Schizophrenia and cell senescence candidate genes screening, machine learning, diagnostic models, and drug prediction

Abstract

BackgroundSchizophrenia (SC) is one of the most common psychiatric diseases. Its potential pathogenic genes and effective treatment methods are still unclear. Cell senescence has been confirmed in mental diseases. A link exists between cellular senescence and immunity, and immune-related problems affect suicide rates in individuals suffering from schizophrenia. Therefore, the aims of this study were to identify candidate genes based on cell senescence that can affect the diagnosis and treatment of schizophrenia.MethodsTwo data sets of schizophrenia were provided by the Gene Expression Omnibus (GEO) database, one was taken as training and the other as a validation group. The genes related to cell senescence were obtained from the CellAge database. DEGs were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). The function enrichment analysis was conducted, followed by machine learning-based identification for least absolute shrinking and selection operators (LASSO) regression. Random Forest were used to identify candidate immune-related central genes and establish artificial neural networks for verification of the candidate genes. The receiver operating characteristic curve (ROC curve) was used for the diagnosis of schizophrenia. Immune cell infiltrates were constructed to study immune cell dysregulation in schizophrenia, and relevant drugs with candidate genes were collected from the DrugBank database.ResultsThirteen co-expression modules were screened for schizophrenia, of which 124 were the most relevant genes.There were 23 intersected genes of schizophrenia (including DEGs and the cellular senescence-related genes), and through machine learning six candidate genes were finally screened out. The diagnostic value was evaluated using the ROC curve data. Based on these results it was confirmed that these candidate genes have high diagnostic value.Two drugs related to candidate genes, Fostamatinib and Ritodine, were collected from the DrugBanks database.ConclusionSix potential candidate genes (SFN, KDM5B, MYLK, IRF3, IRF7, and ID1) had been identified, all of which had diagnostic significance. Fostamatinib might be a drug choice for patients with schizophrenia to develop immune thrombocytopenic purpura (ITP) after treatment, providing effective evidence for the pathogenesis and drug treatment of schizophrenia.

Bioinformatics analysis and prediction of Alzheimer’s disease and alcohol dependence based on Ferroptosis-related genes

“…Multiple studies have demonstrated that neuronal cell death often transpires due to ferroptosis ( Ren et al, 2023 ; Wang D. et al, 2023 ). In our previous research, we have identified connections between psycho-neuro-degeneration and various factors, including programmed cell death (PCD), mitochondrial function, vesicular transport, and cuproptosis ( Feng and Shen, 2023 ; Feng et al, 2023 ; Shen et al, 2023 ).…”

Neuroinflammation and schizophrenia – is there a link?

“…Shortened telomeres in white blood cells serve as a key indicator of cell senescence. Feng et al.‘s study employs genetic tools to explore novel treatments for schizophrenia, highlighting the immunoglobulin gene myosin light chain kinase (MYLK) as a potential drug target for mental health therapeutic intervention ( 92 ).…”

The Future of Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes

“…are gut microbes also known for interfering with the dopaminergic signaling, further linking cellular senescence to insufficient DA [31,32]. This is significant since both treated and untreated SCZ patients were found to exhibit body-wide premature cellular/neuronal aging, linking this condition to abnormal intestinal permeability [33,34]. Indeed, SCZ was associated with increased microbial migration into the host systemic circulation [35][36][37].…”