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

Overview

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.

Primary outcome measures

• Cognitive Function [Time frame: Baseline, week8]
• Plasma Exosome Concentration [Time frame: Baseline]
• The MicroRNA Expression Profile [Time frame: Baseline]
• Plasma Exosome Size Distribution [Time frame: Baseline]

Secondary outcome measures (6)

• Psychiatric Symptoms [Time frame: Baseline, week4, week8, week12]
• Depressive Symptoms [Time frame: Baseline, week4, week8, week12]
• Anxiety Symptoms [Time frame: baseline, week 4, week 8 and week 12]
• Sleep Quality [Time frame: baseline, week 4, week 8 and week 12]
• Aggressive behaviors [Time frame: Baseline]
• Brain Magnetic Resonance Imaging (MRI) [Time frame: Baseline]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

China · 1 center

• Tianjin Anding Hospital — Tianjin

Identifiers

NCT: NCT07139171 · FESW-TJAH

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗