It is difficult to map the underlying circuit pathology in ultra-resistant schizophrenia due to the heterogeneity of the illness and limited studies that have explicitly examined this population. Due to multidimensional symptom domains resistant to clozapine, ultra-resistant schizophrenia can be described as the most severe phenotype of the illness that is mediated by multiple mechanisms far beyond dysregulated striatal hyperdopaminergia and glutamate NMDA receptor hypofunction.