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    Associação entre fatores genéticos e estressores ambientais em crianças e adolescentes em risco de desenvolver doenças mentais
    (Universidade Federal de São Paulo (UNIFESP), 2016-05-31) Carvalho, Carolina Muniz Félix de [UNIFESP]; Belangero, Sintia Iole Nogueira [UNIFESP]; http://lattes.cnpq.br/2623781262478620; http://lattes.cnpq.br/4463074867502277; Universidade Federal de São Paulo (UNIFESP)
    Psychiatric disorders are multifactorial diseases resulting from genetic and environmental influences. The hypothesis gene-environment interaction (G×E) postulates that the effect of the genotype depends on the environmental exposure, suggesting that a genotype may be associated with significantly stressing or traumatic events and increase the risk of developing a psychiatric disorder. Aim. To evaluate the effect of G×E interaction about mental disorder and the general psychopathology of children and adolescents in order to identify possible risk factors for their development. Methods. We evaluated 720 children and adolescents aged 6 to 14 years from a subsample of the High-Risk Cohort Study for Psychiatric Diseases Development of the National Institute for Developmental Psychiatry. The sample was subjected to a diagnostic interview Development and Well-Being Assessment (DAWBA); psychopathology scale Child Behavior Checklist (CBCL) and the collection of blood and saliva. The DNA was extracted from these biological samples and was used to genotype the technique of SNParray Infinium®HumanCore array. We were created statistical models (logistic or linear according to the analyzed outcome). The outcomes analyzed included diagnostic data provided by DAWBA and the score obtained by total CBCL scale, CBCL internalizing and externalizing CBCL. For this we selected 30 genes associated with neurodevelopment, neurotransmission, etiology of mental disorder and extract the genotypes of the SNPs of these candidate genes through bioinformatics tools provided by Plink and Rstudio softwares. We use childhood maltreatment score as environmental variable obtained through a confirmatory factor analysis that combines the responses of parents and children regarding the questioning of physical, emotional, sexual and physical abuse neglect. We tested different statistical models for G×E interaction and therefore, we use the Bonferroni correction for multiple comparisons. Results. We found 5 models of interaction G×E that were statistically significant after Bonferroni correction. Two of these models evaluated the SNPs individually and found that the rare allele of rs1042098 at SLC6A3 gene (allele G; p = 0.043, beta = -7.46) and rs2060886 at TCF4 gene (T allele gene; p = 0.031, beta = -7.83) interacting with the abuse decreases the average externalizing CBCL (scale that measures the externalizing symptoms). The other three models of interaction G×E were significant evaluate the abuse and SNPs that showed little correlated (according to the Pearson correlation) on the same candidate gene and we found that the combination of the genotypes of the rs3742278 (wild homozygous AA), rs9567737 (rare homozygous CC), rs2760345 (heterozygous CT), rs582854 (wild homozygous CC) and rs4942587 (heterozygous AG) at HTR2A gene influences the average externalizing CBCL and total CBCL, as the combination of genotypes of rs1042098 (wild homozygous AA) and rs2042449 (rare homozygous AA) at SLC6A3 gene influences the average externalizing CBCL. In addition to evaluating the interaction between genotypes and variable abuse also investigated whether the haplotypes associated with the presence of abuse could confer risk for developing a mental disorder or influence in child psychopathology, but did not find models of interaction (haplotype×abuse) statistically significant. Conclusion. We found negative when evaluating the children according to the diagnosis obtained by DAWBA, but when we analyze the CBCL scale found positive results; which suggest that the G×E interaction can influence the symptoms of mental disorder. These data corroborate with the proposal of the Research Domain Criteria project that assess mental disorder by symptomatology and not diagnostic.