‘Whole-Body’ Perspectives of Schizophrenia and Related Psychotic Illness: miRNA-143 as an Exemplary Molecule Implicated across Multi-System Dysfunctions

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1185 - 1185

Опубликована: Сен. 20, 2024

A wide array of biological abnormalities in psychotic illness appear to reflect non-cerebral involvement. This review first outlines the evidence for such a whole-body concept schizophrenia pathobiology, focusing particularly on cardiovascular disease, metabolic syndrome and diabetes, immunity inflammation, cancer, gut–brain axis. It then considers roles miRNAs general miRNA-143 particular as they relate epidemiology, treatment schizophrenia. is followed by notable that also implicated each these domains Thus, an exemplar what may be class molecules play role across multiple bodily dysfunction characterize perspective Importantly, existence exemplary molecule implies coordinated rather than stochastic basis. One candidate process would pleiotropic effect genetic risk whole body.

Язык: Английский

---

Multidimensional Epigenetic Clocks Demonstrate Accelerated Aging Across Physiological Systems in Schizophrenia: A Meta-Analysis

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

Опубликована: Окт. 30, 2024

Abstract Importance: Schizophrenia is associated with increased age-related morbidity, mortality, and frailty, which are not entirely explained by behavioral factors. Prior studies using epigenetic clocks have suggested that schizophrenia accelerated aging, however these primarily used unidimensional summarize aging as a single “biological age” score. Objective: This meta-analysis uses multidimensional split into multiple scores to analyze biological in schizophrenia. These novel may provide more granular insights the mechanistic relationships between schizophrenia, premature morbidity mortality. Study selection: Selected included patients schizophrenia-spectrum disorders non- psychiatric controls available DNA methylation data. Seven cross-sectional datasets were for this study, total sample size of 1,891 1,881 controls. Data extraction synthesis: Studies selected consensus Meta-analyses performed fixed-effect models. Main outcomes measures: We analyzed clocks, including causality- enriched CausAge physiological system-specific SystemsAge RetroelementAge, DNAmEMRAge, multi omics-informed OMICmAge. examined clock associations disease status clozapine use, after accounting age sex. Results: Overall SystemsAge, CausAge, OMICmAge demonstrated strict multiple-comparison testing. Ten eleven sub-clocks corresponding different systems strongest effects Heart Lung followed Metabolic Brain systems. The indicated increases both damaging adaptive though weaker compared scores. changes clinical biomarkers, hematologic hepatic markers support well proteins metabolites previously linked Most acceleration at first psychotic episode. Notably, use was Inflammation partially be driven smoking. results survived Bonferroni testing correction. Conclusions relevance: analyses nuanced view identifies organ high risk schizophrenia-related disorders.

Язык: Английский

---

Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis

Schizophrenia, Год журнала: 2024, Номер 10(1)

Опубликована: Ноя. 15, 2024

Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia ≥10 years shorter than the general population because of higher risk other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values aging-related proteins (GrimAge GrimAge2 components) been analyzed multiple However, no investigated up to GrimAge components between controls. Therefore, we aimed conduct regression analyses investigate association seven cohorts. Furthermore, included first-episode psychosis whose illness duration was often our analysis. We integrated these results meta-analyses, noting acceleration GrimAge, GrimAge2, DunedinPACE, increase adrenomedullin, beta-2 microglobulin, cystatin C, plasminogen activation inhibitor-1 levels, or psychosis. These corroborated finding had an increased diabetes, disease, cognitive dysfunction from biological perspective. Patients showed differences when compared Such may lead development novel therapeutic targets relevant diseases perspective aging future.

Язык: Английский

---

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

---