HPA Axis in the Pathomechanism of Depression and Schizophrenia: New Therapeutic Strategies Based on Its Participation

Brain Sciences, Journal Year: 2021, Volume and Issue: 11(10), P. 1298 - 1298

Published: Sept. 30, 2021

The hypothalamic-pituitary-adrenal (HPA) axis is involved in the pathophysiology of many neuropsychiatric disorders. Increased HPA activity can be observed during chronic stress, which plays a key role depression. Overactivity occurs major depressive disorder (MDD), leading to cognitive dysfunction and reduced mood. There also correlation between activation gut microbiota, has significant impact on development MDD. It believed that microbiota influence function through cytokines, prostaglandins, or bacterial antigens various microbial species. schizophrenia varies depends mainly severity disease. This review summarizes involvement pathogenesis disorders, focusing depression schizophrenia, highlights possible these conditions. Although effective antidepressants are available, large proportion patients do not respond initial treatment. discusses new therapeutic strategies affect axis, such as glucocorticoid receptor (GR) antagonists, vasopressin V1B antagonists non-psychoactive CB1 agonists and/or schizophrenia.

Language: Английский

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Biological embedding of experience: A primer on epigenetics

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 117(38), P. 23261 - 23269

Published: Oct. 17, 2019

Biological embedding occurs when life experience alters biological processes to affect later health and well-being. Although extensive correlative data exist supporting the notion that epigenetic mechanisms such as DNA methylation underlie embedding, causal are lacking. We describe specific their potential roles in of experience. also consider nuanced relationships between genome, epigenome, gene expression. Our ability connect landscape its complexity is challenging complicated by influence multiple factors. These include cell type, age, timing experience, sex, sequence. Recent advances molecular profiling epigenome editing, combined with use comparative animal human longitudinal studies, should enable this field transition from analyses.

Language: Английский

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Epigenetics and depression

Dialogues in Clinical Neuroscience, Journal Year: 2019, Volume and Issue: 21(4), P. 397 - 405

Published: Dec. 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.

Language: Английский

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Early life adversity shapes neural circuit function during sensitive postnatal developmental periods

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: Aug. 1, 2022

Abstract Early life adversity (ELA) is a major risk factor for mental illness, but the neurobiological mechanisms by which ELA increases future psychopathology are still poorly understood. Brain development particularly malleable during prenatal and early postnatal life, when complex neural circuits being formed refined through an interplay of excitatory inhibitory input, synaptogenesis, synaptic pruning, myelination, neurogenesis. Adversity that influences these processes sensitive periods can thus have long-lasting pervasive effects on circuit maturation. In this review, we will discuss clinical preclinical evidence impact formation with focus period, how impairments in affect behavior. We provide converging from human animal studies alters functional brain regions, circuits, neurotransmitter systems crucial cognition affective behavior, including hippocampus, hypothalamus-pituitary-adrenal (HPA) axis, networks fear responses cognition, serotonin (5-HT) system. also gene-by-environment (GxE) interactions determine individual differences susceptibility resilience to ELA, as well molecular pathways regulates development, emphasize epigenetic mechanisms. Understanding underlying function may great potential advance strategies better treat or prevent psychiatric disorders their origin life.

Language: Английский

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The cortisol switch between vulnerability and resilience

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 29(1), P. 20 - 34

Published: Jan. 4, 2023

Language: Английский

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The effect of adverse childhood experiences on chronic pain and major depression in adulthood: a systematic review and meta-analysis

British Journal of Anaesthesia, Journal Year: 2023, Volume and Issue: 130(6), P. 729 - 746

Published: April 21, 2023

BackgroundAdverse childhood experiences have been linked to increased multimorbidity, with physical and mental health consequences throughout life. Chronic pain is often associated mood disorders, such as major depressive disorder (MDD); both adverse experiences. It unclear how the effect of on neural processing impacts vulnerability chronic pain, MDD, or both, whether there are shared mechanisms. We aimed assess evidence for central changes in subjects using systematic review meta-analysis.MethodsElectronic databases were systematically searched neuroimaging studies experiences, both. Two independent reviewers screened title, abstracts, full text, assessed quality. After extraction data, activation likelihood estimate meta-analysis was performed identify significant brain regions these comorbidities.ResultsForty-nine 2414 eligible, which 43 investigated MDD six pain. None together. Functional structural abnormalities identified superior frontal, lingual gyrus, hippocampus, insula, putamen, temporal, inferior temporal anterior cerebellum patients exposed In addition, function exposure cingulate parietal lobule, precuneus task-based functional MRI studies.ConclusionsWe found that can result different alterations adults compared those without experiences.Systematic protocolPROSPERO CRD42021233989.

Language: Английский

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Multi-omics data integration methods and their applications in psychiatric disorders

European Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: 69, P. 26 - 46

Published: Jan. 26, 2023

Language: Английский

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Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 27, 2025

Maternal trauma influences infant and adult health outcomes may impact future generations through epigenetic modifications such as DNA methylation (DNAm). Research in humans on the intergenerational transmission of effects is limited. In this study, we assessed DNAm signatures war-related violence by comparing germline, prenatal, direct exposures to across three Syrian refugees. We compared families which a pregnant grandmother versus mother was exposed included control group with no exposure war. collected buccal swab samples survey data from mothers 1-2 children each 48 (n = 131 participants). Based an epigenome-wide association study (EWAS), identified differentially methylated regions (DMPs): 14 were associated germline 21 violence. Most DMPs showed same directionality change exposures, suggesting common response Additionally, age acceleration prenatal children, highlighting critical period utero development. This first report signature violence, has important implications for understanding inheritance trauma.

Language: Английский

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Genes and environments, development and time

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(38), P. 23235 - 23241

Published: Sept. 22, 2020

A now substantial body of science implicates a dynamic interplay between genetic and environmental variation in the development individual differences behavior health. Such outcomes are affected by molecular, often epigenetic, processes involving gene–environment (G–E) that can influence gene expression. Early environments with exposures to poverty, chronic adversities, acutely stressful events have been linked maladaptive compromised health behavior. Genetic impart either enhanced or blunted susceptibility effects such pathogenic environments. However, largely missing from present discourse regarding G–E is role time, “third factor” guiding emergence complex developmental endpoints across different scales time. Trajectories increasingly appear best accounted for complex, interchange among highly elements genes, contexts, time at multiple scales, including neurobiological (minutes milliseconds), genomic (hours minutes), (years months), evolutionary (centuries millennia) This special issue PNAS thus explores timing transactions: The importance timescales plasticity critical periods brain development; epigenetics molecular underpinnings biologically embedded experience; encoding experience biological levels organization; gene-regulatory networks their linkages neuronal networks. Taken together, collection papers offers perspectives on how operates contingently within against backdrop timescales.

Language: Английский

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Glucocorticoids as Mediators of Adverse Outcomes of Prenatal Stress

Trends in Neurosciences, Journal Year: 2020, Volume and Issue: 43(6), P. 394 - 405

Published: April 15, 2020

Language: Английский

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