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+.
Highlights
Schizophrenia has a lifetime risk of ∼1% and is manifested by a disruption in cognition and emotion, along with negative and positive symptoms
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 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)
Summary
Schizophrenia has a lifetime risk of ∼1% and is manifested by a disruption in cognition and emotion, along with negative and positive symptoms. Studies have confirmed that the interaction of genes and environmental factors can affect the symptoms of psychological diseases, whereas childhood abuse is an important environmental factor that can affect the occurrence and development of schizophrenia [4]. The impact of CT on symptoms of schizophrenia may be enhanced due to genetic effects, in the negative sub-domai [6], with a family history of psychosis (FH+) being considered the strongest genetic risk factor for schizophrenia. Neural precursor cell-expressed developmentally downregulated 4 (NEDD4) polymorphisms and childhood trauma (CT) are associated with schizophrenia. Whether NEDD4 interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene–environment interaction effect
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