Grant: Fellowship - Priority Announcement: HMC Prize in Children's Mental Health

Approximately 30% of patients with schizophrenia do not optimally respond to antipsychotics, which is called treatment-resistant schizophrenia (TRS). Clozapine is a unique antipsychotic drug, which has been demonstrated to have greater efficacy for TRS, while mechanisms of action remain unknown. Nonetheless, 40-70% of patients with TRS do not adequately respond to even clozapine, which is called ultra-resistant schizophrenia (URS). The human brain consists of two main components: one is gray matter composed of neurons; the other is white matter composed of glial cells and myelinated axons. Diffusion tensor imaging (DTI), a recent magnetic resonance imaging (MRI) technique, enables the measurement of white matter in humans. White matter abnormalities have been recently found to play an important role in the biological mechanism of schizophrenia. The proposed study aims to investigate white matter in TRS and URS. Fifteen patients with TRS and 15 patients with URS will be included. Brain imaging will take place on MRI with DTI. Our hypothesis is that patients with TRS and URS will demonstrate significantly different white matter structure. We believe that the results could shed light on the mechanism of clozapine, and provide guidance for the treatment of URS.