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Schizophrenia Epigenetics

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https://www.readbyqxmd.com/read/29228394/the-psychiatric-risk-gene-transcription-factor-4-tcf4-regulates-neurodevelopmental-pathways-associated-with-schizophrenia-autism-and-intellectual-disability
#1
Marc P Forrest, Matthew J Hill, David H Kavanagh, Katherine E Tansey, Adrian J Waite, Derek J Blake
Background: Common genetic variants in and around the gene encoding transcription factor 4 (TCF4) are associated with an increased risk of schizophrenia. Conversely, rare damaging TCF4 mutations cause Pitt-Hopkins syndrome and have also been found in individuals with intellectual disability (ID) and autism spectrum disorder (ASD). Methods: Chromatin immunoprecipitation and next generation sequencing were used to identify the genomic targets of TCF4. These data were integrated with expression, epigenetic and disease gene sets using a range of computational tools...
December 8, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29174863/adolescent-environmental-enrichment-prevents-the-emergence-of-schizophrenia-like-abnormalities-in-a-neurodevelopmental-model-of-schizophrenia
#2
Ewelina Bator, Joachim Latusz, Krzysztof Wędzony, Marzena Maćkowiak
In the present study, we investigated whether exposure to an enriched environment (EE) during adolescence might affect the behavioural dysfunction (sensorimotor gating deficit, memory and social interaction impairments) and neurochemical changes (GAD67 expression, histone methylation) induced by methylazoxymethanol (MAM) in the MAM-E17 rat model of schizophrenia. EE was introduced for 7 days in early adolescence (days 23-29), and behavioural and biochemical studies were performed on adult rats at postnatal day 70...
November 22, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29171493/-epigenetic-research-of-cognitive-deficit-in-schizophrenia-some-methodological-considerations
#3
T V Lezheiko, M V Alfimova
AIM: To highlights the problems of assessing cognitive deficits in schizophrenia, relevant to the epigenetic, as well as a wide range of other approaches to the search for biological bases of cognition. MATERIAL AND METHODS: The literature on the weaknesses in the evaluation of cognitive functions in patients with schizophrenia are summarized and discussed. The analysis is illustrated by our experience in developing a cognitive battery and a sample to examine relationships between DNA methylation in blood cells and cognitive deficits in schizophrenia...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29160620/dna-methylation-of-mb-comt-in-malaysian-schizophrenia-patients
#4
Abd Rahim Nour El Huda, Ku Zaifah Norsidah, Rahim Mohd Nabil Fikri, Mohd Noor Hanisah, Abdullah Kartini, A Talib Norlelawati
AIM: This study examined catechol-O-methyltransferase (COMT) DNA methylation in the peripheral blood of schizophrenia patients and also in healthy controls to investigate its potential use as a peripheral biomarker of schizophrenia and its relationships with the clinical variables of schizophrenia patients. METHODS: We examined the DNA methylation levels of COMT using genomic DNA from the peripheral blood of schizophrenia patients (n = 138) and healthy control participants (n = 132); all were Malaysian Malays...
November 21, 2017: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/29106556/location-matters-distinct-dna-methylation-patterns-in-gabaergic-interneuronal-populations-from-separate-microcircuits-within-the-human-hippocampus
#5
W Brad Ruzicka, Sivan Subburaju, Joseph T Coyle, Francine M Benes
Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors.The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects...
November 2, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29070826/genetic-insights-into-the-neurodevelopmental-origins-of-schizophrenia
#6
REVIEW
Rebecca Birnbaum, Daniel R Weinberger
Schizophrenia is a severe neuropsychiatric disorder with a longstanding history of neurobiological investigation. Although the underlying causal mechanisms remain unknown, early neurodevelopmental events have been implicated in pathogenesis, initially by epidemiological and circumstantial data but more recently by brain-specific molecular and genetic findings. Notably, genomic research has recently uncovered discrete risk variants and risk loci associated with schizophrenia, with the potential to elucidate disease mechanisms...
December 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29068870/multiple-tissue-methylation-analysis-of-htr2a-exon-i-in-suicidal-behavior
#7
Ali Bani-Fatemi, John Strauss, Clement Zai, Albert H C Wong, Vincenzo de Luca
OBJECTIVE: The main aim of the current study was to investigate epigenetic alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk factors for suicidal behavior. We also aimed to analyze the epigenetic alterations in two different tissues as epigenetic mechanisms are tissue specific. These epigenetic changes may lead to a better prediction of suicidal behavior. METHODS: Direct CpG methylation analysis was carried out on genomic DNA from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and from post-mortem brain tissues of nine suicide victims and 11 controls...
December 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/29066960/impaired-latent-inhibition-in-gdnf-deficient-mice-exposed-to-chronic-stress
#8
Mona Buhusi, Colten K Brown, Catalin V Buhusi
Increased reactivity to stress is maladaptive and linked to abnormal behaviors and psychopathology. Chronic unpredictable stress (CUS) alters catecholaminergic neurotransmission and remodels neuronal circuits involved in learning, attention and decision making. Glial-derived neurotrophic factor (GDNF) is essential for the physiology and survival of dopaminergic neurons in substantia nigra and of noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression during stress is linked to resilience; on the other hand, the inability to up-regulate GDNF in response to stress, as a result of either genetic or epigenetic modifications, induces behavioral alterations...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29040792/future-of-days-past-neurodevelopment-and-schizophrenia
#9
Daniel R Weinberger
Since a proposal in 1986 that schizophrenia involved early neurodevelopmental deviations beginning in intrauterine life that showed varying expressivity as relevant neural systems matured, our understanding of the developmental components of the pathogenesis of schizophrenia has substantially evolved. This commentary highlights recent genetic and epigenetic evidence that prenatal development is a critical period for the expression of schizophrenia risk. Studies of gene expression have been fairly consistent in showing that genes implicated in schizophrenia show relatively greater expression during fetal than postnatal life...
October 21, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29038785/biological-function-of-microrna193a-3p-in-health-and-disease
#10
REVIEW
Ilaria Grossi, Alessandro Salvi, Edoardo Abeni, Eleonora Marchina, Giuseppina De Petro
MicroRNAs (miRNAs) are a class of small noncoding RNAs that act mainly as negative regulators of gene expression. Several studies demonstrated that miRNAs take part in numerous biological processes, such as proliferation, apoptosis, and migration. The dysregulation of miRNAs has been frequently observed in different types of disease, including cancer. Here, we provide a comprehensive review on the human miR-193a-3p by considering its role in both physiological and pathological contexts. Different mechanisms involved in regulating miR-193a-3p expression have been reported, including epigenetic modifications and transcription factors...
2017: International Journal of Genomics
https://www.readbyqxmd.com/read/29017764/dna-methylation-and-antipsychotic-treatment-mechanisms-in-schizophrenia-progress-and-future-directions
#11
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
#12
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...
November 2017: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/28890420/perinatal-inflammation-and-adult-psychopathology-from-preclinical-models-to-humans
#13
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
#14
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...
November 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
#15
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
#16
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
#17
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
#18
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...
November 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
#19
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
#20
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
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