The impact of epigenomic next-generation sequencing approaches on our understanding of neuropsychiatric disorders

Abstract

Patients suffering from psychiatric disorders have a life span burden, which represents an enormous human, family, social, and economical cost. Several concepts have revolutionized our way of appraising neuropsychiatric disorders (NPDs). They result from a combination of genetic factors and environmental insults, and their etiology finds roots in the neurodevelopmental period. As epigenetic mechanisms tightly control brain development, exposure to adverse conditions disturbing the epigenetic landscape of the fetal brain increases the risk of developing NPDs, due to the persistence of abnormal epigenetic signatures, at distance from the initial stimulus. Here, we review these concepts and discuss recent results based on next-generation sequencing (NGS) approaches that have shed light on the mechanisms that underlie the emergence of NPDs, highlighting the importance of epigenetic phenomena. Because epigenetic mechanisms are potentially reversible, unraveling the epigenetic contribution to the etiology of NPDs is key to the design of future therapeutic strategies. Early diagnosis of patients prone to NPDs for early intervention represents a challenge that waits for biomarkers of vulnerability, and could be decisive for improving the outcome and prognosis of "at-risk" patients.

Keywords: EWAS; epigenetic mechanisms; epigenome-wide association studies; genome-wide association studies; neuropsychiatric disorders; prenatal or maternal environmental insults.