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Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

ABSTRACT: Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph-based connectivity analysis in morphometric similarity mapping and resting-state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm-avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.

SUBMITTER: Tian T

PROVIDER: S-EPMC7749512 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

Tian Tian T Li Jia J Zhang Guiling G Wang Jian J Liu Dong D Wan Changhua C Fang Jicheng J Wu Di D Zhou Yiran Y Zhu Wenzhen W

Brain and behavior 20200930 12

Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain m ...[more]

PMID: 32997444

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Project description:BackgroundChildhood 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Dataset Information

Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

Publications

Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

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