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色氨酸羟化酶、溶质载体家族6成员2、溶质载体家族6成员3、多巴胺D2受体及多巴胺D4受体基因多态性与神经内分泌因子对中国重度抑郁症患者选择性5-羟色胺再摄取抑制剂治疗结局的预测作用

TPH, SLC6A2, SLC6A3, DRD2 and DRD4 Polymorphisms and Neuroendocrine Factors Predict SSRIs Treatment Outcome in the Chinese Population with Major Depression.

作者信息

Yin L, Zhang Y Y, Zhang X, Yu T, He G, Sun X L

机构信息

Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People's Republic of China.

Bio-X Institute, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China.

出版信息

Pharmacopsychiatry. 2015 May;48(3):95-103. doi: 10.1055/s-0034-1398508. Epub 2015 Feb 2.

Abstract

OBJECTIVE

This study was intended to determine whether antidepressant outcome to SSRIs was associated with catecholamine gene polymorphisms and neuroendocrine factors in patients of Chinese Han ethnicity with MDD.

METHOD

A total of 290 MDD patients were recruited and received a 6-week randomized double-blinded treatment. Cortisol, adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), 3'-triiodothyronine (T3), thyroxine (T4), free triiodothyronine (fT3), and free thyroxine (fT4) levels were measured at the baseline. Allele, genotype, and haplotype frequencies of catecholamine genes were compared between responders and non-responders, remission and non-remission groups respectively.

RESULTS

We found that genotype frequency of the rs1800544 polymorphism in the DRD4 gene was significantly different between responders and non-responders (P<0.05). Also the frequency of the rs1800544 CG genotype was significantly higher (P<0.05) in responders (51.4%) than that in non-responders (35.8%). No significant difference was found between responders and non-responders, remission and non-remission groups in the SNPs polymorphisms in the TPH, SLC6A2, SLC6A3, or DRD2 genes. The combination of all neuroendocrine factors, clinical characteristics and gene polymorphisms predicted 74.8% of the variation in SSRI response and 65.5% in SSRI remission.

CONCLUSION

Polymorphisms of the DRD4 gene were associated with SSRI response in Chinese Han MDD patients. A combination of clinical characteristics, neuroendocrine factors, and gene polymorphisms might be able to predict the outcome to SSRIs.

摘要

目的

本研究旨在确定中国汉族重度抑郁症(MDD)患者中,选择性5-羟色胺再摄取抑制剂(SSRI)的抗抑郁疗效是否与儿茶酚胺基因多态性及神经内分泌因子相关。

方法

共招募290例MDD患者,接受为期6周的随机双盲治疗。在基线时测量皮质醇、促肾上腺皮质激素(ACTH)、促甲状腺激素(TSH)、三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(fT3)和游离甲状腺素(fT4)水平。分别比较应答者与无应答者、缓解组与未缓解组之间儿茶酚胺基因的等位基因、基因型和单倍型频率。

结果

我们发现,应答者与无应答者之间,DRD4基因rs1800544多态性的基因型频率存在显著差异(P<0.05)。应答者(51.4%)中rs1800544 CG基因型的频率也显著高于无应答者(35.8%)(P<0.05)。在TPH、SLC6A2、SLC6A3或DRD2基因的单核苷酸多态性(SNP)方面,应答者与无应答者、缓解组与未缓解组之间未发现显著差异。所有神经内分泌因子、临床特征和基因多态性的组合可预测SSRI反应中74.8%的变异及SSRI缓解中65.5%的变异。

结论

DRD4基因多态性与中国汉族MDD患者的SSRI反应相关。临床特征、神经内分泌因子和基因多态性的组合可能能够预测SSRI的疗效。

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