Laboratory of Biological Psychiatry, Tianjin Mental Health Centre, Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, 13 Liulin Road., Hexi District, Tianjin, 300222, China.
Department of Psychiatry, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
J Neural Transm (Vienna). 2022 Jan;129(1):85-93. doi: 10.1007/s00702-021-02415-y. Epub 2021 Nov 12.
Genetic factors play a crucial role for the pathophysiology of treatment-resistant depression (TRD). It has been established that Catechol-O-methyltransferase (COMT) and cyclic amp-response element-binding protein (CREB) are associated with antidepressant response. The aim of this study was to explore the association between single nucleotide polymorphisms (SNPs) in COMT and CREB1 genes and TRD in a Chinese population. We recruited 181 patients with major depressive disorder (MDD) and 80 healthy controls, including 81 TRD patients. Depressive symptoms were assessed with the Hamilton Depression Rating Scale-17 (HDRS). Genotyping was performed using mass spectrometry. Genetic analyses were conducted by PLINK Software. The distribution of COMT SNP rs4818 allele and genotypes were significantly different between TRD and controls. Statistical differences in allele frequencies were observed between TRD and non-TRD groups, including rs11904814 and rs6740584 in CREB1 gene, rs4680 and rs4818 in COMT gene. There were differences in the distribution of HDRS total scores among different phenotypes of CREB1 rs11904814, CREB1 rs6740584, COMT rs4680 and rs4818. Gene-gene interaction effect of COMT-CREB1 (rs4680 × rs6740584) revealed significant epistasis in TRD. There findings indicate that COMT and CREB1 polymorphisms influence the risk of TRD and affect the severity of depressive symptoms of MDD.
遗传因素在治疗抵抗性抑郁症（TRD）的病理生理学中起着至关重要的作用。已经确定儿茶酚-O-甲基转移酶（COMT）和环磷酸腺苷反应元件结合蛋白（CREB）与抗抑郁反应有关。本研究旨在探讨 COMT 和 CREB1 基因单核苷酸多态性（SNPs）与中国人群 TRD 的关系。我们招募了 181 例重度抑郁症（MDD）患者和 80 例健康对照者，包括 81 例 TRD 患者。使用汉密尔顿抑郁评定量表-17（HDRS）评估抑郁症状。采用质谱法进行基因分型。PLINK 软件进行遗传分析。COMT SNP rs4818 等位基因和基因型在 TRD 和对照组之间的分布有显著差异。TRD 和非 TRD 组之间观察到等位基因频率的统计学差异，包括 CREB1 基因中的 rs11904814 和 rs6740584，COMT 基因中的 rs4680 和 rs4818。在 CREB1 rs11904814、CREB1 rs6740584、COMT rs4680 和 rs4818 的不同表型中，HDRS 总分的分布存在差异。COMT-CREB1（rs4680 × rs6740584）的基因-基因相互作用效应显示在 TRD 中存在显著的上位性。这些发现表明 COMT 和 CREB1 多态性影响 TRD 的风险，并影响 MDD 抑郁症状的严重程度。
