Impact of life adversity and gene expression on psychiatric symptoms in children and adolescents: findings from the Brazilian high risk cohort study

Ota, Vanessa Kiyomi, Oliveira, Adrielle Martins, Bugiga, Amanda Victória Gomes, Conceição, Helena B., Galante, Pedro Alexandre Favoretto, Asprino, Paula Fontes, Schäfer, Julia Luiza, Hoffmann, Mauricio Scopel, Bressan, Rodrigo, Brietzke, Elisa, Manfro, Gisele Gus, Grassi-Oliveira, Rodrigo, Gadelha, Ary, Rohde, Luis Augusto, Miguel, Euripedes Constantino, Pan, Pedro Mario, Santoro, Marcos Leite, Salum, Giovanni Abrahao, Carvalho, Carolina Muniz and Belangero, Sintia Iole (2025) Impact of life adversity and gene expression on psychiatric symptoms in children and adolescents: findings from the Brazilian high risk cohort study. Frontiers in Psychiatry, 16. ISSN 1664-0640

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Abstract

Introduction: While the influence of both genetic and environmental factors on the development of psychiatric symptoms is well-recognized, the precise nature of their interaction throughout development remains a subject of ongoing debate. This study investigated the association between the expression of 78 candidate genes, previously associated with psychiatric phenotypes, in peripheral blood and both adversity and psychopathology in a sample of 298 young individuals assessed at two time points from the Brazilian High Risk Cohort Study for Mental Conditions (BHRCS). Methods: Psychopathology was assessed using the Child Behavior Checklist (CBCL), considering the total CBCL, p-factor (i.e. general factor of psychopathology), and internalizing and externalizing symptoms as clinical variables. The life adversities considered in this study includes four composite variables: child maltreatment, stressful life events, threat and deprivation. Gene expression was measured using next-generation sequencing for target genes and differential gene expression was analyzed with the DESeq2 package. Results: Mixed models revealed six genes associated with internalizing symptoms: NR3C1, HSPBP1, SIN3A, SMAD4, and CRLF3 genes exhibited a negative correlation with these symptoms, while FAR1 gene showed a positive correlation. Additionally, we also found a negative association between USP38 gene expression and externalizing symptoms. Finally, DENND11 and PRRC1 genes were negatively associated with deprivation, a latent factor characterized by neglect, parental absence, and measures of material forms of deprivation. No mediation or moderation effect was observed of gene expression on the association between life adversities and psychiatric symptoms, meaning that they might influence distinct pathways. Discussion: Among these nine genes, NR3C1, which encodes a glucocorticoid receptor, is by far the most investigated, being associated with depressive symptoms, early life adversity, and stress. While further research is needed to fully understand the complex relationship between gene expression, life adversities, and psychopathology, our findings provide valuable insights into the molecular mechanisms underlying mental disorders.

Item Type:	Article
Additional Information:	© 2025 The Author(s)
Divisions:	LSE
Subjects:	R Medicine > RJ Pediatrics > RJ101 Child Health. Child health services R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry B Philosophy. Psychology. Religion > BF Psychology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
Date Deposited:	28 Feb 2025 08:48
Last Modified:	07 Mar 2025 14:03
URI:	http://eprints.lse.ac.uk/id/eprint/127463

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