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Epigenetic mechanisms in the pathophysiology of psychotic disorders.

ABSTRACT: Epigenetics is the study of chromatin-the physical material that forms chromosomes, composed of DNA wound around specialized histone proteins-and of how the modification of chromatin acts to establish stable states of gene expression in a cell-specific manner. Chromatin is regulated through three mechanisms: DNA methylation, histone modification, and RNA interference. These basic biological processes form the molecular interface between the genome and the environment, contributing to the regulation of gene expression in health and disease. Investigation of epigenetic mechanisms is yielding exciting insights in many areas of medicine, and a large and rapidly growing literature describes epigenetics as central to many aspects of the pathophysiology of psychotic disorders. This article first discusses speculative points as to why the mechanisms of epigenetics may be satisfying explanatory mechanisms in the etiology of psychotic disorders, then details emerging experimental evidence of roles for the three types of epigenetic mechanisms in these illnesses, and finally discusses these mechanisms as potentially compelling areas of research for the development of future treatments.

SUBMITTER: Ruzicka WB

PROVIDER: S-EPMC5547575 | biostudies-other | 2015 May-Jun

REPOSITORIES: biostudies-other

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Project description:Absolute and relative risks of violence are increased in patients with psychotic disorders, but the contribution of triggers for violent acts to these risks is uncertain.To examine whether a range of triggers for violent acts are associated with risks of violence in patients diagnosed with psychotic disorders and in individuals without a psychiatric diagnosis.Using a sample of all individuals born in Sweden between 1958 and 1988 (N?=?3?123?724), we identified patients in the National Patient Register who were diagnosed with schizophrenia spectrum disorders (n?=?34?903) and bipolar disorder (n?=?29?692), as well as unaffected controls (n?=?2?763?012). We then identified, within each subsample, persons who had experienced any of the following triggers for violent acts between January 1, 2001, and December 15, 2013: exposure to violence, parental bereavement, self-harm, traumatic brain injury, unintentional injuries, and substance intoxication. By using within-individual models, we conducted conditional logistic regression to compare the risk of the individual engaging in violent acts in the week following the exposure to a trigger with the risk during earlier periods of equivalent length. All time-invariant confounders (eg, genetic and early environmental influences) were controlled for by this research design and we further adjusted for time-varying sociodemographic factors.Adjusted odds ratios (aORs) of violent crime occurring in the week following the exposure to a trigger event compared with earlier periods.Among the sample of 2?827?607 individuals (1?492?186 male and 1?335?421 female), all of the examined trigger events were associated with increased risk of violent crime in the week following exposure. The largest 1-week absolute risk of violent crime was observed following exposure to violence (70-177 violent crimes per 10?000 persons). For most triggers, the relative risks did not vary significantly by diagnosis, including unintentional injuries (aOR range, 3.5-4.8), self-harm (aOR range, 3.9-4.2), and substance intoxication (aOR range, 3.0-4.0). Differences by diagnosis included parental bereavement, which was significantly higher in patients with schizophrenia spectrum disorders (aOR, 5.0; 95% CI, 3.0-8.1) compared with controls (aOR, 1.7; 95% CI, 1.3-2.2).In addition to identifying risk factors for violence, clarifying the timing of the triggers may provide opportunities to improve risk assessment and management in individuals with psychotic disorders.

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Epigenetic mechanisms in the pathophysiology of psychotic disorders.

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