Study on the Role and Mechanism of Plasma Exosome microRNAs in Cognitive Impairment in First-episode Schizophrenia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Cognitive Function
研究概览
简要总结
Schizophrenia is a severe mental illness characterised by positive symptoms, negative symptoms, and cognitive symptoms. In recent years, an increasing number of doctors and scholars have focused on cognitive symptoms; however, the mechanisms underlying cognitive impairment remain unclear. Recently, exosome research methods have provided new avenues for investigation. This study applies exosome research methods to first-episode, drug-naive schizophrenia patients to explore gene expression changes associated with cognitive impairment and gain a deeper understanding of the mechanisms underlying cognitive impairment. By integrating basic research with clinical findings, we aim to further investigate the molecular mechanisms underlying cognitive impairment in schizophrenia patients, identify potential intervention targets, and provide insights for future drug development.
详细描述
This single-center, prospective cohort study will enroll 200 drug-naive schizophrenia patients and 100 demographically matched healthy volunteers to identify biological signatures of cognitive impairment and to develop predictive models for subsequent change. At baseline we will administer the MATRICS Consensus Cognitive Battery (MCCB), clinical rating scales, multimodal magnetic resonance imaging (MRI), and collect fasting blood and first-morning urine for multi-omics assays. Participants are re-evaluated at 4, 8 and 12 weeks during naturalistic antipsychotic treatment, repeating cognitive testing, clinical scales, and blood/urine sampling. Primary analyses will link baseline omics to the MCCB overall composite score; secondary analyses will model the longitudinal trajectories of both cognition and biomarkers to derive parsimonious predictors of cognitive gain versus persistent impairment. The resulting biomarker panels are expected to inform future stratified clinical trials and mechanism-based cognitive remediation strategies.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers matched to the patient group on sex, age, and education level;
- •No family history of psychiatric disorders among first- or second-degree relatives (two generations);
- •Ethnic Han Chinese;
- •Able and willing to provide written informed consent.
排除标准
- •Any serious physical illness, including but not limited to uncontrolled hypertension, severe cardiovascular, cerebrovascular, pulmonary, thyroid, or metabolic disease, diabetes, epilepsy, or metabolic syndrome;
- •Current or past diagnosis of substance-induced psychotic disorder, delusional disorder, brief psychotic disorder, or mood disorder with psychotic features;
- •Pregnancy or breastfeeding;
- •Any condition that would interfere with the ability to give informed consent or complete study procedures.
结局指标
主要结局
Cognitive Function
时间窗: Baseline, week8
All participants underwent cognitive function assessment based on the MATRICS Consensus Cognitive Battery (MCCB). The battery covers seven cognitive domains and two composite scores. The MCCB scoring procedure generates standardised T-scores that are corrected for age, gender, and educational level. Higher T-scores indicate better cognitive function.
Plasma Exosome Concentration
时间窗: Baseline
Fasting plasma samples collected at baseline will be processed by standard ultracentrifugation and nanoparticle tracking analysis (NTA) to quantify total exosome concentration, expressed as particles/mL. This single parameter will serve as the primary biomarker to evaluate its association with cognitive impairment in antipsychotic-naïve schizophrenia patients
The MicroRNA Expression Profile
时间窗: Baseline
Levels of microRNAs isolated from plasma-derived exosomes at baseline, quantified by Quantitative Reverse Transcription Polymerase Chain Reaction using a validated panel of schizophrenia- and cognition-related miRNAs, reported as fold-change relative to exogenous spike-in control.
Plasma Exosome Size Distribution
时间窗: Baseline
Fasting plasma samples collected at baseline will be processed by standard ultracentrifugation and nanoparticle tracking analysis (NTA) to quantify total exosome size distribution (mode, mean, and particle diameter range), expressed as particles/mL. This single parameter will serve as the primary biomarker to evaluate its association with cognitive impairment in antipsychotic-naïve schizophrenia patients
次要结局
- Psychiatric Symptoms(Baseline, week4, week8, week12)
- Depressive Symptoms(Baseline, week4, week8, week12)
- Anxiety Symptoms(baseline, week 4, week 8 and week 12)
- Sleep Quality(baseline, week 4, week 8 and week 12)
- Aggressive behaviors(Baseline)
- Brain Magnetic Resonance Imaging (MRI)(Baseline)