Cataloging recent advances in epigenetic alterations in major mental disorders and autism

Epigenomics ◽  
2021 ◽  
Author(s):  
Hamid Mostafavi Abdolmaleky ◽  
Jin-Rong Zhou ◽  
Sam Thiagalingam
Keyword(s):  
Dna Methylation ◽  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Drug Effects ◽  
Tissue Cell ◽  
Epigenetic Alterations ◽  
Cell Specificity ◽  
Aberrant Dna Methylation ◽  
Potential Origin

During the last two decades, diverse epigenetic modifications including DNA methylation, histone modifications, RNA editing and miRNA dysregulation have been associated with psychiatric disorders. A few years ago, in a review we outlined the most common epigenetic alterations in major psychiatric disorders (e.g., aberrant DNA methylation of DTNBP1, HTR2A, RELN, MB-COMT and PPP3CC, and increased expression of miR-34a and miR-181b). Recent follow-up studies have uncovered other DNA methylation aberrations affecting several genes in mental disorders, in addition to dysregulation of many miRNAs. Here, we provide an update on new epigenetic findings and highlight potential origin of the diversity and inconsistencies, focusing on drug effects, tissue/cell specificity of epigenetic landscape and discuss shortcomings of the current diagnostic criteria in mental disorders.

scholarly journals Neuroblastoma and the epigenome

2021 ◽  
Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Disease Diagnosis ◽  
Dna Methyltransferases ◽  
Epigenetic Alterations ◽  
Aberrant Expression ◽  
Tet Proteins ◽  
Relative Paucity ◽  
Underlying Causes ◽  
Aberrant Dna Methylation

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.

A Follow-up Study of Psychiatric Disturbance in a Cape Coloured Community

1973 ◽  
Vol 123 (574) ◽  
pp. 279-283 ◽  
Author(s):  
L. S. Gillis ◽  
G. L. Stone
Keyword(s):  
Mental Disorders ◽  
Natural History ◽  
Psychiatric Disorders ◽  
Longitudinal Studies ◽  
Response To Treatment ◽  
Psychiatric Disturbance ◽  
Follow Up Study ◽  
History Of

Longitudinal studies of psychiatric disturbance in communities are important in order to determine the natural history of mental disorders. Most studies have focused on the prevalence of known psychiatric disorders and response to treatment, but only a few on the follow up of a population not previously recognized as psychiatrically ill (Beiser (1), Hagnell (5), Helgason (6), Myers and Bean (10)). The present study is an attempt to do this, and also to follow up untreated disorder within a community.

scholarly journals Changes in aberrant DNA methylation afterHelicobacter pylorieradication: A long-term follow-up study

2013 ◽  
Vol 133 (9) ◽  
pp. 2034-2042 ◽  
Author(s):  
Cheol Min Shin ◽  
Nayoung Kim ◽  
Hye Seung Lee ◽  
Ji Hyun Park ◽  
Soyeon Ahn ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Follow Up Study ◽  
Long Term Follow Up ◽  
Aberrant Dna Methylation

scholarly journals Residual DNA methylation at remission is prognostic in adult Philadelphia chromosome–negative acute lymphocytic leukemia

Blood ◽  
2009 ◽  
Vol 113 (9) ◽  
pp. 1892-1898 ◽  
Author(s):  
Hui Yang ◽  
Tapan Kadia ◽  
Lianchun Xiao ◽  
Carlos E. Bueso-Ramos ◽  
Koyu Hoshino ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Lymphocytic Leukemia ◽  
Philadelphia Chromosome ◽  
Hazard Ratio ◽  
Lymphocytic Leukemia ◽  
Aberrant Methylation ◽  
Epigenetic Alterations ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns ◽  
Standard Risk

Pretreatment aberrant DNA methylation patterns are stable at time of relapse in acute lymphocytic leukemia (ALL). We hypothesized that the detection of residual methylation alterations at the time of morphologic remission may predict for worse prognosis. We developed a real-time bisulfite polymerase chain reaction assay and analyzed the methylation levels of p73, p15, and p57KIP2 at the time of initial remission in 199 patients with Philadelphia chromosome-negative and MLL− ALL. Residual p73 methylation was detected in 18 (9.5%) patients, p15 in 33 (17.4%), and p57KIP2 in 7 (3.7%); 140 (74%) patients had methylation of 0 genes and 48 (25%) of more than or equal to 1 gene. In 123 (65%) patients, matched pretreatment samples were also studied and compared with remission ones: in 82 of those with initial aberrant methylation of at least one gene, 59 (72%) had no detectable methylation at remission and 23 (28%) had detectable residual methylation. By multivariate analysis, the presence of residual p73 methylation was associated with a significant shorter duration of first complete remission (hazard ratio = 2.68, P = .003) and overall survival (hazard ratio = 2.69, P = .002). In conclusion, detection of epigenetic alterations allows the identification of patients with ALL with standard risk but with poor prognosis.

scholarly journals Duration of untreated symptoms in common mental disorders: association with outcomes

2006 ◽  
Vol 189 (1) ◽  
pp. 79-80 ◽  
Author(s):  
Stephen Kisely ◽  
Anita Scott ◽  
Jennifer Denney ◽  
Gregory Simon
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Mental Disorders ◽  
Psychiatric Disorders ◽  
Prospective Cohort ◽  
Common Mental Disorders ◽  
Specialist Care ◽  
Psychosocial Status ◽  
Psychiatric Outcome

SummaryStudies have assessed the association between a longer duration of untreated symptoms and outcome for psychoses in specialist care. We investigated the effect of longer duration on the outcome of common psychiatric disorders in primary care, where most patients are treated. Patients presenting to primary care for new episodes in 10 countries were recruited into a prospective cohort study. Information on duration of untreated symptoms and psychosocial status was collected for 351 individuals using standardised instruments and this was repeated 1 year later. At 1-year follow-up, longer duration was associated with worse psychiatric outcome even after controlling for potential confounders.

scholarly journals Epigenome Chaos: Stochastic and Deterministic DNA Methylation Events Drive Cancer Evolution

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1800
Author(s):  
Giusi Russo ◽  
Alfonso Tramontano ◽  
Ilaria Iodice ◽  
Lorenzo Chiariotti ◽  
Antonio Pezone
Keyword(s):  
Dna Methylation ◽  
Tumor Heterogeneity ◽  
Tumor Evolution ◽  
Aberrant Methylation ◽  
Epigenetic Alterations ◽  
Cancer Evolution ◽  
Cancer Types ◽  
Chromatin Proteins ◽  
Aberrant Dna Methylation ◽  
Methylation Patterns

Cancer evolution is associated with genomic instability and epigenetic alterations, which contribute to the inter and intra tumor heterogeneity, making genetic markers not accurate to monitor tumor evolution. Epigenetic changes, aberrant DNA methylation and modifications of chromatin proteins, determine the “epigenome chaos”, which means that the changes of epigenetic traits are randomly generated, but strongly selected by deterministic events. Disordered changes of DNA methylation profiles are the hallmarks of all cancer types, but it is not clear if aberrant methylation is the cause or the consequence of cancer evolution. Critical points to address are the profound epigenetic intra- and inter-tumor heterogeneity and the nature of the heterogeneity of the methylation patterns in each single cell in the tumor population. To analyze the methylation heterogeneity of tumors, new technological and informatic tools have been developed. This review discusses the state of the art of DNA methylation analysis and new approaches to reduce or solve the complexity of methylated alleles in DNA or cell populations.

scholarly journals Targeting Epigenetic Modifications in Uveal Melanoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5314
Author(s):  
Pooneh Chokhachi Baradaran ◽  
Zuzana Kozovska ◽  
Alena Furdova ◽  
Bozena Smolkova
Keyword(s):  
Dna Methylation ◽  
Uveal Melanoma ◽  
Histone Modifications ◽  
Tumor Suppressor Genes ◽  
Primary Therapy ◽  
Epigenetic Alterations ◽  
Combination Therapies ◽  
Non Coding Rna ◽  
Aberrant Dna Methylation ◽  
New Generation

Uveal melanoma (UM), the most common intraocular malignancy in adults, is a rare subset of melanoma. Despite effective primary therapy, around 50% of patients will develop the metastatic disease. Several clinical trials have been evaluated for patients with advanced UM, though outcomes remain dismal due to the lack of efficient therapies. Epigenetic dysregulation consisting of aberrant DNA methylation, histone modifications, and small non-coding RNA expression, silencing tumor suppressor genes, or activating oncogenes, have been shown to play a significant role in UM initiation and progression. Given that there is no evidence any approach improves results so far, adopting combination therapies, incorporating a new generation of epigenetic drugs targeting these alterations, may pave the way for novel promising therapeutic options. Furthermore, the fusion of effector enzymes with nuclease-deficient Cas9 (dCas9) in clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) system equips a potent tool for locus-specific erasure or establishment of DNA methylation as well as histone modifications and, therefore, transcriptional regulation of specific genes. Both, CRISPR-dCas9 potential for driver epigenetic alterations discovery, and possibilities for their targeting in UM are highlighted in this review.

Aberrant DNA Methylation Is Associated with Reduced Response to SRC Inhibition in Primary Human Vestibular Schwannoma Cells

2019 ◽  
Author(s):  
Christine Dinh ◽  
Juan Young ◽  
Olena Bracho ◽  
Rahul Mittal ◽  
Denise Yan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vestibular Schwannoma ◽  
Aberrant Dna Methylation

245-LB: Aberrant DNA Methylation as a Contributor to Obesity-Associated Vascular Dysfunction

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 245-LB
Author(s):  
MOHAMED M. ALI ◽  
CHANDRA HASSAN ◽  
MARIO MASRUR ◽  
FRANCESCO BIANCO ◽  
SHANE A. PHILLIPS ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Vascular Dysfunction ◽  
Aberrant Dna Methylation

EPIGENETIC ALTERATIONS ASSOCIATED WITH PREMATURE OVARIAN FAILURE

2008 ◽  
Vol 31 (4) ◽  
pp. 11
Author(s):  
Manda Ghahremani ◽  
Courtney W Hannah ◽  
Maria Peneherrera ◽  
Karla L Bretherick ◽  
Margo R Fluker ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Premature Ovarian Failure ◽  
Promoter Region ◽  
Gene Promoter ◽  
Ovarian Failure ◽  
P Value ◽  
Epigenetic Alterations ◽  
Methylation Array ◽  
Cpg Sites ◽  
Deficient Mice

Background/Purpose: Premature ovarian failure (POF) affects 1% of women with a largely idiopathic and poorly understood etiology. The objective of this study was to identify specific epigenetic alterations by measuring DNA methylation of gene regulatory regions in women with POF vs. controls. Methods: Blood samples were collected from idiopathic POFpatients (Amenorrhea for at least 3 months and 2 serum FSH levels of > 40mIU/ml obtained > 1 month apart prior to age 40) and control women (CW) (healthy pregnancy after age 37 with out a pregnancy loss). Genomic DNA was extracted from EDTA anticoagulated blood and bisulfite converted for analysis using the Illumina Golden Gate Methylation Panel which measures DNA methylation at 1506 CpG sites in the promoter regions of 807 genes in 10 POF and 12 CW. Candidate genes with altered epigenetic marks between POF and CW at a nominal P-value < 0.05 were identified using a t-testcomparison within the Illumina bead studio software. Genes of interest were further analyzed for quantitative methylation at specific CpG sites using pyrosequencing in 30 POF and 30 CW. Results: Comparison of DNA methylation profiles of our initial POF and CW groups identified several genes with statistically significanthyper- or hypo- methylation in the POF group (P < 0.05), including the Androgen Receptor (AR)promoter region, which was significantly hypermethylated. To further validate these results, DNA methylation of the AR gene promoter was quantified bypryosequencing in a larger group of POF and CW. Pyrosequencing further confirmed a significantly higher DNA methylation of the AR promoter region inPOF vs. CW (P=0.007). Conclusions: This is a novel study identifying epigenetic alterations in POF. The hypermethylation of the AR gene in POF patients may cause decreased level of the AR in these women. This is especially interesting given a recent report of induced POF in AR deficient mice^1. Specific epigenetic markers, as identified by DNA methylation array profiling in blood, may serve as useful biomarkers for POF and other fertility disorders. However, it will need to be determined if these methylation changes are present prior to diagnosis, or are a consequence of menopause itself. Reference: 1.Hiroko S. et al. Premature ovarian failure in androgenreceptor deficient mice. PNAS;103:224-9

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