Combining HD-tDCS and iTBS in Treating Negative Symptoms of Schizophrenia

Dysfunction of the dorsolateral prefrontal cortex (DLPFC) is central to the persistence of negative symptoms in schizophrenia. Both HD-tDCS and iTBS targeting the left DLPFC have shown therapeutic benefit. This trial will test the hypothesis that combining HD-tDCS with iTBS yields additive efficacy.

Inclusion Criteria: * Subjects diagnosed with DSM-5 schizophrenia or schizoaffective disorder; * With a clinical presentation characterized by predominant negative symptoms, as determined by psychiatric assessment and a score of at least 20 on the Negative Symptoms Subscale of the Positive and Negative Syndrome Scale (PANSS); * Stable positive and negative symptoms for at least 4 weeks, as documented in medical records and confirmed by clinical judgment and psychiatric interview; Exclusion Criteria: * Unstable medical conditions; * Current psychiatric comorbidity or active substance use disorder (except for tobacco use disorders); * Contraindications for MRI, tDCS or rTMS; * Pregnancy or breastfeeding at the time of enrollment; * History of meningitis, encephalitis, seizures, intracranial neoplasms or surgery, severe head injury or cerebrovascular disease, or a family history of seizures; * rTMS or tDCS treatment within the past 6 months as well as a history of electroconvulsive therapy (ECT); * Any skin lesion at the stimulation sites; * Patients receiving medications that significantly change the seizure threshold; * A history of suicidal behavior within the past 6 months, or symptom worsening and emergence of suicidal ideation during the screening period.