Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/enestler
Angélica Torres-Berrío, Orna Issler, Eric M Parise, Eric J Nestler
Depression is a devastating psychiatric disorder caused by a combination of genetic predisposition and life events, mainly exposure to stress. Early life stress (ELS) in particular is known to "scar" the brain, leading to an increased susceptibility to developing depression later in life via epigenetic mechanisms. Epigenetic processes lead to changes in gene expression that are not due to changes in DNA sequence, but achieved via modulation of chromatin modifications, DNA methylation, and noncoding RNAs. Here we review common epigenetic mechanisms including the enzymes that take part in reading, writing, and erasing specific epigenetic marks. We then describe recent developments in understanding how ELS leads to changes in the epigenome that are manifested in increased susceptibility to depression-like abnormalities in animal models. We conclude with highlighting the need for future studies that will potentially enable the utilisation of the understanding of epigenetic changes linked to ELS for the development of much-needed novel therapeutic strategies and biomarker discovery. .
抑郁症是一种毁灭性的精神疾病,由遗传易感性和生活事件(主要是面临的压力)共同造成。众所周知,早期生活压力(ELS)会给大脑留下 "疤痕",从而通过表观遗传机制增加日后患抑郁症的几率。表观遗传过程会导致基因表达的改变,而这些改变并不是由于 DNA 序列的改变,而是通过染色质修饰、DNA 甲基化和非编码 RNA 的调节实现的。在此,我们回顾了常见的表观遗传机制,包括参与读取、书写和清除特定表观遗传标记的酶。然后,我们将介绍在了解 ELS 如何导致表观基因组变化方面的最新进展,这些变化在动物模型中表现为抑郁症样异常的易感性增加。最后,我们强调了未来研究的必要性,这些研究将有可能利用对与 ELS 相关的表观遗传变化的了解来开发急需的新型治疗策略和发现生物标志物。.
{"title":"Unraveling the epigenetic landscape of depression: focus on early life stress\u2029.","authors":"Angélica Torres-Berrío, Orna Issler, Eric M Parise, Eric J Nestler","doi":"10.31887/DCNS.2019.21.4/enestler","DOIUrl":"10.31887/DCNS.2019.21.4/enestler","url":null,"abstract":"<p><p>Depression is a devastating psychiatric disorder caused by a combination of genetic predisposition and life events, mainly exposure to stress. Early life stress (ELS) in particular is known to \"scar\" the brain, leading to an increased susceptibility to developing depression later in life via epigenetic mechanisms. Epigenetic processes lead to changes in gene expression that are not due to changes in DNA sequence, but achieved via modulation of chromatin modifications, DNA methylation, and noncoding RNAs. Here we review common epigenetic mechanisms including the enzymes that take part in reading, writing, and erasing specific epigenetic marks. We then describe recent developments in understanding how ELS leads to changes in the epigenome that are manifested in increased susceptibility to depression-like abnormalities in animal models. We conclude with highlighting the need for future studies that will potentially enable the utilisation of the understanding of epigenetic changes linked to ELS for the development of much-needed novel therapeutic strategies and biomarker discovery.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/68/e9/DialoguesClinNeurosci-21-341.PMC6952747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/kressler
Hunter Howie, Chuda M Rijal, Kerry J Ressler
Post-traumatic stress disorder (PTSD) is a syndrome which serves as a classic example of psychiatric disorders that result from the intersection of nature and nurture, or gene and environment. By definition, PTSD requires the experience of a traumatic exposure, and yet data suggest that the risk for PTSD in the aftermath of trauma also has a heritable (genetic) component. Thus, PTSD appears to require both a biological (genetic) predisposition that differentially alters how the individual responds to or recovers from trauma exposure. Epigenetics is defined as the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself, and more recently it has come to refer to direct alteration of DNA regulation, but without altering the primary sequence of DNA, or the genetic code. With regards to PTSD, epigenetics provides one way for environmental exposure to be "written" upon the genome, as a direct result of gene and environment (trauma) interactions. This review provides an overview of the main currently understood types of epigenetic regulation, including DNA methylation, histone regulation of chromatin, and noncoding RNA regulation of gene expression. Furthermore, we examine recent literature related to how these methods of epigenetic regulation may be involved in differential risk and resilience for PTSD in the aftermath of trauma. .
创伤后应激障碍(PTSD)是一种综合症,是自然与养育或基因与环境交织导致精神障碍的典型例子。顾名思义,创伤后应激障碍需要经历创伤,但数据表明,创伤后应激障碍的风险也有遗传(基因)因素。因此,创伤后应激障碍似乎需要生物(遗传)易感性,这种易感性会不同程度地改变个体对创伤暴露的反应或恢复方式。表观遗传学被定义为研究通过改变基因表达而不是改变遗传密码本身所引起的生物体变化,最近它开始指直接改变 DNA 的调节,但不改变 DNA 的主要序列或遗传密码。就创伤后应激障碍而言,表观遗传学提供了一种将环境暴露 "写入 "基因组的方法,这是基因与环境(创伤)相互作用的直接结果。本综述概述了目前已知的主要表观遗传调控类型,包括 DNA 甲基化、染色质的组蛋白调控和基因表达的非编码 RNA 调控。此外,我们还研究了与这些表观遗传调控方法如何参与创伤后创伤后应激障碍的不同风险和恢复力相关的最新文献。.
{"title":"A review of epigenetic contributions \u2028to post-traumatic stress disorder\u2029.","authors":"Hunter Howie, Chuda M Rijal, Kerry J Ressler","doi":"10.31887/DCNS.2019.21.4/kressler","DOIUrl":"10.31887/DCNS.2019.21.4/kressler","url":null,"abstract":"<p><p>Post-traumatic stress disorder (PTSD) is a syndrome which serves as a classic example of psychiatric disorders that result from the intersection of nature and nurture, or gene and environment. By definition, PTSD requires the experience of a traumatic exposure, and yet data suggest that the risk for PTSD in the aftermath of trauma also has a heritable (genetic) component. Thus, PTSD appears to require both a biological (genetic) predisposition that differentially alters how the individual responds to or recovers from trauma exposure. Epigenetics is defined as the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself, and more recently it has come to refer to direct alteration of DNA regulation, but without altering the primary sequence of DNA, or the genetic code. With regards to PTSD, epigenetics provides one way for environmental exposure to be \"written\" upon the genome, as a direct result of gene and environment (trauma) interactions. This review provides an overview of the main currently understood types of epigenetic regulation, including DNA methylation, histone regulation of chromatin, and noncoding RNA regulation of gene expression. Furthermore, we examine recent literature related to how these methods of epigenetic regulation may be involved in differential risk and resilience for PTSD in the aftermath of trauma.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/37/78/DialoguesClinNeurosci-21-417.PMC6952751.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/pkenny
Purva Bali, Paul J Kenny
Drugs of abuse can modify gene expression in brain reward and motivation centers, which contribute to the structural and functional remodeling of these circuits that impacts the emergence of a state of addiction. Our understanding of how addictive drugs induce transcriptomic plasticity in addiction-relevant brain regions, particularly in the striatum, has increased dramatically in recent years. Intracellular signaling machineries, transcription factors, chromatin modifications, and regulatory noncoding RNAs have all been implicated in the mechanisms through which addictive drugs act in the brain. Here, we briefly summarize some of the molecular mechanisms through which drugs of abuse can exert their transcriptional effects in the brain region, with an emphasis on the role for microRNAs in this process. .
{"title":"Transcriptional mechanisms of drug addiction\u2029.","authors":"Purva Bali, Paul J Kenny","doi":"10.31887/DCNS.2019.21.4/pkenny","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/pkenny","url":null,"abstract":"<p><p>Drugs of abuse can modify gene expression in brain reward and motivation centers, which contribute to the structural and functional remodeling of these circuits that impacts the emergence of a state of addiction. Our understanding of how addictive drugs induce transcriptomic plasticity in addiction-relevant brain regions, particularly in the striatum, has increased dramatically in recent years. Intracellular signaling machineries, transcription factors, chromatin modifications, and regulatory noncoding RNAs have all been implicated in the mechanisms through which addictive drugs act in the brain. Here, we briefly summarize some of the molecular mechanisms through which drugs of abuse can exert their transcriptional effects in the brain region, with an emphasis on the role for microRNAs in this process.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/75/DialoguesClinNeurosci-21-379.PMC6952748.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/fthibaut
Florence Thibaut
Most studies describing epigenetic modifications have focused on DNA methylation, but fewer studies have focused on histone modifications and noncoding RNAs. Chromatin architecture and CCCTC-binding factor represent important noncoding regulatory elements that warrant further investigation in order to improve our understanding of the genomic basis of complex diseases such as psychiatric disorders. .
{"title":"Epigenetics: the missing link between genes and psychiatric disorders?\u2029.","authors":"Florence Thibaut","doi":"10.31887/DCNS.2019.21.4/fthibaut","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/fthibaut","url":null,"abstract":"<p><p>Most studies describing epigenetic modifications have focused on DNA methylation, but fewer studies have focused on histone modifications and noncoding RNAs. Chromatin architecture and CCCTC-binding factor represent important noncoding regulatory elements that warrant further investigation in order to improve our understanding of the genomic basis of complex diseases such as psychiatric disorders.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/5d/DialoguesClinNeurosci-21-337.PMC6952746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/jday
Jeremy J Day
Numerous neuronal functions depend on the precise spatiotemporal regulation of gene expression, and the cellular machinery that contributes to this regulation is frequently disrupted in neurodevelopmental, neuropsychiatric, and neurological disease states. Recent advances in gene editing technology have enabled increasingly rapid understanding of gene sequence variation and gene regulatory function in the central nervous system. Moreover, these tools have provided new insights into the locus-specific functions of epigenetic modifications and enabled epigenetic editing at specific gene loci in disease contexts. Continued development of clustered regularly interspaced short palindromic repeats (CRISPR)-based tools has provided not only cell-specific modulation, but also rapid induction profiles that permit sophisticated interrogation of the temporal dynamics that contribute to brain health and disease. This review summarizes recent advances in genetic editing, transcriptional modulation, and epigenetic reorganization, with a focus on applications to neuronal systems and potential uses in brain disorders characterized by genetic sequence variation or transcriptional dysregulation. .
{"title":"Genetic and epigenetic editing in\u2028nervous system\u2029.","authors":"Jeremy J Day","doi":"10.31887/DCNS.2019.21.4/jday","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/jday","url":null,"abstract":"<p><p>Numerous neuronal functions depend on the precise spatiotemporal regulation of gene expression, and the cellular machinery that contributes to this regulation is frequently disrupted in neurodevelopmental, neuropsychiatric, and neurological disease states. Recent advances in gene editing technology have enabled increasingly rapid understanding of gene sequence variation and gene regulatory function in the central nervous system. Moreover, these tools have provided new insights into the locus-specific functions of epigenetic modifications and enabled epigenetic editing at specific gene loci in disease contexts. Continued development of clustered regularly interspaced short palindromic repeats (CRISPR)-based tools has provided not only cell-specific modulation, but also rapid induction profiles that permit sophisticated interrogation of the temporal dynamics that contribute to brain health and disease. This review summarizes recent advances in genetic editing, transcriptional modulation, and epigenetic reorganization, with a focus on applications to neuronal systems and potential uses in brain disorders characterized by genetic sequence variation or transcriptional dysregulation.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/d5/DialoguesClinNeurosci-21-359.PMC6952749.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/mszyf
Moshe Szyf
Early life adversity is associated with long-term effects on physical and mental health later in life, but the mechanisms are yet unclear. Epigenetic mechanisms program cell-type-specific gene expression during development, enabling one genome to be programmed in many ways, resulting in diverse stable profiles of gene expression in different cells and organs in the body. DNA methylation, an enzymatic covalent modification of DNA, has been one of the principal epigenetic mechanisms investigated. Emerging evidence is consistent with the idea that epigenetic processes are involved in embedding the impact of early-life experience in the genome and mediating between social environments and later behavioral phenotypes. Whereas there is evidence supporting this hypothesis in animal studies, human studies have been less conclusive. A major problem is the fact that the brain is inaccessible to epigenetic studies in humans and the relevance of DNA methylation in peripheral tissues to behavioral phenotypes has been questioned. In addition, human studies are usually confounded with genetic and environmental heterogeneity and it is very difficult to derive causality. The idea that epigenetic mechanisms mediate the life-long effects of perinatal adversity has attractive potential implications for early detection, prevention, and intervention in mental health disorders will be discussed. .
{"title":"The epigenetics of perinatal stress\u2029.","authors":"Moshe Szyf","doi":"10.31887/DCNS.2019.21.4/mszyf","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/mszyf","url":null,"abstract":"<p><p>Early life adversity is associated with long-term effects on physical and mental health later in life, but the mechanisms are yet unclear. Epigenetic mechanisms program cell-type-specific gene expression during development, enabling one genome to be programmed in many ways, resulting in diverse stable profiles of gene expression in different cells and organs in the body. DNA methylation, an enzymatic covalent modification of DNA, has been one of the principal epigenetic mechanisms investigated. Emerging evidence is consistent with the idea that epigenetic processes are involved in embedding the impact of early-life experience in the genome and mediating between social environments and later behavioral phenotypes. Whereas there is evidence supporting this hypothesis in animal studies, human studies have been less conclusive. A major problem is the fact that the brain is inaccessible to epigenetic studies in humans and the relevance of DNA methylation in peripheral tissues to behavioral phenotypes has been questioned. In addition, human studies are usually confounded with genetic and environmental heterogeneity and it is very difficult to derive causality. The idea that epigenetic mechanisms mediate the life-long effects of perinatal adversity has attractive potential implications for early detection, prevention, and intervention in mental health disorders will be discussed.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/03/DialoguesClinNeurosci-21-369.PMC6952743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/ebinder
Signe Penner-Goeke, Elisabeth B Binder
The risk for major depression is both genetically and environmentally determined. It has been proposed that epigenetic mechanisms could mediate the lasting increases in depression risk following exposure to adverse life events and provide a mechanistic framework within which genetic and environmental factors can be integrated. Epigenetics refers to processes affecting gene expression and translation that do not involve changes in the DNA sequence and include DNA methylation (DNAm) and microRNAs (miRNAs) as well as histone modifications. Here we review evidence for a role of epigenetics in the pathogenesis of depression from studies investigating DNAm, miRNAs, and histone modifications using different tissues and various experimental designs. From these studies, a model emerges where underlying genetic and environmental risk factors, and interactions between the two, could drive aberrant epigenetic mechanisms targeting stress response pathways, neuronal plasticity, and other behaviorally relevant pathways that have been implicated in major depression. .
{"title":"Epigenetics and depression\u2029.","authors":"Signe Penner-Goeke, Elisabeth B Binder","doi":"10.31887/DCNS.2019.21.4/ebinder","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/ebinder","url":null,"abstract":"<p><p>The risk for major depression is both genetically and environmentally determined. It has been proposed that epigenetic mechanisms could mediate the lasting increases in depression risk following exposure to adverse life events and provide a mechanistic framework within which genetic and environmental factors can be integrated. Epigenetics refers to processes affecting gene expression and translation that do not involve changes in the DNA sequence and include DNA methylation (DNAm) and microRNAs (miRNAs) as well as histone modifications. Here we review evidence for a role of epigenetics in the pathogenesis of depression from studies investigating DNAm, miRNAs, and histone modifications using different tissues and various experimental designs. From these studies, a model emerges where underlying genetic and environmental risk factors, and interactions between the two, could drive aberrant epigenetic mechanisms targeting stress response pathways, neuronal plasticity, and other behaviorally relevant pathways that have been implicated in major depression.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/21/77/DialoguesClinNeurosci-21-397.PMC6952745.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/azannas
Anthony S Zannas
Psychosocial stress-especially when chronic, excessive, or occurring early in life-has been associated with accelerated aging and increased disease risk. With rapid aging of the world population, the need to elucidate the underlying mechanisms is pressing, now more so than ever. Among molecular mechanisms linking stress and aging, the present article reviews evidence on the role of epigenetics, biochemical processes that can be set into motion by stressors and in turn influence genomic function and complex phenotypes, including aging-related outcomes. The article further provides a conceptual mechanistic framework on how stress may drive epigenetic changes at susceptible genomic sites, thereby exerting systems-level effects on the aging epigenome while also regulating the expression of molecules implicated in aging-related processes. This emerging evidence, together with work examining related biological processes, begins to shed light on the epigenetic and, more broadly, molecular underpinnings of the long-hypothesized connection between stress and aging. .
{"title":"Epigenetics as a key link between psychosocial stress and aging: concepts, evidence, mechanisms\u2029.","authors":"Anthony S Zannas","doi":"10.31887/DCNS.2019.21.4/azannas","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/azannas","url":null,"abstract":"<p><p>Psychosocial stress-especially when chronic, excessive, or occurring early in life-has been associated with accelerated aging and increased disease risk. With rapid aging of the world population, the need to elucidate the underlying mechanisms is pressing, now more so than ever. Among molecular mechanisms linking stress and aging, the present article reviews evidence on the role of epigenetics, biochemical processes that can be set into motion by stressors and in turn influence genomic function and complex phenotypes, including aging-related outcomes. The article further provides a conceptual mechanistic framework on how stress may drive epigenetic changes at susceptible genomic sites, thereby exerting systems-level effects on the aging epigenome while also regulating the expression of molecules implicated in aging-related processes. This emerging evidence, together with work examining related biological processes, begins to shed light on the epigenetic and, more broadly, molecular underpinnings of the long-hypothesized connection between stress and aging.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/f3/DialoguesClinNeurosci-21-389.PMC6952744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.31887/DCNS.2019.21.4/sakbarian
Prashanth Rajarajan, Schahram Akbarian
Schizophrenia is a debilitating psychiatric disorder with a complex genetic architecture and limited understanding of its neuropathology, reflected by the lack of diagnostic measures and effective pharmacological treatments. Geneticists have recently identified more than 145 risk loci comprising hundreds of common variants of small effect sizes, most of which lie in noncoding genomic regions. This review will discuss how the epigenetic toolbox can be applied to contextualize genetic findings in schizophrenia. Progress in next-generation sequencing, along with increasing methodological complexity, has led to the compilation of genome-wide maps of DNA methylation, histone modifications, RNA expression, and more. Integration of chromatin conformation datasets is one of the latest efforts in deciphering schizophrenia risk, allowing the identification of genes in contact with regulatory variants across 100s of kilobases. Large-scale multiomics studies will facilitate the prioritization of putative causal risk variants and gene networks that contribute to schizophrenia etiology, informing clinical diagnostics and treatment downstream. .
{"title":"Use of the epigenetic toolbox\u2028to contextualize common variants associated with schizophrenia risk\u2029.","authors":"Prashanth Rajarajan, Schahram Akbarian","doi":"10.31887/DCNS.2019.21.4/sakbarian","DOIUrl":"https://doi.org/10.31887/DCNS.2019.21.4/sakbarian","url":null,"abstract":"<p><p>Schizophrenia is a debilitating psychiatric disorder with a complex genetic architecture and limited understanding of its neuropathology, reflected by the lack of diagnostic measures and effective pharmacological treatments. Geneticists have recently identified more than 145 risk loci comprising hundreds of common variants of small effect sizes, most of which lie in noncoding genomic regions. This review will discuss how the epigenetic toolbox can be applied to contextualize genetic findings in schizophrenia. Progress in next-generation sequencing, along with increasing methodological complexity, has led to the compilation of genome-wide maps of DNA methylation, histone modifications, RNA expression, and more. Integration of chromatin conformation datasets is one of the latest efforts in deciphering schizophrenia risk, allowing the identification of genes in contact with regulatory variants across 100s of kilobases. Large-scale multiomics studies will facilitate the prioritization of putative causal risk variants and gene networks that contribute to schizophrenia etiology, informing clinical diagnostics and treatment downstream.\u2029.</p>","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/8b/DialoguesClinNeurosci-21-407.PMC6952750.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37553055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cognition in Mental Health","authors":"","doi":"10.31887/dcns.2019.21.3","DOIUrl":"https://doi.org/10.31887/dcns.2019.21.3","url":null,"abstract":"","PeriodicalId":54343,"journal":{"name":"Dialogues in Clinical Neuroscience","volume":null,"pages":null},"PeriodicalIF":8.3,"publicationDate":"2019-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48393734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}