Schizophrenia is a complex mental disorder whose causes are still far from being known. Although researchers have focused on genetic or environmental contributions to the disease, we still lack a scientific framework that joins molecular and clinical findings. Epigenetic can explain how environmental variables may affect gene expression without modifying the DNA sequence. In fact, neuroepigenomics represents an effort to unify the research available on the molecular pathology of mental diseases, which has been carried out through several approaches ranging from interrogating single DNA methylation events and hydroxymethylation patterns, to epigenome-wide association studies, as well as studying post-translational modifications of histones, or nucleosomal positioning. The high dependence on tissues with epigenetic marks compels scientists to refine their sampling procedures, and in this review, we will focus on findings obtained from brain tissue. Despite our efforts, we still need to refine our hypothesis generation process to obtain real knowledge from a neuroepigenomic framework, to avoid the creation of more noise on this innovative point of view; this may help us to definitively unravel the molecular pathology of severe mental illnesses, such as schizophrenia.
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