Symptom-based depression subtypes: brain dynamic specificity and its association with gene expression profiles

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 28, 2025

At least 227 combinations of symptoms meet the criteria for Major Depressive Disorder (MDD). However, in clinical practice, patients consistently present a regular rather than random manner, and neural basis underlying MDD subtypes remains unclear. To help clarify basis, with were clustered by symptom to investigate underpinning each subtype using functional resonance imaging (fMRI). Four symptom-based identified latent profile analysis according scales. Subsequently, brain dynamics evaluated fMRI, dysregulations attention limbic network observed among subtypes. Correlation between was then assessed via canonical correlation (CCA). The brain-symptom higher when (r = 0.77 0.92) compared entire group 0.5). loading weight CCA showed that transmodal networks contributed most characterized typical depression symptoms, whereas unimodal anxiety insomnia. Finally, gene expression model, along its biological encoding process, performed postmortem atlas revealed distinct enrichments different These findings highlight clusters have specific correlates, providing insights into depression's heterogeneous diagnosis precision medicine opportunities.

Язык: Английский

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Pathomechanisms of Vascular Depression in Older Adults

International Journal of Molecular Sciences, Год журнала: 2021, Номер 23(1), С. 308 - 308

Опубликована: Дек. 28, 2021

Depression in older individuals is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, associated disability, cognitive decline, increased mortality The factors predicting the risk late-life depression (LLD) are incompletely understood. reciprocal relationship depressive age- disease-related processes has generated pathogenic hypotheses provided various treatment options. heterogeneity complicates research into underlying cascade, involved LLD considerably differ from those early life depression. Evidence suggests that variety vascular mechanisms, particular cerebral small vessel disease, generalized microvascular, endothelial dysfunction, as well metabolic factors, including diabetes, inflammation may induce subcortical white gray matter lesions by compromising fronto-limbic other important neuronal networks, contribute to development LLD. "vascular depression" hypothesis postulates cerebrovascular disease or can predispose, precipitate, perpetuate geriatric syndromes, based on their frequent after stroke. Vascular burden deficits specific form LLD, depression, which marked decreased integrity, executive functional poorer response antidepressive therapy than major without factors. Other such neurodegeneration neuroimmune regulatory dysmechanisms, briefly discussed. Treatment planning should consider modest antidepressants, while provide promising targets for its successful prevention treatment. However, effectiveness needs further investigation, intervention studies needed assess interventions appropriate effective clinical practice.

Язык: Английский

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Sex differences in depression: An immunological perspective

Brain Research Bulletin, Год журнала: 2023, Номер 196, С. 34 - 45

Опубликована: Фев. 28, 2023

Depression is a heterogenous disorder with symptoms that present differently across individuals. In subset of people depression associated alterations the immune system may contribute to onset and symptomology. Women are twice as likely develop on average have more sensitive adaptive innate when compared men. Sex differences in pattern recognition receptors (PRRs), release damage-associated molecular patterns (DAMPs), cell populations, circulating cytokines play critical role inflammation onset. immunity change response repair damage caused by dangerous pathogens or molecules body. This article reviews evidence for sex specific responses account higher rate women.

Язык: Английский

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Investigating the Potential Mechanisms and Therapeutic Targets of Inflammatory Cytokines in Post-stroke Depression

Molecular Neurobiology, Год журнала: 2023, Номер 61(1), С. 132 - 147

Опубликована: Авг. 17, 2023

Язык: Английский

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Astroglial Connexin 43-Mediated Gap Junctions and Hemichannels: Potential Antidepressant Mechanisms and the Link to Neuroinflammation

Cellular and Molecular Neurobiology, Год журнала: 2023, Номер 43(8), С. 4023 - 4040

Опубликована: Окт. 24, 2023

Язык: Английский

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Unraveling the Role of the Blood-Brain Barrier in the Pathophysiology of Depression: Recent Advances and Future Perspectives

Molecular Neurobiology, Год журнала: 2024, Номер 61(12), С. 10398 - 10447

Опубликована: Май 10, 2024

Язык: Английский

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Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway

Free Radical Biology and Medicine, Год журнала: 2024, Номер 221, С. 261 - 272

Опубликована: Май 28, 2024

Despite of yet unknown mechanism, microvascular deposition oligomeric Tau (oTau) has been implicated in alteration the Blood-Brain Barrier (BBB) function Alzheimer's disease (AD) brains. In this study, we employed an vitro BBB model using primary mouse cerebral endothelial cells (CECs) to investigate mechanism underlying effects oTau on function. We found that exposing CECs induced oxidative stress through NADPH oxidase, increased damage proteins, decreased proteasome activity, and expressions tight junction (TJ) proteins including occludin, zonula occludens-1 (ZO-1) claudin-5. These were suppressed by pretreatment with Fasudil, a RhoA/ROCK signaling inhibitor. Consistent biochemical alterations, basolateral side disrupted integrity BBB, as indicated increase FITC-dextran transport across model, decrease trans electrical resistance (TEER). also transmigration peripheral blood mononuclear (PBMCs) model. functional alterations Fasudil. Taken together, our findings suggest targeting pathway can be potential therapeutic strategy maintain AD.

Язык: Английский

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Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice

Journal of Biological Chemistry, Год журнала: 2022, Номер 298(8), С. 102185 - 102185

Опубликована: Июнь 24, 2022

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating need novel strategies. Here, we report increased ceramide levels in the blood plasma patients murine stress-induced models MDD. These correlated with severity human were independent age, sex, or body mass index. In addition, intravenous injection anti-ceramide antibodies neutral ceramidase rapidly abrogated MDD, from mice induced depression-like behavior untreated mice, which was by ex vivo preincubation ceramidase. Mechanistically, demonstrate accumulated endothelial cells hippocampus stressed evidenced quantitative measurement purified cells. We found inhibited activity phospholipase D (PLD) vitro thereby decreased phosphatidic acid hippocampus. Finally, show PLD indicating significance this pathway pathogenesis. Our data indicate controls formation hippocampal mediates propose neutralization could represent rapid-acting targeted

Язык: Английский

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Stress induces major depressive disorder by a neutral sphingomyelinase 2-mediated accumulation of ceramide-enriched exosomes in the blood plasma

Journal of Molecular Medicine, Год журнала: 2022, Номер 100(10), С. 1493 - 1508

Опубликована: Авг. 31, 2022

Abstract Major depressive disorder (MDD) is a very common, severe disease with lifetime prevalence of ~ 10%. The pathogenesis MDD unknown and, unfortunately, therapy often insufficient. We have previously reported that ceramide levels are increased in the blood plasma patients and mice experimental MDD. Here, we demonstrate ceramide-enriched exosomes stress-induced Genetic studies reveal neutral sphingomyelinase 2 required for formation plasma. Accordingly, induced deficiency prevented from development Intravenous injection microparticles or ceramide-loaded MDD-like behavior untreated mice, which was abrogated by ex vivo pre-incubation purified anti-ceramide antibodies ceramidase. Mechanistically, inhibited phospholipase D (PLD) endothelial cells vitro hippocampus thereby decreased phosphatidic acid hippocampus, has been shown to mediate ceramide. In summary, our data indicate released into upon stress Key messages Stress induces Ceramide-enriched major (MDD). Deficiency protects Neutralization digestion prevents inhibit hippocampus.

Язык: Английский

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The roles of extracellular vesicles in major depressive disorder

Frontiers in Psychiatry, Год журнала: 2023, Номер 14

Опубликована: Март 9, 2023

Major depressive disorder (MDD) is a serious mental disease characterized by depressed mood, loss of interest and suicidal ideation. Its rising prevalence has rendered MDD one the largest contributors to global burden. However, its pathophysiological mechanism still unclear, reliable biomarkers are lacking. Extracellular vesicles (EVs) widely considered important mediators intercellular communication, playing an role in many physiological pathological processes. Most preclinical studies focus on related proteins microRNAs EVs, which can regulate energy metabolism, neurogenesis, neuro-inflammation other processes development MDD. The purpose this review describe current research progress EVs highlight their potential roles as biomarkers, therapeutic indicators drug delivery carriers for treatment

Язык: Английский

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