Depression

The Lancet, Год журнала: 2018, Номер 392(10161), С. 2299 - 2312

Опубликована: Ноя. 1, 2018

Язык: Английский

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Major depressive disorder

Nature Reviews Disease Primers, Год журнала: 2016, Номер 2(1)

Опубликована: Сен. 15, 2016

Язык: Английский

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Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms

World Psychiatry, Год журнала: 2018, Номер 17(3), С. 243 - 257

Опубликована: Сен. 7, 2018

This paper reviews the research evidence concerning intergenerational transmission of trauma effects and possible role epigenetic mechanisms in this transmission. Two broad categories epigenetically mediated are highlighted. The first involves developmentally programmed effects. These can result from influence offspring's early environmental exposures, including postnatal maternal care as well utero exposure reflecting stress during pregnancy. second includes changes associated with a preconception parents that may affect germline, impact fetoplacental interactions. Several factors, such sex-specific following parental developmental stage at time exposure, explain different paternal trauma. most compelling work to date has been done animal models, where opportunity for controlled designs enables clear interpretations transmissible Given paucity human studies methodological challenges conducting studies, it is not attribute humans single set biological or other determinants time. Elucidating through prospective, multi-generational ultimately yield cogent understanding how individual, cultural societal experiences permeate our biology.

Язык: Английский

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Functions and mechanisms of epigenetic inheritance in animals

Nature Reviews Molecular Cell Biology, Год журнала: 2018, Номер 19(12), С. 774 - 790

Опубликована: Ноя. 13, 2018

Язык: Английский

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The WPA- Lancet Psychiatry Commission on the Future of Psychiatry

The Lancet Psychiatry, Год журнала: 2017, Номер 4(10), С. 775 - 818

Опубликована: Сен. 23, 2017

Язык: Английский

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The Role of m6A/m-RNA Methylation in Stress Response Regulation

Neuron, Год журнала: 2018, Номер 99(2), С. 389 - 403.e9

Опубликована: Июль 1, 2018

Highlights•m6A/m mRNA methylation in the adult mouse brain is regulated by stress•m6A/m regulation region, time, and gene specific•Mettl3 Fto cKO alter m6A/m, fear memory, expression, synaptic plasticity•The m6A/m glucocorticoid response impaired major depressive disorder patientsSummaryN6-methyladenosine (m6A) N6,2′-O-dimethyladenosine (m6Am) are abundant modifications that regulate transcript processing translation. The role of both, here termed stress vivo currently unknown. Here, we provide a detailed analysis epitranscriptome using m6A/m-seq, global gene-specific measurements. We show exposure glucocorticoids region time specifically its regulatory network. demonstrate deletion methyltransferase Mettl3 or demethylase neurons alters epitranscriptome, increases changes transcriptome to plasticity. Moreover, report patients following stimulation. Our findings indicate represents novel layer complexity expression after dysregulation may contribute pathophysiology stress-related psychiatric disorders.Graphical abstract

Язык: Английский

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Is the HPA Axis as Target for Depression Outdated, or Is There a New Hope?

Frontiers in Psychiatry, Год журнала: 2019, Номер 10

Опубликована: Фев. 28, 2019

Major depressive disorder (MDD) is a very common stress-related mental that carries huge burden for affected patients and the society. It associated with high mortality derives from suicidality development of serious medical conditions such as heart diseases, diabetes stroke. Although range effective antidepressants are available, more than 50% do not respond to first treatment they prescribed around 30% fail even after several attempts. The heterogeneous condition MDD, lack biomarkers matching right treatments situation almost all available drugs only targeting serotonin, norepinephrine or dopamine signaling, without regulating other potentially dysregulated systems may explain insufficient status. hypothalamic-pituitary-adrenal (HPA) axis one these systems, there numerous robust evidence it implicated in MDD conditions, but up date no specific drug HPA components approved test routinely used clinical setting identifying treatment. Is still hope many years breakthrough agents axis? This review will cover tests detecting altered function options glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH1) tryptophan 2,3-dioxygenase (TDO) inhibitors FK506 binding protein 5 (FKBP5) antagonists.

Язык: Английский

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Trauma, PTSD, and the Developing Brain

Current Psychiatry Reports, Год журнала: 2017, Номер 19(10)

Опубликована: Авг. 19, 2017

Язык: Английский

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Understanding the Molecular Mechanisms Underpinning Gene by Environment Interactions in Psychiatric Disorders: The FKBP5 Model

Biological Psychiatry, Год журнала: 2018, Номер 83(10), С. 821 - 830

Опубликована: Март 21, 2018

Язык: Английский

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Epigenetics and depression

Dialogues in Clinical Neuroscience, Год журнала: 2019, Номер 21(4), С. 397 - 405

Опубликована: Дек. 31, 2019

The risk for major depression is both genetically and environmentally determined. It has been proposed that epigenetic mechanisms could mediate the lasting increases in following exposure to adverse life events provide a mechanistic framework within which genetic environmental factors can be integrated. Epigenetics refers processes affecting gene expression translation do not involve changes DNA sequence include methylation (DNAm) microRNAs (miRNAs) as well histone modifications. Here we review evidence role of epigenetics pathogenesis from studies investigating DNAm, miRNAs, modifications using different tissues various experimental designs. From these studies, model emerges where underlying factors, interactions between two, drive aberrant targeting stress response pathways, neuronal plasticity, other behaviorally relevant pathways have implicated depression.

Язык: Английский

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