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Evidence for an Interaction Between NEDD4 and Childhood Trauma on Clinical Characters of Schizophrenia With Family History of Psychosis.

ABSTRACT: Background: Neural precursor cell-expressed developmentally downregulated 4 (NEDD4) polymorphisms and childhood trauma (CT) are associated with schizophrenia. However, whether NEDD4 interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene-environment interaction effect. Methods: We recruited 289 schizophrenia patients and 487 controls and genotyped rs2303579, rs3088077, rs7162435, rs11550869, and rs62043855 in their NEDD4 gene. Results: We found significant differences in the rs2303579 and rs3088077 between the two groups. Patients with the rs2303579 CC genotype had higher scores compared with other genotype (P = 0.026) in the test of positive schizophrenia syndrome scores, whereas patients with the rs3088077 TT (P = 0.037) and rs7162435 CC genotypes (P = 0.009) had higher scores compared with the other genotypes in the test of excitement factor. Patients with a family history of psychosis (FH+) reported higher negative scores (P = 0.012) than those without. Patients exposed to physical abuse (PA) reported a lower language learning and memory score (P = 0.017) and working memory score (P = 0.047) than those not. Patients exposed to sexual abuse (SA) reported a lower reasoning and problem-solving skills score (P = 0.025); those exposed to emotional neglect (EN) reported a lower social cognition score (P = 0.044); and those exposed to physical neglect reported a lower social cognition score (P = 0.036) but higher visual learning and memory score (P = 0.032). Rs3088077 could interact with EN to increase risk for schizophrenia. Optimal model rs62043855 × EA, rs3088077 × rs7162435 × rs11550869 × SA × EN and rs2303579 × rs7162435 × rs11550869 × rs62043855 × EA × PA could explain positive symptom, excitement symptom and working memory, respectively, in FH+ group. Conclusion: The study highlighted that the combined interaction of NEDD4 and CT may be associated with symptoms of schizophrenia especially for those with FH+.

SUBMITTER: Bi XJ

PROVIDER: S-EPMC8060471 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundExisting survey measures of childhood trauma history generally fail to take into account the relational-socioecological environment in which childhood maltreatment occurs. Variables such as the relationship between the perpetrator and the victim, the emotional availability of caregivers, witnessing the abuse of others, and the respondent's own thoughts, feelings, and actions in response to maltreatment are rarely assessed by current measures.MethodsTo address these concerns, the current study further investigated the family dynamics of childhood maltreatment using the Childhood Attachment and Relational Trauma Screen (CARTS) in 1,782 persons assessed online.ResultsPaired differences in means between item-rated descriptiveness of self, mothers, and fathers suggested that respondents' relationship with their biological fathers was less positive and secure than their relationship with their biological mothers, and that biological fathers were more often the perpetrator of emotional, physical, and sexual abuse than biological mothers. However, results further suggested that ratings between self, mothers, and fathers were positively correlated such that, for example, reports of a mother's or a respondent's own abusive behavior were more likely in the presence of reports of a father's abusive behavior. In addition, analyses evaluating witnessing violence demonstrated that fathers were rated as more often violent toward mothers than the reverse, although intimate partner violence was also frequently bidirectional. Analyses of sibling ratings further demonstrated that older brothers were either as or more frequently abusive when compared with parents. Finally, results suggested that childhood emotional, physical, and sexual abuse were much more often perpetrated by family members than extra-familial and non-family members.ConclusionsIn so far as these findings are consistent with the prior childhood trauma and attachment literature, the current study further supports the utility of the CARTS as a means of assessing the family dynamics of childhood attachment and maltreatment within a relational-socioecological framework.

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Evidence for an Interaction Between NEDD4 and Childhood Trauma on Clinical Characters of Schizophrenia With Family History of Psychosis.

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