjects with a minimum score of 8 on the seven item Panic on neuroimaging data, animal models, and genetic studies, the Disorder Severity Scale, Chinese version (PDSS-CV) qualified for the 5-HT1A receptor gene, located on chromosome 5 (5q11.2–13), is a putative candidate gene for PD [7]. Of several gene polymorphisms, studies have focused on a functional C-1019G single nucleotide *Corresponding author: Hengfen L, Department of Psychiatry, The First Affiliated polymorphism (SNP rs6295) located in the promoter of HTR1A, which Hospital of Zhengzhou University, Zhengzhou 450002, Henan Province, P. R. regulates HTR1A transcription, and is associated with schizophrenia, China, Tel: +8637166913114; E-mail: [email protected] bipolar disorder, anxiety, depression-related personality traits, and Received October 04, 2017; Accepted October 25, 2017; Published October 27, antidepressant responses [8-10]. In particular, two very recent studies 2017 reported the C-1019G polymorphism was associated with clinical Citation: Wenhui C, Qian L, Suxia C, Jianyue P, Hengfen L (2017) Escitalopram responses in Japanese and Caucasian PD patients [11,12]. Additionally, Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene this polymorphism and a nearby functional polymorphism are in strong Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients. J Depress Anxiety S12: 006. doi:10.4172/2167-1044.S12-006 linkage disequilibrium [13]. Based on these results, we hypothesized that other HTR1A polymorphisms in strong linkage disequilibrium with Copyright: © 2017 Wenhui C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted rs6295 might also influence the clinical response. Two polymorphisms use, distribution, and reproduction in any medium, provided the original author and of HTR1A (rs10042486 and rs1364043) were previously found to be source are credited. J Depress Anxiety Mixed symptoms & Syndromes of Anxiety & Depression ISSN: 2167-1044 JDA an open access journal Citation: Wenhui C, Qian L, Suxia C, Jianyue P, Hengfen L (2017) Escitalopram Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients. J Depress Anxiety S12: 006. doi:10.4172/2167-1044. S12-006 Page 2 of 4 study. Patients with substance abuse, severe organic mental disorders, Variables Responders Non-responders t p or concomitant major psychiatric disorders were excluded. The mean Age 29.03 ± 6.79 31.56 ± 6.40 -1.67 0.10 age of patients was 30.61±6.51 years (± SD) and ranged from 18 to 60 Escitalopram dose 16.55 ± 3.80 17.50 ± 2.73 -1.27 0.21 years. The clinical response to treatment was assessed using the PDSS- PDSS score (baseline) 20.97 ± 2.21 21.08 ± 2.00 -0.24 0.81 CV at the beginning of treatment and every two weeks thereafter. It took PDSS score (week 2) 17.07 ± 1.91 17.48 ± 2.05 -0.87 0.39 5 to 7 days before patients received the full therapeutic escitalopram PDSS score (week 4) 10.24 ± 1.02 12.00 ± 1.41 -5.83 <0.01 dose (10-20 mg/day). A significant clinical response was defined as a Table 1: The mean age, escitalopram dose, and PDSS score between responders 50% decrease in PDSS-CV total score within 4 weeks of escitalopram and non-responders in PD patients. treatment. Genotype Responders [n (% )] Non-responders [n (% )] χ2 p Polymorphism genotyping rs6295 Genomic DNA was extracted from EDTA-treated venous blood us- GG 13 (30.2) 30 (69.8) ing standard techniques and DNA extraction kits (Wizard Genomic DNA CG 9 (36.0) 16 (64.0) 6.79 0.04 purification kit; Promega, USA). Genotyping for the three SNPs (rs6295, CC 7 (77.8) 2 (22.2) rs10042486, and rs1364043) was performed using polymerase chain re- rs10042486 action (PCR) and post-PCR ligase detection reaction (LDR) assays. Ge- CC 1 (33.3) 2 (66.7) nomic DNA was amplified using the following primers: rs6295 (sense: CT 11 (42.3) 15 (57.7) 0.54 0.83 5′-ACGGAGGTACCGTTTTGTTG-3′, antisense: 3′-CCCAGAGTG- TT 17 (35.4) 31 (64.6) GCAATAGGAGA-5′), rs10042486 (sense: 5′-GGTTGGAGTTTCT- rs1364043 CAGTAATTGG-3′, antisense: 3′-TGGGGATTGGGAAGAATTA- GG 10 (35.7) 18 (64.3) AA-5′), rs1364043 (sense: 5′-AAGCGAACTCAAACAGCAAAA-3′, GT 17 (41.5) 24 (58.5) 0.78 0.70 antisense: 3′-TTTGAAGAGGGCACAATTCC-5′). PCR reactions had TT 2 (25.0) 6 (75.0) a final volume of 20 μl containing 100 ng genomic DNA, dNTPs (0.2 Table 2: Genotype distributions in the responders and non-responders after mM of each), 1.0 ng/l template, 2.0 mM PCR buffer, 0.6 mM Mg2+, 0.2 escitalopram treatment for 4 weeks. U/ml HOT Start Taq DNA polymerase, 9.8 μl H O, 4 μl Q-solution, and 2 dose, and PDSS-CV score of the responders and non-responders 0.4 pM primer mix. After an initial denaturation step of 15 min at 95°C, are presented in (Table 1) These two groups showed no significant DNA was amplified by 35 cycles of denaturation at 94°C for 30 s, an- differences in PDSS-CV scores at baseline, age, or escitalopram dose nealing at 53°C for 1 min, and extension at 72°C for 1 min, followed by (p>0.05). a final extension step at 72°C for 10 min. Successful amplification was confirmed by running 2 μl of the PCR product mixture on agarose gels The genotype distributions for the three SNPs in the responders stained with ethidium bromide. and non-responders after 4 weeks of escitalopram treatment are shown in (Table 2) The C/C genotype of C-1019G showed better response LDR assays were performed in a final volume of 10 μl containing to escitalopram, compared to the C/G and G/G genotypes (χ2=6.79, ≥1 μl PCR products, 6.95 μl H O, 0.05 μl ligase, 1 μl probe mix, and 2 p=0.04). However, this difference was not significant after adjusting the 1 μl buffer. The initial denaturation for 2 min at 95°C was followed by significance level for multiple tests (for k=3 groups and k × (k-1)/2=3 35 cycles of denaturation at 94°C for 30 s and annealing and extension comparisons, the corrected significance level is 0.017).
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