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Major depressive disorder, schizophrenia, and bipolar disorder are three major psychiatric disorders that significantly impact the well-being and overall health of patients. Some researches indicate that abnormalities in the gut microbiota can trigger certain psychiatric diseases. Microbiota-derived extracellular vesicles have the ability to transfer bioactive compounds into host cells, altering signaling and biological processes, ultimately influencing the mental health and illness of the host. This review aims to investigate the emerging roles of microbiota-derived extracellular vesicles in these three major psychiatric disorders and discusses their roles as diagnostic biomarkers and therapies for these psychiatric disorders.

Schizophrenia (SCZ) imposes a significant burden on patients and their families because of its high prevalence rate and disabling nature. Given the lack of definitive conclusions regarding its pathogenesis, physicians heavily rely on patients’ subjective symptom descriptions for diagnosis because reliable diagnostic biomarkers are currently unavailable. The role of the inflammatory response in the pathogenesis of SCZ has been supported by some studies. The findings of these studies showed abnormal changes in the levels of inflammatory factors, such as cytokines (CKs), in both peripheral blood and cerebrospinal fluid (CSF) among individuals affected by SCZ. The findings imply that inflammatory factors could potentially function as risk indicators for the onset of SCZ. Consequently, researchers have directed their attention towards investigating the potential utility of CKs as viable biomarkers for diagnosing SCZ. Extracellular vesicles (EVs) containing disease-specific components exhibit remarkable stability and abundance, making them promising candidates for biomarker discovery across various diseases. CKs encapsulated within EVs secreted by immune cells offer valuable insights into disease progression. This review presents a comprehensive analysis summarizing the relationship between CKs and SCZ and emphasizes the vital role of CKs encapsulated within EVs in the pathogenesis and development of SCZ.

Schizophrenia is a serious mental disease that is regulated by multiple genes and influenced by multiple factors. Due to the complexity of its etiology, the pathogenesis is still unclear. MicroRNAs belong to a class of small non-coding RNAs that are highly conserved in endogenous evolution and play critical roles in multiple biological pathways. In recent years, aberrant miRNA expression has been implicated in schizophrenia, with certain miRNAs emerging as potential diagnostic and prognostic biomarkers for this disorder. In this review, our objective is to investigate the differential expression of miRNAs in schizophrenia, elucidate their potential mechanisms of action, and assess their feasibility as biomarkers. The PubMed electronic database and Google Scholar were searched for the years 2003 to 2024. The study focused on schizophrenia and miRNA as the research topic, encompassing articles related to biomarkers, etiology, action mechanisms, and differentially expressed genes associated with schizophrenia and miRNA. A total of 1488 articles were retrieved, out of which 49 were included in this scope review. This study reviewed 49 articles and identified abnormal expression of miRNA in different tissues of both schizophrenia patients and healthy controls, suggesting its potential role in the pathogenesis and progression of schizophrenia. Notably, several specific miRNAs, including miR-34a, miR-130b, miR-193-3p, miR-675-3p, miR-1262, and miR-218-5p, may serve as promising biological markers for diagnosing schizophrenia. Furthermore, this study summarized potential mechanisms through which miRNAs may contribute to the development of schizophrenia. The studies within the field of miRNA’s role in schizophrenia encompass a broad spectrum of focus. Several selected studies have identified dysregulated miRNAs associated with schizophrenia across various tissues, thereby highlighting the potential utility of specific miRNAs as diagnostic biomarkers for this disorder. Various mechanisms underlying dysregulated miRNAs in schizophrenia have been explored; however, further investigations are needed to determine the exact mechanisms by which these dysregulated miRNAs contribute to the pathogenesis of this condition. The exploration of miRNA’s involvement in the etiology and identification of biomarkers for schizophrenia holds significant promise in informing future clinical trials and advancing our understanding in this area.

As one of common and severe mental illnesses, schizophrenia is difficult to be diagnosed exactly. Both its pathogenesis and the causes of its development are still uncertain because of its etiology complexity. At present, the diagnosis of schizophrenia is mainly based on the patient’s symptoms and signs, lacking reliable biomarkers that can be used for diagnosis. Circular RNAs in extracellular vesicles (EV circRNAs) can be used as promising candidate biomarkers for schizophrenia and other diseases, for they are not only high stability and disease specificity, but also are rich in contents and easy to be detected. The review is to focus on the research progress of the correlation between circRNAs and schizophrenia, and then to explores the possibility of EV circRNAs as new biomarkers for the schizophrenia diagnosis.

Abstract Background At present, the schizophrenia diagnoses are based on the clinical symptoms and behaviors neglecting the laboratory test indicators. Results To better investigate the diagnostic potential of miRNAs for schizophrenia, we selected 14 candidate miRNAs and examined their expressions in the serums of 40 schizophrenia patients and 40 healthy controls by qRT-PCR. Ultimately three abnormally expressed microRNAs were identified, i.e., miR-34a-5p, miR-432-5p and miR-449a. Then, binary regression analysis was employed to combine 3 dysregulated miRNAs. ROC analysis revealed that the AUC of the combination of miR-432-5p + miR-449a in serums was 0.841 (95% CI: 0.791~0.887) with 90% sensitivity and 80% specificity. The AUC of the combination of miR-34a-5p + miR-432-5p + miR-449a in serums was 0.843 (95% CI: 0.791~0.887) with 90% sensitivity and 77.5% specificity. The results indicated that the combined model of miR-432-5p + miR-449a and miR-34a-5p + miR-432-5p + miR-449a have better prediction performances. Conclusions The study concludes that the two miRNAs combinations have the potential to be used as biomarkers for schizophrenia diagnoses. The finding may be conducive to overcoming the dilemmas faced by current schizophrenia diagnosis.

Abstract The diagnosis of schizophrenia is currently based on the symptoms and bodily signs rather than on the pathological and physiological markers of the patient. In the search for new molecular targeted therapy medicines, and recurrence of early-warning indicators have become the major focus of contemporary research, because they improve diagnostic accuracy. Biomarkers reflect the physiological, physical and biochemical status of the body, and so have extensive applicability and practical significance. The ascertainment of schizophrenia biomarkers will help diagnose, stratify of disease, and treat of schizophrenia patients. The detection of biomarkers from blood has become a promising area of schizophrenia research. Recently, a series of studies revealed that, MiRNAs play an important role in the genesis of schizophrenia, and their abnormal expressions have the potential to be used as biomarkers of schizophrenia. This article presents and summarizes the value of peripheral blood miRNAs with abnormal expression as the biomarker of schizophrenia.

Objective: Schizophrenia (SCZ) is a prevalent chronic mental disorder characterized by a high recurrence rate and significant disability. Currently, no satisfactory pharmacological treatments have been identified. Although Ningshen Wendan decoction (NSWDD) has shown promising results in improving cognitive function in patients with schizophrenia, its underlying mechanism of action remains unclear. Methods: This study systematically investigated the mechanisms of NSWDD in SCZ treatment using network pharmacology and molecular docking approaches. Results: Analysis of the interaction genes revealed 307 common targets of NSWDD and SCZ. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated the involvement of multiple signaling pathways including interleukin 17 signaling pathway, multiple virus infections, Advanced glycosylation end products (AGEs) - receptor of AGEs (AGEs-RAGE) signaling pathway, tumor necrosis factor signaling pathway, and Hypoxia-inducible factor-1 (HIF-1) signaling pathway as key pathways influenced by NSWDD in treating SCZ. These pathways are associated with various biological processes such as transcriptional regulation, apoptosis regulation, gene expression regulation, and external stimulus-response. Molecular docking simulations indicated favorable binding interactions between components of NSWDD and target proteins via intermolecular forces. Conclusion: The study provided initial insights into the internal molecular mechanisms underlying the beneficial effect of NSWDD on SCZ through multi-target modulation across multiple pathways. [ABSTRACT FROM AUTHOR]

Background: Psychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders.Aims: To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population.Method: We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene and carried out case-control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population.Results: We found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction).Conclusions: Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background Refractive errors and high myopia are the most common ocular disorders, and both of them are leading causes of blindness in the world. Recently, genetic association studies in European and Japanese population identified that common genetic variations located in 15q14 and 15q25 were associated with high myopia. To validate whether the same variations conferred risk to high myopia in the Han Chinese population, we genotyped 1,461 individuals (940 controls and 521 cases samples) recruited of Han Chinese origin. Result We found rs8027411 in 15q25 (P = 0.012 after correction, OR = 0.78) was significantly associated with high myopia but rs634990 in 15q14 (P = 0.54 after correction), OR = 0.88) was not. Conclusions Our findings supported that 15q25 is a susceptibility locus for high myopia, and gene RASGRF1 was possible to play a role in the pathology of high myopia. [ABSTRACT FROM AUTHOR]

Background Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, which codes for subunit alpha-lC of the Cavl.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder. Aims To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population. Method We carried out a case-control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPS in the CACNAIC gene were genotyped in all samples. Results We found that rs1006737 was associated with both schizophrenia (Pallele =0.0014, Pgenotype = 0.006, odds ratio (OR)= 1.384, 95% Cl 1.134-1.690) and major depressive = disorder (Pallele =0.0007, Pgenotype 0.003, OR = 1.425, 95% CI 1.160-1.752). Conclusions Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: Psychiatric disorders such as schizophrenia and major depressive disorder (MDD) are likely to be caused by multiple susceptibility genes, each with small effects in increasing the risk of illness. Identifying DNA variants associated with schizophrenia and MDD is a crucial step in understanding the pathophysiology of these disorders., Aims: To investigate whether the SP4 gene plays a significant role in schizophrenia or MDD in the Han Chinese population., Method: We focused on nine single nucleotide polymorphisms (SNPs) harbouring the SP4 gene and carried out case-control studies in 1235 patients with schizophrenia, 1045 patients with MDD and 1235 healthy controls recruited from the Han Chinese population., Results: We found that rs40245 was significantly associated with schizophrenia in both allele and genotype distributions (Pallele = 0.0005, Pallele = 0.004 after Bonferroni correction; Pgenotype = 0.0023, Pgenotype = 0.0184 after Bonferroni correction). The rs6461563 SNP was significantly associated with schizophrenia in the allele distributions (Pallele = 0.0033, Pallele = 0.0264 after Bonferroni correction)., Conclusions: Our results suggest that common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population., (© The Royal College of Psychiatrists 2016.)

Background: Common psychiatric disorders are highly heritable, indicating that genetic factors play an important role in their aetiology. The CACNA1C gene, which codes for subunit alpha-1C of the Cav1.2 voltage-dependent L-type calcium channel, has been consistently found to be the shared risk gene for several kinds of mental disorder., Aims: To investigate whether CACNA1C is a susceptibility gene for schizophrenia and major depressive disorder in the Han Chinese population., Method: We carried out a case-control study of 1235 patients with schizophrenia, 1045 with major depressive disorder and 1235 healthy controls. A tag single nucleotide polymorphism (SNP) rs1006737 along with another 10 tag SNPs in the CACNA1C gene were genotyped in all samples., Results: We found that rs1006737 was associated with both schizophrenia (P(allele) = 0.0014, P(genotype) = 0.006, odds ratio (OR) = 1.384, 95% CI 1.134-1.690) and major depressive disorder (P(allele) = 0.0007, P(genotype) = 0.003, OR = 1.425, 95% CI 1.160-1.752)., Conclusions: Our findings support CACNA1C being a risk gene for both schizophrenia and major depressive disorder in the Han Chinese population.