PDF(Pubmed)
Abstract：
BACKGROUND: Childhood trauma is one of the most extensively studied and well-supported environmental risk factors for the development of mental health problems. The human tryptophan hydroxylase 2 (TPH2) gene is one of the most promising candidate genes in numerous psychiatric disorders. However, it is now widely acknowledged that neither genetic variation nor environmental exposure alone can fully explain all the phenotypic variance observed in psychiatric disorders. Therefore, it is necessary to consider the interaction between the two factors in psychiatric research.
METHODS: We enrolled a sizable nonclinical cohort of 786 young, healthy adults who underwent structural MRI scans and completed genotyping, the Childhood Trauma Questionnaire (CTQ) and behavioural scores. We identified the interaction between childhood trauma and the TPH2 rs7305115 gene polymorphism in the gray matter volume (GMV) of specific brain subregions and the behaviour in our sample using a multiple linear regression framework. We utilized mediation effect analysis to identify environment /gene-brain-behaviour relationships.
RESULTS: We found that childhood trauma and TPH2 rs7305115 interacted in both behaviour and the GMV of brain subregions. Our findings indicated that the GMV of the right posterior parietal thalamus served as a significant mediator supporting relationship between childhood trauma (measured by CTQ score) and anxiety scores in our study population, and the process was partly modulated by the TPH2 rs7305115 gene polymorphism. Moreover, we found only a main effect of childhood trauma in the GMV of the right parahippocampal gyrus area, supporting the relationship between childhood trauma and anxiety scores as a significant mediator.
CONCLUSIONS: Our findings suggest that early-life trauma may have a specific and long-term structural effect on brain GMV, potentially leading to altered cognitive and emotional processes involving the parahippocampal gyrus and thalamus that may also be modulated by the TPH2 gene polymorphism. This finding highlights the importance of considering genetic factors when examining the impact of early-life experiences on brain structure and function. Gene‒environment studies can be regarded as a powerful objective supplement for targeted therapy, early diagnosis and treatment evaluation in the future.
METHODS: We enrolled a sizable nonclinical cohort of 786 young, healthy adults who underwent structural MRI scans and completed genotyping, the Childhood Trauma Questionnaire (CTQ) and behavioural scores. We identified the interaction between childhood trauma and the TPH2 rs7305115 gene polymorphism in the gray matter volume (GMV) of specific brain subregions and the behaviour in our sample using a multiple linear regression framework. We utilized mediation effect analysis to identify environment /gene-brain-behaviour relationships.
RESULTS: We found that childhood trauma and TPH2 rs7305115 interacted in both behaviour and the GMV of brain subregions. Our findings indicated that the GMV of the right posterior parietal thalamus served as a significant mediator supporting relationship between childhood trauma (measured by CTQ score) and anxiety scores in our study population, and the process was partly modulated by the TPH2 rs7305115 gene polymorphism. Moreover, we found only a main effect of childhood trauma in the GMV of the right parahippocampal gyrus area, supporting the relationship between childhood trauma and anxiety scores as a significant mediator.
CONCLUSIONS: Our findings suggest that early-life trauma may have a specific and long-term structural effect on brain GMV, potentially leading to altered cognitive and emotional processes involving the parahippocampal gyrus and thalamus that may also be modulated by the TPH2 gene polymorphism. This finding highlights the importance of considering genetic factors when examining the impact of early-life experiences on brain structure and function. Gene‒environment studies can be regarded as a powerful objective supplement for targeted therapy, early diagnosis and treatment evaluation in the future.
摘要：
背景：儿童创伤是心理健康问题发展的最广泛研究和得到充分支持的环境风险因素之一。人类色氨酸羟化酶2（TPH2）基因是许多精神疾病中最有希望的候选基因之一。然而,现在人们普遍承认，无论是遗传变异还是环境暴露都不能完全解释在精神疾病中观察到的所有表型变异。因此,在精神病学研究中，有必要考虑这两个因素之间的相互作用。
方法：我们招募了786名年轻人的相当大的非临床队列，健康成年人接受了结构MRI扫描并完成了基因分型，儿童创伤问卷（CTQ）和行为评分。我们使用多元线性回归框架确定了儿童期创伤与特定脑亚区灰质体积（GMV）中TPH2rs7305115基因多态性之间的相互作用以及样本中的行为。我们利用中介效应分析来识别环境/基因-大脑-行为关系。
结果：我们发现儿童创伤和TPH2rs7305115在行为和大脑亚区域的GMV中相互作用。我们的发现表明，在我们的研究人群中，右顶叶后丘脑的GMV是儿童期创伤（通过CTQ评分衡量）和焦虑评分之间的重要中介支持关系。该过程部分受到TPH2rs7305115基因多态性的调控。此外，我们发现儿童期创伤仅在右侧海马旁回的GMV中产生主要影响，支持童年创伤和焦虑评分之间的关系，作为一个重要的中介。
结论：我们的研究结果表明，生命早期创伤可能对大脑GMV具有特定的长期结构影响，可能导致涉及海马旁回和丘脑的认知和情绪过程改变，这也可能受到TPH2基因多态性的调节。这一发现强调了在检查早期生活经历对大脑结构和功能的影响时考虑遗传因素的重要性。基因环境研究可以被视为靶向治疗的有力客观补充，未来的早期诊断和治疗评估。
方法：我们招募了786名年轻人的相当大的非临床队列，健康成年人接受了结构MRI扫描并完成了基因分型，儿童创伤问卷（CTQ）和行为评分。我们使用多元线性回归框架确定了儿童期创伤与特定脑亚区灰质体积（GMV）中TPH2rs7305115基因多态性之间的相互作用以及样本中的行为。我们利用中介效应分析来识别环境/基因-大脑-行为关系。
结果：我们发现儿童创伤和TPH2rs7305115在行为和大脑亚区域的GMV中相互作用。我们的发现表明，在我们的研究人群中，右顶叶后丘脑的GMV是儿童期创伤（通过CTQ评分衡量）和焦虑评分之间的重要中介支持关系。该过程部分受到TPH2rs7305115基因多态性的调控。此外，我们发现儿童期创伤仅在右侧海马旁回的GMV中产生主要影响，支持童年创伤和焦虑评分之间的关系，作为一个重要的中介。
结论：我们的研究结果表明，生命早期创伤可能对大脑GMV具有特定的长期结构影响，可能导致涉及海马旁回和丘脑的认知和情绪过程改变，这也可能受到TPH2基因多态性的调节。这一发现强调了在检查早期生活经历对大脑结构和功能的影响时考虑遗传因素的重要性。基因环境研究可以被视为靶向治疗的有力客观补充，未来的早期诊断和治疗评估。
