Efficacy and Safety of Individualized Sequential Accelerated Theta Burst Stimulation in Improving Cognitive Function in Schizophrenia

Sequential Dual-Site Accelerated Theta Burst Stimulation Targeting the Frontoparietal and Default Mode Networks for Cognitive Impairment in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Study

The goal of this clinical trial is to learn if sequential dual-site accelerated theta burst stimulation (SD-aTBS) targeting the frontoparietal network and default mode network works to improve cognitive function in adults with schizophrenia. It will also learn about the safety of SD-aTBS. The main questions it aims to answer are:

Does SD-aTBS improve cognitive function in participants with schizophrenia? What are the neurobiological mechanisms (brain network and synaptic plasticity changes) underlying the effects of SD-aTBS? Researchers will compare real SD-aTBS to sham stimulation to see if SD-aTBS is effective and safe for treating cognitive impairment in schizophrenia.

Participants will:

Receive real SD-aTBS or sham stimulation for 10 consecutive working days Complete clinical symptom assessments, cognitive function tests, MRI scans, and EEG recordings at baseline, after treatment, and 1 month after treatment Undergo SV2A-PET scans at baseline and 1 month after treatment

Inclusion Criteria:

1. Age 18-35 years.
2. Meets the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed by the Structured Clinical Interview for DSM-5 (SCID-5).
3. Duration of illness ≤ 8 years.
4. Taking no more than 2 antipsychotic medications, with a stable antipsychotic dose for at least 4 weeks prior to enrollment, and no expected change in the medication regimen throughout the treatment and follow-up period.

（4）Presence of significant cognitive impairment (overall deficit score of MCCB plus supplementary tests ≥ 0.5).

（5）The participant and their guardian agree to participate in the study and provide written informed consent.

Exclusion Criteria:

1. Current or lifetime co-occurrence of any other DSM-5 psychiatric disorder.
2. Concurrent use of mood stabilizers, antidepressants, or excessive benzodiazepines (lorazepam equivalent > 2 mg/day).
3. Presence of severe or acute physical illness, including a history of epilepsy, traumatic brain injury, intracranial space-occupying or infectious disease, acute cardiovascular or cerebrovascular disease, acute respiratory disease, or acute hematologic disease.
4. Any contraindication to transcranial magnetic stimulation (TMS), PET scanning, or magnetic resonance imaging (MRI).
5. Receipt of any other electrical or stimulation therapy within 3 months prior to enrollment.
6. Current use of medications known to interact with SV2A (e.g., levetiracetam, loratadine, quinine).

Withdrawal Criteria

1. Occurrence of a serious adverse event possibly related to the intervention (e.g., seizure, symptom relapse requiring immediate hospitalization).
2. Onset of a new severe illness during the study (e.g., cardiovascular event, severe infection, severe hepatic or renal dysfunction).
3. A change in the antipsychotic medication regimen during the study - including a dose adjustment of ≥ 25%, or a switch to a different antipsychotic medication.
4. Poor adherence, inability to complete the full intervention, failure to return for follow-up as required, or inability to cooperate with the examinations and assessments.
5. Pregnancy.
6. Voluntary withdrawal of informed consent by the participant.
7. Any other condition judged by the investigator to render the participant unable to complete the study or likely to affect the study results.