Hippocampus DBS in Treatment-resistant Schizophrenia

The goal of this clinical trial is to assess the efficacy and safety of hippocampus-targeted deep brain stimulation (DBS) in treatment-resistant schizophrenia. The main question it aims to answer are:whether patients with treatment-resistant schizophrenia can benefit from hippocampus-targeted DBS;what is the neural and electrophysiological mechanism underlying the treatment effect of hippocampus-targeted DBS.

Inclusion Criteria:Male or female aged between 18 and 55 years.Having a diagnosis of schizophrenia according to DSM-IV criteriaHaving a chronic, recurrent course of disease with a five-year minimum durationDetermined to be treatment-resistant as demonstrated by:Persistence of positive symptoms which have not responded to appropriate treatments for at least 2 years.Inadequate response from adequate trials of two different classes of antipsychotic drugs (not including clozapine), at least 8 weeks.Inadequate response from adequate trial of clozapine, at least 3 months, or unable to tolerate clozapine because of intolerable side effects.Presence of persistent positive symptom defined as i) requiring a score of 4 (moderate) or more on at least 2 of the next PANSS items: delusions, conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content; or as ii) requiring a score of 6 (severe) or more on at least 1 of the above PANSS items.Maintaining stable pharmacological treatment for two months preceding screening visit.Informed consentExclusion Criteria:Neurological diseaseSevere physical illnessContraindications to neurosurgery, MRI or PET-CT;Substance abuse or dependenceMental retardationFemale patients who are pregnant or breastfeedingSevere suicide risk and tendencies