Shared Epigenetic Etiology Underlying Autism Spectrum Disorder and Schizophrenia

Abstract

Schizophrenia and autism spectrum disorder (ASD) are two common neurodevelopmental disorders that are associated with severe disability and reduced quality of life. Research has demonstrated a number of parallels in both the symptomology and pathology of ASD and schizophrenia, including cognitive and social deficits, delusions, immune irregularities, and decreased brain volume. Moreover, while a multitude of studies have examined the genetic underpinnings of both disorders, mutations alone cannot account for the complexity of disease pathology nor the extensive similarities observed between both disorders. To this end, this thesis aims to elucidate the similarities in epigenetic abnormalities which characterize ASD and schizophrenia. First, I make the case that abnormal histone acetylation and methylation patterns contribute to both pathologies, focusing in particular on the role of H3K4 methylation. Then, I characterize the DNA methylome landscapes in ASD and schizophrenia, building the argument that aberrant epigenetic modifications are a large contributor to immune system dysfunction and disruption of GABAergic pathways. In addition, I suggest a specific epigenetic mechanism by which abnormal RELN expression may be linked to maternal immune activation. Finally, I discuss the general contribution of non-coding RNAs to schizophrenic and ASD pathology, arguing for improved presentation of data within the existing literature and pointing out gaps in our current understanding. The compilation and analysis of existing research– as accomplished by this thesis– represents a necessary first step in generating a holistic understanding of the shared epigenetic etiologies in ASD and schizophrenia.