Research question and Objective 1: The impact of clozapine on cognitive function, associated with the levels of inflammatory markers (found in bodily fluids). Rationale: Inflammation levels may be associated with the effect of clozapine on cognitive function. Patients respond to clozapine differently, in terms of inflammatory response, and cognitive effects, and the reason for this is unknown. This line of research will help elucidate this and will involve performing association analyses of inflammatory levels and the cognitive outcome of clozapine treatment in patients.
Research question and Objective 2: The impact of clozapine on cognitive function, and the role of microglia, astrocyte, and neuron polygenic scores (using GWAS data). Rationale: Variations in genes are associated with variance in cognitive functioning in schizophrenia. Gene variation in microglia, astrocyte, and neuron may be associated with differential effects of cognitive outcomes in clozapine treatment. If we can identify a cluster of genes responsible for improving or diminishing cognitive function, this research will not only contribute to improved understanding of the mechanism of differential response to clozapine treatment, but also inform better and urgently needed treatments for schizophrenia.
Research question and Objective 3:The effect of clozapine on cognitive function, and its association with metabolic syndrome
Control group = haloperidol (1st gen APD), aripiprazole (3rd gen APD). Rationale: The development of metabolic syndrome may worsen cognition in clozapine treatment.
Research question and Objective 4:The impact of clozapine on mortality, and its association with metabolic syndrome. Patients on clozapine treatment have a high incidence of developing metabolic syndrome (~30%), and this may contribute to the early mortality observed in schizophrenia patients.