Dysregulation of DNA Methylation During Development as a Potential Mechanism Contributing to Obsessive Compulsive Disorders and Autism

Abstract

Autism Spectrum Disorder (ASD) is a pervasive developmental disorder, that is rising at a concerning rate. However, underlying mechanisms are still to be discovered. Obsessions and compulsions are the most debilitating aspect of these disorders (OCD), and they are the treatment priority for patients. SAPAP3 knock out mice present a reliable mouse model for repetitive compulsive behaviour and are mechanistically closely related to the ASD mouse model Shank3 on a molecular level and AMPA receptor net effect. The phenotype of SAPAP3 knock out mice is obsessive grooming that leads to self-inflicted lesions by 4 months of age. Recent studies have accumulated evidence, that epigenetic mechanisms are important effectors in psychiatric conditions such as ASD and OCD. Methylation is the most studied mechanism, that recently leads to drug developments for more precise cancer treatments. We injected SAPAP3 mice with an epigenetic demethylation drug RG108 during pregnancy and delayed the onset of the phenotype in the offspring by 4 months. This result gives us clues about the possible mechanisms involved in OCD and ASD. Additionally, it shows that the modulation of methylation mechanisms during development might be explored as a preventative treatment in the cases of the high inherited risk of certain mental health conditions.