Can the Schizophrenia Epigenome Provide Clues for the Molecular Basis of Pathogenesis?

Abstract

Schizophrenia (SCZ), a major mental disease affecting approximately 1% of individuals worldwide, is characterized by symptoms such as delusions, hallucinations, loosening of associations, disorganized speech and behavior, illogical thinking, social isolation and cognitive deficit. Epidemiologic and genetic studies indicate that SCZ is a complex and multifactorial illness in origin, influenced by both environmental and genetic factors. Several reports support an association between SCZ and environmental factors such as birth in winter or early spring, urban birth, paternal age, famine, nutritional and perinatal complications. On the other hand, extensive genetic studies also suggest that approximately 45% of monozygotic twins, and 10% of the first degree relatives of patients with SCZ, including dizygotic twins may eventually become affected by the same disease. In addition to the implication of hundreds of SNPs based on association studies, recently a large number of genes and copy number variations, each with very small effect have been identified as causative factors in largescale whole-genome scans of thousands of cases and controls [1]. Despite all these efforts, uncovering key genes with specific mutations correlating to the SCZ pathogenesis remains elusive. Because of the poor success rate with genetic studies and the increasing awareness of the contribution of the environmental factors, efforts have been made by others and us in examining the potential role of epigenetic changes involving DNA methylation, histone modifications and dysregulation of noncoding miRNAs, along with target gene mutations in SCZ pathogenesis. Interestingly, whole-genome transcriptome analyses of SCZ and other major