Abstract
Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes. We constructed the protein–protein interaction networks (interactomes) of six anxiety disorders and noted enrichment for striatal expression among common genes in the interactomes. Five of these interactomes shared distinctive overlaps with the interactomes of genes that were differentially expressed in two striatal compartments (striosomes and matrix). Generalized anxiety disorder and social anxiety disorder interactomes showed exclusive and statistically significant overlaps with the striosome and matrix interactomes, respectively. Systematic gene expression analysis with the anxiety disorder interactomes constrained to contain only those genes that were shared with striatal compartment interactomes revealed a bifurcation among the disorders, which was influenced by the anterior cingulate cortex, nucleus accumbens, amygdala and hippocampus, and the dopaminergic signaling pathway. Our results indicate that the functionally distinct striatal pathways constituted by the striosome and the matrix may influence the etiological differentiation of various anxiety disorders.
Highlights
Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes
Note that (a) DisGeNET catalogs gene-disease associations described in animal models such as rats and mice, in addition to those described in human studies, and (b) many of the genes cataloged in DisGeNET may not share a causal relationship with the disease, and may instead only be associated with disease susceptibility or endophenotypes
We computed the distribution of genes expressed in a specific brain region among anxiety disorders (ADs)-associated genes and compared it with the background distribution of genes expressed in this particular brain region among all the genes that were assayed for expression in any brain regions
Summary
Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes. We constructed the protein–protein interaction networks (interactomes) of six anxiety disorders and noted enrichment for striatal expression among common genes in the interactomes. Five of these interactomes shared distinctive overlaps with the interactomes of genes that were differentially expressed in two striatal compartments (striosomes and matrix). The effect of genetic mutations and abnormal gene expression may affect proteins and PPIs, posing deeper implications for disease development, such as multiple pathophenotypes that cannot be attributed to a single genotype in a disease[34] Such effects can be explained through the analysis of the interactome, which allows examination of shared genetics, biological pathways and s ymptomatology[30,31,32,33]
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