| Schizophrenia is a severe mental illness characterized by confusion and dysfunction in thinking,emotions,behavior,and other aspects,often leading to significant social,academic,and occupational impairment.Patients often experience symptoms such as hallucinations,delusions,cognitive impairments,emotional apathy or excessive excitement,disorganized speech,and peculiar behavior.The exact causes of the disease are not yet fully understood,but it has been proven that factors such as genetics,brain imaging,and behavior can affect its incidence.Schizophrenia imposes a considerable burden on society,making it necessary to identify its mechanisms and search for reliable treatment response biomarkers to guide precise and efficient treatment.However,accurate and reliable treatment response biomarkers that can combine imaging and genetic features are currently lacking.Therefore,this study focuses on structural and functional changes before and after treatment with risperidone,as well as methylation level data in schizophrenia patients,to find potential genetic and imaging biomarkers for predicting dopamine antagonist treatment response.The main research content is as follows:1.Chapter 3 investigates the dopamine circuitry mechanism in the treatment of schizophrenia and the search for dopamine circuitry biomarkers in the treatment of schizophrenia.Through studying the imaging features of the dopamine circuitry before and after treatment in schizophrenia patients,it was found that treatment with risperidone causes imaging changes in the dopamine circuitry,and there is a significant correlation between changes in the gray matter volume of the right caudate nucleus and clinical scale changes.In addition,it was also found that changes in the right posterior cingulate MD are related to changes in the VBM value of the right caudate nucleus,as well as changes in PANSS-G,revealing the potential of risperidone in affecting the entire brain through the dopamine circuitry in the treatment of schizophrenia.At the molecular level,using correlation analysis and enrichment analysis,the physiological correlation between dopamine circuitry imaging changes after 8 weeks of treatment with antipsychotic drugs as dopamine receptor antagonists was validated,providing strong evidence for using the gray matter volume of the right caudate nucleus as a biomarker for early treatment response in schizophrenia influenced by the dopamine circuitry.These findings represent an important step in exploring dopamine receptor antagonists as treatment response biomarkers across multiple data types.2.Regarding the lack of cross-omics biomarkers for dopamine receptor antagonist treatment response in schizophrenia,Chapter 3 of this study builds an MSN network based on structural imaging data before and after treatment in schizophrenia patients to investigate its longitudinal changes.The study found that the combination of neural networks and DNAm patterns is complementary in exploring treatment response biomarkers: MSNs can serve as biomarkers for cognitive function and general psychopathological symptoms treatment response,while DNAm is used for negative and positive symptom treatment response.In addition,Chapter 3 uses a whole-brain transcriptome dataset and cell-type enrichment to validate the physiological correlation of longitudinal changes in MSNs after 8 weeks of antipsychotic treatment as dopamine receptor antagonists at the molecular level,providing strong evidence for using MSNs as early biomarkers of treatment response influenced by dopamine circuits in schizophrenia.These findings represent an important step in exploring biomarkers for dopamine receptor antagonist treatment response on the basis of multiple omics types rather than a single omics type.Through the above two parts of the study,the imaging changes and biomarkers of the dopamine circuit in the treatment of schizophrenia with risperidone were found,and the genetic biomarkers of the treatment response related to the effects of the treatment on the whole brain structural network were found,which contributed to the understanding of the mechanism and process of the treatment of schizophrenia with dopamine receptor antagonists. |
