Toledo-Lozano Christian Gabriel, López-Hernández Luz Berenice, Suárez-Cuenca Juan Antonio, Villalobos-Gallegos Luis, Jiménez-Hernández Dulce Adeí, Alcaraz-Estrada Sofía Lizeth, Mondragón-Terán Paul, Joya-Laureano Lilia, Coral-Vázquez Ramón Mauricio, García Silvia
Department of Clinical Research, Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City 03229, Mexico.
Life Cycle Department, Autonomous University of Guadalajara, Zapopan 45129, Mexico.
Behav Sci (Basel). 2023 Sep 26;13(10):795. doi: 10.3390/bs13100795.
Major depressive disorder (MDD) is a mood disorder with a high prevalence worldwide that causes disability and, in some cases, suicide. Although environmental factors play a crucial role in this disease, other biological factors may predispose individuals to MDD. Genetic and environmental factors influence mental disorders; therefore, a potential combined effect of / gene variants may be a target for the study of susceptibility to MDD. This study aimed to evaluate the effects of and gene variants when combined with adverse childhood experiences (ACEs) on the susceptibility and severity of symptoms in MDD.
A case-control study was performed, including 345 individuals, 175 MDD cases and 170 controls. Genotyping was performed using real-time PCR with hydrolysis probes. The analysis of the and gene variants of and , respectively, was performed either alone or in combination with ACEs on the severity of depression, as determined through specific questionnaires, including DSM-IV diagnostic criteria for MDD.
According to individual effects, the presence of ACEs, as well as the allele G of the rs1465107 of , is associated with a higher severity of depression, more significantly in females. Furthermore, the allele G of was associated with the severity of depression, even after being adjusted by gene variants and ACEs (IRR = 1.67, = 0.01). In males, the allele G of was shown to interact with SNP with ACEs (IRR = 1.70, < 0.001). According to combined effect analyses, the severity of depression was associated with ACEs when combined with either allele of or allele of , whereas SNP risk association was influenced by gender.
The severity of depression is related to either individual or combined effects of temperamental traits and genetic susceptibility of specific genes such as and .
重度抑郁症（MDD）是一种在全球范围内患病率很高的情绪障碍，会导致残疾，在某些情况下还会导致自杀。尽管环境因素在这种疾病中起着关键作用，但其他生物学因素可能使个体易患MDD。遗传和环境因素会影响精神障碍；因此，基因变异的潜在联合效应可能是MDD易感性研究的一个靶点。本研究旨在评估基因变异与童年不良经历（ACEs）相结合时对MDD易感性和症状严重程度的影响。
进行了一项病例对照研究，包括345名个体，175例MDD病例和170名对照。使用带有水解探针的实时PCR进行基因分型。分别对基因和基因的变异进行单独分析，或与ACEs联合分析其对抑郁严重程度的影响，抑郁严重程度通过特定问卷确定，包括MDD的DSM-IV诊断标准。
根据个体效应，ACEs的存在以及基因rs1465107的G等位基因与更高的抑郁严重程度相关，在女性中更为显著。此外，基因的G等位基因与抑郁严重程度相关，即使在经基因变异和ACEs校正后（IRR = 1.67，= 0.01）。在男性中，基因的G等位基因显示与ACEs的单核苷酸多态性相互作用（IRR = 1.70，< 0.001）。根据联合效应分析，当ACEs与基因的等位基因或基因的等位基因联合时，抑郁严重程度与之相关，而单核苷酸多态性风险关联受性别影响。
抑郁严重程度与气质特征和特定基因（如基因和基因）的遗传易感性的个体或联合效应有关。
