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.
Subject(s)
Epigenesis, Genetic , Genetic Predisposition to Disease , Genome-Wide Association Study , Mental Disorders/genetics , Biomarkers , Environment , Epigenomics/methods , Evolution, Molecular , Gene-Environment Interaction , Genome-Wide Association Study/methods , High-Throughput Nucleotide Sequencing , Humans , Inheritance Patterns , Mental Disorders/diagnosisABSTRACT
Perinatal inflammation can lead to fetal/neonatal inflammatory syndrome, a risk factor for brain lesions, especially in the white matter. Perinatal inflammation is associated with increased incidence of cerebral palsy in humans and animal models and there is a strong relationship with increased incidence of autism and schizophrenia in humans. Perinatal inflammation causes acute microglial and astroglial activation, blood-brain barrier dysfunction, and disrupts oligodendrocyte maturation leading to hypomyelination. Inflammation also sensitizes the brain to additional perinatal insults, including hypoxia-ischemia. Furthermore, long after the primary cause of inflammation has resolved, gliosis may also persist and predispose to neurodegenerative diseases including Alzheimer's and Parkinson's disease, but this relation is still hypothetical. Finding of acute and chronic changes in brain structure and function due to perinatal inflammation highlights the need for treatments. As gliosis appears to be involved in the acute and chronic effects of perinatal inflammation, modulating the glial phenotype may be an effective strategy to prevent damage to the brain.
