SA72 - GENE EXPRESSION IN BLOOD OF ADOLESCENTS WITH PSYCHIATRIC DISORDERS

Abstract

Background Neuropsychiatric disorders represent a large public health and economic burden at a national and global level, and delineating the genetic architecture of mental disorders across molecular levels will aid in the development of novel treatment and prevention strategies. Whereas most psychiatric disorders are moderately to highly heritable and there are evidences of shared genetic etiology for psychiatric disorders, we aimed to investigate gene expression profiling in adolescents with psychiatric disorders from a large prospective community school-based study in Brazil, the High Risk Cohort (HRC) Study for Psychiatric Disorders. Methods This is a cross-sectional study comprised of adolescents from the HRC. Participants were assessed using the structured diagnostic interview Development and Well-Being Assessment (DAWBA) to evaluate psychiatric diagnosis according to the DSM-IV and psychopathology measures were assessed using Child Behavior Checklist (CBCL). Transcriptome in blood was compared between 23 adolescents with at least one psychiatric disorder (PD group) and 25 healthy controls (HC group) with no previous psychiatric disorder and low psychopathology symptoms. Blood gene expression profiling was measured using HumanHT-12 v4.0 Expression BeadChip (Illumina) and the 100 most associated genes list was brought forth to assess whether they were enriched for any Gene Ontology (GO) Biological Process category or canonical pathway (by KEGG - Kyoto Encyclopedia of Genes and Genomes) using the Enrichr tool. Results The most prevalent diagnosis in PD group was anxiety disorders (44%), followed by major depression (28%), conduct disorders (28%) and attention deficit hyperactivity disorder (ADHD – 24%), knowing that some of those diagnoses were overlapped. We have not found differentially expressed genes between the PD and HC groups after multiple comparisons correction. The 100 most associated genes were enriched with GO “proteasome-mediated ubiquitin-dependent protein catabolic process” (p=0.0005) and “proteasomal protein catabolic process” (p=0.0007); and with the KEGG “proteasome Homo sapiens” (p=0.020) and “lysosome Homo sapiens” (p=0.023) canonical pathways. Discussion Although we have not found a significant gene expression profiling, likely by the sample size, our cohort is a very well clinically characterized and unique sample of adolescents with psychiatric disorders and healthy controls from HRC Study. Degradation of proteins by the ubiquitin-proteasome system is an essential biological process in the development of eukaryotic organisms. The proteasome pathway has been associated with neurodevelopmental syndromes and early onset of some psychiatric disorder. Therefore, our results suggest that this pathway could be associated with early onset psychiatric disorders.