AUTHOR=Bi Xiao-Jiao , Hu Lei , Qiao Dong-Dong , Han Chao , Sun Meng-Meng , Cui Kai-Yan , Wang Li-Na , Yang Li-Min , Liu Lan-Fen , Chen Zhe-Yu 

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

JOURNAL=Frontiers in Psychiatry

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.608231

DOI=10.3389/fpsyt.2021.608231

ISSN=1664-0640

ABSTRACT=<p><bold>Background:</bold> Neural precursor cell-expressed developmentally downregulated 4 (<italic>NEDD4</italic>) polymorphisms and childhood trauma (CT) are associated with schizophrenia. However, whether <italic>NEDD4</italic> interacts with CT on symptoms of schizophrenia remains unknown. This study aimed to investigate the gene–environment interaction effect.</p><p><bold>Methods:</bold> We recruited 289 schizophrenia patients and 487 controls and genotyped rs2303579, rs3088077, rs7162435, rs11550869, and rs62043855 in their <italic>NEDD4</italic> gene.</p><p><bold>Results:</bold> 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 (<italic>P</italic> = 0.026) in the test of positive schizophrenia syndrome scores, whereas patients with the rs3088077 TT (<italic>P</italic> = 0.037) and rs7162435 CC genotypes (<italic>P</italic> = 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 (<italic>P</italic> = 0.012) than those without. Patients exposed to physical abuse (PA) reported a lower language learning and memory score (<italic>P</italic> = 0.017) and working memory score (<italic>P</italic> = 0.047) than those not. Patients exposed to sexual abuse (SA) reported a lower reasoning and problem-solving skills score (<italic>P</italic> = 0.025); those exposed to emotional neglect (EN) reported a lower social cognition score (<italic>P</italic> = 0.044); and those exposed to physical neglect reported a lower social cognition score (<italic>P</italic> = 0.036) but higher visual learning and memory score (<italic>P</italic> = 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.</p><p><bold>Conclusion:</bold> The study highlighted that the combined interaction of <italic>NEDD4</italic> and CT may be associated with symptoms of schizophrenia especially for those with FH+.</p>