scholarly journals S17. GLOBAL DNA METHYLATION IN CURRENT AND EMERGENT SUICIDAL IDEATION: ANALYSIS IN SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S36-S37
Author(s):  
Ali Bani-Fatemi ◽  
Roger Raymond ◽  
Jose Nobrega ◽  
Vincenzo De Luca

Abstract Background Several lines of evidence have shown that epigenetic mechanisms influence suicidal behavior, but do not indicate specific susceptibility variants. In a recent study, analysis of global methylation levels found that psychiatric patients with a history of suicide attempt (SA) had significantly higher levels of 5-methyl cytosine (5mC), suggesting that patients with a history of SA have global hypermethylation of their genome. However, there is no study investigated the link between global DNA methylation and suicidal ideation (SI) in schizophrenia. In this study, we analyzed global DNA methylation in suicide ideators and non-ideators in a sample of schizophrenia patients to find if global DNA methylation can predict SI in schizophrenia. Methods There are several methods of detecting total 5-methylcytosine content in the genome. We used Cell Biolabs’ Global DNA Methylation ELISA Kit, which is a competitive enzyme immunoassay developed for rapid detection and quantitation of 5’-methyl-2’-deoxycytidine (5MedCyd) in DNA extracted from white blood cells (WBC). We digested the genomic DNA, extracted from WBC, into single nucleotides and the quantity of 5MedCyd was determined by comparing its absorbance with that of a known 5MedCyd standard curve. We measured global DNA methylation in predicting current and emergent suicidal ideation. Results In the analysis of current SI in our schizophrenia patients, the average quantity of 5MedCyd was 7.56 ± 0.77 ng 5mC/µg DNA for suicide ideators and 8.72 ± 1.97 ng 5mC/µg DNA for non-ideators. There was no evidence of a significant difference between these two groups in our analysis (p=0.176). Also, we did not find a significant difference between global DNA methylation change (global DNA methylation change between baseline and three-month follow-up visits) in patients with and without emergent SI (p=0.121). Discussion This preliminary analysis did not find a predictive role of global DNA methylation in SI in patients with schizophrenia. The small sample size, used in this pilot study, is probably responsible for the fact that the results found here did not support those of previous research, showing that methylation levels are higher in patients with a history of a suicide attempt.

2004 ◽  
Vol 95 (3_suppl) ◽  
pp. 1092-1094 ◽  
Author(s):  
Charles James Palmer

116 consecutively admitted depressed inpatients were divided into three groups based on self-reported history of suicidal ideation and history of suicide attempt. Participants in Group 1 ( M age 34.0, SD = 14.0), 13 men and 24 women, reported no history of suicidal ideation or history of suicide attempt. Group 2 ( M age 34.0, SD = 8.6), 14 men and 25 women, reported having a history of suicidal ideation but no history of suicide attempt. Group 3 ( M age 34.0 yr., SD = 6.3), 14 men and 26 women, reported a history of suicidal ideation and at least one suicide attempt. Each participant completed the Suicide Risk Scale and the Self-esteem Scale. Analysis of variance with Tukey post hoc comparisons yielded a significant difference between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3 on the Suicide Risk Scale. There was a significant difference between Group 1 and Group 2 and between Group 1 and Group 3 on the Self-esteem Scale. These data indicated that suicide ideation and suicide attempt history significantly elevated suicide risk. Self-esteem was significantly decreased by suicide ideation and suicide attempt history.


2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ali Bani-Fatemi ◽  
Roger Raymond ◽  
Christopher Adanty ◽  
Nasia Dai ◽  
Philip Gerretsen ◽  
...  

Crisis ◽  
2018 ◽  
Vol 39 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Nina Hallensleben ◽  
Lena Spangenberg ◽  
Thomas Forkmann ◽  
Dajana Rath ◽  
Ulrich Hegerl ◽  
...  

Abstract. Background: Although the fluctuating nature of suicidal ideation (SI) has been described previously, longitudinal studies investigating the dynamics of SI are scarce. Aim: To demonstrate the fluctuation of SI across 6 days and up to 60 measurement points using smartphone-based ecological momentary assessments (EMA). Method: Twenty inpatients with unipolar depression and current and/or lifetime suicidal ideation rated their momentary SI 10 times per day over a 6-day period. Mean squared successive difference (MSSD) was calculated as a measure of variability. Correlations of MSSD with severity of depression, number of previous depressive episodes, and history of suicidal behavior were examined. Results: Individual trajectories of SI are shown to illustrate fluctuation. MSSD values ranged from 0.2 to 21.7. No significant correlations of MSSD with several clinical parameters were found, but there are hints of associations between fluctuation of SI and severity of depression and suicidality. Limitations: Main limitation of this study is the small sample size leading to low power and probably missing potential effects. Further research with larger samples is necessary to shed light on the dynamics of SI. Conclusion: The results illustrate the dynamic nature and the diversity of trajectories of SI across 6 days in psychiatric inpatients with unipolar depression. Prediction of the fluctuation of SI might be of high clinical relevance. Further research using EMA and sophisticated analyses with larger samples is necessary to shed light on the dynamics of SI.


2020 ◽  
Vol 9 (6) ◽  
pp. 778-789
Author(s):  
Letícia Bernardini ◽  
Eduardo Barbosa ◽  
Mariele Feiffer Charão ◽  
Gabriela Goethel ◽  
Diana Muller ◽  
...  

Abstract Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.


2021 ◽  
Vol 22 (3) ◽  
pp. 1388
Author(s):  
Natalia Maćkowska ◽  
Monika Drobna-Śledzińska ◽  
Michał Witt ◽  
Małgorzata Dawidowska

Distinct DNA methylation signatures, related to different prognosis, have been observed across many cancers, including T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological neoplasm. By global methylation analysis, two major phenotypes might be observed in T-ALL: hypermethylation related to better outcome and hypomethylation, which is a candidate marker of poor prognosis. Moreover, DNA methylation holds more than a clinical meaning. It reflects the replicative history of leukemic cells and most likely different mechanisms underlying leukemia development in these T-ALL subtypes. The elucidation of the mechanisms and aberrations specific to (epi-)genomic subtypes might pave the way towards predictive diagnostics and precision medicine in T-ALL. We present the current state of knowledge on the role of DNA methylation in T-ALL. We describe the involvement of DNA methylation in normal hematopoiesis and T-cell development, focusing on epigenetic aberrations contributing to this leukemia. We further review the research investigating distinct methylation phenotypes in T-ALL, related to different outcomes, pointing to the most recent research aimed to unravel the biological mechanisms behind differential methylation. We highlight how technological advancements facilitated broadening the perspective of the investigation into DNA methylation and how this has changed our understanding of the roles of this epigenetic modification in T-ALL.


2020 ◽  
Author(s):  
Louis Favril

Background: Mental disorders are overrepresented in prisoners, placing them at an increased risk of suicide. Advancing our understanding of how different mental disorders relate to distinct stages of the suicidal process—the transition from ideation to action—would provide valuable information for clinical risk assessment in this high-risk population. Methods: Data were drawn from a representative sample of 1212 adults (1093 men) incarcerated across 13 New Zealand prisons, accounting for 14% of the national prison population. Guided by an ideation-to-action framework, three mutually exclusive groups of participants were compared on the presence of mental disorders assessed by validated DSM-IV diagnostic criteria: prisoners without any suicidal history (controls; n = 778), prisoners who thought about suicide but never made a suicide attempt (ideators; n = 187), and prisoners who experienced suicidal ideation and acted on such thoughts (attempters; n = 247). Results: One-third (34.6%) of participants reported a lifetime history of suicidal ideation, of whom 55.6% attempted suicide (19.2% of all prisoners). Suicidal outcomes in the absence of mental disorders were rare. Whilst each disorder increased the odds of suicidal ideation (OR range 1.73–4.13) and suicide attempt (OR range 1.82–4.05) in the total sample (n = 1212), only a select subset of disorders was associated with suicide attempt among those with suicidal ideation (n = 434). Drug dependence (OR = 1.65, 95% CI 1.10-2.48), alcohol dependence (OR = 1.89, 95% CI 1.26-2.85), and posttraumatic stress disorder (OR = 2.09, 95% CI 1.37-3.17) distinguished attempters from ideators. Conclusion: Consistent with many epidemiological studies in the general population, our data suggest that most mental disorders are best conceptualized as risk factors for suicidal ideation rather than for suicide attempt. Once prisoners consider suicide, other biopsychosocial factors beyond the mere presence of mental disorders may account for the progression from thoughts to acts of suicide.


2021 ◽  
Author(s):  
Thanit Saeliw ◽  
Tiravut Permpoon ◽  
Nutta Iadsee ◽  
Tewin Tencomnao ◽  
Tewarit Sarachana ◽  
...  

Abstract BackgroundLong interspersed nucleotide element-1 (LINE-1) and Alu elements are retrotransposons whose abilities cause abnormal gene expression and genomic instability. Several studies have focused on DNA methylation profiling of gene regions, but the locus-specific methylation of LINE-1 and Alu elements has not been identified in autism spectrum disorder (ASD).MethodsHere, DNA methylation age was predicted using Horvath’s method. We interrogated locus- and family-specific methylation profiles of LINE-1 and Alu elements (22,352 loci) in ASD blood using publicly-available Illumina Infinium 450K methylation datasets from heterogeneous ASD (n = 52), ASD with 16p11.2 del (n = 7), and ASD with Chromodomain Helicase DNA-binding 8 (CHD8) variants (n = 15). The differentially methylated positions of LINE-1 and Alu elements corresponding to genes were combined with transcriptome data from multiple ASD studies. ROC curve was conducted to examine the specificity of target loci.ResultsEpigenetic age acceleration was significantly decelerated in ASD children over the age of 11 years. DNA methylation profiling revealed LINE-1 and Alu methylation signatures in each ASD risk loci by which global methylation were notably hypomethylated exclusively in ASD with CHD8 variants. When LINE-1 and Alu elements were clustered into subfamilies, we found methylation changes in a family-specific manner in L1P, L1H, HAL, AluJ, and AluS families in the heterogeneous ASD and ASD with CHD8 variants. Our results showed that LINE-1 and Alu methylation within target genes is inversely related to the expression level in each ASD variant. Moreover, LINE-1 and Alu methylation signatures can be used to predict ASD individuals from non-ASD.LimitationsIntegration of methylome and transcriptome datasets was performed from different ASD cohorts. The small sample size of the validation cohort used post-mortem brain tissues and necessitates future validation in a larger cohort.ConclusionsThe DNA methylation signatures of the LINE-1 and Alu elements in ASD, as well as their functional impact on ASD-related genes, have been studied. These findings are considered for further research into DNA methylation profiles and the expression of the LINE-1 and Alu elements in post-mortem brain tissue, which has been linked to ASD pathogenesis.


Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 503-513 ◽  
Author(s):  
Benjamin B Parrott ◽  
John A Bowden ◽  
Satomi Kohno ◽  
Jessica A Cloy-McCoy ◽  
Matthew D Hale ◽  
...  

Epigenetic modifications are key mediators of the interactions between the environment and an organism's genome. DNA methylation represents the best-studied epigenetic modification to date and is known to play key roles in regulating transcriptional activity and promoting chromosome stability. Our laboratory has previously demonstrated the utility of the American alligator (Alligator mississippiensis) as a sentinel species to investigate the persistent effects of environmental contaminant exposure on reproductive health. Here, we incorporate a liquid chromatography–tandem mass spectrometry method to directly measure the total (global) proportion of 5-methyl-2′-deoxycytidine (5mdC) in ovarian and whole blood DNA from alligators. Global DNA methylation in ovaries was significantly elevated in comparison with that of whole blood. However, DNA methylation appeared similar in juvenile alligators reared under controlled laboratory conditions but originating from three sites with dissimilar environmental qualities, indicating an absence of detectable site-of-origin effects on persistent levels of global 5mdC content. Analyses of tissues across individuals revealed a surprising lack of correlation between global methylation levels in blood and ovary. In addition, global DNA methylation in blood samples from juvenile alligators was elevated compared with those from adults, suggesting that age, as observed in mammals, may negatively influence global DNA methylation levels in alligators. To our knowledge, this is the first study examining global levels of DNA methylation in the American alligator and provides a reference point for future studies examining the interplay of epigenetics and environmental factors in a long-lived sentinel species.


2020 ◽  
Vol 10 (2) ◽  
pp. 94-104
Author(s):  
Laura K. Stein ◽  
Alana Kornspun ◽  
John Erdman ◽  
Mandip S. Dhamoon

Background and Purpose: Rates of depression after ischemic stroke (IS) and myocardial infarction (MI) are significantly higher than in the general population and associated with morbidity and mortality. There is a lack of nationally representative data comparing depression and suicide attempt (SA) after these distinct ischemic vascular events. Methods: The 2013 Nationwide Readmissions Database contains >14 million US admissions for all payers and the uninsured. Using International Classification of Disease, 9th Revision, Clinical Modification Codes, we identified index admission with IS (n = 434,495) or MI (n = 539,550) and readmission for depression or SA. We calculated weighted frequencies of readmission. We performed adjusted Cox regression to calculate hazard ratio (HR) for readmission for depression and SA up to 1 year following IS versus MI. Analyses were stratified by discharge home versus elsewhere. Results: Weighted depression readmission rates were higher at 30, 60, and 90 days in patients with IS versus MI (0.04%, 0.09%, 0.12% vs. 0.03%, 0.05%, 0.07%, respectively). There was no significant difference in SA readmissions between groups. The adjusted HR for readmission due to depression was 1.49 for IS versus MI (95% CI 1.25–1.79, p < 0.0001). History of depression (HR 3.70 [3.07–4.46]), alcoholism (2.04 [1.34–3.09]), and smoking (1.38 [1.15–1.64]) were associated with increased risk of depression readmission. Age >70 years (0.46 [0.37–0.56]) and discharge home (0.69 [0.57–0.83]) were associated with reduced hazards of readmission due to depression. Conclusions: IS was associated with greater hazard of readmission due to depression compared to MI. Patients with a history of depression, smoking, and alcoholism were more likely to be readmitted with depression, while advanced age and discharge home were protective. It is unclear to what extent differences in type of ischemic tissue damage and disability contribute, and further investigation is warranted.


BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e027449
Author(s):  
Habte Belete ◽  
Eyaya Misgan

AimTo assess the prevalence and associated factors of suicidal behaviour (suicidal ideation, plan or suicide attempt) in postpartum mothers.MethodAn institutional cross-sectional study was employed from March to April 2017.SettingTwo primary health centres and one referral hospital in northwestern Ethiopia.ParticipantsA total of 1065 mothers aged ≥18 years during routine postnatal care were included and 988 of them completed the study. Those who were unable to communicate due to illness were not included.Outcome measureMothers who visit for routine postnatal care were assessed for suicidal behaviour using a suicidal screening tool. Logistic analysis was employed with adjusted OR (AOR) and 95% CI, and with p value less than 0.05 as the level of significance.ResultsThe prevalence of suicidal behaviour (suicidal ideation, plan or suicide attempt) was found at 14.0% (138/988) (95% CI 12.00 to 16.00) in postpartum mothers. Poor wealth of the mother (AOR=2.80, 95% CI 1.18 to 6.84), unplanned pregnancy of the current child (AOR=2.28, 95% CI 1.48 to 3.54), history of rape (AOR=2.26, 95% CI 1.42 to 3.61) and sickness of the new child (AOR=1.68, 95% CI 1.12 to 2.52) were significantly associated with suicidal behaviours.ConclusionSuicidal behaviour was found pretty high among postpartum mothers and was associated with poor wealth, unplanned pregnancy, history of rape and sickness of the new infant. It is recommended to screen mothers for possible suicidal behaviour during routine postnatal care.


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