Studies of co-expression gene networks of the orbitofrontal cortex and striatum (postmortem study) of patients with OCD and controls

Abstract

Obsessive Compulsive Disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions with a worldwide prevalence of 1% to 3%. Functional neuroimaging studies indicate that OCD is a heterogeneous disorder; the neuronal systems activated the orbitofrontal cortex, the cingulate cortex and the striatum. Genetic and epidemiological studies identified environment as well as genetic components in the pathogenesis of OCD. The fact that complete concordance in twin studies is not found demonstrates the important role of the environment in the disease etiology. More than 60 candidate genes were studied in association with OCD however results were inconclusive. Recently, a Genome Wide Association Study (GWAS) revealed SNPs (single nucleotide polymorphism) marginally associated with OCD, from which several were characterized as eQTLs (expression quantitative trait loci) in brain regions. The study of the transcriptiome may be an indirect way of observing the alterations influenced by the environment. Numerous studies have been demonstrating that a gene can participate in the etiology of several diseases as well as that several diseases share the same susceptibility genes. Genes do not encode diseases, but sets of genes form regulatory networks that can result in different behaviors. Using the wide complexity of phenotypic dimensions of OCD will help us to understand the gene interaction networks of specific areas of the brain. The objectives of this study are: (1) to compare the transcriptome of the frontal cortex (orbitofrontal) of cases OCD/OSC and controls (postmortem) and (2) to compare the cortico-striatal co-expression between cases and controls by gene networks co-expression and protein-protein (PPI) interaction networks using the transcriptome data of the striatum from the project in progress "Investigação de Circuitos Neuronais e Marcadores Biológicos Envolvidos no Transtorno Obsessivo-Compulsivos por meio de Paradigmas Comportamentais de Medo e Ansiedade" (FAPESP 2011/21357-9) and the data of the frontal cortex proposed in this project. (AU)