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https://www.readbyqxmd.com/read/29325449/analysis-of-dna-methylation-in-young-people-limited-evidence-for-an-association-between-victimization-stress-and-epigenetic-variation-in-blood
#1
Sarah J Marzi, Karen Sugden, Louise Arseneault, Daniel W Belsky, Joe Burrage, David L Corcoran, Andrea Danese, Helen L Fisher, Eilis Hannon, Terrie E Moffitt, Candice L Odgers, Carmine Pariante, Richie Poulton, Benjamin S Williams, Chloe C Y Wong, Jonathan Mill, Avshalom Caspi
OBJECTIVE: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become "embedded" in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation. METHOD: The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994-1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years...
January 12, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29277323/epigenetic-changes-in-the-crh-gene-are-related-to-severity-of-suicide-attempt-and-a-general-psychiatric-risk-score-in-adolescents
#2
Jussi Jokinen, Adrian E Boström, Ali Dadfar, Diana M Ciuculete, Andreas Chatzittofis, Marie Åsberg, Helgi B Schiöth
The aim of this study, comprising 88 suicide attempters, was to identify hypothalamic-pituitary-adrenal (HPA) -axis coupled CpG-sites showing methylation shifts linked to severity of the suicide attempt. Candidate methylation loci were further investigated as risk loci for a general psychiatric risk score in two cohorts of adolescents (cohort 1 and 2). The genome-wide methylation pattern was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. Subjects were stratified into high-risk and low-risk groups based on the severity of the suicidal behavior...
December 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29249826/gene-expression-associated-with-ptsd-in-world-trade-center-responders-an-rna-sequencing-study
#3
Pei-Fen Kuan, Monika A Waszczuk, Roman Kotov, Sean Clouston, Xiaohua Yang, Prashant K Singh, Sean T Glenn, Eduardo Cortes Gomez, Jianmin Wang, Evelyn Bromet, Benjamin J Luft
The gene expression approach has provided promising insights into the pathophysiology of posttraumatic stress disorder (PTSD). However, few studies used hypothesis-free transcriptome-wide approach to comprehensively understand gene expression underpinning PTSD. A transcriptome-wide expression study using RNA sequencing of whole blood was conducted in 324 World Trade Center responders (201 with never, 81 current, 42 past PTSD). Samples from current and never PTSD reponders were randomly split to form discovery (N = 195) and replication (N = 87) cohorts...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29203717/hsp90-and-fkbp51-complex-regulators-of-psychiatric-diseases
#4
REVIEW
Marangelie Criado-Marrero, Theo Rein, Elisabeth B Binder, James T Porter, John Koren, Laura J Blair
Mood disorders affect nearly a quarter of the world's population. Therefore, understanding the molecular mechanisms underlying these conditions is of great importance. FK-506 binding protein 5 (FKBP5) encodes the FKBP51 protein, a heat shock protein 90 kDa (Hsp90) co-chaperone, and is a risk factor for several affective disorders. FKBP51, in coordination with Hsp90, regulates glucocorticoid receptor (GR) activity via a short negative feedback loop. This signalling pathway rapidly restores homeostasis in the hypothalamic-pituitary-adrenal (HPA) axis following stress...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29190830/reduced-functional-connectivity-of-fronto-parietal-sustained-attention-networks-in-severe-childhood-abuse
#5
Heledd Hart, Lena Lim, Mitul A Mehta, Antonia Chatzieffraimidou, Charles Curtis, Xiaohui Xu, Gerome Breen, Andrew Simmons, Kah Mirza, Katya Rubia
Childhood maltreatment is associated with attention deficits. We examined the effect of childhood abuse and abuse-by-gene (5-HTTLPR, MAOA, FKBP5) interaction on functional brain connectivity during sustained attention in medication/drug-free adolescents. Functional connectivity was compared, using generalised psychophysiological interaction (gPPI) analysis of functional magnetic resonance imaging (fMRI) data, between 21 age-and gender-matched adolescents exposed to severe childhood abuse and 27 healthy controls, while they performed a parametrically modulated vigilance task requiring target detection with a progressively increasing load of sustained attention...
2017: PloS One
https://www.readbyqxmd.com/read/29190094/active-glucocorticoids-have-a-range-of-important-adverse-developmental-and-physiological-effects-on-developing-zebrafish-embryos
#6
Raffael Alois Willi, Susanne Faltermann, Timm Hettich, Karl Fent
Glucocorticoids in aquatic systems originating from natural excretion and medical use may pose a risk to fish. Here, we analyzed physiological and transcriptional effects of clobetasol propionate (CLO), cortisol and cortisone in zebrafish embryos as single compounds and binary mixtures. CLO and cortisol, but not cortisone showed a concentration-dependent decrease in muscle contraction, increase in heart rate, and accelerated hatching. CLO also induced immobilization and edema at high concentrations. Transcription analysis covering up to 26 genes showed that mostly genes related to glucose metabolism, immune system and development were differentially expressed at 91 ng/L and higher...
December 22, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29189098/the-effects-of-ovarian-hormones-on-stressor-induced-hormonal-responses-glucocorticoid-receptor-expression-and-translocation-and-genes-related-to-receptor-signaling-in-adult-female-rats
#7
Matthew R Green, Marina L Marcolin, Cheryl M McCormick
Estradiol potentiates hypothalamic-pituitary-adrenal activity and delays the return of glucocorticoid secretion to baseline after a stressor exposure in female rats; we investigated whether estradiol effects involve actions on glucocorticoid receptor (GR) translocation and expression of receptor co-chaperones. In Experiment 1 intact females and ovariectomized (OVX) females were treated for four days with vehicle (VEH), 17β-estradiol benzoate (EB), or EB and progesterone (EB + P). Samples were taken from rats in the home cage (baseline) or after 30 min of restraint stress in a plastic restrainer (post-restraint) (n = 10/group)...
November 30, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29182159/epigenetic-changes-of-fkbp5-as-a-link-connecting-genetic-and-environmental-risk-factors-with-structural-and-functional-brain-changes-in-major-depression
#8
Leonardo Tozzi, Chloe Farrell, Linda Booij, Kelly Doolin, Zsofia Nemoda, Moshe Szyf, Florence B Pomares, Julian Chiarella, Veronica O'Keane, Thomas Frodl
The gene for the glucocorticoid receptor regulator FK506 binding protein 5 (FKBP5) plays a role for risk, response to treatment and changes in brain areas in major depressive disorder (MDD). Chronic stress is associated with lower methylation of FKBP5. Our aim was to investigate whether methylation of FKBP5 reflected exposure to childhood adversity in MDD and controls and whether it was associated with structure and function of emotional processing regions. FKBP5 intron 7 GR response element region methylation and rs1360780 allelic status were assessed from whole blood in 56 MDD adults and 50 controls...
November 28, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29180230/glucocorticoids-genes-and-brain-function
#9
REVIEW
Grzegorz R Juszczak, Adrian M Stankiewicz
The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
November 24, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29170369/stress-responsive-fkbp51-regulates-akt2-as160-signaling-and-metabolic-function
#10
Georgia Balsevich, Alexander S Häusl, Carola W Meyer, Stoyo Karamihalev, Xixi Feng, Max L Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen, Matthias H Tschöp, Theo Rein, Nils C Gassen, Mathias V Schmidt
The co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Here we show that FKBP51 plays a role in energy and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat diet-induced weight gain, show improved glucose tolerance and increased insulin signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist, SAFit2, recapitulates the effects of FKBP51 deletion on both body weight regulation and glucose tolerance...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29162190/early-life-stress-fk506-binding-protein-5-gene-fkbp5-methylation-and-inhibition-related-prefrontal-function-a-prospective-longitudinal-study
#11
Madeline B Harms, Rasmus Birn, Nadine Provencal, Tobias Wiechmann, Elisabeth B Binder, Sebastian W Giakas, Barbara J Roeber, Seth D Pollak
Individuals who have experienced high levels of childhood stress are at increased risk for a wide range of behavioral problems that persist into adulthood, yet the neurobiological and molecular mechanisms underlying these associations remain poorly understood. Many of the difficulties observed in stress-exposed children involve problems with learning and inhibitory control. This experiment was designed to test individuals' ability to learn to inhibit responding during a laboratory task. To do so, we measured stress exposure among a community sample of school-aged children, and then followed these children for a decade...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29162188/from-child-maltreatment-to-emerging-adult-problem-drinking-identification-of-a-multilevel-internalizing-pathway-among-african-american-youth
#12
Elizabeth D Handley, Fred A Rogosch, Dante Cicchetti
The present study tested the role of FKBP5 binding protein 5 (FKBP5) genetic variation in an internalizing pathway from child maltreatment to emerging adult problem drinking among a sample of African American youth (N = 280) followed prospectively from ages 11 to 20. Specifically, whether childhood internalizing symptoms and emerging adult tension reduction alcohol expectancies sequentially mediate the effect of child maltreatment on emerging adult problem drinking and whether FKBP5 moderates these associations were investigated...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29162173/change-in-fk506-binding-protein-5-fkbp5-methylation-over-time-among-preschoolers-with-adversity
#13
Stephanie H Parade, Justin Parent, Kantoniony Rabemananjara, Ronald Seifer, Carmen J Marsit, Bao-Zhu Yang, Huiping Zhang, Audrey R Tyrka
FK506 binding protein 5 (FKBP5) alters stress response system functioning, and childhood maltreatment is associated with methylation of the FKBP5 gene. Yet it is unknown if maltreatment contributes to change in FKBP5 methylation over time. The current study draws upon a sample of 231 preschoolers, including 123 with child welfare documentation of moderate to severe maltreatment in the past 6 months, to understand if maltreatment contributes to change in FKBP5 methylation over a 6-month period. Review of child protection records and semistructured interviews in the home were used to assess maltreatment and exposure to other contextual stressors, as well as service utilization...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29101603/hypothalamic-pituitary-adrenal-axis-variants-and-childhood-trauma-influence-anxiety-sensitivity-in-south-african-adolescents
#14
Jacqueline S Womersley, Lindi I Martin, Lize van der Merwe, Soraya Seedat, Sian M J Hemmings
Anxiety sensitivity (AS) is characterised by the fear of anxiety-related symptoms and is a risk factor for the development of anxiety-related disorders. We examined whether genetic variation in three stress response genes, CRHR1, NR3C1, and FKBP5, interact with childhood trauma (CT) to predict AS in South African adolescents. Xhosa (n = 634) and Coloured (n = 317) students completed self-report measures of AS and CT, and a total of eighteen polymorphisms within CRHR1, NR3C1, and FKBP5 were genotyped. Differences in AS based on genetic variation and CT were analysed within population and gender groups using multiple linear regression...
November 4, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29100496/gene-expression-profiling-of-upregulated-mrnas-in-granulosa-cells-of-bovine-ovulatory-follicles-following-stimulation-with-hcg
#15
Jacques G Lussier, Mame N Diouf, Valérie Lévesque, Jean Sirois, Kalidou Ndiaye
BACKGROUND: Ovulation and luteinization of follicles are complex biological processes initiated by the preovulatory luteinizing hormone surge. The objective of this study was to identify genes that are differentially expressed in bovine granulosa cells (GC) of ovulatory follicles. METHODS: Granulosa cells were collected during the first follicular wave of the bovine estrous cycle from dominant follicles (DF) and from ovulatory follicles (OF) obtained 24 h following injection of human chorionic gonadotropin (hCG)...
November 3, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/29084233/genetically-defined-elevated-homocysteine-levels-do-not-result-in-widespread-changes-of-dna-methylation-in-leukocytes
#16
Pooja R Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E Marioni, Vinh Truong, Lisette Stolk, Marian Beekman, Marc Jan Bonder, Lude Franke, Christian Gieger, Tianxiao Huan, M Arfan Ikram, Sonja Kunze, Liming Liang, Jan Lindemans, Chunyu Liu, Allan F McRae, Michael M Mendelson, Martina Müller-Nurasyid, Annette Peters, P Eline Slagboom, John M Starr, David-Alexandre Trégouët, André G Uitterlinden, Marleen M J van Greevenbroek, Diana van Heemst, Maarten van Iterson, Philip S Wells, Chen Yao, Ian J Deary, France Gagnon, Bastiaan T Heijmans, Daniel Levy, Pierre-Emmanuel Morange, Melanie Waldenberger, Sandra G Heil, Joyce B J van Meurs
BACKGROUND: DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation. METHODS: Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies...
2017: PloS One
https://www.readbyqxmd.com/read/29075152/lps-regulates-the-expression-of-glucocorticoid-receptor-%C3%AE-and-%C3%AE-isoforms-and-induces-a-selective-glucocorticoid-resistance-in-vitro
#17
Maria Luisa Molina, Julia Guerrero, John A Cidlowski, Héctor Gatica, Annelise Goecke
BACKGROUND: This study was aimed to evaluate the effect of LPS in glucocorticoid receptor (GR) isoforms expression on different cell lines and PBMC from healthy donors in vitro and glucocorticoid sensitivity of PBMC in vitro. METHODS: U-2 OS cell lines expressing GR isoforms, different cell lines (CEM, RAJI, K562 and HeLa) or PBMC from healthy donors, were cultured or not with LPS. The expression of GRα and GRβ was evaluated by Western blot. Glucocorticoid sensitivity was evaluated in PBMC treated with LPS, testing genes which are transactivated or transrepressed by glucocorticoid...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/29074884/evidence-for-stress-like-alterations-in-the-hpa-axis-in-women-taking-oral-contraceptives
#18
Johannes Hertel, Johanna König, Georg Homuth, Sandra Van der Auwera, Katharina Wittfeld, Maik Pietzner, Tim Kacprowski, Liliane Pfeiffer, Anja Kretschmer, Melanie Waldenberger, Gabi Kastenmüller, Anna Artati, Karsten Suhre, Jerzy Adamski, Sönke Langner, Uwe Völker, Henry Völzke, Matthias Nauck, Nele Friedrich, Hans Joergen Grabe
Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased circulating cortisol levels in those using oral contraceptives. For women taking oral contraceptives, we observed alterations in circulating phospholipid levels and elevated triglycerides and found evidence for increased glucocorticoid signalling as the transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were increased in whole blood...
October 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056292/epigenetics-and-gene-expression-profile-in-first-episode-psychosis-the-role-of-childhood-trauma
#19
REVIEW
Simona Tomassi, Sarah Tosato
Childhood Trauma (CT) mediation of the epigenome and its impact on gene expression profile could provide a mechanism for the gene-environment interaction underling psychosis. We reviewed the evidence concerning epigenetic and gene expression modifications associated with CT in both First-Episode Psychosis (FEP) and healthy subjects. In order to explore the relative role of psychosis itself in determining these modifications, evidence about FEP and epigenetics/gene expression was also summarized. We performed a systematic search on PubMed, last updated in December 2016...
October 19, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29052817/androgen-signaling-in-esophageal-adenocarcinoma-cell-lines-in-vitro
#20
Helen M Palethorpe, Paul A Drew, Eric Smith
BACKGROUND: We showed previously that nuclear localization of the androgen receptor (AR) and expression of the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma (EAC) tissues were associated with decreased patient survival, suggesting a role for androgens in this cancer. AIM: To investigate the effect of the AR ligand 5α-dihydrotestosterone (DHT) on AR-expressing EAC cell lines in vitro. METHODS AND RESULTS: In tissue resection specimens from EAC patients, FKBP5 expression was positively associated with proliferation as measured by Ki-67 expression...
December 2017: Digestive Diseases and Sciences
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