The interplay between the genome and the exposome in psychosis spectrum

This thesis presents several studies investigating the processes and mechanisms that underlie the development of psychosis in large epidemiological datasets. The first part of this thesis focuses on understanding symptom dimensions within the trajectories towards clinical outcomes. Mechanisms and processes associated with subclinical and clinical psychosis expression are evaluated. The second part of this thesis focuses on the environmental and genetic factors affecting the development of psychosis expression across the psychosis spectrum. The thesis presents the first systematic analyses of gene-environmental interaction using a cumulative molecular genetic score (polygenic risk score) for schizophrenia. Further, a new methodological tool, the exposome score for schizophrenia (a cumulative environmental score including exposures such as childhood adversities and cannabis use) was developed and applied to study environmental effects on psychosis phenotypes in the general population and in clinical samples. The thesis substantially contributes to the understanding of genetic and environmental effects on psychosis across the spectrum.