Genomic impact of environmental risk factors for psychosis

Abstract

Aim of this thesis Considering the need to understand how the environment impacts on psychosis risk and what the underlying mechanisms are, we here combine epidemiological genetic studies for gene discovery with cellular studies that further interrogate the functional meaning of the identified genes. The aim of this thesis is to define which (epi)genomic determinants lead to neuropsychological dysfunctions and psychiatric disorders in combination with selected detrimental environmental factors (cannabis use, maternal malnutrition, and childhood adversity). The general approach of the studies in this thesis is firstly to identify the involved genes using (epi)genome-wide approach and subsequently, to investigate in vitro the potential functional pathway and to provide additional mechanistic evidence. Main research questions • Which genes confer the increased risk to psychosis on those that use cannabis? • Which genes are epigenetically changed by in utero famine exposure? • What is the role of genes epigenetically changed due to childhood adversity in the etiology of bipolar disorders? Hypothesis We hypothesize that the interaction between gene and environment is not only on gene transcription level, but also on the epigenetic level.