Abstract
The heritability of major depression has been documented in a number of epidemiologic studies. Twin studies have estimated the heritability at about 37% and these estimation can rise up to 70% if severity, relapse rate and age of onset are considered. Despite the relative importance of genetic risk factors in the pathogenesis of this disease, molecular genetic studies, including large genome-wide association studies, only a very small number of candidate genes, explaining little of the variance have been identified. This fact has been termed “missing heritability” and could be accounted by a number of factors including that the presumed causal variants are not tagged by the current genetic approaches, that major depression is truly polygenic, with each polymorphism only contributing very small increases in risk, unaccounted environmental influences and complex epigenetic factors. Epigenetics refers to the regulation of DNA transcription without alteration of the original sequence and is controlled by DNA methylation, histone modifications and non-coding RNAs and can be transmitted through generations. A number of clinical and preclinical studies suggest that epigenetic mechanisms could play an important role in the pathogenesis and treatment of major depression. So far, most studies investigated genes within the hypothalamicpituitary- adrenal (HPA) axis or the neurotrophin system. It is also of interest that current psychopharmacologic drugs including antidepressants, antipsychotics and mood stabilizers may exert some of their effects by inducing epigenetic changes. Most notably, epigenetic alterations are potentially reversible and accessibe for drug treatment, which lead to the development of novel classes of antidepressant drugs.
Keywords: Major depression, gene, epigenetic, GWAS, antidepressant missing heritability, SNP, HPA-axis, relapse rate, age of onset, neurotrophin system
Current Pharmaceutical Design
Title:Epigenetics, Depression and Antidepressant Treatment
Volume: 18 Issue: 36
Author(s): Andreas Menke, Torsten Klengel and Elisabeth B. Binder
Affiliation:
Keywords: Major depression, gene, epigenetic, GWAS, antidepressant missing heritability, SNP, HPA-axis, relapse rate, age of onset, neurotrophin system
Abstract: The heritability of major depression has been documented in a number of epidemiologic studies. Twin studies have estimated the heritability at about 37% and these estimation can rise up to 70% if severity, relapse rate and age of onset are considered. Despite the relative importance of genetic risk factors in the pathogenesis of this disease, molecular genetic studies, including large genome-wide association studies, only a very small number of candidate genes, explaining little of the variance have been identified. This fact has been termed “missing heritability” and could be accounted by a number of factors including that the presumed causal variants are not tagged by the current genetic approaches, that major depression is truly polygenic, with each polymorphism only contributing very small increases in risk, unaccounted environmental influences and complex epigenetic factors. Epigenetics refers to the regulation of DNA transcription without alteration of the original sequence and is controlled by DNA methylation, histone modifications and non-coding RNAs and can be transmitted through generations. A number of clinical and preclinical studies suggest that epigenetic mechanisms could play an important role in the pathogenesis and treatment of major depression. So far, most studies investigated genes within the hypothalamicpituitary- adrenal (HPA) axis or the neurotrophin system. It is also of interest that current psychopharmacologic drugs including antidepressants, antipsychotics and mood stabilizers may exert some of their effects by inducing epigenetic changes. Most notably, epigenetic alterations are potentially reversible and accessibe for drug treatment, which lead to the development of novel classes of antidepressant drugs.
Export Options
About this article
Cite this article as:
Menke Andreas, Klengel Torsten and B. Binder Elisabeth, Epigenetics, Depression and Antidepressant Treatment, Current Pharmaceutical Design 2012; 18 (36) . https://dx.doi.org/10.2174/138161212803523590
DOI https://dx.doi.org/10.2174/138161212803523590 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- 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
-
Ultrasound Assisted Synthesis of 2-alkynyl Pyrazolo[1,5-a]pyrimidines as Potential Anti-cancer Agents
Letters in Drug Design & Discovery Recent Advances in Diagnostic and Therapeutic Approaches for Breast Cancer: A Comprehensive Review
Current Pharmaceutical Design Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets Recent Advances in Biological Tissue Imaging with Time-of-Flight Secondary Ion Mass Spectrometry: Polyatomic Ion Sources, Sample Preparation, and Applications
Current Pharmaceutical Design A Functional Scaffold in Marine Alkaloid: An Anticancer Moiety for Human
Current Medicinal Chemistry Interplay between the APOE Genotype and Possible Plasma Biomarkers in Alzheimer’s Disease
Current Alzheimer Research Antiproliferative Effects of Molecular Iodine in Cancers
Current Chemical Biology Tumor Promoters - Microcystin-LR, Nodularin and TNF-α and Human Cancer Development
Anti-Cancer Agents in Medicinal Chemistry Are the Antioxidant Properties of Carvedilol Important for the Protection of Cardiac Mitochondria?
Current Vascular Pharmacology Biotransformation of Microcystins in Eukaryotic Cells - Possible Future Research Directions
Mini-Reviews in Medicinal Chemistry Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer’s Diseases
Current Alzheimer Research Apoptosis-Inducing Effects of Amaryllidaceae Alkaloids
Current Medicinal Chemistry Ras-Induced Resistance to Lapatinib is Overcome by MEK Inhibition
Current Cancer Drug Targets Evaluation of the Anticancer Activities of the Plant Alkaloids Sanguinarine and Chelerythrine in Human Breast Adenocarcinoma Cells
Anti-Cancer Agents in Medicinal Chemistry Immunoproteasome in Cancer and Neuropathologies: A New Therapeutic Target?
Current Pharmaceutical Design Combining Angiogenesis Inhibitors with Radiation: Advances and Challenges in Cancer Treatment
Current Pharmaceutical Design Positron Emission Tomography Imaging of Tumor Hypoxia
Current Medical Imaging Molecular Chaperone Activity and Biological Regulatory Actions of the TPR-Domain Immunophilins FKBP51 and FKBP52
Current Protein & Peptide Science Pleiotropic Effects of Cathepsin D
Endocrine, Metabolic & Immune Disorders - Drug Targets Current Management of Fetal and Neonatal Renal Tumors
Current Pediatric Reviews