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W27. POLYGENIC RISK SCORE AND HOUSEHOLD DEPRIVATION ARE RELATED TO INTERNALIZING SYMPTOMS IN YOUTH

2023; Elsevier BV; Volume: 75; Linguagem: Inglês

10.1016/j.euroneuro.2023.08.217

1873-7862

Síntia Belangero, Adrielle De Oliveira, Carolina Muniz Carvalho, Vanessa Kiyomi Ota, Amanda Bugiga, Pedro Mário Pan, Jessica Mauer, Jair de Jesus Mari, Marcos Santoro, Eurípedes C. Miguel, Maurício Scopel Hoffmann, Giovanni Abrahão Salum,

Child and Adolescent Psychosocial and Emotional Development

Internalizing symptoms are present in early life and are associated with a high prevalence of psychiatric disorders in adulthood. Heritability studies suggest that the underlying cause of internalizing is likely due to genetic variants and environmental factors, with heritability estimated at 40-50%. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) studies have identified single nucleotide polymorphisms (SNPs) account for approximately 5.63% of the phenotypic variance in internalizing traits. Furthermore, previous studies suggest that environmental factors, such as deprivation events like physical and emotional neglect, parental absence, and material deprivation, play a crucial role in the manifestation of internalizing symptoms. Thus, we aimed to investigate the association between PRS and symptoms of the internalizing psychopathology dimension. Further, we evaluated the interaction between PRS and childhood deprivation and its association with internalizing symptoms. A sample of 2189 children and adolescents aged 9-18 was selected from the Brazilian High-Risk Cohort Study (BHRCS) for Mental Disorders. The Strengths and Difficulties Questionnaire (SDQ), specifically the emotional domain, was used as behavioral screening for internalizing problems, and it was reported by both parents and through self-report. Traumatic events related to household deprivation were assessed using the Development and Well-Being Assessment (DAWBA). The PRS was calculated using the PRSice 2 software, based on the largest GWAS of internalizing symptoms in youth. Linear mixed models (LMM) were employed for interaction models, and Generalized Additive Models were used for directed associations. These models were adjusted for the first ten principal components of genetic data, age, sex, and site (as a random variable) in the LMM. All statistical analyses were conducted using RStudio software, and a significance level of 5% was adopted. We found a positive interaction between the internalizing PRS and deprivation, which was associated with an increased risk of internalizing psychopathology in youth (F-value: 4.326, p-value: 0.037) according to the parent's report. Moreover, we observed a small relationship between internalizing PRS and SDQ self-report measures, which explains 7.35% of the variance present in internalizing problems in this cohort (R-sq = 0.058, p=0.021). We did not find significant associations with self-report internalizing psychopathology in an interaction with deprivation, nor in the direct association between PRS and parent report. We observed an association between PRS and its interaction with deprivation and internalizing symptoms. Our results support previous findings indicating that gene-environment interactions influence the development of complex traits within the internalizing spectrum, such as depression and anxiety. The observed direct effects in the self-report measures and their association with PRS support previous studies indicating a higher SNP-based heritability in internalizing symptoms. This study highlights the combined influence of PRS and traumatic events (deprivation) as potential underlying factors in the pathophysiology of internalizing symptoms. These findings may contribute to the identification of potential biological markers related to the onset of mental disorders based on internalizing symptoms.