The (neuro)inflammatory system in anxiety disorders and PTSD: Potential treatment targets

Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown, С. 108825 - 108825

Опубликована: Фев. 1, 2025

Язык: Английский

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A microglia-containing cerebral organoid model to study early life immune challenges

Brain Behavior and Immunity, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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Antipsychotic exposure and infection risk in people with schizophrenia spectrum disorders during the COVID-19 pandemic: a Danish nationwide registry study

The Lancet Psychiatry, Год журнала: 2024, Номер 11(10), С. 796 - 806

Опубликована: Сен. 3, 2024

Язык: Английский

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In silico identification of novel ligands targeting stress-related human FKBP5 protein in mental disorders

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0320017 - e0320017

Опубликована: Март 17, 2025

FK506-binding protein 51 (FKBP51 or FKBP5) serves as a crucial stress modulator implicated in mental disorders, presenting potential target for intervention. Inhibitors like SAFit2, rapamycin, and tacrolimus exhibit promising interactions with this protein. Despite these advances, challenges persist diversifying FKBP5 ligands, prompting further exploration of interaction partners. Hence, study aims to identify other ligands. Employing molecular docking, we generated complexes various ligands (rapamycin, tacrolimus, SAFit2-Selective antagonist FKBP51 by induced fit, ascomycin, pimecrolimus, rosavin, salidroside, curcumin, apigenin, uvaricin, ruscogenin, neoruscogenin, pumicalagin, castalagin, grandinin). We identified the top 3 best which ruscogenin neoruscogenin had notable abilities cross blood-brain barrier have high gastrointestinal absorption, curcumin. Toxicity predictions show be least toxic based on oral toxicity classification (Class VI). Tyrosine (Tyr113) formed consistent all complex, reinforcing their involvement modulation. Molecular dynamic (MD) simulation validated strong between our three key provided an understanding stability complex. The binding free energy (ΔG) (based pharmacological properties) from MD analysis is -31.78 kcal/mol -30.41 -27.6 These molecules, therefore, can serve therapeutic molecules biomarkers research stress-impacted disorders. While offering implications disorders attenuating impact, it emphasize that ligands’ transition clinical applications necessitates extensive experimental research, including trials, unravel intricate neural pathways involved interactions.

Язык: Английский

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Longitudinal analysis of proinflammatory and anti-inflammatory cytokines in the cerebrospinal fluid and peripheral blood of treatment-naïve first-episode psychosis patients, and their correlation with psychosis severity and cognitive impairment in sub-Saharan Africa

BMJ Open, Год журнала: 2025, Номер 15(4), С. e098347 - e098347

Опубликована: Апрель 1, 2025

Background Inflammation is indicated as one of the factors that play a role in development schizophrenia, with several studies having found considerable inconsistencies their results. Few have investigated inflammation primary psychosis blood and cerebrospinal fluids simultaneously, aim this study being to investigate expression fluid inflammatory cytokines treatment-naive first-episode psychotic participants. Methods analysis This combined cross-sectional prospective observational study, which currently taking place Durban, South Africa, will recruit 60 participants (30 cases 30 matched controls). The objective describe baseline CSF longitudinal expression/levels persons diagnosed (FEP) for 12 months. secondary associations between severity, neurocognitive performance, antipsychotic response metabolic changes at different time points (baseline, 3, 6 months). Interventions We collect sociodemographic details all participants, Positive Negative Symptoms Scale, Patient Health Questionnaire-9, Childhood Trauma Repeatable Battery Assessment Neuropsychological Status Update, markers (venous lumbar puncture fluid) those FEP. Data from controls only be collected point no follow-ups (cross-sectional). Ethics dissemination protocol has been approved by University KwaZulu-Natal Biomedical Research Committee (BREC/00004714/2022). nested an ongoing titled burden HIV Psychosis African setting: HIV-infected non-infected patients First-Episode (BREC 571/18). results actively disseminated through peer-reviewed journal publications conference presentations.

Язык: Английский

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A microglia-containing cerebral organoid model to study early life immune challenges

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 26, 2024

Prenatal infections and activation of the maternal immune system have been proposed to contribute causing neurodevelopmental disorders (NDDs), chronic conditions often linked brain abnormalities. Microglia are resident cells play a key role in neurodevelopment. Disruption microglial functions can lead abnormalities increase risk developing NDDs. How as well fetal affect human neurodevelopment NDDs remains unclear. An important reason for this knowledge gap is fact that impact exposure prenatal factors has challenging study context. Here, we characterized model cerebral organoids (CO) with integrated microglia (COiMg). These express typical markers respond inflammatory stimuli. The presence influences organoid development, including cell density neural differentiation, regulates expression several ciliated mesenchymal markers. Moreover, COiMg without show similar but also distinct responses Additionally, IFN-γ induced significant transcriptional structural changes organoids, appear be regulated by microglia. Specifically, interferon-gamma (IFN-γ) was found alter genes autism. This provides valuable tool how perturbations processes.

Язык: Английский

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A genetic study of immunity in depression and interactions with childhood maltreatment

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 16, 2024

Genetic and environmental factors contribute to depression. Among the latter, early life adversity immune dysregulation have been consistently linked with Childhood maltreatment (CM) is believed induce later in life. However, it not known how CM might interact genetic occurrence of We investigated variability 2,370 genes from 20 pathways associates lifetime depression at gene- pathway-level, this interacts CM. The analysis was carried out 13,309 individuals (1,867 cases) Generation Scotland (GS) Study. interaction a subset 749 (99 GS an independent sample 509 (96 German BiDirect (BD) Study for which both data available. Interactions different types were tested using subscales childhood trauma questionnaire (CTQ). These results meta-analyzed obtain general gene-CM interactions. found association GHR gene (false discovery rate –FDR– =0.03, z = 4.2) Reactome “RUNX1-regulated transcription involved myeloid cell differentiation pathway” (FDR 0.016, beta 1.2) GS. After meta-analysis, 56 interactions associated < 0.05) BD. exert functions hematopoiesis, pathogen recognition stress responses, among others. Network suggested macrophages as main expressing types. Our underscore involvement hematopoietic alterations development

Язык: Английский

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Multimorbidity in Severe Mental Illness as Part of the Neurodevelopmental Continuum: Physical Health-Related Endophenotypes of Schizophrenia—A Narrative Review

Brain Sciences, Год журнала: 2024, Номер 14(7), С. 725 - 725

Опубликована: Июль 19, 2024

Background. The majority of deaths in patients with schizophrenia and other severe mental illnesses (SMIs) are caused by natural causes, such as cardiovascular diseases (CVDs). increased risk CVD somatic SMIs cannot be fully explained the contribution traditional factors, behavioral patients’ lifestyle peculiarities, influence antipsychotics. present review has following main objectives: (1) to aggregate evidence that neurodevelopmental disorders basis SMIs; (2) provide a studies have addressed shared genetic architecture SMI disease; (3) propose substantiate consideration independent endophenotypes SMIs, which will make it possible place research within framework concepts “neurodevelopmental continuum gradient” “endophenotype”. Methods. A comprehensive literature search was performed on 1 July 2024. using PubMed Google Scholar databases up June Results. current reveals considerable overlap between susceptibility loci for CVDs. We observed can considered distinct physical health-related endophenotypes. Conclusions. In this narrative review, results recent CVDs summarized. Reframing multisystem disease should contribute activation new SMIs.

Язык: Английский

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Impacts beyond the brain: Unraveling molecular mechanisms linking psychiatric, metabolic, and inflammatory conditions

Neuron, Год журнала: 2024, Номер 112(17), С. 2827 - 2829

Опубликована: Сен. 1, 2024

Язык: Английский

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The Inflammation in Schizophrenia: Biomarkers and Association with Pathogenesis

Springer eBooks, Год журнала: 2024, Номер unknown, С. 1 - 28

Опубликована: Янв. 1, 2024

Язык: Английский

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