Neuroepigenetics of Schizophrenia

Giovanna Punzi, Rahul Bharadwaj, Gianluca Ursini

Research output: Contribution to journalArticle

Abstract

Schizophrenia is a complex disorder of the brain, where genetic variants explain only a portion of risk. Neuroepigenetic mechanisms may explain the remaining share of risk, as well as the transition from susceptibility to the actual disease. Here, we discuss the most recent findings in the field of brain epigenetics applied to the study of schizophrenia. Methylome studies have found several candidates exhibiting methylation modifications in association with the disorder, but genes affected do not always overlap. Notably, these studies converge in that genes within the schizophrenia risk loci or genes differentially methylated in patients affected with the disorder are dynamically regulated during early life. They also imply that schizophrenia-associated genetic variation may affect DNA methylation in fetal and adult brains. Histone modifications may help mediating the effect of genetic risk variants associated with schizophrenia, and regulating chromatin higher-order structure. The 3D-organization of chromatin in the brain creates physical interactions within chromosomes, so that schizophrenia-associated genetic variants can be linked with genes distant from their loci; this suggests that chromatin conformation matters in the mechanism of risk for the disorder. Non-coding RNAs provide a novel and complex mechanism of gene regulation potentially significant for schizophrenia, as proposed by research on specific microRNAs and long non-coding RNAs (lncRNAs). Finally, a recent study in epitranscriptomics identifies RNA methylation as a further epigenetic mechanism active in human brain and specifically in a portion of the transcriptome associated with schizophrenia susceptibility. These findings indicate that, as expected from the complexity of the brain and its development, several epigenetic mechanisms may intervene in the etiopathogenesis of schizophrenia. An understanding of their roles calls for research approaches integrating the investigation of different epigenetic mechanisms and of environmental and genetic risk, in the context of development.

Original languageEnglish (US)
JournalProgress in Molecular Biology and Translational Science
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Schizophrenia
Epigenomics
Brain
Chromatin
Genes
Methylation
Histone Code
Long Noncoding RNA
Untranslated RNA
Inborn Genetic Diseases
Brain Diseases
DNA Methylation
MicroRNAs
Transcriptome
Research
Chromosomes
RNA

Keywords

  • Chromatin organization
  • Development
  • DNA methylation
  • Epigenetics
  • Epitranscriptomics
  • Histone modifications
  • Non-coding RNAs
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Neuroepigenetics of Schizophrenia. / Punzi, Giovanna; Bharadwaj, Rahul; Ursini, Gianluca.

In: Progress in Molecular Biology and Translational Science, 01.01.2018.

Research output: Contribution to journalArticle

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