Polygenic Risk for Schizophrenia and Personality Traits in Individuals Without Non-Affective Psychosis

Published: Jan. 1, 2025

Language: Английский

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Role of CDH2 and DCHS2 genes in classification of affective-delusional and hallucinatory-paranoid psychopathological syndromes of paranoid schizophrenia

Vestnik nevrologii psihiatrii i nejrohirurgii (Bulletin of Neurology Psychiatry and Neurosurgery), Journal Year: 2025, Volume and Issue: 1, P. 80 - 90

Published: Jan. 15, 2025

Positive symptoms in paranoid schizophrenia are caused by mutations a separate group of genes common with bipolar disorder type I. This fact suggests the presence genetically determined substrate severe psychopathological syndromes within schizophrenia, such as affective-delusional and hallucinatory-paranoid syndromes. Dysfunction expression involved processes brain formation development is considered one possible causes mental illness. Objective. Based on results examining patients leading hallucinatory-delusional syndromes, identify correlation genomic variants rs1944294‑T CDH2 gene, rs11935573‑G rs12500437‑G/T DCHS2 gene associated syndrome. Material methods. The study participants were Caucasian, not blood relatives lived Russia. diagnosis (F20.00 F20.01) was established during clinical interview. Two groups formed to conduct study. first included (n=27) an second (n=45) Results. Statistical analysis distribution identified alleles did reveal significant rs6265 BDNF syndrome schizophrenia. absence reliable indicates presumed role for picture part symptom complex

Language: Английский

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Integrating rare variant genetics and brain transcriptome data implicates novel schizophrenia putative risk genes

Schizophrenia Research, Journal Year: 2025, Volume and Issue: 276, P. 205 - 213

Published: Feb. 1, 2025

Language: Английский

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Clinical Free Text Summaries and LLMs: A Case Study on LLM-supported Identification of Intellectual Disabilities in Clinical Free Text Summaries (Preprint)

Published: Feb. 6, 2025

Free-text clinical data that is unstructured and narrative in nature can provide a rich source of patient information. However, the information contained within routinely collected health typically captured as free-text, extracting research quality phenotypes from these remains challenge. Manually reviewing free-text notes time-consuming process not suitable for large scale datasets. On other hand, automatically be challenging task due to medical researchers lacking gold-standard annotated references purpose-built resources including software. Recent language models (LLMs) have ability understand natural instructions (prompts) which helps them adapt different domains tasks without need specific training data. This makes applications, though their use this field still limited. In paper, we analyse how in-context-learning techniques utilised text classification real-world scenario, where only few examples are available. For this, sought develop pipeline, based on “few-shot” learning framework, summaries derived discharge interviews cohort 1121 individuals with severe mental illnesses. Our main aim was identify those confirmed or strongly suspected comorbid intellectual disability (ID). A secondary take advantage complementary independent cohort, form high-quality genomic dataset. designed proof-of-concept study assess whether identified by our LLM-based having ID were also carriers genetic variants known confer risk general population. We explore novel approaches performing summaries, using an intermediate Information Extraction step human-in-the-loop approach order maximise performance LLMs. perform experiments two models, Flan-T5 LLaMA, dataset free diagnosed illness. genetics-based experiment, published de novo mutations been called. rare variant association analyses through Firth’s penalised likelihood approach, logistic regression framework appropriate sparse Results show two-stage consisting extraction manual validation effective identifying disabilities information, needing single example per label. further validated demonstrating classified LLMs significantly enriched genes associated disability. Recently developed in-context combined approaches, highly beneficial categorisation when there lack study, used illness who disability, biologically clinically meaningful subgroup patients. showcases one applications method suggests broad uses supporting records.

Language: Английский

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Manic symptoms in schizophrenia spectrum disorders

Brain medicine :, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 7

Published: Feb. 11, 2025

This study investigated the presence of manic symptoms in stable patients diagnosed with schizophrenia spectrum disorders (SSDs) aiming to identify their association clinical symptoms. A total 75 out-patients, 41.3% female [47.81 (±10.521) year-old] were assessed using Young Mania Rating Scale (YMRS), Positive and Negative Syndrome (PANSS), Generalized Anxiety Disorder-7 scale (GAD-7), Risk Assessment Suicidality (RASS). Participants divided into two groups based on YMRS scores: Group 1, without or minimal mania (YMRS ≤ 10) 2, distinct > 10). We performed statistical analysis IBM SPSS version 29.0. Our revealed a positive significant correlation between score PANSS ( r 2 = 0.516, p 2.15 × 10 −6 ), PANSS-Positive subscore 0.600, 1.31 −8 ) PANSS-General Psychopathology 0.444, 6.646 −5 Bonferroni corrected at 0.0004. Moreover, as by subscale differed significantly [ t (73) 3.982, 0.00016, d 1.040]. Linear regression showed that severity predicted occurrence could serve pilot study, observing SSDs recruitment goes on, it is expected yield more robust evidence prevalence associations forming phenotypic characterization basis for further dimensional research psychopathology etiopathogenesis SSDs.

Language: Английский

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Dissecting Schizophrenia Biology Using Pleiotropy with Cognitive Genomics

Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Identification of Schizophrenia‐Risk Regulatory Variant rs1399178 in the Non‐coding Region With Its Impact on NRF1 Binding

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: Feb. 28, 2025

ABSTRACT Aims The challenges in identifying functional variants from genome‐wide association studies (GWAS) and unraveling regulatory mechanisms schizophrenia research persist, particularly intronic regions. A non‐coding variant, rs1399178, associated with risk, is identified its impact on NRF1 binding investigated. Methods This study focuses GWAS risk loci, using genomics, expression analyses structural analysis to identify 736 single‐nucleotide polymorphisms (SNPs) that disrupt transcription factor (TF) binding. Results Among these SNPs, rs1399178 stands out as a bifunctional intergenic SNP can switch between acting promoter an enhancer, potentially influencing MLH1 LRRFIP2 via quantitative trait loci analysis. Importantly, mutation of the G allele significantly diminishes affinity nuclear respiratory 1 (NRF1). Structural provides further insight into this alteration protein–nucleic acid complex formation. Conclusion Based our data, model proposed which confers by modifying profiles, thereby regulating abundance target genes through promoter‐enhancer switching. novel insights variants, highlighting intricate nature genetic interactions potential therapeutic targets.

Language: Английский

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What clinicians should know about the contribution of modern behavioral genetics to psychiatric problems

Psychological Medicine, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Language: Английский

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Exploring the Potential of Precision Medicine in Neuropsychiatry: A Commentary on New Insights for Tailored Treatments Based on Genetic, Environmental, and Lifestyle Factors

Genes, Journal Year: 2025, Volume and Issue: 16(4), P. 371 - 371

Published: March 24, 2025

Neuropsychiatric disorders are complex conditions with multifactorial etiologies, in which genetics play a pivotal role. Despite significant advancements psychiatric research, traditional treatment options remain largely symptomatic, focusing on clinical signs without fully addressing the underlying biological causes. However, recent developments precision medicine—an approach that tailors treatments based genetic, environmental, and lifestyle factors—hold great promise for transforming of these disorders. By identifying specific genetic markers understanding gene–environment interactions, medicine can offer more personalized effective treatments, leading to better patient outcomes. Our primary aim was explore how integrating data environmental factors could enhance neuropsychiatric such as schizophrenia, bipolar disorder, depression. The secondary examine potential pharmacogenomics gene therapy improving therapeutic strategies. results indicate while progress has been made, challenges remain, including complexity interactions need granular phenotypic data. In conclusion, revolutionize by providing individualized care considers makeup, influences, factors, paving way therapies improved

Language: Английский

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A review of antipsychotic therapy effectiveness and tolerability among individuals with copy number variants relevant to schizophrenia

Psychiatric Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Although numerous copy number variants (CNVs) are considered pathogenic with respect to the development of schizophrenia, only eight loci have reached genome-wide significance. Reviews/studies characterizing antipsychotic use in this context exist for three corresponding CNV syndromes. As these disorders also predispose neurodevelopmental anomalies and various medical comorbidities, affected individuals may be particularly sensitive side effects medications. such, review sought identify describe all reports among other significant schizophrenia risk CNVs (2p16.3 deletions/NRXN1 variants, 15q13.3 16p11.2 deletions, 7q11.23 duplications, 1q21.1 deletions or duplications). Only 10 eligible articles describing 29 were included. While treatment response was reasonably good most individuals, despite variability existing across specific syndromes, rarely reported. Above all, highlights need more case reports/series published.

Language: Английский

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