SA115 - EVALUATION OF GENE EXPRESSION IN EARLY SUBSTANCE ABUSE

Abstract

Background Psychiatric disorders cause an enormous burden of suffering, high morbidity and mortality rates. They are complex diseases characterized by alterations in multiple genes, combined with environmental factors, such as substance abuse. At the time these disorders are diagnosed, most patients need care and treatment for the rest of their lives and few remit completely. Therefore, it is very important to understand the genetic and environmental factors responsible to the transition to a disorder. Thus, longitudinal studies from childhood to adulthood may be very useful to understand the triggers before the transition to psychiatric disorders. The aim of this study is to compare gene expression profiles in a longitudinal cohort of early adolescents with and without substance abuse (alcohol, tobacco, marijuana and others). Methods In this study, we used a subsample of a Brazilian High Risk Cohort (HRC) for Psychiatric Disorders, consisting of 110 adolescents selected from 750 individuals. To evaluate whether the participants have any disorder (such as ADHD, anxiety), interviewers applied the DAWBA (Development and Well-Being Assessment) in all participants. Their parents answered a drug abuse questionnaire. For the transcriptome, we used the HumanHT-12 v4 Expression BeadChip, comparing substance abusers (N= 98) and non-substance abusers (N= 12). Using methylumi and limma R packages we used the list of the top 100 differentially expressed genes to create a network based in co-expression genes by Cytoscape software and to identify enriched pathways (Reactome base data) and Biological Process (GO base data). Results We found an association between substance abuse and emotional disorder (X-squared=5.01, p=0.025), where among 110 participants, 17 have the disorder, being 5 of them substance abusers, whereas among the remaining 93 (with no disorder), 7 were substance abusers. On the other hand, participants who have any type of hyperactivity had never used drugs. Using the most differentially expressed genes (top 100), we found a total of 18 pathways and 2 biological process significantly associated with substance use and psychiatric disorder. Among them, the most associated were related to immune system and rRNA processing (p-values Discussion Although, we found an association between emotional disorders and substance abuse, we cannot say whether this is a cause or consequence. The understanding of the biological alterations that trigger the psychiatric disorders and their association with substance abuse, might help to develop prevention strategies to psychiatric disorders and avoid substance abuse. Furthermore, we found no substance abusers with ADHD which may be related with their age (very young individuals). Although we have found no significant co-expression network, we identified 18 pathways as well as 2 biological processes related to immune system, rRNA processing, among others. Therefore, our results suggest that these pathways could be associated with substance abuse in adolescents. It is also worth to mention that our cohort is a very well clinically characterized and unique sample of adolescents with psychiatric disorders and healthy controls, and we are running next year the 3rd year follow up which may increase the sample size of substance abuser and individuals with psychiatric disorders.