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psychiatric epigenetics

Karem H Alzoubi, Omar F Khabour, Mohammad Ahmad
Posttraumatic stress disorder (PTSD) is a disabling prevalent and difficult-to-treat psychiatric disorder, which can develop after the exposure to severe traumatic events such as those occurring during wars and natural disasters. Pentoxifylline (PTX) is a potent antioxidant, which has an important role in prevention of cognitive dysfunctions. In the present study, the effect of PTX on memory impairment induced by PTSD was investigated using the rat animal model. PTSD-like behavior was induced in animals using a single-prolonged stress (SPS) rat model of PTSD (2 h restrain, 20 min forced swimming, 15 min rest, 1-2 min diethyl ether exposure)...
March 17, 2018: Brain Research Bulletin
Daniel L McCartney, Rosie M Walker, Stewart W Morris, Susan M Anderson, Barbara J Duff, Riccardo E Marioni, J Kirsty Millar, Shane E McCarthy, Niamh M Ryan, Stephen M Lawrie, Andrew R Watson, Douglas H R Blackwood, Pippa A Thomson, Andrew M McIntosh, W Richard McCombie, David J Porteous, Kathryn L Evans
Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA)...
March 19, 2018: NPJ Schizophrenia
Caroline M Nievergelt, Allison E Ashley-Koch, Shareefa Dalvie, Michael A Hauser, Rajendra A Morey, Alicia K Smith, Monica Uddin
Posttraumatic stress disorder (PTSD) after exposure to a traumatic event is a highly prevalent psychiatric disorder. Heritability estimates from twin studies as well as from recent molecular data (single nucleotide polymorphism-based heritability) indicate moderate to high heritability, yet robust genetic variants for PTSD have not yet been identified and the genetic architecture of this polygenic disorder remains largely unknown. To date, fewer than 10 large-scale genome-wide association studies of PTSD have been published, with findings that highlight the unique challenges for PTSD genomics, including a complex diagnostic entity with contingency of PTSD diagnosis on trauma exposure and the large genetic diversity of the study populations...
February 2, 2018: Biological Psychiatry
Daniel Pensold, Geraldine Zimmer
The correct establishment of inhibitory circuits is crucial for cortical functionality and defects during the development of γ-aminobutyric acid-expressing cortical interneurons contribute to the pathophysiology of psychiatric disorders. A critical developmental step is the migration of cortical interneurons from their site of origin within the subpallium to the cerebral cortex, orchestrated by intrinsic and extrinsic signals. In addition to genetic networks, epigenetic mechanisms such as DNA methylation by DNA methyltransferases (DNMTs) are suggested to drive stage-specific gene expression underlying developmental processes...
2018: Journal of Experimental Neuroscience
Alexander N Yatsenko, Paul J Turek
PURPOSE: To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring. METHODS: Review of published PubMed literature. RESULTS: Advanced paternal age (> 40 years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10)...
March 9, 2018: Journal of Assisted Reproduction and Genetics
Shlomo Yeshurun, Anthony J Hannan
In recent years, striking new evidence has demonstrated non-genetic inheritance of acquired traits associated with parental environmental exposures. In particular, this transgenerational modulation of phenotypic traits is of direct relevance to psychiatric disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. Here we review the recent progress in this field, with an emphasis on acquired traits of psychiatric illnesses transmitted epigenetically via the male lineage. We discuss the transgenerational effects of paternal exposure to stress vs...
March 8, 2018: Molecular Psychiatry
Julie Sadino, Zoe Donaldson
Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related, but non-monogamous meadow and montane voles, have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species...
March 7, 2018: ACS Chemical Neuroscience
Katherine G Akers, Yoan Chérasse, Yuki Fujita, Sakthivel Srinivasan, Takeshi Sakurai, Masanori Sakaguchi
Neural stem and progenitor cells continue to generate new neurons in particular regions of the brain during adulthood. One of these neurogenic regions is the dentate gyrus (DG) of the hippocampus, which plays an important role in cognition and emotion. By exploiting this innate neuronal regeneration mechanism in the DG, new technologies have the potential to promote resistance to or recovery from brain dysfunction or degeneration. However, a deeper understanding of how adult DG neurogenesis is regulated by factors such as sleep and epigenetic modifications of gene expression could lead to further breakthroughs in the clinical application of neural stem and progenitor cells...
February 27, 2018: Stem Cells
Dongdong Lin, Jiayu Chen, Nora Perrone-Bizzozero, Juan R Bustillo, Yuhui Du, Vince D Calhoun, Jingyu Liu
BACKGROUND: One of the major challenges in current psychiatric epigenetic studies is the tissue specificity of epigenetic changes since access to brain samples is limited. Peripheral tissues have been studied as surrogates but the knowledge of cross-tissue genetic-epigenetic characteristics remains largely unknown. In this work, we conducted a comprehensive investigation of genetic influence on DNA methylation across brain and peripheral tissues with the aim to characterize cross-tissue genetic-epigenetic effects and their roles in the pathophysiology of psychiatric disorders...
February 26, 2018: Genome Medicine
Pamela Prini, Franceso Rusconi, Erica Zamberletti, Marina Gabaglio, Federica Penna, Mauro Fasano, Elena Battaglioli, Daniela Parolaro, Tiziana Rubino
BACKGROUND: Increasing cannabis consumption among adolescents, studies that link its early use with mental illnesses, and the political debate on cannabis legalization together call for an urgent need to study molecular underpinnings of adolescent brain vulnerability. The emerging role of epigenetic mechanisms in psychiatric diseases led us to hypothesize that epigenetic alterations could play a role in causes and subsequent development of the depressive/psychotic-like phenotype induced by adolescent, but not adult, Δ9-tetrahydrocannabinol (THC) exposure in female rats...
March 2018: Journal of Psychiatry & Neuroscience: JPN
Bianca Ho, Keelin Greenlaw, Abeer Al Tuwaijri, Sanny Moussette, Francisco Martínez, Elisa Giorgio, Alfredo Brusco, Giovanni Battista Ferrero, Natália D Linhares, Eugênia R Valadares, Marta Svartman, Vera M Kalscheuer, Germán Rodríguez Criado, Catherine Laprise, Celia M T Greenwood, Anna K Naumova
BACKGROUND: Sexual dimorphism in DNA methylation levels is a recurrent epigenetic feature in different human cell types and has been implicated in predisposition to disease, such as psychiatric and autoimmune disorders. To elucidate the genetic origins of sex-specific DNA methylation, we examined DNA methylation levels in fibroblast cell lines and blood cells from individuals with different combinations of sex chromosome complements and sex phenotypes focusing on a single autosomal region--the differentially methylated region (DMR) in the promoter of the zona pellucida binding protein 2 (ZPBP2) as a reporter...
February 20, 2018: Biology of Sex Differences
Erika J Wolf, Hannah Maniates, Nicole Nugent, Adam X Maihofer, Don Armstrong, Andrew Ratanatharathorn, Allison E Ashley-Koch, Melanie Garrett, Nathan A Kimbrel, Adriana Lori, Va Mid-Atlantic Mirecc Workgroup, Allison E Aiello, Dewleen G Baker, Jean C Beckham, Marco P Boks, Sandro Galea, Elbert Geuze, Michael A Hauser, Ronald C Kessler, Karestan C Koenen, Mark W Miller, Kerry J Ressler, Victoria Risbrough, Bart P F Rutten, Murray B Stein, Robert J Ursano, Eric Vermetten, Christiaan H Vinkers, Monica Uddin, Alicia K Smith, Caroline M Nievergelt, Mark W Logue
BACKGROUND: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. METHODS: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186)...
December 27, 2017: Psychoneuroendocrinology
Nina Alexander, Clemens Kirschbaum, Matthis Wankerl, Benjamin J Stauch, Tobias Stalder, Susann Steudte-Schmiedgen, Markus Muehlhan, Robert Miller
Exposure to childhood trauma (CT) has been linked to sustained dysregulations of major stress response systems, including findings of both exaggerated and attenuated hypothalamus-pituitary-adrenal (HPA) axis activity. Likewise, CT constitutes a common risk factor for a broad range of psychiatric conditions that involve distinct neuroendocrine profiles. In this study, we investigated the role of epigenetic variability in a stress-related gene as a potential mediator or moderator of such differential trajectories in CT survivors...
January 31, 2018: Psychoneuroendocrinology
Dong-Yao Wang, Joel Kosowan, James Samsom, Laura Leung, Kai-Lai Zhang, Ying-Xiang Li, Yan Xiong, Jian Jin, Arturas Petronis, Gabriel Oh, Albert H C Wong
Epigenetic gene-regulation abnormalities have been implicated in various neuropsychiatric disorders including schizophrenia and depression, as well as in the regulation of mood and anxiety. In addition, epigenetic mechanisms are involved in the actions of psychiatric drugs. Current anxiolytic drugs have significant shortcomings, and development of new medications is warranted. Two proteins, G9a (also known as EHMT2 or KMT1C) and GLP (G9a-like protein, also known as EHMT1 or KMT1D), which methylate lysine 9 of histone H3 (H3K9), could be promising anxiolytic targets...
February 8, 2018: Acta Pharmacologica Sinica
Devanand S Manoli, Jessica Tollkuhn
The sexual differentiation of the mammalian nervous requires the precise coordination of the temporal and spatial regulation of gene expression in diverse cell types. Sex hormones act at multiple developmental time points to specify sex-typical differentiation during embryonic and early development and to coordinate subsequent responses to gonadal hormones later in life by establishing sex-typical patterns of epigenetic modifications across the genome. Thus, mutations associated with neuropsychiatric conditions may result in sexually dimorphic symptoms by acting on different neural substrates or chromatin landscapes in males and females...
January 24, 2018: Annals of the New York Academy of Sciences
Izabela M Krzyzewska, Judith B M Ensink, Laura Nawijn, Adri N Mul, Saskia B Koch, Andrea Venema, Vinod Shankar, Jessie L Frijling, Dirk J Veltman, Ramon J L Lindauer, Miranda Olff, Marcel M A M Mannens, Mirjam van Zuiden, Peter Henneman
Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that may develop after a traumatic event. Here we aimed to identify epigenetic and genetic loci associated with PTSD. We included 73 traumatized police officers with extreme phenotypes regarding symptom severity despite similar trauma history: n = 34 had PTSD and n = 39 had minimal PTSD symptoms. Epigenetic and genetic profiles were based on the Illumina HumanMethylation450 BeadChip. We searched for differentially methylated probes (DMPs) and differentially methylated regions (DMRs)...
January 23, 2018: European Journal of Human Genetics: EJHG
Qingzhong Wang, Bhaskar Roy, Gustavo Turecki, Richard C Shelton, Yogesh Dwivedi
OBJECTIVE: Proinflammatory cytokines have recently received considerable attention for their role in suicidal behavior; however, how the expression of cytokine genes is regulated is not clearly known. The authors examined underlying mechanisms of critical cytokine gene tumor necrosis factor-alpha (TNF-α) dysregulation in the brains of individuals who died by suicide. METHOD: TNF-α expression was examined in the dorsolateral prefrontal cortex of the postmortem brains of persons with and without major depressive disorder who died by suicide and of persons with major depressive disorder who died of causes other than suicide...
January 24, 2018: American Journal of Psychiatry
Laura Orsolini, Fabiola Sarchione, Federica Vellante, Michele Fornaro, Ilaria Matarazzo, Giovanni Martinotti, Alessandro Valchera, Marco Di Nicola, Alessandro Carano, Massimo Di Giannantonio, Giampaolo Perna, Luigi Olivieri, Domenico De Berardis
BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible of the schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well supposed. Accordingly, it has been recently investigated the role of an acute inflammatory phase protein, the C-reactive protein (CRP)...
January 19, 2018: Current Neuropharmacology
Pierre-Eric Lutz, Daniel Almeida, Raoul Belzeaux, Ipek Yalcin, Gustavo Turecki
Preclinical and clinical studies have demonstrated that the kappa opioid receptor (KOR) regulates reward, hedonic tone and emotions. At therapeutic level, on-going clinical trials are assessing the potential of targeting the KOR for the management of depression, anxiety disorders and substance use disorders. However, genetic polymorphisms in the KOR gene that potentially contribute to its implication in these phenotypes have been poorly studied. Here we investigated an insertion-deletion in the promoter region of KOR (rs35566036), recently associated with alcohol addiction, in a cohort of depressed subjects who died by suicide, as well as psychiatrically healthy individuals...
January 11, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Mihoko Shimada, Takeshi Otowa, Taku Miyagawa, Tadashi Umekage, Yoshiya Kawamura, Miki Bundo, Kazuya Iwamoto, Tempei Ikegame, Mamoru Tochigi, Kiyoto Kasai, Hisanobu Kaiya, Hisashi Tanii, Yuji Okazaki, Katsushi Tokunaga, Tsukasa Sasaki
Major depressive disorder is a common psychiatric disorder that is thought to be triggered by both genetic and environmental factors. Depressive symptoms are an important public health problem and contribute to vulnerability to major depression. Although a substantial number of genetic and epigenetic studies have been performed to date, the detailed etiology of depression remains unclear and there are no validated biomarkers. DNA methylation is one of the major epigenetic modifications that play diverse roles in the etiology of complex diseases...
January 5, 2018: Journal of Human Genetics
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