Gene-level analysis reveals the genetic aetiology and therapeutic targets of schizophrenia.

Genome-wide association studies (GWASs) have reported multiple risk loci for schizophrenia (SCZ). However, the majority of the associations were from populations of European ancestry. Here we conducted a large-scale GWAS in Eastern Asian populations (29,519 cases and 44,392 controls) and identified ten Eastern Asian-specific risk loci, two of which have not been previously reported.

Disorder-specific neurodynamic features in schizophrenia inferred by neurodynamic embedded contrastive variational autoencoder model.

Neurodynamic models that simulate how micro-level alterations propagate upward to impact macroscopic neural circuits and overall brain function may offer valuable insights into the pathological mechanisms of schizophrenia (SCZ). In this study, we integrated a neurodynamic model with the classical Contrastive Variational Autoencoder (CVAE) to extract and evaluate macro-scale SCZ-specific features, including subject-level, region-level parameters, and time-varying states. Firstly, we demonstrated the robust fitting of the model within our multi-site dataset.

Mitochondrial Dysfunction and Cognitive Impairment in Schizophrenia: The Role of Inflammation.

Background And Hypothesis: The complex immune-brain interactions and the regulatory role of mitochondria in the immune response suggest that mitochondrial damage reported in schizophrenia (SZ) may be related to abnormalities observed in immune and brain functions.

Study Design: Mitochondrial DNA copy number (mtDNA CN), a biomarker of mitochondrial function, was assessed in peripheral blood leukocytes (PBLs) of 121 healthy individuals and 118 SZ patients before and after 8 weeks of antipsychotic treatment, and a meta-analysis related to blood mtDNA CN was conducted. Plasma C-reactive protein (CRP) levels in SZ patients were obtained from the medical record system.

Autophagy defects at weaning impair complement-dependent synaptic pruning and induce behavior deficits.

Autophagy is crucial for synaptic plasticity and the architecture of dendritic spines. However, the role of autophagy in schizophrenia (SCZ) and the mechanisms through which it affects synaptic function remain unclear. In this study, we identified 995 single nucleotide polymorphisms (SNPs) across 19 autophagy-related genes that are associated with SCZ.

Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment response and white matter density deficits.

Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure.

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia.

Background: The striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients.

Mapping Brain Synergy Dysfunction in Schizophrenia: Understanding Individual Differences and Underlying Molecular Mechanisms.

To elucidate the brain-wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information-resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time-series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally-specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole-brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ.

Abnormal regional homogeneity as a potential imaging indicator for identifying adolescent-onset schizophrenia: Insights from resting-state functional magnetic resonance imaging.

Background: In patients with schizophrenia, there is abnormal regional functional synchrony. However, whether it also in patients with adolescent-onset schizophrenia (AOS) remains unclear. The goal of this study was to analyze the regional homogeneity (ReHo) of resting functional magnetic resonance imaging to explore the functional abnormalities of the brain in patients with AOS.

Age-related changes in behavior profile in male offspring of rats treated with poly I:C-induced maternal immune activation in early gestation.

Background: Autism and schizophrenia are environmental risk factors associated with prenatal viral infection during pregnancy. It is still unclear whether behavior phenotypes change at different developmental stages in offspring following the activation of the maternal immune system.

Methods: Sprague-Dawley rats received a single caudal vein injection of 10 mg/kg polyinosinic:polycytidylic acid (poly I:C) on gestational day 9 and the offspring were comprehensively tested for behaviors in adolescence and adulthood.

Human umbilical cord blood mesenchymal stem cells mediate microglia activation and improve anxiety-like behavior in MIA-induced offspring of schizophrenic rats.

Current treatments for schizophrenia (SCZ) remain largely ineffective in one-third of patients. Recent studies using stem cell therapy show a close relationship between stem cell immunomodulatory function and neuroinflammation in SCZ. To better investigate the efficacy of stem cell therapy for SCZ, human umbilical cord blood mesenchymal stem cells (hUC-MSC) with powerful immunomodulatory effects were administered to rats via the tail vein (once a week for 5 consecutive weeks starting from the weaning period) using a maternal immune activation (MIA) rodent model.

Shared Genetic Determinants of Schizophrenia and Autism Spectrum Disorder Implicate Opposite Risk Patterns: A Genome-Wide Analysis of Common Variants.

Background And Hypothesis: The synaptic pruning hypothesis posits that schizophrenia (SCZ) and autism spectrum disorder (ASD) may represent opposite ends of neurodevelopmental disorders: individuals with ASD exhibit an overabundance of synapses and connections while SCZ was characterized by excessive pruning of synapses and a reduction. Given the strong genetic predisposition of both disorders, we propose a shared genetic component, with certain loci having differential regulatory impacts.

Study Design: Genome-Wide single nucleotide polymorphism (SNP) data of European descent from SCZ (N cases = 53 386, N controls = 77 258) and ASD (N cases = 18 381, N controls = 27 969) were analyzed.

Right superior frontal gyrus: A potential neuroimaging biomarker for predicting short-term efficacy in schizophrenia.

Antipsychotic drug treatment for schizophrenia (SZ) can alter brain structure and function, but it is unclear if specific regional changes are associated with treatment outcome. Therefore, we examined the effects of antipsychotic drug treatment on regional grey matter (GM) density, white matter (WM) density, and functional connectivity (FC) as well as associations between regional changes and treatment efficacy. SZ patients (n = 163) and health controls (HCs) (n = 131) were examined by structural magnetic resonance imaging (sMRI) at baseline, and a subset of SZ patients (n = 77) were re-examined after 8 weeks of second-generation antipsychotic treatment to assess changes in regional GM and WM density.

Serum S100B protein and white matter changes in schizophrenia before and after medication.

Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain.

Reduced functional connectivity of the right dorsolateral prefrontal cortex at rest in obsessive-compulsive disorder.

Background: Neuroimaging studies have revealed the role of the right dorsolateral prefrontal cortex (DLPFC) in the neurobiological mechanism of obsessive-compulsive disorder (OCD). However, only a few studies have examined the functional connectivity (FC) pattern of the right DLPFC at rest in OCD.

Objective: The aim of this research is to examine the FC patterns of the right DLPFC at rest in OCD.

Levels of neuronal pentraxin 2 in plasma is associated with cognitive function in patients with schizophrenia.

Rationale: The precise diagnosis and treatment of cognitive impairment remains a major challenge in the field of schizophrenia (SCZ) research. Synaptic dysfunction and loss are thought to be closely related to the occurrence and development of SCZ and may be involved in cognitive dysfunction.

Objectives: The purpose of this study was to investigate whether neuronal pentraxins (NPTXs) plays a role in the etiology of SCZ and provide evidence of its possible therapeutic value a new target for drug development.

Lactate levels in the brain and blood of schizophrenia patients: A systematic review and meta-analysis.

Background: The pathophysiological mechanisms of schizophrenia are still unclear. Converging evidence suggests that energy metabolism abnormalities are involved in schizophrenia, and support its role in the pathophysiology of this disease. Lactate plays an important role in energy metabolism.

Palmitoylated Sept8-204 modulates learning and anxiety by regulating filopodia arborization and actin dynamics.

Septin proteins are involved in diverse physiological functions, including the formation of specialized cytoskeletal structures. Septin 8 (Sept8) is implicated in spine morphogenesis and dendritic branching through palmitoylation. We explored the role and regulation of a Sept8 variant in human neural-like cells and in the mouse brain.

Genome-wide meta-analysis, functional genomics and integrative analyses implicate new risk genes and therapeutic targets for anxiety disorders.

Anxiety disorders are the most prevalent mental disorders. However, the genetic etiology of anxiety disorders remains largely unknown. Here we conducted a genome-wide meta-analysis on anxiety disorders by including 74,973 (28,392 proxy) cases and 400,243 (146,771 proxy) controls.

Decreased CNNM2 expression in prefrontal cortex affects sensorimotor gating function, cognition, dendritic spine morphogenesis and risk of schizophrenia.

Genome-wide association studies (GWASs) have reported multiple single nucleotide polymorphisms (SNPs) associated with schizophrenia, yet the underlying molecular mechanisms are largely unknown. In this study, we aimed to identify schizophrenia relevant genes showing alterations in mRNA and protein expression associated with risk SNPs at the 10q24.32-33 GWAS locus.

Impaired erythropoietin-producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats.

An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin-producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission.

Cortical anatomical variations, gene expression profiles, and clinical phenotypes in patients with schizophrenia.

Background And Hypothesis: Schizophrenia (SZ) patients display significant structural brain abnormalities; nevertheless, the genetic mechanisms regulating cortical anatomical variations and their correlation with the disease phenotype are still ambiguous.

Study Design: We characterized anatomical variation using a surface-based method derived from structural magnetic resonance imaging of patients with SZ and age- and sex-matched healthy controls (HCs). Partial least-squares regression was performed across cortex regions between anatomical variation and average transcriptional profiles of SZ risk genes and all qualified genes from the Allen Human Brain Atlas.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.

Background: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment.