Chapters authored
Genetics and Epigenetics of Schizophrenia
Schizophrenia (SCZ) is a complex mental disorder, with a longstanding history of neurobiological investigation. It is more common in those persons who are genetically predisposed to the disorder. Since Kraepelin, psychiatrists were aware that the SCZ tended to run in families. Its heritability is up to 85%. Although the etiology of SCZ is unknown, it is now thought to be multifactorial, with multiple susceptibility genes interacting with environmental and developmental factors. There is a huge amount of genetic studies, including polymorphisms, expression, methylation, microRNAs, and epigenomics. However, identifying genes for SCZ using traditional genetic approaches has thus far proven quite difficult. Reasons for this include the complexity, heterogeneity, and comorbidity of this disorder, and also the poor definition of the clinical phenotype. Important approaches to find the relation between genotype and phenotype and may be causal genetic factors are endophenotypes and pathway analysis. However, genetic researchers need to consider carefully the models of causality they choose. There is a pathophysiological pathway that extends from genes, through proteins, neurons, neural circuits, neural regions, mental functions, external behaviors, and symptoms of SCZ. In this chapter, the genetics and epigenetics of SCZ are briefly discussed.
Part of the book: Psychotic Disorders
The Role of Epigenetics in Psychosis
Epigenetics (genome - environment interaction) is the study of mitotically heritable, but reversible changes in gene expression without any change in DNA modifications and the chromatin structure. Transition to psychosis is a complex and longitudinal process during which epigenetic changes have been hypothesized and investigated. This process is especially important in individuals at high/ultrahigh risk for psychosis, before the development of full-blown psychosis. Psychoses is a range of complex disorders, where genetic variants explain only a portion of risk. Neuro-epigenetic mechanisms may explain the remaining share of risk, as well as the transition from susceptibility to the actual disease. There is a need for computational model of psychosis integrating genetic risk with environmental factors (epigenetic) associated with the disorder to discover its pathophysiological pathways. Epigenetic dysregulation of many genes has been widely speculated that are important factors involved in etiology, pathophysiology, and course of the psychoses, such as schizophrenia, and mood disorders with psychotic features. In addition, the role of epigenetic changes, including histone and DNA modifications and also targeting microRNAs in the treatment of psychoses is a new field of investigations.
Part of the book: Psychosis