Investigation of the causal effects of biological and environmental factors on the etiology of psychiatric disorders

• Grant number: 20/10599-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2021
• Effective date (End): April 30, 2024
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Carolina Muniz Felix de Carvalho
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Psychiatric disorders are multifactorial diseases, resulting from the interplay between genetic and environmental risk factors. However, it is underlying causal mechanisms linking them to the psychopathology spectrum. Traumatic experiences can be considered one of the main environmental risk factors across multiple mental illnesses. This widespread effect is probably due to the impact of traumatic experiences on several molecular processes and biological pathways. For example, childhood trauma is associated with premature telomere shortening. Telomeres are repeats of "TTAGGG" that protect the chromosome ends from deterioration or fusion with neighboring chromosomes. Their repeat length shortens with cell division acting as biomarkers of cellular aging and stress. Very limited information is available regarding the causal mechanisms linking genetic variation, traumatic experience, and telomere shortening to psychiatric disorders. The proposed project will investigate genetic association and causation linking traumatic experience to psychiatric disorders via its effect on telomere length in 2,247 children and adolescents from São Paulo or the Rio Grande do Sul. These individuals were previously evaluated psychiatrically using the Development and Well-Being Assessment (DAWBA) instrument, based on these data, the general psychopathology model was generated. In addition, the parents of the participants already completed the Life History Instrument questionnaire about traumatic experiences lived by the children. After clinical evaluations, peripheral blood was collected, and extracted DNA was used for genotyping with Infinium Global Screening array (Illumina). With genome-wide data available, we will conduct several analyses to investigate the polygenic architectures of our traits of interest. Using external large-scale GWAS as references, we will calculate polygenic risk scores for psychiatric illnesses, general psychopathology, trauma response, and telomeric length in our cohort. In parallel, we will also use the genome-wide data to estimate the SNP-heritability of the investigated phenotypes (i.e., psychiatric diseases, psychopathology, trauma response, and telomeric length). Finally, we will apply a one-sample Mendelian randomization approach to investigate the causal pathways linking traumatic experiences and telomere length to the psychopathology spectrum. The expected findings of the proposed project will provide insights into the possible causal role of biological and environmental factors in the development of psychiatric diseases in children and adolescents. (AU)