Dissecting the shared genetic landscape of anxiety, depression, and schizophrenia

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 18, 2024

Numerous studies highlight the genetic underpinnings of mental disorders comorbidity, particularly in anxiety, depression, and schizophrenia. However, their shared loci are not well understood. Our study employs Mendelian randomization (MR) colocalization analyses, alongside multi-omics data, to uncover potential targets for these conditions, thereby informing therapeutic drug development strategies.

Language: Английский

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MAMMALIAN COPPER HOMEOSTASIS: PHYSIOLOGIC ROLES AND MOLECULAR MECHANISMS

Physiological Reviews, Journal Year: 2024, Volume and Issue: 105(1), P. 441 - 491

Published: Aug. 22, 2024

In the past decade, evidence for numerous roles of copper (Cu) in mammalian physiology has grown exponentially. The discoveries Cu involvement cell signaling, autophagy, motility, differentiation, and regulated death (cuproptosis) have markedly extended list already known functions Cu, such as a cofactor essential metabolic enzymes, protein structural component, regulator trafficking. Novel unexpected transporting proteins enzymes been identified, new disorders homeostasis described. Significant progress made mechanistic studies two classic metabolism, Menkes disease Wilson’s disease, which paved way novel approaches to their treatment. discovery cuproptosis role metastatic growth increased interest targeting homeostatic pathways treat cancer. this review, we summarize established concepts field discuss how decade expand modify these concepts. brain metabolism functional speciation recently discovered attracted significant attention are highlighted review.

Language: Английский

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Structural dynamics of a phenoxy-bridged heteronuclear Cu(II)/Hg(II)-Salen complex: synthesis, characterization, DFT insights, and Hirshfeld surface analysis

Journal of the Iranian Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Trace Elements Levels in Major Depressive Disorder—Evaluation of Potential Threats and Possible Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15071 - 15071

Published: Oct. 11, 2023

The multifactorial etiology of major depressive disorder (MDD) includes biological, environmental, genetic, and psychological aspects. Recently, there has been an increasing interest in metallomic studies psychiatry, aiming to evaluate the role chosen trace elements MDD as well progression symptoms. This narrative review aims summarize available literature on relationship between concentration serum patients with onset this psychiatric condition. authors reviewed PubMed, Web Science, Scopus databases searching for that had investigated so far further evaluated them paper. Ultimately, 15 were evaluated, namely, zinc, magnesium, selenium, iron, copper, aluminium, cadmium, lead, mercury, arsenic, calcium, manganese, chromium, nickel, phosphorus. association psychiatry developing dynamically recently. According results current research, metallomics might act a potential screening tool while at same time providing assessment severity Either deficiencies or excessive amounts be associated symptoms even disease among people predisposed MDD.

Language: Английский

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Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular Ca2+ Levels and ROS/p53/p38 Axis

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 46 - 46

Published: Jan. 3, 2025

Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated effects myricitrin (1–20 μg/mL) on copper-induced toxicity (0.5 mM CuSO4) neuroblastoma SH-SY5Y line. At non-toxic concentrations, exacerbated copper’s toxic effects. The myricitrin-induced decrease survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase lower GSH/GSSG ratio. In combination copper, activated caspase-3/7, promoted nuclear chromatin changes, compromised membrane integrity. protein level, upregulated p53 PUMA expression. were alleviated by p38 inhibitor SB203580, intracellular calcium chelator BAPTA-AM, NMDA receptor blocker MK-801, highlighting significant role ROS/p53/p38 axis death critical involvement ions apoptosis atomic force microscopy used assess surface morphology nanomechanical properties cells, revealing changes following treatment. research highlights potential emphasizes need caution when considering flavonoid supplementation conditions elevated levels.

Language: Английский

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A Prospective Study of a Whole Blood Metal Mixture and Depressive Symptoms among Black Women from Detroit, Michigan

NeuroToxicology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Magnesium Hexacyanoferrate Mitigates Sepsis-Associated Encephalopathy through Inhibiting Microglial Activation and Neuronal Cuproptosis

Biomaterials, Journal Year: 2025, Volume and Issue: unknown, P. 123279 - 123279

Published: March 1, 2025

Language: Английский

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NMR-Based Structural Insights on Folic Acid and Its Interactions with Copper(II) Ions

Inorganics, Journal Year: 2024, Volume and Issue: 12(9), P. 248 - 248

Published: Sept. 12, 2024

Folic acid (FA) is an essential vitamin involved in crucial metabolic processes, while copper(II) ions play significant roles various biological functions. This study aims to investigate the interaction between FA and Cu2+ using 1H 13C NMR spectroscopy under different pH levels concentrations. The research employed detailed analysis explore how binds FA, focusing on changes chemical shifts, diffusion coefficients, copper-induced paramagnetic effects. key findings reveal that predominantly coordinates with pteridine ring (PTE) of minimal involvement from glutamic (Glu) moiety. strongly concentration-dependent: at lower concentrations, effectively PTE ring, higher intermolecular interactions among molecules hinder copper binding. also observed pronounced effects p-aminobenzoic protons, negligible Glu signals. These results provide new insights into structural characteristics FA-Cu2+ complexes, contributing a better understanding their biochemical implications for folate metabolism.

Language: Английский

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Association between Dietary Copper Intake and Depressive Symptoms in American Adults

Statistics and Applications, Journal Year: 2024, Volume and Issue: 13(02), P. 315 - 325

Published: Jan. 1, 2024

Language: Английский

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Genetic Causal Associations between Various Serum Minerals and Risk of Depression: A Mendelian Randomization Study

Actas Españolas de Psiquiatría, Journal Year: 2024, Volume and Issue: 52(3), P. 211 - 220

Published: June 5, 2024

Background: Previous observational studies have discovered a connection between depression and mineral status. Confirming this potential is challenging due to confounding factors reverse causality which inherent in studies. Materials Methods: We performed Mendelian randomization (MR) analysis estimate the causal association of serum minerals with depression. Leveraging summary-level data on depression, genome-wide study (GWAS) was applied. The were collected from FinnGen Biobank database. MR assessments representing produced by inverse-variance weighted approaches multiplicative random fixed effects. Result: Sensitivity analyses validate reliability results. A noteworthy correlation emerged zinc levels reduced risk An odds ratio (OR) 0.917 for associated one standard deviation increase (OR = 0.968; 95% CI 0.953–0.984, p 1.19 × 10-4, effects model inverse variance (IVW)); 0.928; 0.634–1.358, 0.766, Egger). supported causation. However, did not exhibit an other minerals. Conclusions: In summary, higher concentration causally risk. This outcome may assist clinicians regulation specific intake, particularly high-risk patients deficiencies.

Language: Английский

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