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.
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.
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.
This study will recruit two groups from the outpatient and inpatient services of Tianjin Anding Hospital and surrounding communities in Tianjin, China. The patient cohort will consist of 200 Han Chinese adults aged 18-65 years who are in their first episode of schizophrenia or schizophreniform disorder and have never received antipsychotics or received them for ≤4 weeks lifetime and ≤2 weeks immediately before enrollment. The healthy control cohort will include 100 Han Chinese adults matched to the patient group on sex, age, and education; they must have no personal or family history of major psychiatric disorders and show no cognitive impairment on formal testing.
Cohort
Prospective
Not listed
Cognitive Function
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
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
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
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
Psychiatric Symptoms
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
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
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
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.
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