The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda.
The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda.
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DOI：
10.3389/fgene.2021.649055
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发表时间：
2021
影响因子：
3.7
通讯作者：
Hemmings SMJ
中科院分区：
文献类型：
--
作者：
Kalungi A;Womersley JS;Kinyanda E;Joloba ML;Ssembajjwe W;Nsubuga RN;Seedat S;Hemmings SMJ
背景：艾滋病毒阳性（HIV+）儿童和青少年的内化精神障碍（IMDs）与不良的疾病结局相关，例如艾滋病毒疾病进展更快。尽管有研究表明，应激性生活事件和易受伤害因素的相互作用减缓了imd的发展，但潜在的病因在很大程度上是未知的。5 -羟色胺转运基因[溶质载体家族6成员A4 (SLC6A4)]和人类色氨酸羟化酶2基因（TPH2）多态性与imd的发生有关。本研究探讨了急性应激与imd之间的关系，以及慢性应激与SLC6A4和TPH2基因变异的调节作用。假设：急性应激通过遗传和环境脆弱性因素增加发生imd的风险。方法：在368名患有任何内化精神障碍（抑郁症、焦虑症或创伤后应激障碍）的HIV阳性儿童和青少年（5-17岁）以及368名年龄和性别匹配的HIV阳性对照中，对SLC6A4 （5-HTTLPR、rs25531、5-HTTLPR-rs25531和STin2 VNTR）和TPH2 （rs1843809、rs1386494、rs4570625和rs34517220）的多态性进行基因分型。通过层次聚类分析得出慢性和急性应激类别。采用Logistic回归分析评估慢性应激和各选择多态性对急性应激与imd相关性的独立调节作用。结果：我们观察到严重急性应激与imd之间有统计学意义的关联（p = 0.001）。与经历轻度急性压力的儿童和青少年相比，经历严重急性压力的儿童和青少年发生imd的可能性是后者的两倍（p = 0.001）。慢性应激与严重急性应激相互作用可增加imd的风险（p = 0.033）。急性应激与5-HTTLPR-rs25531 S-A-S-A单倍型相互作用，增加乌干达HIV阳性儿童和青少年患imd的风险（p = 0.049）。我们没有发现急性应激、慢性应激和5-HTTLPR-rs25531在imd中的联合相互作用的证据。结论：与经历轻度急性压力的HIV阳性儿童和青少年相比，经历严重急性压力的HIV阳性儿童和青少年患内化精神障碍（IMD）的几率更高。慢性应激和5-HTTLPR-rs25531独立调节急性应激与imd之间的关联。
Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.
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4.8
作者：
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作者：
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Spector TD
DOI：
10.1017/s1461145708009565
发表时间：
2009-04-01
影响因子：
4.8
作者：
Armbruster, Diana;Moser, Dirk Alexander;Brocke, Burkhard
通讯作者：
Brocke, Burkhard