Abstract
Early life adversity is associated with both persistent disruptions in the hypothalamicpituitary- adrenal (HPA) axis and psychiatric symptoms. Glucocorticoid receptors (GRs), which are encoded by the NR3C1 gene, bind to cortisol and other glucocorticoids to create a negative feedback loop within the HPA axis to regulate the body’s neuroendocrine response to stress. Excess methylation of a promoter sequence within NR3C1 that attenuates GR expression, however, has been associated with both early life adversity and psychopathology. As critical regulators within the HPA axis, GRs and their epigenetic regulation may mediate the link between early life adversity and the onset of psychopathology. The present review discusses this work as one mechanism by which stress may get under the skin to disrupt HPA functioning at an epigenetic level and create long-lasting vulnerabilities in the stress regulatory system that subsequently predispose individuals to psychopathology. Spanning prenatal influences to critical periods of early life and adolescence, we detail the impact that early adversity has on GR expression, physiological responses to stress, and their implications for long-term stress management. We next propose a dual transmission hypothesis regarding both genomic and nongenomic mechanisms by which chronic and acute stress propagate through numerous generations. Lastly, we outline several directions for future research, including potential reversibility of methylation patterns and its functional implications, variation in behavior determined solely by NR3C1, and consensus on which specific promoter regions should be studied.
Keywords: NR3C1, HPA axis, Stress, Glucocorticoid receptor, Psychopathology, Methylation.
Current Genomics
Title:How Stress Gets Under the Skin: Early Life Adversity and Glucocorticoid Receptor Epigenetic Regulation
Volume: 19 Issue: 8
Author(s): Patrick Z. Liu*Robin Nusslock
Affiliation:
- Department of Psychology, Northwestern University, Evanston, IL 60208,United States
Keywords: NR3C1, HPA axis, Stress, Glucocorticoid receptor, Psychopathology, Methylation.
Abstract: Early life adversity is associated with both persistent disruptions in the hypothalamicpituitary- adrenal (HPA) axis and psychiatric symptoms. Glucocorticoid receptors (GRs), which are encoded by the NR3C1 gene, bind to cortisol and other glucocorticoids to create a negative feedback loop within the HPA axis to regulate the body’s neuroendocrine response to stress. Excess methylation of a promoter sequence within NR3C1 that attenuates GR expression, however, has been associated with both early life adversity and psychopathology. As critical regulators within the HPA axis, GRs and their epigenetic regulation may mediate the link between early life adversity and the onset of psychopathology. The present review discusses this work as one mechanism by which stress may get under the skin to disrupt HPA functioning at an epigenetic level and create long-lasting vulnerabilities in the stress regulatory system that subsequently predispose individuals to psychopathology. Spanning prenatal influences to critical periods of early life and adolescence, we detail the impact that early adversity has on GR expression, physiological responses to stress, and their implications for long-term stress management. We next propose a dual transmission hypothesis regarding both genomic and nongenomic mechanisms by which chronic and acute stress propagate through numerous generations. Lastly, we outline several directions for future research, including potential reversibility of methylation patterns and its functional implications, variation in behavior determined solely by NR3C1, and consensus on which specific promoter regions should be studied.
Export Options
About this article
Cite this article as:
Liu Z. Patrick*, Nusslock Robin , How Stress Gets Under the Skin: Early Life Adversity and Glucocorticoid Receptor Epigenetic Regulation, Current Genomics 2018; 19 (8) . https://dx.doi.org/10.2174/1389202919666171228164350
DOI https://dx.doi.org/10.2174/1389202919666171228164350 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Advanced AI Techniques in Big Genomic Data Analysis
The thematic issue on "Advanced AI Techniques in Big Genomic Data Analysis" aims to explore the cutting-edge methodologies and applications of artificial intelligence (AI) in the realm of genomic research, where vast amounts of data pose both challenges and opportunities. This issue will cover a broad spectrum of AI-driven strategies, ...read more
Advanced Computational Algorithms and Artificial Intelligence in Clinical Pharmacogenomics
In the era of personalized medicine, understanding the relationship between genetics and drug response is crucial. This issue delves into innovative methodologies, leveraging deep computational analysis and artificial intelligence, to enhance the field of Clinical Pharmacogenomics. The interdisciplinary approach harnesses the power of advanced high-throughput genotyping technologies, sophisticated computational analysis, ...read more
Applications of Single-cell Sequencing Technology in Reproductive Medicine
Single cell sequencing (SCS) technology utilizes individual cells' genetic material to sequence their genome, transcriptome, and epigenetics at the molecular level. It offers insights into cell heterogeneity and enables the study of limited biological materials. Since its recognition as a valuable technique in 2011, single cell sequencing has yielded numerous ...read more
Big Data in Cancer Research
Cancer is a significant threat to human life and health, remaining a highly aggressive killer. It is a leading cause of death worldwide and represents a crucial medical issue for humanity. However, in the past decade, the effectiveness of new synthetic anticancer agents has not matched the current clinical speculation. ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Ketamine-Induced Neurotoxicity and Changes in Gene Expression in the Developing Rat Brain
Current Neuropharmacology Alcoholic Neuropathy: Involvement of Multifaceted Signalling Mechanisms
Current Molecular Pharmacology Immunobiologic Agents in Dermatology
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Micro-RNA in Disease and Gene Therapy
Current Drug Discovery Technologies Fructose-1,6-bisphosphatase Inhibitors: A Review of Recent (2000- 2017) Advances and Structure-Activity Relationship Studies
Current Medicinal Chemistry Positron Emission Tomography: Applications In Drug Discovery and Drug Development
Current Topics in Medicinal Chemistry Drugs as Possible Triggers of Takotsubo Cardiomyopathy: A Comprehensive Literature Search - Update 2015
Current Clinical Pharmacology Frequency of Depression and its Correlation with Serum Carnitine Level in HIV/AIDS Patients
Current HIV Research Multitarget Therapeutic Effect of Fasudil in APP/PS1transgenic Mice
CNS & Neurological Disorders - Drug Targets Role of Monitoring Thiopurine Methyltransferase (TPMT) Activity in the Individualized Therapy with Azathioprine or 6-Mercaptopurine
Current Pharmacogenomics and Personalized Medicine Using Protein-protein Interaction Network Information to Predict the Subcellular Locations of Proteins in Budding Yeast
Protein & Peptide Letters Targeting Proteasomes with Naturally Occurring Compounds in Cancer Treatment
Current Cancer Drug Targets Social Behavior as an Endophenotype for Psychiatric Disorders Development of Mouse Models
Current Genomics Gap Junctions as Therapeutic Targets in Brain Injury Following Hypoxia- Ischemia
Recent Patents on CNS Drug Discovery (Discontinued) Insulin Therapy for Improving Cardiac Surgical Outcomes
Current Drug Targets Update on the Biologic Role of the Vitamin D Endocrine System
Current Vascular Pharmacology Commentary: Gut Microbiota and Brain Function: A New Target for Brain Diseases?
CNS & Neurological Disorders - Drug Targets Editorial
Adolescent Psychiatry Substance-Related and Addictive Disorders as a Risk Factor of Suicide and Homicide among Patients with ADHD: A Mini Review
Current Drug Abuse Reviews Functional Switch From Pro-Neurotrophins to Mature Neurotrophins
Current Protein & Peptide Science