Grant: CIHR Fellowship

Schizophrenia (Sz) is a chronic, progressive mental illness that affects 1% of the population. The current treatment for Sz includes the medications labelled 'antipsychotics (APs)' to block the action of dopamine. Unfortunately, APs do not work in 30% of patients (TRS: treatment-resistant schizophrenia). Clozapine (CLZ) is the only effective antipsychotic for TRS; its earlier introduction is recommended by the national guidelines. However, only 7% of patients with Sz are treated with CLZ and the average treatment duration before CLZ was 9.7 years in Canada. That could be attributable to the lack of biomarker of TRS. Recently, studies using positron emission tomography (PET) have suggested that those who respond to first-line AP treatment (TnRS: treatment non-resistant Sz) showed increased DA synthesis and release in the striatum compared to those with TRS. However, PET is not widely available in clinical practice and limited because of its high costs and the short half-life of radioligands. On the other hand, magnetic resonance imaging (MRI) is more accessible, less costly, and is able to examine the dopaminergic function by measuring neuromelanin (NM), which is a byproduct of the synthesis of monoamine neurotransmitters, including noradrenaline and dopamine. This technique has already been investigated in Parkinson's disease, but not for any psychiatric disorders such as Sz. This study will measure NM signals using neuromelanin-sensitive MRI (NM-MRI) in the substantia nigra, which contains the majority of dopamine neurons, and compare among patients with TRS (n=23), TnRS (n=23), and healthy control participants (n=23). We hypothesize that NM-MRI signals will be increased in TnRS in comparison with controls and TRS. Our approach will validate a broadly available biomarker to predict antipsychotic treatment response. NM-MRI scanning can then be included in the criteria of TRS.