Chronic stress, neuroinflammation, and depression: an overview of pathophysiological mechanisms and emerging anti-inflammatories

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Май 11, 2023

In a subset of patients, chronic exposure to stress is an etiological risk factor for neuroinflammation and depression. Neuroinflammation affects up 27% patients with MDD associated more severe, chronic, treatment-resistant trajectory. Inflammation not unique depression has transdiagnostic effects suggesting shared underlying psychopathologies metabolic disorders. Research supports association but necessarily causation Putative mechanisms link dysregulation the HPA axis immune cell glucocorticoid resistance resulting in hyperactivation peripheral system. The extracellular release DAMPs DAMP-PRR signaling creates feed forward loop that accelerates central inflammation. Higher plasma levels inflammatory cytokines, most consistently interleukin IL-1β, IL-6, TNF-α, are correlated greater depressive symptomatology. Cytokines sensitize axis, disrupt negative feedback loop, further propagate reactions. Peripheral inflammation exacerbates (neuroinflammation) through several including disruption blood-brain barrier, cellular trafficking, activation glial cells. Activated cells chemokines, reactive oxygen nitrogen species into extra-synaptic space dysregulating neurotransmitter systems, imbalancing excitatory inhibitory ratio, disrupting neural circuitry plasticity adaptation. particular, microglial toxicity plays role pathophysiology neuroinflammation. Magnetic resonance imaging (MRI) studies show reduced hippocampal volumes. Neural dysfunction such as hypoactivation between ventral striatum ventromedial prefrontal cortex underlies melancholic phenotype Chronic administration monoamine-based antidepressants counters response, delayed therapeutic onset. Therapeutics targeting mediated immunity, generalized specific pathways, nitro-oxidative have enormous potential advance treatment landscape. Future clinical trials will need include system perturbations biomarker outcome measures facilitate novel antidepressant development. this overview, we explore correlates elucidate pathomechanisms development biomarkers therapeutics.

Язык: Английский

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Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Авг. 30, 2023

Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis poorly understood. The heritability estimate of MDD 30-40%, suggesting genetics alone do not account for most the risk major depression. Another factor known to associate with involves environmental stressors such as childhood adversity recent life stress. Recent studies have emerged show biological impact factors in other stress-related disorders mediated by variety epigenetic modifications. These modification alterations contribute abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission neuroglia dysfunction, which are involved pathophysiology MDD. Furthermore, marks been associated diagnosis treatment evaluation modifications holds promise further understanding heterogeneous etiology complex phenotypes MDD, may identify new therapeutic targets. Here, we review preclinical clinical findings, including DNA methylation, histone modification, noncoding RNA, RNA chromatin remodeling In addition, elaborate on contribution these mechanisms pathological trait variability depression discuss how can be exploited purposes.

Язык: Английский

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The molecular pathophysiology of depression and the new therapeutics

MedComm, Год журнала: 2022, Номер 3(3)

Опубликована: Июль 21, 2022

Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand molecular pathophysiology of depression, it still unclear. Current treatments for depression are inadequate individuals, because limited effectiveness, delayed efficacy (usually two weeks), side effects. Consequently, novel drugs with increased speed action effectiveness required. Ketamine has shown have rapid, reliable, long-lasting antidepressant effects in treatment-resistant MDD patients represent breakthrough therapy MDD; however, concerns regarding its efficacy, potential misuse, remain. In this review, we aimed summarize mechanisms pharmacological depression. We focused on fast treatment clarified safety, tolerability, ketamine metabolites treatment, along review mechanisms, research challenges, future clinical prospects.

Язык: Английский

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Association between organophosphorus pesticide exposure and depression risk in adults: A cross-sectional study with NHANES data

Environmental Pollution, Год журнала: 2022, Номер 316, С. 120445 - 120445

Опубликована: Окт. 18, 2022

Язык: Английский

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Mood and microbes: a comprehensive review of intestinal microbiota’s impact on depression

Frontiers in Psychiatry, Год журнала: 2024, Номер 15

Опубликована: Фев. 9, 2024

Depression is considered a multifaceted and intricate mental disorder of growing concern due to its significant impact on global health issues. The human gut microbiota, also known as the “second brain,” has an important role in CNS by regulating it through chemical, immunological, hormonal, neurological processes. Various studies have found bidirectional link between brain gut, emphasizing onset depression therapies. biological molecular processes underlying microbiota are required, association may represent novel study. However, profound insights into stratification diversity still uncommon. This article investigates emerging evidence bacterial relationship brain’s system potential pathogenicity relevance. interplay immune system, nervous neurotransmitter synthesis, neuroplasticity transitions widely studied. consequences stress, dietary fibers, probiotics, prebiotics, antibiotics GB axis being Multiple revealed this led development effective microbiota-based drugs for both prevention treatment. Therefore, results support hypothesis that influences provide promising area research improved knowledge etiology disease future

Язык: Английский

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Adherence to a Mediterranean Diet Is Inversely Associated with Anxiety and Stress but Not Depression: A Cross-Sectional Analysis of Community-Dwelling Older Australians

Nutrients, Год журнала: 2024, Номер 16(3), С. 366 - 366

Опубликована: Янв. 26, 2024

Diet quality may be an important modifiable risk factor for mental health disorders. However, these findings have been inconsistent, particularly in older adults. We explored the independent associations between adherence to a Mediterranean diet (MedDiet) and severity of symptoms related depression, anxiety stress adults from Australia. This was cross-sectional analysis Australians ≥ 60 years. MedDiet assessed using Adherence Screener (MEDAS), Depression, Anxiety Stress Scale (DASS−21) used assess negative emotional symptoms. A total n = 294 participants were included final analyses (70.4 ± 6.2 years). inversely associated with (β −0.118; CI: −0.761, −0.012; p 0.043) age, gender, BMI, physical activity, sleep, cognitive ability perform activities daily living. Furthermore, −0.151; −0.680, −0.073; 0.015) activity sleep. no relationship depressive observed. showed that is but not depression. Exploring use longitudinal robust clinical trials are needed better elucidate

Язык: Английский

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Neurotransmitter-mediated artificial synapses based on organic electrochemical transistors for future biomimic and bioinspired neuromorphic systems

Journal of Semiconductors, Год журнала: 2025, Номер 46(1), С. 011604 - 011604

Опубликована: Янв. 1, 2025

Abstract Organic electrochemical transistors have emerged as a solution for artificial synapses that mimic the neural functions of brain structure, holding great potentials to break bottleneck von Neumann architectures. However, current rely primarily on electrical signals, and little attention has been paid vital role neurotransmitter-mediated synapses. Dopamine is key neurotransmitter associated with emotion regulation cognitive processes needs be monitored in real time advance development disease diagnostics neuroscience. To provide insights into involvement, this review proposes three steps towards future biomimic bioinspired neuromorphic systems. We first summarize OECT-based dopamine detection devices, then advances resultant advanced Finally, by exploring challenges opportunities related such systems, we perspective biomimetic

Язык: Английский

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Effect of combination therapy of methylfolate with antidepressants in patients with depressive disorder

BMC Pharmacology and Toxicology, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 22, 2025

To determine the relative effectiveness of combination therapy antidepressants with low-dose methylfolate versus antidepressant monotherapy in patients depressive disorder. In an open-label clinical trial, forty-four disorder (6A70, 6A71, and 6A72 according to ICD-11) received evidence-based (either escitalopram 10-20 mg, sertraline 50-100 fluoxetine 20-40 duloxetine 30-60 mirtazapine 15-30 venlafaxine 75-150 trazodone amitriptyline 25-75 or clomipramine mg orally daily for 4 weeks). The experimental group, Group B was additionally given a dose 800 µg four weeks. psychometric testing depression achieved through administration Patient Health Questionnaire-9 (PHQ-9) on days 0, 14, 28, find improvement score day remission rate decrease time lag 14. Adverse effects were analyzed by self-assessment questionnaire observe tolerability. paired sample t-test independent applied analysis using SPSS v27.0. p-value ≤ 0.05 considered statistically significant. On low showed 40.33% symptoms, compared 26.43% (p-value < 0.05). This treatment strategy had no effect time-lag outcomes 14 28 not found Only one patient reported insomnia, while another mentioned irritability. Combination may provide safe effective NCT05931965.ClinicalTrials.gov. https://classic.clinicaltrials.gov/ct2/show/NCT05931965

Язык: Английский

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Emerging biologic frontiers for Sjogren’s syndrome: Unveiling novel approaches with emphasis on extra glandular pathology

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 17, 2024

Primary Sjögren’s Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due trial complications. This review addresses the absence of molecular-target-based approach therapy development highlights novel research on drug targets clinical trials. A literature search identified potential pSS treatment recent advances molecular understanding. Overlooking extraglandular symptoms like fatigue depression notable gap Emerging agents targeting cytokines, signal pathways, immune responses have efficacy. These could complement existing methods symptom alleviation. Improved grading systems accounting are needed. The future may involve gene, stem-cell, tissue-engineering therapies. narrative offers insights into advancing management through innovative interventions.

Язык: Английский

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Gut Microbiota Alterations and Their Functional Differences in Depression According to Enterotypes in Asian Individuals

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13329 - 13329

Опубликована: Авг. 28, 2023

This study aimed to investigate alterations in the gut microbiota of patients with depression compared those healthy individuals based on enterotypes as a classification framework. Fecal bacteria FASTA/Q samples from 333 Chinese participants, including 107 (Healthy group) and 226 suffering (DP group), were analyzed. The participants classified into three enterotypes: Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), Prevotellaceae (ET-P). An α-diversity analysis revealed no significant differences microbial diversity between Healthy DP groups across all enterotypes. However, there substantial composition for β-diversity, particularly within ET-L ET-B. group ET-B exhibited higher abundance Proteobacteria, while linear discriminant (LDA) showed an increased relative specific genera, such Mediterraneibacter, Blautia, Bifidobacterium, Clostridium. Within ET-L, Clostridium, Collinsella, Corynebacterium significantly LDA ANOVA-like differential expression-2 (ALDEx2) analyses. At species level Blautia luti, provencensis, glucerasea, Clostridium innocuum, porci, leptum primary identified using machine learning approach. A network more tightly interconnected community than suggests potentially stronger functional relationship among ET-L. metabolic pathways related glucose metabolism, tryptophan tyrosine neurotransmitter immune-related functions strong negative associations depression, These findings provide insights gut-brain axis its role pathogenesis thus contributing our understanding underlying mechanisms Asian individuals. Further research is warranted explain mechanistic links explore their potential use precision medicine interventions.

Язык: Английский

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