The goal of this clinical trial is to evaluate the efficacy of personalized dual-target rTMS for treating patients with refractory schizophrenia and to investigate its underlying neural mechanisms using functional MRI.

The main questions it seeks to address are:

Does the dual-target rTMS protocol improve clinical symptoms in patients with refractory schizophrenia? What neural circuit changes, as assessed by functional MRI, occur following rTMS treatment?

Participants will:

Undergo personalized, dual-target rTMS treatment daily for 3 weeks. Complete baseline and post-treatment assessments, including clinical symptom scales (PANSS, HAMA, HAMD) and neuropsychological tests (MoCA, DST, VFT, Stroop Test, and AVLT).

Have structural and resting-state functional MRI scans before and after treatment.

Be monitored for any treatment-related adverse events.

This open-label clinical trial aimed to evaluate the efficacy and underlying neural mechanisms of a personalized dual-target rTMS protocol for treating patients with refractory schizophrenia. Patients with refractory schizophrenia were prospectively recruited and underwent 3 weeks of rTMS treatment.

Before treatment, structural and resting-state functional MRI data were collected from each patient. Clinical symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD). For patients experiencing auditory verbal hallucinations, the Auditory Hallucination Rating Scale (AHRS) was also administered. Additionally, a battery of neuropsychological tests was conducted, including the Montreal Cognitive Assessment (MoCA), Digit Span Test (DST), Verbal Fluency Test (VFT), Stroop Test, and Chinese Auditory Verbal Learning Test (AVLT).

After completing the 3-week rTMS treatment, clinical symptom severity, treatment-related adverse events, and structural and resting-state functional MRI data were reassessed.

Inclusion Criteria:

1. diagnosed by independent psychiatrists using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition;
2. disease duration longer than six years;
3. hospitalization two or more times;
4. aged 18-60 years;
5. a stable dosage of antipsychotic medication for at least four weeks before inclusion, and retention of this stable dose for the duration of the study.

Exclusion Criteria:

1. accompanied by other mental illnesses or histories;
2. pregnant;
3. a history of severe head trauma or neurological disease;
4. focal brain lesions on T1- or T2-weighted fluid-attenuated inversion-recovery MRI;
5. a history of rTMS or electroconvulsive therapy in the six months prior to the study; and
6. metal objects in the head or any other contraindication to MRI.