The Long Game: Towards a better understanding of the molecular and genetic aspects of clozapine

Abstract

The aim of this thesis was to gain more insight into how clozapine influences processes in the body, with the hope that this would help us better understand and perhaps even predict its effects and adverse effects. The studies described here bring science a small step closer to this goal. The use of cell models as an intermediary step to patient-related research has shown some success, showing activation of cholesterol metabolism after clozapine and a gene was found that links to clozapine-induced viability reduction in lymphoblasts. In addition, it is now clear where in the neutrophil of clozapine users the autofluorescence is located and we can hypothesize that the protein producing the fluorescence is produced in the early phase of neutrophil development. This thesis has brought us a small step closer to a better understanding of the mechanisms of action of clozapine. However, there is still a great need for more knowledge. Future research should focus on cell / organoid / animal model research and on collecting as large a patient cohort as possible to validate and complement the results from fundamental research.