Pathogenesis Of Schizophrenia Research Articles

Identification of differentially expressed genes of blood leukocytes for Schizophrenia.

Schizophrenia (SCZ) is a severe neurodevelopmental disorder with brain dysfunction. This study aimed to use bioinformatic analysis to identify candidate blood biomarkers for SCZ. The study collected peripheral blood leukocyte samples of 9 SCZ patients and 20 healthy controls for RNA sequencing analysis. Bioinformatic analyses included differentially expressed genes (DEGs) analysis, pathway enrichment analysis, and weighted gene co-expression network analysis (WGCNA). This study identified 1,205 statistically significant DEGs, of which 623 genes were upregulated and 582 genes were downregulated. Functional enrichment analysis showed that DEGs were mainly enriched in cell chemotaxis, cell surface, and serine peptidase activity, as well as involved in Natural killer cell-mediated cytotoxicity. WGCNA identified 16 gene co-expression modules, and five modules were significantly correlated with SCZ (p < 0.05). There were 106 upregulated genes and 90 downregulated genes in the five modules. The top ten genes sorted by the Degree algorithm were RPS28, BRD4, FUS, PABPC1, PCBP1, PCBP2, RPL27A, RPS21, RAG1, and RPL27. RAG1 and the other nine genes belonged to the turquoise and pink module respectively. Pathway enrichment analysis indicated that these 10 genes were mainly involved in processes such as Ribosome, cytoplasmic translation, RNA binding, and protein binding. This study finds that the gene functions in key modules and related enrichment pathways may help to elucidate the molecular pathogenesis of SCZ, and the potential of key genes to become blood biomarkers for SCZ warrants further validation.

Establishment of a Mitochondrial Metabolism-Related Diagnostic Model in Schizophrenia Based on LASSO Algorithm.

Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes (MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs. Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website. A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified. Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.

The effect of phencyclidine-mediated blockade of NMDA receptors in the early postnatal period on glutathione and sulfur amino acid levels in the rat brain as a potential causative factor of schizophrenia-like behavior in adulthood

BackgroundPhencyclidine, an NMDA receptor antagonist, is frequently used to model behavioral and neurochemical changes correlated with schizophrenia in laboratory animals. The present study aimed to examine the effects of repeated administration of phencyclidine during early postnatal development on the contents of glutathione and sulfur-containing amino acids, as well as the activity of antioxidant enzymes in the brain of 12-day-old rats, and schizophrenia-like symptoms in adulthood.MethodsMale Sprague-Dawley pups were administered phencyclidine (10 mg/kg) or saline subcutaneously on the postnatal days p2, p6, p9 and p12. In 12-day-old pups, 4 h after the last dose of phencyclidine, the levels of glutathione, cysteine, methionine, and homocysteine, and the enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were measured in the frontal cortex, hippocampus, and striatum. In 70-72-day-old rats, schizophrenia-like symptoms were assessed using behavioral tests.ResultsBiochemical data showed that perinatal phencyclidine treatment significantly reduced glutathione and cysteine levels in all brain structures studied, methionine was diminished in the striatum, and homocysteine in both the frontal cortex and striatum. GR activity was increased in the frontal cortex while SODactivity was decreased in the hippocampus. Behaviorally, perinatal phencyclidine induced long-term deficits in social and cognitive function and a decrease in locomotor activity assessed as the time of walking. Finally, perinatal treatment with phencyclidine resulted in a significant reduction in body weight gain over time.ConclusionOur research provides further evidence for the usefulness of the phencyclidine-induced neurodevelopmental model of schizophrenia for studying the pathogenesis of schizophrenia.

Neutrophil-Lymphocyte Ratio Values in Schizophrenia: A Comparison between Oral and Long-Acting Antipsychotic Therapies.

Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used to treat this condition by inhibiting D2 dopamine and 5HT2 serotonin receptors. The selection of the appropriate mode of delivery for these drugs is based on factors such as patient adherence, clinical presentation, and patient preferences. However, additional drivers of treatment selection are required in clinical practice. Mounting evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of schizophrenia. NLR, a cost-effective biomarker of inflammation, has increased in several psychiatric conditions and may represent a valid method for studying the inflammatory stage in schizophrenia, relapse, and the first episode of psychosis. The aim of this study is to evaluate whether there are any variations in NLR values between patients given oral antipsychotics and those given long-acting antipsychotics. The study included 50 individuals with schizophrenia, either acute or in the follow-up phase. NLR was obtained by calculating the ratio of absolute neutrophil count (cells/μL) and absolute lymphocyte count (cells/μL). Patients on long-acting antipsychotics exhibited significantly lower mean NLR scores (1.5 ± 0.7) compared to those on oral antipsychotics (2.2 ± 1.3) (p < 0.05). NLR appears promising as a neuroinflammatory biomarker. This study reveals significantly lower NLR values in patients on long-acting antipsychotics, which may signify reduced systemic inflammation and improved adherence.

Integration of proteinogenic amino acids in the pathogenesis of schizophrenia

Integration of proteinogenic amino acids in the pathogenesis of schizophrenia

Decreased serum VEGF and NRG1β1 levels in male patients with chronic schizophrenia: VEGF correlation with clinical symptoms and cognitive deficits

BackgroundVascular endothelial growth factor (VEGF) and neuregulin1 (NRG1) are multifunctional trophic factors reported to be dysregulated in schizophrenia. However, the relationships between serum concentrations and schizophrenia symptoms have differed markedly across studies, possibly because schizophrenia is a highly heterogenous disorder. The aim of this study was to investigate the associations of serum VEGF and NRG1 with clinical symptoms and cognitive deficits specifically in male patients with chronic schizophrenia. MethodsThe study included 79 male patients with chronic schizophrenia and 79 matched healthy individuals. Serum VEGF, NRG1β1, S100B, S100A8, and neuropilin1 were measured using the Luminex liquid suspension chip detection method, psychopathological symptom severity using the Positive and Negative Symptom Scale (PANSS), and cognitive dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). ResultsSerum VEGF and NRG1β1 concentrations were significantly lower in male chronic schizophrenic patients than healthy controls (P < 0.05), while serum S100B, S100A8, and neuropilin1 concentrations did not differ between groups (P > 0.05). Serum VEGF concentration was negatively correlated with PANSS negative subscore (beta = −0.220, t = −2.07, P = 0.042), general psychopathology subscore (beta = -0.269, t = −2.55, P = 0.013), and total score (beta = -0.234, t = −2.12, P = 0.038), and positively correlated with RBANS language score (beta = 0.218, t = 2.03, P = 0.045). Alternatively, serum NRG1β1 concentration was not correlated with clinical symptoms or cognitive deficits (all P > 0.05). ConclusionDysregulation of VEGF and NRG1β1 signaling may contribute to the pathogenesis of chronic schizophrenia in males. Moreover, abnormal VEGF signaling may contribute directly or through intermediary processes to neuropsychiatric and cognitive symptom expression.

Inflammation in Schizophrenia? A review of alterations in patients

Schizophrenia is a psychotic psychiatric disorder that significantly impacts the social life of the patient. A better understanding of pathogenesis of this disorder is of utmost importance to caregivers. Recent studies have shown evidence of inflammatory reactions involving the pathogenesis of Schizophrenia. Biochemical analysis of CSF has reported an increased count of IL-6 and IL-8 along with other inflammatory substances. Histopathological studies of brain of the affected individuals have presented microglial dysfunction along with several other changes, observed by different researchers. Also, mothers suffering from any particular condition that involved inflammation in the gestational period have been observed to lead to the development of Schizophrenia or related disorders in offspring. Gut-Brain Axis has recently acquired a huge interest among medical researchers. A lot of psychiatric conditions are nowadays being attributed to gut microbiota. Gut microbiota analysis among Schizophrenia patients has shown significant alteration of gut microflora, for example, an increased number of Lactobacillus sp. All these studies, when taken into consideration, can give a holistic approach towards the way the pathology of Schizophrenia being viewed, and thus allow professionals to provide better careto the patients.

Interaction between RNF4 and SART3 is associated with the risk of schizophrenia

The pathogenesis of schizophrenia (SCZ) is heavily influenced by genetic factors. Ring finger protein 4 (RNF4) and squamous cell carcinoma antigen recognized by T cells 3 (SART3) are thought to be involved in nervous system growth and development via oxidative stress pathways. Moreover, they have previously been linked to SCZ. Yet the role of RNF4 and SART3 in SCZ remains unclear. Here, we investigated how these two genes are involved in SCZ by studying their variants observed in patients. We first observed significantly elevated mRNA levels of RNF4 and SART3 in the peripheral blood in both first-episode (n = 30) and chronic (n = 30) SCZ patients compared to controls (n = 60). Next, we targeted-sequenced three single nucleotide polymorphisms (SNPs) in SART3 and six SNPs in RNF4 for association with SCZ using the genomic DNA extracted from peripheral blood leukocytes from SCZ participants (n = 392) and controls (n = 572). We observed a combination of SNPs that included rs1203860, rs2282765 (both in RNF4), and rs2287550 (in SART3) was associated with increased risk of SCZ, suggesting common pathogenic mechanisms between these two genes. We then conducted experiments in HEK293T cells to better understand the interaction between RNF4 and SART3. We observed that SART3 lowered the expression of RNF4 through ubiquitination and downregulated the expression of nuclear factor E2-related factor 2 (NRF2), a downstream factor of RNF4, implicating the existence of a possible shared regulatory mechanism for RNF4 and SART3. In conclusion, our study provides evidence that the interaction between RNF4 and SART3 contributes to the risk of SCZ. The findings shed light on the underlying molecular mechanisms of SCZ and may lead to the development of new therapies and interventions for this disorder.

Exploring the role of eosinophil cationic protein (ECP) in schizophrenia: Insights and implications.

Schizophrenia, a multifaceted neuropsychiatric disorder characterized by disruptions in perception, cognition, and behavior, has been associated with neuroinflammatory processes. Emerging research has increasingly recognized the potential involvement of immune-related factors in the pathogenesis of schizophrenia, prompting investigations into biomarkers associated with inflammatory cascades. Among these biomarkers, Eosinophil Cationic Protein (ECP), traditionally known for its role in eosinophil-mediated immune responses, has garnered attention for its putative association with neuroinflammation in schizophrenia. This paper critically examines the current understanding of the role of ECP in schizophrenia. ECP, a cytotoxic protein released by eosinophils, has diverse immunomodulatory effects and has been identified in altered concentrations in individuals with schizophrenia. Studies have reported elevated levels of ECP in peripheral fluids of schizophrenia patients, suggesting a possible link between ECP dysregulation and the inflammatory milieu characteristic of the disorder. Moreover, the potential implications of ECP in neuroinflammatory processes relevant to schizophrenia pathophysiology are discussed. ECP's role in modulating immune responses and its potential impact on neuronal function, synaptic plasticity, and neurotoxicity within the central nervous system (CNS) are considered, highlighting the potential contribution of ECP to the neuroinflammatory mechanisms underlying schizophrenia. In conclusion, while the precise role of ECP in schizophrenia pathogenesis warrants further elucidation, exploring its association with neuroinflammation holds promise in unraveling new biomarkers and therapeutic avenues for managing this complex psychiatric disorder.

Copy number deletion of PLA2G4A affects the susceptibility and clinical phenotypes of schizophrenia

Phospholipase A2(PLA2) superfamily is recognized as being involved in the pathogenesis of schizophrenia by affecting lipid homeostasis in cell membranes. We hypothesized that PLA2 gene copy number variation (CNV) may affect PLA2 enzyme expression and be associated with schizophrenia risk. This study indicated that in the discovery stage, an increased copy number of PLA2G6 and the deletion of PLA2G3, PLA2G4A, PLA2G4F and PLA2G12F was associated with increased risk of schizophrenia. CNV segments involving six PLA2 genes were detected in publicly available datasets, including two deletion segments specific to the PLA2G4A gene. The relationship between the deletion of PLA2G4A and susceptibility to schizophrenia was then reaffirmed in the validation group of 806 individuals. There was a significant correlation between PLA2G4A deletion and the symptoms of poverty of thought in male patients and erotomanic delusion in females. Furthermore, ELISA results demonstrate a significant decrease in peripheral blood cytosolic PLA2(cPLA2) levels in patients with the PLA2G4A deletion genotype compared to those with normal and copy number duplicate genotypes. These data suggest that the functional copy number deletion in the PLA2G4A gene is associated with the risk of schizophrenia and clinical phenotypes by reducing the expression of cPLA2, which may be an indicator of susceptibility to schizophrenia.

The associations of psychopathology and metabolic parameters with serum bilirubin levels in patients with acute-episode and drug-free schizophrenia: a 5-year retrospective study using an electronic medical record system

BackgroundThe oxidative system plays an important role in the pathogenesis of schizophrenia. Inconsistent associations were found between hyperbilirubinemia and psychopathology as well as glycolipid metabolism in patients with schizophrenia at different episodes. This current study aimed to examine these associations in patients with acute-episode and drug-free (AEDF) schizophrenia.MethodsThis is a retrospective study using 5 years of data from May 2017 to May 2022 extracted from the electronic medical record system of Chaohu Hospital of Anhui Medical University. Healthy controls (HCs) from the local medical screening center during the same period were also included. Participants’ data of the bilirubin levels [total bilirubin (TB), conjugated bilirubin (CB), unconjugated bilirubin (UCB)], glycolipid metabolic parameters and the score of the Brief Psychiatric Rating Scale (BPRS) were collected.ResultsA total of 1468 case records were identified through the initial search. After screening, 89 AEDF patients and 100 HCs were included. Compared with HCs, patients had a higher CB level, and lower levels of glycolipid metabolic parameters excluding high density lipoprotein-cholesterol (HDL-C) (all P < 0.001). Binary logistic regression analyses revealed that high bilirubin levels in the patients were independently associated with higher total and resistance subscale scores of BPRS, a higher HDL-C level, and lower total cholesterol and triglyceride levels (all P < 0.05).ConclusionBilirubin levels are elevated in patients with AEDF schizophrenia. Patients with high bilirubin levels have more severe psychopathology and relatively optimized glycolipid metabolism. In clinical practice, regular monitoring of bilirubin levels in this patient population should be carried out.

Current understanding of the etiology and pathogenesis of schizophrenia

The current literature data on the etiology and pathogenesis of schizophrenia were analyzed. The research method is the analysis of scientific papers on this problem over the past 5 years, presented in the databases of eLibrary, National Library of Medicine and electronic versions of the journals “World Psychiatry Journal”, “The Lancet Psychiatry”, “Schizophrenia Bulletin” and others. Genetic, neurotransmitter, psycho-traumatic, sociocultural and other theories of the origin and development of schizophrenia are analyzed in the review. Schizophrenia is a disease difficult to verify and genetically determined. According to modern theories, the occurrence of schizophrenia and the appearance of symptoms can be influenced by metabolic disorders of neurotransmitters, psycho-traumatic factors, socio-cultural aspects of human life, while the anatomical subcortical structures of the brain are damaged.

Structural and Functional Characteristics of the Dorsolateral Prefrontal Cortex in Schizophrenia Spectrum Disorders and Their Associations with Onset Age

Background: the dorsolateral prefrontal cortex (DLPFC) is one of the latest brain structures to mature during the ontogeny, and its structural and functional abnormalities play an important role in the pathogenesis of schizophrenia. As schizophrenia spectrum disorders usually start before the complete brain maturation and their earlier onset is coupled with worse prognosis, we suggested that earlier illness onset is related to more pronounced aberrations of the DLPFC. The aim of study was to analyze the associations of the onset age of schizophrenia spectrum disorders with structural and functional characteristics of the DLPFC that differentiated patients with schizophrenia spectrum disorders from healthy controls. Patients and methods: male patients with a diagnosis of schizophrenia spectrum disorders (n = 82) and healthy controls (n = 86) underwent structural MRI and functional resting-state fMRI. Cortical thickness and whole-brain functional connectivity of the DLPFC as well as local coherence and amplitude of low-frequency fluctuations of haemodynamic signal in the DLPFC were analyzed. Results: patients demonstrated a decreased gray matter thickness in the DLPFC bilaterally along with aberrant (predominantly decreased) functional connectivity of the DLPFC with other brain structures in each hemisphere. These measures were not associated with the age of illness onset. Conclusions: structural and functional abnormalities revealed in this study coincide with conventional view on the DLPFC as one of the key regions in schizophrenia spectrum disorders pathogenesis, however, these aberrations were not related to the age of psychosis onset. Possible interpretations of our results and limitations of the study are discussed in the article.

Interactions between genetic and environmental factors and schizophrenia: Insights from KPNA1-deficient mice

The interactions between genetic and environmental factors (G x E interactions) play a crucial role in the pathogenesis of schizophrenia. The administration of phencyclidine, a psychotropic drug, to Kpna1-deficient mice induces behavioral abnormalities resembling schizophrenia. In the nucleus accumbens of these mice, the expressions of dopamine receptors, an RNA editing enzyme, and cytoplasmic dynein demonstrate gene-environment interaction-dependent alterations. Kpna1-deficient mice may be useful as a gene-environment interaction model for schizophrenia and provide insights into its pathogenesis. Further, changes in gene expression in the nucleus accumbens may be involved in the development of schizophrenia.

Neuronal autoantibodies in the cerebrospinal fluid of 148 patients with schizophrenia and 151 healthy controls

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.

Eosinophils and Cognitive Impairment in Schizophrenia: A New Perspective.

Schizophrenia is a complex psychiatric disorder characterized by a wide array of cognitive impairments. While research has predominantly focused on the neurological aspects of schizophrenia, emerging evidence suggests that the immune system, specifically eosinophils, may play a significant role in the cognitive deficits associated with the disorder. This review presents a novel perspective on the interplay between eosinophils and cognitive impairment in schizophrenia. Eosinophils, traditionally associated with allergic responses and inflammation, have garnered limited attention within the realm of neuropsychiatry. Recent studies have hinted at a potential link between eosinophil activation and the pathogenesis of schizophrenia. In this comprehensive review, we delve into the world of eosinophils, elucidating their nature, functions, and interactions with the immune system. We examine the cognitive deficits observed in individuals with schizophrenia and discuss existing theories on the etiology of these impairments, focusing on immune system involvement. The paper also highlights the evolving body of research that supports the idea of eosinophilic influence on schizophrenia-related cognitive deficits. Furthermore, we explore potential mechanisms through which eosinophils may exert their effects on cognitive function in schizophrenia, including interactions with other immune cells and inflammatory pathways. By discussing the clinical implications and potential therapeutic avenues stemming from this newfound perspective, we underscore the practical significance of this emerging field of research. While this paper acknowledges the limitations and challenges inherent in studying eosinophils within the context of schizophrenia, it serves as a posit for novel thought in this vexing disease space as well as a call to action for future research endeavors. By providing a comprehensive survey of the existing literature and posing unanswered questions, we aim to inspire a reimagining of the relationship between eosinophils and cognitive impairment in schizophrenia, ultimately advancing our understanding and treatment of this debilitating disorder.

Progress in The Research of Lactate Metabolism Disruption And Astrocyte-Neuron Lactate Shuttle Impairment in Schizophrenia: A Comprehensive Review.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder widely recognized for its impaired bioenergy utilization. The astrocyte-neuron lactate shuttle (ANLS) plays a critical role in brain energy supply. Recent studies have revealed abnormal lactate metabolism in SCZ, which is associated with mitochondrial dysfunction, tissue hypoxia, gastric acid retention, oxidative stress, neuroinflammation, abnormal brain iron metabolism, cerebral white matter hypermetabolic activity, and genetic susceptibility. Furthermore, astrocytes, neurons, and glutamate abnormalities are prevalent in SCZ with abnormal lactate metabolism, which are essential components for maintaining ANLS in the brain. Therefore, an in-depth study of the pathophysiological mechanisms of ANLS in SCZ with abnormal lactate metabolism will contribute to a better understanding of the pathogenesis of SCZ and provide new ideas and approaches for the diagnosis and treatment of SCZ.

Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice

Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.

Neuroinflammation and Schizophrenia: New Therapeutic Strategies through Psychobiotics, Nanotechnology, and Artificial Intelligence (AI).

The prevalence of schizophrenia, affecting approximately 1% of the global population, underscores the urgency for innovative therapeutic strategies. Recent insights into the role of neuroinflammation, the gut-brain axis, and the microbiota in schizophrenia pathogenesis have paved the way for the exploration of psychobiotics as a novel treatment avenue. These interventions, targeting the gut microbiome, offer a promising approach to ameliorating psychiatric symptoms. Furthermore, advancements in artificial intelligence and nanotechnology are set to revolutionize psychobiotic development and application, promising to enhance their production, precision, and effectiveness. This interdisciplinary approach heralds a new era in schizophrenia management, potentially transforming patient outcomes and offering a beacon of hope for those afflicted by this complex disorder.

Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders

BackgroundEndothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. MethodsThe study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. ResultsThe total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. ConclusionsIn our study, patients with schizophrenia – including the drug-naïve – have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.