Lay summary
Recent MRI techniques have been developed to study connectivity over the entire brain. Resting state functional MRI (fMRI) has been used to map functional connectivity whereas diffusion MRI allows the mapping of structural networks covering the entire brain. In combination with advanced network analysis tools, such techniques were able to characterize global connectivity patterns of the human brain. Regional structural and functional changes have been repeatedly reported from MRI studies in psychotic disorders these modifications are likely related to changes in connectivity. The early phase of psychosis has become an important research topic in psychiatry for several reasons. (a) There is accumulating evidence that critical brain modifications occur early in the disease process. (b) Studying patients in the early phase of psychosis is a good way to avoid confounds like chronic drug treatment and coping mechanisms. (c) Finally, early intervention might be the most efficient way to improve outcome.The global aim of this project is to (1) identify and characterize structural and functional network modifications occurring in the early phase of psychosis with (2) their time course and (3) assess their relation to genetic, psychopathological and neuropsychological scores. In addition to these three main goals, we will (a) see if differences in network topologies can be identified between psychosis subgroups, i.e. affective and non-affective psychosis; (b) in the setting of an ongoing clinical drug trial, we will try to quantify functional connectivity changes occurring with NAC supplementation.Many aspects of the disease mechanisms in schizophrenia are still unresolved. The effective structural and functional networks involvements, their temporal dynamics and relation to genetics and clinical scores are not clear. These questions are specifically addressed by studying the early phase of psychosis. The additional benefit of studying that phase of the disease is that if reliable imaging biomarkers are identified, they may pave the way to early diagnosis of schizophrenia and its differentiation from affective psychosis. Beyond the specific contributions of this project to a better understanding of the disease, our conclusions will likely modify significantly our way to consider imaging in neuro-psychiatric diseases by emphasizing the importance of considering the brain as a network. If we succeed in this endeavor we will not only impact diagnostics and treatment of schizophrenia but also pave the way for new similar approaches to other neuro-psychiatric diseases.