Polygenic and Polyenvironment Interplay in Schizophrenia-Spectrum Disorder and Affective Psychosis; the EUGEI First Episode Study.

Background: Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.

Methods: We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry.

Reducing mental health distress and preventing depression in young people in the community: A multimethod observational study with a real-world and prospective 12-month controlled approach: mental health distress in community youths.

Community-based youth mental health (YMH) platforms are challenging to evaluate. Using a multi-method approach, we examined the efficacy of an integrated YMH program in Hong Kong. The real-world outcomes of 1047 participants were compared with a propensity score (PS) matched control group randomly selected from the community (study 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.

Background: The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Methods: Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank.

Integrated Transcriptome Analysis Reveals Novel Molecular Signatures for Schizophrenia Characterization.

Schizophrenia (SCZ) is a complex psychiatric disorder presenting challenges for characterization. The current study aimed to identify and evaluate disease-responsive essential genes (DREGs) to enhance the molecular characterization of SCZ. RNA-sequencing data from PsychENCODE (536 SCZ patients, 832 controls) and peripheral blood transcriptome data from 144 recruited subjects (59 SCZ patients, 6 non-SCZ psychiatric patients, 79 controls) are analyzed.

Excess mortality and life-years lost in people diagnosed with depression: A 20-year population-based cohort study of 126,573 depressed individuals followed for 1,139,073 persons-years.

Depression is associated with premature mortality, but evidence is mainly derived from Western countries. Very limited research has evaluated shortened lifespan in depression using life-years-lost (LYLs), a recently developed mortality metric taking into account the illness onset for life expectancy estimation. Temporal trends of differential mortality gap are understudied.

Long-term metabolic side effects of second-generation antipsychotics in Chinese patients with schizophrenia: A within-subject approach with modelling of dosage effects.

Background: Second-generation antipsychotics (SGAs) are commonly used to treat schizophrenia (SCZ), but SGAs may differ in the severity of side effects. Long-term studies are lacking, and previous observational studies have limitations, such as failure to account for confounding factors and short follow-up durations.

Aims: To compare the long-term anthropometric and metabolic side effects of seven SGAs in a Chinese population, using a within-subject approach to reduce the risk of confounding.

Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.

Background And Hypothesis: Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets.

Study Design: To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders.

Computational Retinal Microvascular Biomarkers from an OCTA Image in Clinical Investigation.

Retinal structural and functional changes in humans can be manifestations of different physiological or pathological conditions. Retinal imaging is the only way to directly inspect blood vessels and their pathological changes throughout the whole body non-invasively. Various quantitative analysis metrics have been used to measure the abnormalities of retinal microvasculature in the context of different retinal, cerebral and systemic disorders.

Whole-exome sequencing in a Chinese sample provides preliminary evidence for the link between rare/low-frequency immune-related variants and early-onset schizophrenia.

Rare and low-frequency variants contribute to schizophrenia (SCZ), and may influence its age-at-onset (AAO). We examined the association of rare or low-frequency deleterious coding variants in Chinese patients with SCZ. We collected DNA samples in 197 patients with SCZ spectrum disorder and 82 healthy controls (HC), and performed exome sequencing.

Mendelian randomization: causal inference leveraging genetic data.

Mendelian randomization (MR) leverages genetic information to examine the causal relationship between phenotypes allowing for the presence of unmeasured confounders. MR has been widely applied to unresolved questions in epidemiology, making use of summary statistics from genome-wide association studies on an increasing number of human traits. However, an understanding of essential concepts is necessary for the appropriate application and interpretation of MR.

Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele.

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT).

Association of neurotransmitter pathway polygenic risk with specific symptom profiles in psychosis.

A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 205 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls.

INSIDER: Interpretable sparse matrix decomposition for RNA expression data analysis.

RNA sequencing (RNA-Seq) is widely used to capture transcriptome dynamics across tissues, biological entities, and conditions. Currently, few or no methods can handle multiple biological variables (e.g.

Temporal changes in brain morphology related to inflammation and schizophrenia: an omnigenic Mendelian randomization study.

Background: Over the past several decades, more research focuses have been made on the inflammation/immune hypothesis of schizophrenia. Building upon synaptic plasticity hypothesis, inflammation may contribute the underlying pathophysiology of schizophrenia. Yet, pinpointing the specific inflammatory agents responsible for schizophrenia remains a complex challenge, mainly due to medication and metabolic status.

Improved estimation of functional enrichment in SNP heritability using feasible generalized least squares.

Functional enrichment results typically implicate tissue or cell-type-specific biological pathways in disease pathogenesis and as therapeutic targets. We propose generalized linkage disequilibrium score regression (g-LDSC) that requires only genome-wide association studies (GWASs) summary-level data to estimate functional enrichment. The method adopts the same assumptions and regression model formulation as stratified linkage disequilibrium score regression (s-LDSC).

SumVg: Total Heritability Explained by All Variants in Genome-Wide Association Studies Based on Summary Statistics with Standard Error Estimates.

Genome-wide association studies (GWAS) are commonly employed to study the genetic basis of complex traits/diseases, and a key question is how much heritability could be explained by all single nucleotide polymorphisms (SNPs) in GWAS. One widely used approach that relies on summary statistics only is linkage disequilibrium score regression (LDSC); however, this approach requires certain assumptions about the effects of SNPs (e.g.

A Bayesian fine-mapping model using a continuous global-local shrinkage prior with applications in prostate cancer analysis.

The aim of fine mapping is to identify genetic variants causally contributing to complex traits or diseases. Existing fine-mapping methods employ Bayesian discrete mixture priors and depend on a pre-specified maximum number of causal variants, which may lead to sub-optimal solutions. In this work, we propose a Bayesian fine-mapping method called h2-D2, utilizing a continuous global-local shrinkage prior.

Dynamic structure-function coupling across three major psychiatric disorders.

Background: Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure-function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).

Methods: We quantified the dynamic structure-function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

Background: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis.

Methods: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study.