Epigenetic management of major psychosis

Epigenetic mechanisms are thought to play a major role in the pathogenesis of the major psychoses (schizophrenia and bipolar disorder), and they may be the link between the environment and the genome in the pathogenesis of these disorders. This paper discusses the role of epigenetics in the management of major psychosis: (1) the role of epigenetic drugs in treating these disorders. At present, there are three categories of epigenetic drugs that are being actively investigated for their ability to treat psychosis: drugs inhibiting histone deacetylation; drugs decreasing DNA methylation; and drugs targeting microRNAs; and (2) the role of epigenetic mechanisms in electroconvulsive therapy in these disorders

Global Levels of Histone Modifications in Peripheral Blood Mononuclear Cells of Subjects with Exposure to Nickel

Background: Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro

Risk of Ovarian Cancer and Inherited Variants in Relapse-Associated Genes

Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95 % CI 0.66–0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p,0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95 % CI 1.02–1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasiv

Intimate partner violence against women in western Ethiopia: prevalence, patterns, and associated factors

<p>Abstract</p> <p>Background</p> <p>Intimate partner violence against women is the psychological, physical, and sexual abuse directed to spouses. Globally it is the most pervasive yet underestimated human rights violation. This study was aimed at investigating the prevalence, patterns and associated factors of intimate partner violence against women in Western Ethiopia.</p> <p>Methods</p> <p>A cross-sectional, population based household survey was conducted from January to April, 2011 using standard WHO multi-country study questionnaire. A sample of 1540 ever married/cohabited women aged 15-49 years was randomly selected from urban and rural settings of East Wollega Zone, Western Ethiopia. Data were principally analyzed using logistic regression.</p> <p>Results</p> <p>Lifetime and past 12 months prevalence of intimate partner violence against women showed 76.5% (95% CI: 74.4-78.6%) and 72.5% (95% CI: 70.3-74.7%), respectively. The overlap of psychological, physical, and sexual violence was 56.9%. The patterns of the three forms of violence are similar across the time periods. Rural residents (AOR 0.58, 95% CI 0.34-0.98), literates (AOR 0.65, 95% CI 0.48-0.88), female headed households <b>(</b>AOR 0.46, 95% CI 0.27-0.76) were at decreased likelihood to have lifetime intimate partner violence. Yet, older women were nearly four times (AOR 3.36, 95% CI 1.27-8.89) more likely to report the incident. On the other hand, abduction (AOR 3.71, 95% CI 1.01-13.63), polygamy (AOR 3.79, 95% CI 1.64-0.73), spousal alcoholic consumption (AOR 1.98, 95% CI 1.21-3.22), spousal hostility (AOR 3.96, 95% CI 2.52-6.20), and previous witnesses of parental violence (AOR 2.00, 95% CI 1.54-2.56) were factors associated with an increased likelihood of lifetime intimate partner violence against women.</p> <p>Conclusion</p> <p>In their lifetime, three out of four women experienced at least one incident of intimate partner violence. This needs an urgent attention at all levels of societal hierarchy including policymakers, stakeholders and professionals to alleviate the situation.</p

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

Epigenetic biomarkers in psychiatric disorders

The discovery of biomarkers in psychiatric disorders may help in the diagnosis, prevention and treatment of patients with these disorders. Here, I discuss the potential role of epigenetic biomarkers, that is, epigenetically altered genes and/or expression patterns of proteins or metabolites, in psychiatric disorders. Before epigenetic biomarkers can be clinically applied in these disorders, several issues need to be addressed. These include establishing a connection between biomarkers and the disease process; determining the predictive quality of the biomarkers; determining the effects of disease heterogeneity on the biomarkers; and identifying sample sources for the biomarkers that are easily accessible for testing