Abstract
BackgroundObsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls.ResultsThere were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences.ConclusionsDNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
Highlights
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas
Cortical areas [anterior cingulate gyrus (ACC), dorsolateral prefrontal cortex and orbitofrontal cortex (OFC)] maintain the main projections to the ventral striatum areas [nucleus accumbens (NAC), caudate nucleus (CN) and putamen (PT)] [2, 4], both involved with OCD symptoms, paradigms [5], and treatment response [6]
Our findings confirm the involvement of previously associated genes and biological processes in OCD as well as report differences related to specific brain areas
Summary
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. Cortical areas [anterior cingulate gyrus (ACC), dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC)] maintain the main projections to the ventral striatum areas [nucleus accumbens (NAC), caudate nucleus (CN) and putamen (PT)] [2, 4], both involved with OCD symptoms, paradigms [5], and treatment response [6]. Diffusion-weighted magnetic resonance imaging was associated with gene expression alterations confirming the tripartite model of striatum organization and connection model [8] We explored this model by using the differentially expressed (DEGs) and coexpressed genes modules in CN, NAC and PT brain tissues from OCD cases and controls, revealing the involvement of cell communication, cell response, synaptic transmission and plasticity for all striatum areas [9]
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