Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders

Schiele, Miriam A.; Domschke, Katharina

doi:10.1111/gbb.12423

Cited by 159 publications

(101 citation statements)

References 183 publications

(156 reference statements)

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“…Chronic exposure to environmental stressors, including but not limited to work-related stress, has been implicated in the patho-etiology of various mental disorders and represents a substantial cause of morbidity, imposing a considerable societal disease burden (1). An individual's response to detrimental environmental influences is affected by an interplay of its intrinsic genetic configuration and its susceptibility or resilience toward external stimuli, which has led to a growing understanding of gene-environment interactions in the onset, course, and treatment of mental disorders (2). Epigenetics has emerged as a molecular correlate of this intersection, and a converging body of evidence has been collected outlining the effects of early-life stress and traumatic experiences, but less so of chronic psychosocial stressors on the expression of candidate genes involved in psychopathology (3).…”

Section: Introductionmentioning

confidence: 99%

Epigenetics Underlying Susceptibility and Resilience Relating to Daily Life Stress, Work Stress, and Socioeconomic Status

2020

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Susceptibility and resilience to mental disorders result from a complex choreography of gene-environment interactions with epigenetics at the intersection of external psychological stressors and internal biological systems. Increasing awareness of the growing disease burden influenced by daily life stress ("daily hassles"), work-related stress, and low socioeconomic status (SES) has resulted in a novel interest into their underlying molecular signatures. This review offers a brief outline of psychiatric epigenetics and a comprehensive overview of recent findings exploring the relationship of various occupational stressors and DNA methylation in epigenome-wide association studies (EWAS) and in candidate gene studies including the serotonin transporter (SLC6A4; 5-HTTLPR), melatonin receptor 1A (MTNR1A), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), and the protein family of DNA methyltransferases (DNMTs). Conceptual and methodological challenges of epigenetic investigations with a special focus on gene-environment interactions are highlighted and discussed. The findings are integrated into a pathophysiological framework featuring epigenetic plasticity factors and work-related stress as a possible central detrimental component targetable by workplace interventions. Finally, the potential of dynamic epigenetic biomarkers of treatment response to pharmacotherapy or psychotherapy is expanded upon.

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Section: Introductionmentioning

confidence: 99%

Epigenetics Underlying Susceptibility and Resilience Relating to Daily Life Stress, Work Stress, and Socioeconomic Status

2020

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“…Epigenetic mechanisms regulate chromatin structure and gene expression without altering the DNA sequence [188,189]. They play an important role in the fine-tuning of development-related genes and are involved in the development of the brain; thus, epigenetic dysregulation can cause neurodevelopmental disorders, including ASD.…”

Section: Epigenetic Dysregulation Underlying Asdmentioning

confidence: 99%

Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder

Yoon

Choi

Lee

et al. 2020

JCM

106

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Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by difficulties in social interaction, language development delays, repeated body movements, and markedly deteriorated activities and interests. Environmental factors, such as viral infection, parental age, and zinc deficiency, can be plausible contributors to ASD susceptibility. As ASD is highly heritable, genetic risk factors involved in neurodevelopment, neural communication, and social interaction provide important clues in explaining the etiology of ASD. Accumulated evidence also shows an important role of epigenetic factors, such as DNA methylation, histone modification, and noncoding RNA, in ASD etiology. In this review, we compiled the research published to date and described the genetic and epigenetic epidemiology together with environmental risk factors underlying the etiology of the different phenotypes of ASD.

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“…Epigenetics is involved in various biological phenomena, including gene expression and cell differentiation (Portela and Esteller 2010). Epigenetic mechanisms, such as DNA methylation, have been suggested to play an important role in disease pathogenesis at the intersection of genetic and environmental factors (Klengel and Binder 2015;Schiele and Domschke 2018), and may be a possible explanation for missing heritability (Trerotola et al 2015;Bourrat et al 2017).…”

Section: Epigenome-wide Association Studies (Ewas) Of Pdmentioning

confidence: 99%

Genetic and epigenetic analyses of panic disorder in the post-GWAS era

Morimoto

Ono²,

Kurotaki

et al. 2020

J Neural Transm

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Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.

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Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders

Cited by 159 publications

References 183 publications

Epigenetics Underlying Susceptibility and Resilience Relating to Daily Life Stress, Work Stress, and Socioeconomic Status

Epigenetics Underlying Susceptibility and Resilience Relating to Daily Life Stress, Work Stress, and Socioeconomic Status

Genetic and Epigenetic Etiology Underlying Autism Spectrum Disorder

Genetic and epigenetic analyses of panic disorder in the post-GWAS era

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