Schizophrenia etiology

Schizophrenia is a serious mental illness with unknown etiology, and shows increasing incidence and high lifetime prevalence rate. The main receptors related to the disease are DRD2 and 5-HTR2A. Thus, a comprehensive understanding of the interaction mode between antipsychotic drugs with relevant receptors is very important for developing more effective drugs. 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models constructed in this work provided a new method for studying the interaction between atypical antipsychotics and the two receptors...

BACKGROUND: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. METHODS: The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method...

Schizophrenia (SCZ) is a complex and heterogeneous neuropsychiatric disorder that lacks objective diagnostic indicators and the pathogenesis remain unclear. Genetic factors may exert a significant impact on the development of the condition. While obtaining brain tissue for biopsy in the course of adjuvant diagnosis of SCZ patients may not be possible, the collection of peripheral blood is more accessible and easier to implement. In recent years, the development and application of RNA sequencing technology has made seeking biomarkers of SCZ becomes more feasible...

Understanding the temporal and spatial brain locations etiological for psychiatric disorders is essential for targeted neurobiological research. Integration of genomic insights from genome-wide association studies with single-cell transcriptomics is a powerful approach although past efforts have necessarily relied on mouse atlases. Leveraging a comprehensive atlas of the adult human brain, we prioritized cell types via the enrichment of SNP-heritabilities for brain diseases, disorders, and traits, progressing from individual cell types to brain regions...

BACKGROUND: Stress plays an important role in the etiology of schizophrenia. However, the mechanisms by which chronic physiological stress and perceived stress relate to the clinical features of schizophrenia may differ. We aimed to elucidate the relationships among chronic physiological stress indexed by allostatic load (AL), perceived stress, and clinical symptoms in individuals with first-episode schizophrenia (FES). METHODS: Individuals with FES (n = 90, mean age = 28...

BACKGROUND: The concept of schizotypal personality disorder (SPD) emerged from observations of personality characteristics common in relatives of schizophrenic patients. While often studied in family designs, few studies and none with genetic measures, have examined SPD in epidemiological samples. METHODS: We studied individuals born in Sweden 1940-2000 with an ICD-10 diagnosis of SPD with no prior schizophrenia (SZ) diagnosis ( n = 2292). Demographic features, patterns of comorbidity, and Family Genetic Risk Scores (FGRS) were assessed from multiple Swedish registries...

The dopamine D4 receptor 7-repeat allele (D4.7 R) has been linked with psychiatric disorders such as attention-deficit-hyperactivity disorder, autism, and schizophrenia. However, the highly diverse study populations and often contradictory findings make it difficult to draw reliable conclusions. The D4.7 R has the potential to explain individual differences in behavior. However, there is still a great deal of ambiguity surrounding whether it is causally connected to the etiology of psychiatric disorders. Therefore, humanized D4...

Quetiapine, a pharmacological agent within the class of atypical antipsychotics, is characterized by its efficacy in mood stabilization and its role in the modulation of serotonergic and dopaminergic pathways. Its therapeutic utility is broad, encompassing the management of acute psychotic episodes, schizophrenia, bipolar disorder, and treatment-resistant depressive states. Quetiapine's effectiveness extends to depressive disorders that do not exhibit classic psychotic features, with a side effect profile that is less burdensome than many alternative psychotropic medications...

This review examines the substantial involvement of Single Nucleotide Polymorphisms (SNPs) and microRNAs (miRNAs) in the etiology and susceptibility to Schizophrenia, with particular emphasis on the dopaminergic, glutamatergic, and GABAergic systems. It elucidates the potential of SNPs to disrupt miRNA-mRNA interactions, leading to alterations in the regulatory mechanisms of Schizophrenia risk genes and subsequently influencing the susceptibility to Schizophrenia. Specific attention is given to the impact of SNPs in DICER, DROSHA , and DGCR8 , as well as the potential for changes in DRD2 gene expression driven by miR-9 and miR-326, heightening the likelihood of Schizophrenia development...

OBJECTIVE: To study the causes of clozapine treatment discontinuation and measure clozapine-induced myocarditis (CIM) rates in an Australian region, to compare the observed rates of CMI with reports from Australia and the world, and discuss factors related to CIM incidence rates in the region. METHODS: The study is a retrospective clinical audit of 327 patients prescribed clozapine. All patients were monitored by the mandatory CIM monitoring protocol for the first six weeks of treatment...

Schizophrenia (SZ) is a chronic and devastating mental illness that affects around 20 million individuals worldwide. Cognitive deficits and structural and functional changes of the brain, abnormalities of brain ECM components, chronic neuroinflammation, and devastating clinical manifestation during SZ are likely etiological factors shown by affected individuals. However, the pathophysiological events associated with multiple regulatory pathways involved in the brain of this complex disorder are still unclear...

Machine learning has been increasingly used to obtain individualized neuroimaging signatures for disease diagnosis, prognosis, and response to treatment in neuropsychiatric and neurodegenerative disorders. Therefore, it has contributed to a better understanding of disease heterogeneity by identifying disease subtypes that present significant differences in various brain phenotypic measures. In this review, we first present a systematic literature overview of studies using machine learning and multimodal MRI to unravel disease heterogeneity in various neuropsychiatric and neurodegenerative disorders, including Alzheimer disease, schizophrenia, major depressive disorder, autism spectrum disorder, multiple sclerosis, as well as their potential in transdiagnostic settings...

The establishment of 3'aQTLs comprehensive database provides an opportunity to help explore the functional interpretation from the genome-wide association study (GWAS) data of psychiatric disorders. In this study, we aim to search novel susceptibility genes, pathways, and related chemicals of five psychiatric disorders via GWAS and 3'aQTLs datasets. The GWAS datasets of five psychiatric disorders were collected from the open platform of Psychiatric Genomics Consortium (PGC, https://www.med.unc.edu/pgc/ ) and iPSYCH ( https://ipsych...

The insulin and dopaminergic systems in the brain are associated with schizophrenia and Parkinson's disease with respect to etiology and treatment. The present study investigated the crosstalk between the insulin receptor (IR) and dopamine receptor and found that insulin stimulation selectively inhibits signaling of D3 R in a PKCβII-dependent manner. Upon insulin stimulation, E3 ligase enzyme Mdm2 moves out of the nucleus to ubiquitinate PKCβII. Subsequently, ubiquitinated PKCβII translocates to the cell membrane and interacts with D3 R in a phosphorylation-dependent manner at S229/257, resulting in the attenuation of D3 R signaling and initiating clathrin-mediated endocytosis and downregulation...

BACKGROUND: Research on peripheral (e.g., blood-based) biomarkers for psychiatric illness has typically been low-throughput in terms of both the number of subjects and the range of assays performed. Moreover, traditional case-control studies examining blood-based biomarkers are subject to potential confounds of treatment and other exposures common to patients with psychiatric illnesses. Our research addresses these challenges by leveraging large-scale, high-throughput proteomics data and Mendelian Randomization (MR) to examine the causal impact of circulating proteins on psychiatric phenotypes and cognitive task performance...

BACKGROUND: Schizophrenia (SCZ) is a severe neuropsychiatric disorder of complex, poorly understood etiology, associated with both genetic and environmental factors. De novo mutations (DNMs) represent a new source of genetic variation in SCZ, however, in most cases their biological significance remains unclear. We sought to investigate molecular disease pathways connected to DNMs in SCZ by combining human induced pluripotent stem cell (hiPSC) based disease modeling and CRISPR-based genome editing...

PURPOSE: This clinical focus article aims to provide a comprehensive overview of schizophrenia and understanding of communication disorders resulting from its psychopathology. Schizophrenia is a spectrum disorder with varying levels of symptom expression. It is characterized by positive and negative symptoms that can cause communication disorders of different severity levels. Communication difficulties manifest as a range of symptoms such as alogia, disorganized speech, and impaired social communication...

Schizophrenia (SCZ) is a complex neurodevelopmental disorder characterized by the manifestation of psychiatric symptoms in early adulthood. While many research avenues into the origins of SCZ during brain development have been explored, the contribution of endothelial/vascular dysfunction to the disease remains largely elusive. To model the neuropathology of SCZ during early critical periods of brain development, we utilized patient-derived induced pluripotent stem cells (iPSCs) to generate 3D cerebral organoids and define cell-specific signatures of disease...

BACKGROUND: Observational studies have explored the association of psychiatric disorders and the risk of brain cancers. However, the causal effect of specific mental illness on glioma remains elusive due to the lack of solid evidence. METHODS: We performed a two-sample bidirectional Mendelian randomization (MR) analysis to explore the causal relationships between 5 common psychiatric disorders (schizophrenia, major depressive disorder, bipolar disorder, autism spectrum disorder, and panic disorder) and glioma...

(1) Background: Childhood-onset schizophrenia (COS) is a rare type of psychotic disorder characterized by delusions, hallucinations, grossly disorganized behavior, and poor psychosocial functioning. The etiology of COS is unknown, but neurodevelopmental factors are likely to play a critical role. A potential neurodevelopmental anomaly marker is the dorsal visual system dysfunction, which is implicated in motion perception, spatial functions, and attention. (2) Methods: To elucidate the role of the dorsal visual system in COS, we investigated 21 patients with COS and 21 control participants matched for age, sex, education, IQ, and parental socioeconomic status...