Enriching ultra-high risk for psychosis cohorts based on accumulated exposure to environmental risk factors for psychotic disorders DOI Creative Commons

Brian O’Donoghue,

Dominic Oliver, Hellen Geros

et al.

Psychological Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 9

Published: Nov. 25, 2024

Abstract Background and hypothesis Transition to psychosis rates within ultra-high risk (UHR) services have been declining. It may be possible ‘enrich’ UHR cohorts based on the environmental characteristics seen more commonly in first-episode cohorts. This study aimed determine whether transition varied according accumulated exposure factors at individual (migrant status, asylum seeker/refugee indigenous population, cannabis/methamphetamine use), family (family history or parental separation), neighborhood (population density, social deprivation, fragmentation) level. Methods The included people aged 15–24 who attended PACE clinic from 2012 2016. Cox proportional hazards models (frequentist Bayesian) were used assess association between psychosis. status was determined using CAARMS. Benjamini–Hochberg correct for multiple comparisons frequentist analyses. Results Of 461 young included, 55.5% female median follow-up 307 days (IQR: 188–557) 17.6% ( n = 81) transitioned a psychotic disorder. proportion increased incrementally number of individual-level present (HR 1.51, 95% CIs 1.19–1.93, p < 0.001, corr 0.01). family- neighborhood-level exposures did not increase > 0.05). Cannabis use only specific factor significantly associated with 1.89, 1.22–2.93, 0.03, BF 6.74). Conclusions There is dose–response relationship psychosis-related patients. If replicated, this could incorporated into novel approach identifying highest-risk individuals clinical services.

Language: Английский

Does Cannabis Use Contribute to Schizophrenia? A Causation Analysis Based on Epidemiological Evidence DOI Creative Commons

Sepehr Pourebrahim,

Tuba Ahmad,

Elisabeth Rottmann

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 368 - 368

Published: March 4, 2025

Cannabis abuse has been linked to acute psychotic symptoms as well the development of schizophrenia. Although association described, causation not yet investigated. Therefore, we investigated whether cannabis or cannabinoid use is causal for schizophrenia, conducting a systematic literature review according PRISM guidelines. Epidemiological studies and randomized clinical trials investigating links between psychosis-like events (PLE) schizophrenia were identified (according guidelines), relevant included in Forest plot analysis. Confounder analysis was performed using funnel plot, Hill causality criteria used estimate causation. A total 18 fulfilled search criteria; 10 forest plot. All reported an increased risk PLE nine ten studies, significant increase; overall OR calculated be 2.88 (CI 2.24 3.70), with twofold-higher during adolescence. effects indicated by The high likelihood contribution development. Cannabinoids likely contribute chronic especially if taken This effect increases THC concentration frequency use, stronger males than females. points possibility selective toxicity on synaptic plasticity adolescence, compared adult use. should regulated discouraged, prevention efforts strengthened, reference

Language: Английский

Citations

0
Novel multimodal precision medicine approaches and the relevance of developmental trajectories in bipolar disorder DOI Creative Commons
Olav B. Smeland,

Cecilie Busch,

Ole A. Andreassen

et al.

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

Published: March 1, 2025

Language: Английский

Citations

0
Transdiagnostic and Disorder-Level GWAS Enhance Precision of Substance Use and Psychiatric Genetic Risk Profiles in African and European Ancestries DOI Creative Commons
Yousef Khan, Christal N. Davis, Zeal Jinwala

et al.

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

Published: May 1, 2025

Language: Английский

Citations

0
The genetic landscape of substance use disorders DOI Creative Commons
Zachary F. Gerring, Jackson G. Thorp, Jorien L. Treur

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(11), P. 3694 - 3705

Published: May 29, 2024

Abstract Substance use disorders represent a significant public health concern with considerable socioeconomic implications worldwide. Twin and family-based studies have long established heritable component underlying these disorders. In recent years, genome-wide association of large, broadly phenotyped samples identified regions the genome that harbour genetic risk variants associated substance These enabled discovery putative causal genes improved our understanding relationships among other traits. Furthermore, integration data clinical information has yielded promising insights into how individuals respond to medications, allowing for development personalized treatment approaches based on an individual’s profile. This review article provides overview advances in genetics demonstrates may be used reduce burden disease improve outcomes.

Language: Английский

Citations

3
Leveraging the Genetics of Psychiatric Disorders to Prioritize Potential Drug Targets and Compounds DOI Creative Commons
Nadine Parker, Elise Koch, Alexey Shadrin

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 24, 2024

Summary Background Genetics has the potential to inform biologically relevant drug treatment and repurposing which may ultimately improve patient care. In this study, we combine methods leverage genetics of psychiatric disorders prioritize targets compounds. Methods We used largest available genome-wide association studies, in European ancestry, four [i.e., attention deficit hyperactivity disorder (ADHD), bipolar disorder, depression, schizophrenia] along with genes encoding targets. With data, conducted enrichment analyses incorporating novel specific GSA-MiXeR tool. then a series molecular trait using large-scale transcriptomic proteomic datasets sampled from brain blood tissue. This included use UK Biobank data for proteome-wide study disorders. accumulated evidence, compounds each disorder. Findings reveal candidate shared across multiple as well disorder-specific Drug prioritization indicated genetic support several currently psychotropic medications including antipsychotic paliperidone top ranked schizophrenia. also observed other commonly psychotropics (e.g., clozapine, risperidone, duloxetine, lithium, valproic acid). Opportunities were revealed such cholinergic drugs ADHD, estrogens gabapentin enacarbil Our findings indicate liability schizophrenia is associated reduced expression CYP2D6, gene metabolizer neurotransmitters, suggesting risk poor response altered neurotransmission. Interpretation Here present complimentary comprehensive that highlight utility informing development opportunities refining treatment.

Language: Английский

Citations

3
Sourcing Bivariate Genetic Overlap for Polygenic Prediction using MiXeR-Pred DOI Creative Commons
Nadine Parker, Weiqiu Cheng, Guy Hindley

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 2024

Abstract The past two decades have seen the advent and mass application of genome-wide association studies (GWAS). observation that complex phenotypes are polygenic has contributed to development score (PGS) for understanding individual-level genetic predisposition. There been substantial advances in PGS methodology recent years. However, few methods leverage pleiotropic nature prediction. Here, we present MiXeR-Pred, a novel approach prediction builds on an established MiXeR framework source overlap with secondary phenotype inform primary phenotype. We apply MiXeR-Pred using both bipolar disorder schizophrenia as along following phenotypes: education attainment, major depressive disorder, measures cortical brain morphology. compare predictions derived from each phenotype’s GWAS addition multi-trait analysis (MTAG) approach, which can use correlated boost discovery show improves performance when compared MTAG PGS, regardless Not only be used further our pleiotropy among phenotypes, but it also provides conceptualization how one improve ultimately contribute advancements personalized medicine. tool is available at https://github.com/precimed/mixer-pred .

Language: Английский

Citations

3
Psychiatric disorders and brain white matter exhibit genetic overlap implicating developmental and neural cell biology DOI
Nadine Parker, Weiqiu Cheng, Guy Hindley

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(11), P. 4924 - 4932

Published: Sept. 27, 2023

Language: Английский

Citations

7
Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking DOI Creative Commons
Emma C. Johnson, Isabelle Austin-Zimmerman,

Hayley HA Thorpe

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 18, 2024

Abstract Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use disorders. There is interest in understanding the extent to which these relationships are causal, what shared genetic factors play a role. We explored between (Scz), disorder (CanUD), ever-regular (Smk) using largest available genome-wide studies of phenotypes individuals African European ancestries. All three were positively genetically correlated (r g s = 0.17 – 0.62).Causal inference analyses suggested presence horizontal pleiotropy, but evidence for bidirectional causal was also found all even after correcting pleiotropy. identified 439 pleiotropic loci ancestry data, 150 novel (i.e., not significant original studies). Of loci, 202 had lead variants showed convergent effects same direction effect) on Scz, CanUD, Smk. Genetic across strong correlations risk-taking, executive function, several mental health conditions. Our results suggest that both pleiotropy mechanisms may role relationship Smk, longitudinal, prospective needed confirm relationship.

Language: Английский

Citations

1
Genome-wide association studies of lifetime and frequency cannabis use in 131,895 individuals DOI Creative Commons
Hayley H. A. Thorpe, Pierre Fontanillas, John J. Meredith

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 16, 2024

Cannabis is one of the most widely used drugs globally. Decriminalization cannabis further increasing consumption. We performed genome-wide association studies (GWASs) lifetime (N=131,895) and frequency (N=73,374) use. Lifetime use GWAS identified two loci, near CADM2 (rs11922956, p=2.40E-11) another GRM3 (rs12673181, p=6.90E-09). Frequency locus (rs4856591, p=8.10E-09; r2 =0.76 with rs11922956). Both traits were heritable genetically correlated previous GWASs disorder (CUD), as well other substance cognitive traits. Polygenic scores (PGSs) for associated phenotypes in AllofUs participants. Phenome-wide study PGS a hospital cohort replicated associations mood disorders, uncovered celiac infectious diseases. This work demonstrates value CUD transition risk factors.

Language: Английский

Citations

1
The impact of schizophrenia genetic load and heavy cannabis use on the risk of psychotic disorder in the EU-GEI case-control and UK Biobank studies DOI Creative Commons
Isabelle Austin-Zimmerman, Edoardo Spinazzola, Diego Quattrone

et al.

Psychological Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 13

Published: Dec. 6, 2024

Abstract Background The association between cannabis and psychosis is established, but the role of underlying genetics unclear. We used data from EU-GEI case-control study UK Biobank to examine independent combined effect heavy use schizophrenia polygenic risk score (PRS) on for psychosis. Methods Genome-wide summary statistics Psychiatric Genomics Consortium Genomic Psychiatry Cohort were calculate disorder (CUD) PRS 1098 participants 143600 Biobank. Both datasets had information use. Results In both samples, independently increased Schizophrenia was not associated with patterns in cases or controls cases. It lifetime daily among without psychosis, substantially reduced when CUD included model. sample, regular users high-potency highest odds being a case (OR adjusted = 5.09, 95% CI 3.08–8.43, p 3.21 × 10 −10 ). found no evidence interaction Conclusions Regular remains strong predictor psychotic PRS, which does seem be These are important findings at time increasing potency worldwide.

Language: Английский

Citations

1