Descrizione del progetto
Comprendere i meccanismi che modulano il rischio e la resilienza nei disturbi mentali
Di fronte alle avversità, alcune persone danno il meglio di sé e sono in grado di mantenere prestazioni fisiche e mentali sane; altre, invece, non dispongono della capacità di affrontare situazioni critiche. Questa borsa di studio individuale europea standard delle azioni Marie Skłodowska-Curie intende rivoluzionare la nostra comprensione degli eterogenei meccanismi che modulano il rischio e la resilienza nei disturbi mentali. Il progetto ToPP, finanziato dall’UE, amplierà l’innovativo quadro di modellizzazione normativa al fine di integrare informazioni in merito al grado di affinità genetica (modello normativo genetico). Esso descriverà la distanza di ciascun individuo in riferimento allo standard di salute per la popolazione empirica di un processo biologico. La distanza verrà calcolata integrando informazioni sull’affinità, quantificata da strumenti bioinformatici basati su polimorfismi a singolo nucleotide nel genoma o nelle relazioni familiari.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
0313 Oslo
Norvegia