Characterization of the gene expression profile in children and adolescents at risk for mental disorders

Abstract

Neuropsychiatric disorders are the main cause of years lost because of disability in the worldwide young people. Many of these disorders present a high heritability, suggesting that the genome contains a large amount of information with a diagnosis potential. However, polygenic nature of these diseases, added to the influence of environmental factors makes it difficult to explore this information. Mental disorders and early environmental factors (such as neglect and abuse) appear to alter the expression of certain genes, as well as genetic variants. The aim of this study is to identify gene expression changes in blood of children and adolescents at risk for mental disorders after a 3-year follow-up. For this we will select 200 children/adolescents from the "Instituto da Psiquiatria do Desenvolvimento" cohort that have the baseline and the 3-year follow-up data, and we expect to divide them into four groups, based on the Child Behavior Checklist (CBCL): 1) subjects without psychopathology in the baseline, but with symptoms after 3 years (incident group); 2) subjects without psychopathology and that continued to be healthy (control group); 3) subjects with psychopathology in the baseline and that continued with symptoms (persistent group); 4) subjects with psychopathology, but that were healthy after 3 years (remitted group). Blood was collected from all participants and RNA was isolated. Gene expression will be analyzed using Illumina HT12 microarrays (which targets more than 47,000 probes) for 120 subjects and we will validate the most significant results in the remaining 80 subjects using qRT-PCR technique with SYBR® Green detection method. Besides that, will also be correlated, early environmental factors, such as abuse, with gene expression. We intend to help identify risk factors for mental disorders in order to act in the early prevention and diagnosis. (AU)