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

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.

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

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.

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

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.

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.

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.

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.

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.

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.