Genetic and Epigenetic Alterations Underlie Oligodendroglia Susceptibility and White Matter Etiology in Psychiatric Disorders

Abstract

Numerous genetic risk loci are found to associate with major neuropsychiatric disorders represented by schizophrenia. The pathogenic roles of genetic risk loci in psychiatric diseases are further complicated by the association with cell lineage- and/or developmental stage-specific epigenetic alterations. Besides aberrant assembly and malfunction of neuronal circuitry, an increasing volume of discoveries clearly demonstrate impairment of oligodendroglia and disruption of white matter integrity in psychiatric diseases. Nonetheless, whether and how genetic risk factors and epigenetic dysregulations for neuronal susceptibility may affect oligodendroglia is largely unknown. In this mini-review, we will discuss emerging evidence regarding the functional interplay between genetic risk loci and epigenetic factors, which may underlie compromised oligodendroglia and myelin development in neuropsychiatric disorders. Transcriptional and epigenetic factors are the major aspects affected in oligodendroglia. Moreover, multiple disease susceptibility genes are connected by epigenetically modulated transcriptional and post-transcriptional mechanisms. Oligodendroglia specific complex molecular orchestra may explain how distinct risk factors lead to the common clinical expression of white matter pathology of neuropsychiatric disorders.