The schizophrenia syndrome, circa 2024: What we know and how that informs its nature

Schizophrenia Research, Journal Year: 2023, Volume and Issue: 264, P. 1 - 28

Published: Dec. 12, 2023

Language: Английский

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From Serendipity to Precision: Integrating AI, Multi-Omics, and Human-Specific Models for Personalized Neuropsychiatric Care

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 167 - 167

Published: Jan. 12, 2025

Background/Objectives: The dual forces of structured inquiry and serendipitous discovery have long shaped neuropsychiatric research, with groundbreaking treatments such as lithium ketamine resulting from unexpected discoveries. However, relying on chance is becoming increasingly insufficient to address the rising prevalence mental health disorders like depression schizophrenia, which necessitate precise, innovative approaches. Emerging technologies artificial intelligence, induced pluripotent stem cells, multi-omics potential transform this field by allowing for predictive, patient-specific interventions. Despite these advancements, traditional methodologies animal models single-variable analyses continue be used, frequently failing capture complexities human conditions. Summary: This review critically evaluates transition serendipity precision-based in research. It focuses key innovations dynamic systems modeling network-based approaches that use genetic, molecular, environmental data identify new therapeutic targets. Furthermore, it emphasizes importance interdisciplinary collaboration human-specific overcoming limitations Conclusions: We highlight precision psychiatry’s transformative revolutionizing care. paradigm shift, combines cutting-edge systematic frameworks, promises increased diagnostic accuracy, reproducibility, efficiency, paving way tailored better patient outcomes

Language: Английский

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The Landscape of Shared and Divergent Genetic Influences across 14 Psychiatric Disorders

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Psychiatric disorders display high levels of comorbidity and genetic overlap 1,2 . Genomic methods have shown that even for schizophrenia bipolar disorder, two long-thought to be etiologically distinct 3 , the majority signal is shared 4 Furthermore, recent cross-disorder analyses uncovered over a hundred pleiotropic loci across eight 5 However, full scope disorder-specific basis psychopathology remains largely uncharted. Here, we address this gap by triangulating suite cutting-edge statistical functional genomic applied 14 childhood- adult-onset psychiatric (1,056,201 cases). Our identify characterize five underlying factors 6 explain variance individual (∼66% on average) are associated with 268 loci. We observed particularly polygenic 7 local correlation 8 very few 9 defined by: ( i ) disorder (“SB factor”), ii major depression, PTSD, anxiety (“internalizing factor”). At level, multiple 10–12 which demonstrated SB factor was substantially enriched in genes expressed excitatory neurons, whereas internalizing oligodendrocyte biology. By comparison, all broad biological processes (e.g., transcriptional regulation). These results indicate increasing differentiation function at different risk, from quite general vulnerability more specific pathways subsets disorders. observations may inform neurobiologically valid nosology implicate novel targets therapeutic developments designed treat commonly occurring comorbid presentations.

Language: Английский

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Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(6), P. 1857 - 1868

Published: Feb. 9, 2024

Language: Английский

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Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank

Nature Mental Health, Journal Year: 2024, Volume and Issue: 2(8), P. 960 - 974

Published: July 4, 2024

Language: Английский

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Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 27, 2025

Background Posttraumatic stress disorder (PTSD) commonly cooccurs with traumatic brain injury (TBI) in military populations and is a significant predictor of poor long-term outcomes; however, it unclear to what extent specific biological variables are associated comorbidity. This PROSPERO-registered systematic review evaluates the current body literature on genetic peripheral biomarkers comorbid TBI PTSD. Methods Searches were conducted four databases (PubMed, PsycInfo, PTSDPubs, Scopus). We included published studies examining differences among civilian, military, veteran participants both PTSD compared those alone as well as, some cases, healthy controls. Data extracted from evidence quality was assessed. Results Our final analysis 16 studies, majority which based data active duty participants. The results suggest that multiple gene variants likely contribute cumulative risk TBI. An elevated circulating level pro-inflammatory cytokine IL-6 most consistently replicated blood-based indicator illness, mTBI alone. Conclusion Several protein markers cellular inflammation appear be promising indicators chronic pathology Additional research needed determine how such factors indicate, predict, comorbidity they represent viable targets for development novel diagnostic tools therapeutic interventions.

Language: Английский

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Beyond Discrete Classifications: A Computational Approach to the Continuum of Cognition and Behavior in Children

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Psychiatry is undergoing a shift toward precision medicine, demanding personalized approaches that capture the complexity of cognition and behavior. Here, we introduce novel referential four robust, replicable, generalizable cognitive behavioral profiles. These were derived from most prominent pediatric cohort (n=10,843) validated in two independent cohorts (n=195 n=271). We demonstrate profiles’ longitudinal stability consistency with clinical diagnoses while exposing critical discrepancies across parent-reported, youth-reported, expert-derived diagnoses. Beyond validation, showcase real-world utility our approach by linking profiles to environmental factors, revealing associations between parental influences youths’ Our fuzzy profiling framework moves beyond discrete classification, offering powerful tool refine psychiatric evaluation intervention. provide an open-source framework, enabling researchers clinicians fast-track implementation foster data-driven, domain-based diagnosis. findings advocate for broadening scope assessment.

Language: Английский

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Causal effect of physical activity and sedentary behaviors on the risk of osteoarthritis: a univariate and multivariate Mendelian randomization study

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 8, 2023

Abstract There is still a lot of ambiguity about the link between physical activity (PA), sedentary behaviors (SBs) and osteoarthritis (OA). This study aimed to investigate causal relationship PA/SBs on risk OA. A univariate multivariate Mendelian randomization (MR) analysis was conducted effect five PA phenotypes three SB overall OA, knee hip total arthroplasty, arthroplasty (TKA). MR methods used were inverse-variance weighting, MR-Egger regressions, weighted median. Sensitivity examined horizontal pleiotropy heterogeneity, confirmed reliability results. After false discovery rate, light do-it-yourself (DIY) activities decreased for OA (OR: 0.32, 95% CI 0.16–0.65), 0.26, 0.12–0.51). Resulting in walking pleasure 0.87, 0.70–1.04) 0.14, 0.06–0.32) also observed. Television viewing, however, significantly increased TKA. MVMR findings revealed independent impacts watching television taking into account BMI, smoking, education. suggested that DIY beneficial preventing TKA with prolonged watching.

Language: Английский

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The pleiotropic architecture of human impulsivity across biological scales

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 29, 2023

Abstract Impulsivity is a complex psychological construct that represents core feature of many psychiatric and neurological conditions. Here, we used multivariate methods to formally model the genetic architecture impulsivity in humans, advancing genomic discovery revealing pervasive pleiotropy largely counters theories as unitary construct. We identified 18 loci 93 genes with diverse effects GWAS TWAS analyses, respectively, including hotspot at 17q21.31 harbors involved neurodevelopmental neurodegenerative disorders. Downstream analyses revealed heterogeneous signals were localized specific biological correlates, expression brain tissue during fetal development cortical alterations inferior frontal gyrus. Polygenic score suggested liability for different forms may differentiate across development, operating via broad pathways early life but affecting outcomes by adulthood. Collectively, our study generates new insights into pleiotropic impulsivity, which provides more comprehensive understanding its multi-faceted biology.

Language: Английский

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Beyond the Web of Genetic Risk for Schizophrenia: A Quest for a Modern Framework of Dysconnectivity

Biological Psychiatry, Journal Year: 2023, Volume and Issue: 94(2), P. 100 - 102

Published: June 26, 2023

Language: Английский

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