Towards Precision Psychiatry

ended

The intricacies of the human mind and its disorders are one of the remaining modern-day enigmas. Whereas recent advances in brain imaging and genetics are currently changing the clinical neurosciences by identifying novel general mechanisms of complex traits underlying risk and resilience at the group level, our understanding of individual-level causes and mechanisms of mental disorder has remained almost unchanged which is important because clinical management must be performed at the individual level. During the Marie Sklodowska Curie Actions-Standard European-Individual Fellowship (MSCA-SE-IF) I will address this challenge. Initially, I will expand our innovative normative modeling framework to incorporate information on degree of genetic relatedness (Genetic Normative Model). Similar to growth charts in pediatrics, for which a child’s height is compared to the normative height at her/his age, we describe the distance of each individual in reference to the empirical population/healthy norm of a biological process. We compute this distance while also incorporating information on relatedness quantified by bioinformatic tools based on single-nucleotide polymorphisms across the genome or familiar relationships. We apply this approach in two discrete ways. First, we map the distance between individuals in reference to this norm based on their degree of genetic relatedness (Genetic Mapping), and second, we place individuals showing symptoms of mental disorders in reference to the estimated norm. In this way we can dissect pathophysiological mechanisms on a case by case basis (Disorder Mapping). This individualized approach has the potential to revolutionize our understanding of the heterogeneous mechanisms modulating risk and resilience of mental disorders and requires a joint effort across disciplines. Therefore, while hosted at NORMENT, a center of excellence in Norway, I will spend a secondment at the University of Oxford mentored by world leading experts.