Study on the Role and Mechanism of Plasma Exosome microRNAs in Cognitive Impairment in First-episode Schizophrenia

Recruiting

• Conditions: Schizophrenia

• Registration Number: NCT07139171
• Lead Sponsor: Tianjin Anding Hospital

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study Start: 2022-11-11
• Status Verified: 2025-08
• Study First Submitted: 2025-08-18
• Study First Submitted QC: 2025-08-18
• Last Update Submitted: 2025-08-18
• Study First Posted: 2025-08-24
• Last Update Posted: 2025-08-24
• Primary Completion: 2025-10-01
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Cognitive Function	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 and Size Distribution	Baseline	Fasting plasma samples collected at baseline will be processed by standard ultracentrifugation and nanoparticle tracking analysis (NTA) to quantify total exosome concentration and 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
The MicroRNA Expression Profile	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.

Secondary Outcome Measures

Name	Time	Method
Psychiatric Symptoms	Baseline, week4, week8, week12	The psychiatric symptoms of schizophrenia were assessed in all enrolled patients using the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item clinician-rated scale yielding a total score ranging from 30 (least symptomatic) to 210 (symptomatic), where higher scores indicate more severe psychopathology.
Depressive Symptoms	Baseline, week4, week8, week12	The Hamilton Depression Scale-24 (HAMD-24) was used to assess the severity of depressive symptoms. Each item was scored on a scale of 0 (none) to 4 (severe); the total score ranged from 0 to 76, with higher scores indicating more severe depressive symptoms.
Anxiety Symptoms	baseline, week 4, week 8 and week 12	The Hamilton Anxiety Scale (HAMA) is used to assess the severity of anxiety symptoms. Each item is scored on a scale of 0 (none) to 4 (very severe), with a total score range of 0-56. Higher scores indicate more severe anxiety symptoms.
Sleep Quality	baseline, week 4, week 8 and week 12	The Pittsburgh Sleep Quality Index (PSQI) is used to assess sleep quality and sleep disorders over the past month. The questionnaire includes seven subscale scores (subjective sleep quality, sleep onset latency, sleep duration, habitual sleep efficiency, sleep disturbances, sleep medication use, and daytime functioning), with each subscale scored on a scale of 0 to 3. The sum of the seven subscale scores constitutes the PSQI total score, ranging from 0 to 21, with higher scores indicating poorer sleep quality.
Aggressive behaviors	Baseline	The Modified Open Aggression Scale (MOAS) is a four-component scale administered by clinicians or observers that quantifies verbal aggression, aggression toward objects, self-aggression, and physical aggression toward others. Each component consists of five items, with scores ranging from 0 (none) to 4 (extreme). The scores from each component are added together to produce a total weighted score ranging from 0 to 40, with higher scores indicating more severe overall aggressive behaviour.
Brain Magnetic Resonance Imaging (MRI)	Baseline	Multimodal 3 T MRI acquired at baseline, including T1-weighted anatomical imaging, diffusion tensor imaging (DTI) and resting-state functional MRI. Extracted metrics-cortical thickness, regional gray-matter volume, fractional anisotropy, mean diffusivity, and amplitude of low-frequency fluctuation-will be used to quantify structural and functional alterations associated with cognitive impairment.

Trial Locations

Locations (1)

Tianjin Anding Hospital; 🇨🇳 Tianjin, China