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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#1
REVIEW
Ellen S Ovenden, Nathaniel W McGregor, Robin A Emsley, Louise Warnich
Antipsychotic response in schizophrenia is a complex, multifactorial trait influenced by pharmacogenetic factors. With genetic studies thus far providing little biological insight or clinical utility, the field of pharmacoepigenomics has emerged to tackle the so-called "missing heritability" of drug response in disease. Research on psychiatric disorders has only recently started to assess the link between epigenetic alterations and treatment outcomes. DNA methylation, the best characterised epigenetic mechanism to date, is discussed here in the context of schizophrenia and antipsychotic treatment outcomes...
October 7, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28942748/nutritional-psychiatry-the-present-state-of-the-evidence
#2
Wolfgang Marx, Genevieve Moseley, Michael Berk, Felice Jacka
Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness...
September 25, 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28890420/perinatal-inflammation-and-adult-psychopathology-from-preclinical-models-to-humans
#3
REVIEW
Amaicha Mara Depino
Perinatal environment plays a crucial role in brain development and determines its function through life. Epidemiological studies and clinical reports link perinatal exposure to infection and/or immune activation to various psychiatric disorders. In addition, accumulating evidence from animal models shows that perinatal inflammation can affect various behaviors relevant to psychiatric disorders such as schizophrenia, autism, anxiety and depression. Remarkably, the effects on behavior and brain function do not always depend on the type of inflammatory stimulus or the perinatal age targeted, so diverse inflammatory events can have similar consequences on the brain...
September 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28887651/a-cell-culture-model-for-investigation-of-synapse-influenceability-epigenetics-expression-and-function-of-gene-targets-important-for-synapse-formation-and-preservation-in-sh-sy5y-neuroblastoma-cells-differentiated-by-retinoic-acid
#4
Kirsten Jahn, C Wieltsch, N Blumer, M Mehlich, H Pathak, A Q Khan, H Hildebrandt, H Frieling
SH-SY5Y neuroblastoma cells are frequently used for different neuronal cell culture models. As there is no "gold-standard", miscellaneous protocols exist to differentiate these cells into a neuronal cell type. Here, the aim was to find a differentiation condition making cells suitable for investigation of influenceability of synapses by environmental conditions in pharmacologic experiments. For this purpose, effects on synapse molecules should be somehow rateable and cells should be usable for functional analysis like calcium imaging...
September 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28884721/-a-search-of-target-regions-for-association-studies-between-dna-methylation-and-cognitive-impairment-in-schizophrenia
#5
N V Kondratiev, M V Alfimova, V E Golimbet
AIM: To develop a strategy for the search for candidate genes and targets for epigenetic studies of cognitive impairments in patients with schizophrenia. MATERIAL AND METHODS: A search for literature on epigenetics of schizophrenia and cognitive functions was performed. Single nucleotide polymorphisms (SNPs) that can create or abolish a site for DNA methylation or transcription factor sites were determined using a custom script. RESULTS AND CONCLUSION: Eight candidate genes, including BDNF, COMT, RELN, SNRPN, PSMA4, FAM63B, IL-1RAP, MAD1L1, as well as 750 targets in CpG islands in the linkage regions identified in GWAS of schizophrenia and 406 targets in SNV located within transcription factor binding sites were selected...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28883405/modeling-a-linkage-between-blood-transcriptional-expression-and-activity-in-brain-regions-to-infer-the-phenotype-of-schizophrenia-patients
#6
El Chérif Ibrahim, Vincent Guillemot, Magali Comte, Arthur Tenenhaus, Xavier Yves Zendjidjian, Aida Cancel, Raoul Belzeaux, Florence Sauvanaud, Olivier Blin, Vincent Frouin, Eric Fakra
Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression...
September 7, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28879201/wnt-%C3%AE-catenin-pathway-and-epigenetic-mechanisms-regulate-the-pitt-hopkins-syndrome-and-schizophrenia-risk-gene-tcf4
#7
Krista M Hennig, Daniel M Fass, Wen-Ning Zhao, Steven D Sheridan, Ting Fu, Serkan Erdin, Alexei Stortchevoi, Diane Lucente, Jannine D Cody, David Sweetser, James F Gusella, Michael E Talkowski, Stephen J Haggarty
Genetic variation within the transcription factor TCF4 locus can cause the intellectual disability and developmental disorder Pitt-Hopkins syndrome (PTHS), whereas single-nucleotide polymorphisms within noncoding regions are associated with schizophrenia. These genetic findings position TCF4 as a link between transcription and cognition; however, the neurobiology of TCF4 remains poorly understood. Here, we quantitated multiple distinct TCF4 transcript levels in human induced pluripotent stem cell-derived neural progenitors and differentiated neurons, and PTHS patient fibroblasts...
July 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28872674/the-methylazoxymethanol-acetate-rat-model-molecular-and-epigenetic-effect-in-the-developing-prefrontal-cortex-an-editorial-highlight-for-epigenetic-mechanisms-underlying-nmda-receptor-hypofunction-in-the-prefrontal-cortex-of-juvenile-animals-in-the-mam-model
#8
EDITORIAL
Xiyu Zhu, Felipe V Gomes, Anthony A Grace
This Editorial highlights an article by Gulchina and colleagues in the current issue of the Journal of Neurochemistry, in which the authors describe molecular and epigenetic changes in the developing prefrontal cortex of the rats exposed to methylazoxymethanol acetate (MAM). They found an NMDAR hypofunction present in the prefrontal cortex of juvenile MAM rats which was associated with abnormal epigenetic regulation of the Grin2b gene. These changes may be related to early cognitive impairments observed in MAM rats and schizophrenia patients...
September 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28872641/polyunsaturated-fatty-acid-deficiency-during-neurodevelopment-in-mice-models-the-prodromal-state-of-schizophrenia-through-epigenetic-changes-in-nuclear-receptor-genes
#9
M Maekawa, A Watanabe, Y Iwayama, T Kimura, K Hamazaki, S Balan, H Ohba, Y Hisano, Y Nozaki, T Ohnishi, M Toyoshima, C Shimamoto, K Iwamoto, M Bundo, N Osumi, E Takahashi, A Takashima, T Yoshikawa
The risk of schizophrenia is increased in offspring whose mothers experience malnutrition during pregnancy. Polyunsaturated fatty acids (PUFAs) are dietary components that are crucial for the structural and functional integrity of neural cells, and PUFA deficiency has been shown to be a risk factor for schizophrenia. Here, we show that gestational and early postnatal dietary deprivation of two PUFAs-arachidonic acid (AA) and docosahexaenoic acid (DHA)-elicited schizophrenia-like phenotypes in mouse offspring at adulthood...
September 5, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28871179/epigenetic-analysis-confirms-no-accelerated-brain-aging-in-schizophrenia
#10
Joanne Voisey, Bruce R Lawford, C Phillip Morris, Leesa F Wockner, Ernest P Noble, Ross McD Young, Divya Mehta
Epigenetic aging is associated with several biological mechanisms and diseases. We assessed two brain data sets, one small (n = 48) and one large (n = 392), to test epigenetic aging in schizophrenia. DNA methylation age from frontal cortex was significantly correlated with chronological age but no significant differences in DNA methylation age acceleration between schizophrenia cases and controls were observed in both data sets. Our results were consistent with a previous study investigating schizophrenia and epigenetic aging in superior temporal gyrus...
September 4, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28869584/an-xqtl-map-integrates-the-genetic-architecture-of-the-human-brain-s-transcriptome-and-epigenome
#11
Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci...
October 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28864976/overview-of-human-oxytocin-research
#12
Keith M Kendrick, Adam J Guastella, Benjamin Becker
Social dysfunction is a core symptom of many psychiatric disorders and current medications have little or no remedial effects on this. Following on from extensive studies on animal models demonstrating that the neuropeptide oxytocin plays an important role in social recognition and bonding, human-based research has explored its therapeutic potential for social dysfunction in psychiatric disorders. Here we outline the historical background of this human-based research and some of the current methodological challenges it is facing...
September 2, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28777307/epigenomics-of-major-depressive-disorders-and-schizophrenia-early-life-decides
#13
REVIEW
Anke Hoffmann, Vincenza Sportelli, Michael Ziller, Dietmar Spengler
Brain development is guided by the interactions between the genetic blueprint and the environment. Epigenetic mechanisms, especially DNA methylation, can mediate these interactions and may also trigger long-lasting adaptations in developmental programs that increase the risk of major depressive disorders (MDD) and schizophrenia (SCZ). Early life adversity is a major risk factor for MDD/SCZ and can trigger persistent genome-wide changes in DNA methylation at genes important to early, but also to mature, brain function, including neural proliferation, differentiation, and synaptic plasticity, among others...
August 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28746897/parkinsonian-features-in-aging-gfap-hmox1-transgenic-mice-overexpressing-human-ho-1-in-the-astroglial-compartment
#14
Wei Song, Marisa Cressatti, Hillel Zukor, Adrienne Liberman, Carmela Galindez, Hyman M Schipper
Epigenetic influences mediating brain iron deposition, oxidative mitochondrial injury, and macroautophagy in Parkinson disease and related conditions remain enigmatic. Here, we show that selective overexpression of the stress protein, heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age results in nigrostriatal hypodopaminergia associated with locomotor incoordination and stereotypy; downregulation of tyrosine hydroxylase, DAT, LMX1B, Nurr1, Pitx3 and DJ-1 mRNA and/or protein; overproduction of α-synuclein and ubiquitin; oxidative stress; basal ganglia siderosis; mitochondrial damage/mitophagy; and augmented GABAergic systems (increased GABA, GAD67 and reelin)...
June 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28699694/the-epigenomics-of-schizophrenia-in-the-mouse
#15
REVIEW
Behnam Javidfar, Royce Park, Bibi S Kassim, Lucy K Bicks, Schahram Akbarian
Large-scale consortia including the Psychiatric Genomics Consortium, the Common Minds Consortium, BrainSeq and PsychENCODE, and many other studies taken together provide increasingly detailed insights into the genetic and epigenetic risk architectures of schizophrenia (SCZ) and offer vast amounts of molecular information, but with largely unexplored therapeutic potential. Here we discuss how epigenomic studies in human brain could guide animal work to test the impact of disease-associated alterations in chromatin structure and function on cognition and behavior...
September 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28696411/combined-study-of-genetic-and-epigenetic-biomarker-risperidone-treatment-efficacy-in-chinese-han-schizophrenia-patients
#16
Y Shi, M Li, C Song, Q Xu, R Huo, L Shen, Q Xing, D Cui, W Li, J Zhao, L He, S Qin
Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort...
July 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28691768/microbiome-inflammation-epigenetic-alterations-and-mental-diseases
#17
REVIEW
Reza Alam, Hamid M Abdolmaleky, Jin-Rong Zhou
Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis...
July 10, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28689755/accelerated-aging-in-schizophrenia-and-related-disorders-future-research
#18
Brian Kirkpatrick, Brian K Kennedy
Several lines of evidence suggest schizophrenia is a segmental progeria, that is, some but not all aspects of accelerated aging may be present. However, the evidence has not been consistent. Problems with matching and confounding may account for some of these discrepancies. Given the etiopathophysiological heterogeneity of schizophrenia, it is possible that only a specific pathophysiological group within schizophrenia is associated with progeroid features, while others are not, or that one group is associated with a particular segment of aging features, while other progeroid features are found in another pathophysiological subgroup...
July 6, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28682228/-genetics-and-epigenetics-of-schizophrenia-and-other-psychoses
#19
Boris Chaumette, Oussama Kebir, Marie-Odile Krebs
Schizophrenia and other psychoses are categorical psychiatric diagnoses corresponding to frequent and heterogeneous disorders. Their physiopathology still remains largely unknown despite numerous recent advances. In particular, the last decade has identified different types of genetic variants, thanks to emergence of high-throughput methods. These methods allow both the identification of rare variants with a large effect such as punctual mutations or copy-number variants and the identification of frequent variants with a limited effect such as polymorphisms...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28670349/epigenetic-mechanisms-during-ageing-and-neurogenesis-as-novel-therapeutic-avenues-in-human-brain-disorders
#20
REVIEW
Raúl Delgado-Morales, Roberto Carlos Agís-Balboa, Manel Esteller, María Berdasco
Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation...
2017: Clinical Epigenetics
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