Neurodevelopment, brain vasculature and schizophrenia

Schizophrenia is a mental disorder that arises from abnormal neurodevelopment, led by genetic and environmental factors. Several lines of evidence suggest the involvement of both the nervous and vascular system in the etiology and pathophysiology of schizophrenia. In this thesis, human-induced pluripotent stem cell-derived neurons were used to study early neurodevelopment in schizophrenia. To investigate physiological adult neurogenesis and the possible contribution of the cerebral vasculature to the pathophysiology of schizophrenia, single-cell gene expression profiling of post-mortem brain tissues was performed. Our findings suggest that impairments in neuronal communication may already be present during early developmental stages in schizophrenia, compromising the ability of the nervous system for fast and efficient reorganization. This could converge in the development of neural circuits that are more sensitive to harmful or stressful external factors. Conversely, we identified few transcriptional changes between schizophrenia and control brain vasculature, which were limited to pericytes and ependymal cells, suggesting no major involvement of the brain vasculature in schizophrenia. Together, our data and observations contribute to the understanding of schizophrenia brain pathology, as well as to our knowledge of human neurodevelopment and brain vasculature heterogeneity