A Caspi

A Gladkevich

A Steptoe

Ariel Knafo

B Rollins

BM Kudielka

BM Way

BS McEwen

C Kirschbaum

D Moser

DA Lewis

David Mankuta

EA Young

EE Sundermann

FA Champagne

Florina Uzefovsky

G Miller

G Weidner

GE Miller

GP Chrousos

H Lefebvre

I Shalev

IC Weaver

Idan Shalev

IH Gotlib

Ilana Kremer

IMH van

IS Federenko

J Tost

JB Mitchell

JD Turner

JJ Walker

JP Herman

JV Seale

L Pan

L Sher

L Westberg

LA Weiss

LC Klein

M Bartels

Marsha Kaitz

MB Solomon

MJ Meaney

MJ Weiser

MR Munafo

N Nicolson

N Risch

NC Vamvakopoulos

P Laplante

PO McGowan

Qing Song

R Kumsta

R Philibert

R Uher

RA Philibert

RH Belmaker

RH Oakley

Richard P. Ebstein

RM Shansky

S Wust

Salomon Israel

Shany Edelman

SR Alt

SR Bornstein

SS Dickerson

T Canli

TF Oberlander

TG Dinan

U Moser

VK Patchev

WJ Miller

WR Lovallo

Y Chida

ZA Kaminsky

PLoS ONE

PubMed

Crossref

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (NR3C1) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress

Richard P Ebstein

Directory of Open Access Journals

Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self.

Edelman Shany

Shalev Idan

Uzefovsky Florina

Israel Salomon

Knafo Ariel

Kremer Ilana

Mankuta David

Kaitz Marsha

Ebstein Richard P.

Public Library of Science (PLOS)

<div><p>Evidence suggests that the reactivity of the Hypothalamus-Pituitary-Adrenal axis (HPAA) is modulated by both genetic and environmental variables. Of special interest are the underlying molecular mechanisms driving gender differences to psychosocial stressors. Epigenetic mechanisms that sculpt the genome are ideal candidates for mediating the effects of signals on the HPAA. In the current study, we analyzed by pyrosequencing, bisulfite-treated buccal DNA from male and female university students who participated in the Trier Social Stress Test (TSST). A linear regression model was used to ascertain the effects of sex, CpG methylation and genes on stress response. Total cortisol output (area under the curve, AUC) was significantly predicted by glucocorticoid receptor (<em>NR3C1</em>) exon 1F methylation (averaged across 39 CpG sites) solely in female subjects. A single CpG site located in the exon 1F noncanonical nerve growth factor-inducible protein A (NGFI-A) transcription factor was a highly significant predictor of AUC in female subjects. Additionally, variations in the estrogen receptor alpha (ESR1) and the serotonin transporter promoter (5-HTTLPR) genes were independent additive predictors of AUC. The full model accounted for half of the variance (50.06%) in total cortisol output. Notably, this is the first demonstration that epigenetic changes at the GR exon 1F correlate with HPAA reactivity. These findings have important implications for understanding the molecular mechanisms underlying gender differences in stress-related disorders and underscore the unique value of modeling both epigenetic and genetic information in conferring vulnerability to stress.</p> </div

Shany Edelman (119200)

Idan Shalev (119204)

Florina Uzefovsky (119208)

Salomon Israel (119212)

Ariel Knafo (119217)

Ilana Kremer (119222)

David Mankuta (119226)

Marsha Kaitz (119229)

Richard P. Ebstein (115583)

The Francis Crick Institute

A review of estrogen receptor alpha gene (ESR1) polymorphisms, mood, and cognition.

Activation of 5-HT1A receptor subtype in the paraventricular nuclei of the hypothalamus induces CRH and ACTH release in the rat.

Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research.

Analysis of whole genome biomarker expression in blood and brain.

Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women.

BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.

Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness.

Characterization of a glucocorticoid receptor gene (GR, NR3C1) promoter polymorphism reveals functionality and extends a haplotype with putative clinical relevance.

Chronic psychosocial factors and acute physiological responses to laboratory-induced stress in healthy populations: a quantitative review of 30 years of investigations.

Common polymorphisms in the glucocorticoid receptor gene are associated with adrenocortical responses to psychosocial stress.

Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women.

de Geus EJ (2003) Heritability of cortisol levels: review and simultaneous analysis of twin studies.

Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed.

DNA methylation analysis by pyrosequencing.

DNA methylation profiles in monozygotic and dizygotic twins.

Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome.

Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health.

Epigenetic programming by maternal behavior.

Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.

Estrogen impairs glucocorticoid dependent negative feedback on the hypothalamic-pituitary-adrenal axis via estrogen receptor alpha within the hypothalamus.

Estrogen receptor (ER)beta isoforms rather than ERalpha regulate corticotropin-releasing hormone promoter activity through an alternate pathway.

Estrogen, stress and the brain: progress toward unraveling gender discrepancies in major depressive disorder.

Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/ inflammatory reaction.

Gender specificity in the neural regulation of the response to stress: new leads from classical paradigms.

Gene x Environment Interactions at the Serotonin Transporter Locus. Biol Psychiatry.

Glucocorticoid receptor gene polymorphisms and glucocorticoid sensitivity of subdermal blood vessels and leukocytes. Biol Psychol.

Glucocorticoid signaling in the cell. Expanding clinical implications to complex human behavioral and somatic disorders.

Gonadal steroid replacement reverses gonadectomy-induced changes in the corticosterone pulse profile and stress-induced hypothalamic-pituitary-adrenal axis activity of male and female rats.

Health psychology: developing biologically plausible models linking the social world and physical health.

Homologous down regulation of the glucocorticoid receptor: the molecular machinery.

HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression. Biol Psychiatry.

Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women.

Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis.

Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene.

Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.

Long story short: the serotonin transporter in emotion regulation and social cognition.

Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling.

Lymphocytes as a neural probe: potential for studying psychiatric disorders.

Major depressive disorder.

Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring.

Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma.

Natural variations in maternal care are associated with estrogen receptor alpha expression and estrogen sensitivity in the medial preoptic area.

Origin of ultradian pulsatility in the hypothalamic-pituitary-adrenal axis.

Positive affect and psychobiological processes relevant to health.

Postnatal masculinization alters the HPA axis phenotype in the adult female rat.

Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses.

Role of genotype in the cycle of violence in maltreated children.

Salivary cortisol levels and stress reactivity in human aging.

Seeing the unexpected: how sex differences in stress responses may provide a new perspective on the manifestation of psychiatric disorders.

Serotonin and the regulation of hypothalamic-pituitaryadrenal axis function.

Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-HT7 receptor.

Serotonin transporter mRNA levels are associated with the methylation of an upstream CpG island.

Serotonin-induced stimulation of cortisol secretion from human adrenocortical tissue is mediated through activation of a serotonin4 receptor subtype.

Sex differences in HPA axis responses to stress: a review.

Sex differences in psychopathology: Of gonads, adrenals and mental illness. Physiol Behav.

Sex-specific association between the 5-HTT gene-linked polymorphic region and basal cortisol secretion.

Social influences on health: is serotonin a critical mediator?

Stress, social support and health-related behavior: a study of smoking, alcohol consumption and physical exercise.

Structure of the glucocorticoid receptor (NR3C1) gene 59 untranslated region: identification, and tissue distribution of multiple new human exon 1.

The ‘Trier Social Stress Test’–a tool for investigating psychobiological stress responses in a laboratory setting.

The gender gap in heart disease: lessons from Eastern Europe.

The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFIA binding site in human hippocampus.

The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent.

The human brain revisited: opportunities and challenges in postmortem studies of psychiatric disorders.

The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression:

The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies.

The role of gonadal steroids in hypothalamic-pituitary-adrenal axis regulation.

The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus.

The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress.

The sex-specific genetic architecture of quantitative traits in humans.

The transcription factor nerve growth factor-inducible protein a mediates epigenetic programming: altering epigenetic marks by immediate-early genes.

Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochem Pharmacol.

Type D personality: the heart, stress, and cortisol.

Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge.

http://scholarbank.nus.edu.sg/bitstream/10635/49860/3/2012-Epigenetic_and_Genetic_Factors_Predict-published.PDF

Epigenetic and Genetic Factors Predict Women's Salivary Cortisol following a Threat to the Social Self

Abstract

Similar works

Full text

Available Versions

Crossref

Directory of Open Access Journals

Public Library of Science (PLOS)

The Francis Crick Institute