Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

Dudley, Kevin J.; Li, Xiang; Kobor, Michæl S.; Kippin, Tod E.; Bredy, Timothy W.

doi:10.1016/j.neubiorev.2010.12.016

Cited by 152 publications

(121 citation statements)

References 94 publications

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“…Although DNA methylation is the best characterized epigenetic mechanism (Dudley et al, 2011), post-translational histone modifications represent an equally important avenue to investigate, as these modifications may also affect gene expression by altering binding of transcription factors (Elliott et al, 2010). Previously, our group showed significant increases in H3K4me3 in OAZ1 of suicide completers.…”

Section: Discussionmentioning

confidence: 98%

“…Phenotypic changes in gene expression that are elicited by mechanisms other than DNA sequence variation, including epigenetic factors, have been increasingly investigated. To date, DNA methylation, histone modifications, and non-coding RNAs are among the most well-studied mechanisms of epigenetic regulation (Dudley, Li, Kobor, Kippin, & Bredy, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

Gross

Fiori

Labonté

et al. 2013

Journal of Psychiatric Research

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Suicide is among the leading causes of death worldwide. The polyamine system has been increasingly implicated in the neurobiology of suicide. Previous research has indicated that epigenetic mechanisms play a role in explaining dysregulation of polyamine genes in suicide completers. Nevertheless, regulatory mechanisms explaining polyamine biosynthetic genes displaying dysregulated expression in suicide completers, including ornithine decarboxylase antizymes 1 and 2 (OAZ1 and OAZ2), S-adenosylmethionine decarboxylase (AMD1), and arginase 2 (ARG2), have yet to be elucidated. In this study, we investigated methylation patterns in the promoter region of OAZ1, OAZ2, AMD1, and ARG2 in Brodmann area 44 from a group of 33 suicide completers and 31 non-suicide controls. We found significant site-specific differences in methylation in the promoter of ARG2 and AMD1 that were also significantly negatively correlated with gene expression. These findings provide further support for a role for the involvement of epigenetic modifications in the regulation of genes associated with polyamine biosynthesis, and which may contribute to the complexity of suicidal behaviors.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

Gross

Fiori

Labonté

et al. 2013

Journal of Psychiatric Research

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“…Epidemiological evidence also links environmental factors, especially exposure to stressful life events, with an increased risk for depression (Hammen, 2005;Kessler, 1997). However, there is a remarkable individual variability in vulnerability to environmental stress, with many psychiatric disorders associated with a history of stress and most individuals showing normal outcomes despite stress exposure (Dudley et al, 2011). Owing to the lack of success of traditional genetic or environmental approaches alone to explain MDD, a recent prevalent theory in the field has focused on the interplay between genetic and environmental factors, specifically how susceptibility and resilience to disease is determined by the penetrance of highly complex genetic variation moderated by environmental cues and possibly stochastic or random events during brain development (Kendler, 1998;Lesch, 2011;Vialou et al, 2012).…”

Section: Introduction: Why Epigenetics?mentioning

confidence: 99%

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Sun

Kennedy

Nestler

2012

Neuropsychopharmacol

347

233

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Major depressive disorder is a chronic, remitting syndrome involving widely distributed circuits in the brain. Stable alterations in gene expression that contribute to structural and functional changes in multiple brain regions are implicated in the heterogeneity and pathogenesis of the illness. Epigenetic events that alter chromatin structure to regulate programs of gene expression have been associated with depression-related behavior, antidepressant action, and resistance to depression or 'resilience' in animal models, with increasing evidence for similar mechanisms occurring in postmortem brains of depressed humans. In this review, we discuss recent advances in our understanding of epigenetic contributions to depression, in particular the role of histone acetylation and methylation, which are revealing novel mechanistic insight into the syndrome that may aid in the development of novel targets for depression treatment.

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“…Esta alteração resulta na inibição ou em uma atividade genética aumentada do DNA (Dudley, Li, Kobor, Kippin, & Bredy, 2011). Baixos níveis de metilação resultam na ativação aumentada do DNA, e assim com a ativação de genes que promovem o crescimento celular, a instabilidade cromossômica, e a perda de imprinting-fenômeno no qual certos genes são expressos apenas por um alelo, enquanto o outro é metilado (inativado).…”

Section: Epigenéticaunclassified

Epigenética, Cuidados Maternais e Vulnerabilidade ao Estresse: Conceitos Básicos e Aplicabilidade

Noro¹,

Gon²

2015

Psicol. Reflex. Crit.

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ResumoCuidados maternais são experiências do início da vida que têm sido consistentemente relacionados com alterações na expressão gênica por meio de mecanismos epigenéticos como a metilação do DNA ou a modifi cação de suas histonas. O objetivo deste trabalho é apresentar uma investigação teórica sobre cuidados maternais enquanto evento ambiental que pode produzir alterações epigené-ticas atuantes na composição da vulnerabilidade ao estresse. A investigação teve por base estudos empíricos e de revisão de literatura com animais não humanos sobre Epigenética, estresse e cuidados maternais. Apresenta também alguns estudos com humanos que mostram tais efeitos, destacando-se aqueles que infl uenciam ou são infl uenciados pelo comportamento operante. A partir da investigação realizada encontrou-se que cuidados maternais pós-parto são uma condição ambiental que produz efeitos no eixo hipotálamo-pituitária-adrenal (HPA), participando da composição da vulnerabilidade ao estresse. Seus possíveis efeitos fi siológicos no condicionamento operante sinalizam alternativas para intervenções baseadas na plasticidade da formação do epigenoma. Este conhecimento, além de promover a aproximação entre a Epigenética e a Análise do Comportamento em nível básico por meio de estudos com animais não humanos, poderá contribuir em nível aplicado para um melhor entendimento do neurodesenvolvimento infantil e adequado planejamento de intervenções efetivas com mães e fi lhos. Palavras-chave: Cuidados maternais, Epigenética, vulnerabilidade ao estresse, neurodesenvolvimento, Análise do Comportamento. AbstractMaternal care is an early life experience that has been consistently related to alterations in the genetic expression through epigenetic mechanisms such as DNA methylation or DNA histone modifi cation. The present study aims to present a theoretical investigation about maternal care as an environmental event that may produce epigenetic alterations related to the biological bases of stress vulnerability. The research was based on empirical studies as well as literature review on non-human animals concerning epigenetics, stress and maternal care. It also presents some studies on humans that show such effects, particularly the ones that infl uence or are infl uenced by the operant behavior. Post-natal maternal care is found to cause effects on the hypothalamic-pituitary-adrenal (HPA) axis activity participating in the building of stress vulnerability. Its possible physiological effects on the operant conditioning point out to alternatives to intervention based on the plasticity of the epigenome formation. This knowledge enhances the proximity between Epigenetics and Behavior Analysis at a basic level through studies with non-human animals and at an applied level through a better understanding of child neurodevelopment and proper planning of effective intervention with mothers and children. Keywords: Maternal care, Epigenetics, stress vulnerability, neurodevelopment, Behavior Analysis. * Endereço para correspondência: R. Prof. Samuel Moura, 367...

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Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders

Cited by 152 publications

References 94 publications

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

Effects of promoter methylation on increased expression of polyamine biosynthetic genes in suicide

Epigenetics of the Depressed Brain: Role of Histone Acetylation and Methylation

Epigenética, Cuidados Maternais e Vulnerabilidade ao Estresse: Conceitos Básicos e Aplicabilidade

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