About the project
Causal models implementing cognitive, biological, and genetic mechanisms are lacking, and identifying mechanisms is crucial to improve mental health care. Psychotic disorders are heritable, involving aberrant development of brain networks.
Objectives
In this large-scale multi-disciplinary and translational effort, we combine advanced multimodal fusion of brain imaging data, clinical information and genetics to (1) characterize the hierarchy of the structural and functional neuronal breakdown in psychosis, its developmental profiles and genetic modifiers, (2) develop multimodal classifiers to identify clinically predictive genotype-phenotype patterns, and (3) describe the genetic mapping and hierarchical clustering of the discriminative brain patterns based on phenotypic and genetic correlations to identify genetic pleiotropy between risk and sustainment of disease and brain networks in a lifespan perspective.
Outcomes
Our unique approach includes state-of-the art technology and tools for data integration, and builds on the joint efforts of a cross-disciplinary international team. Anecdotal observations and statistical evidence have suggested overlap between a range of traits and disorders. Novel biostatistical tools have finally enabled us to quantify the genetic correlations between traits using high-density genotype data, which have created an avenue for genetic dissection of complex traits, allowing for new discoveries and hypotheses. These methods provide a biostatistical platform for challenging historical conventions, paving the way toward a new nosology of complex disorders. We leverage these exciting new developments to propose a genetically informed hierarchical clustering of brain imaging and clinical traits, with a particular emphasis on neurodevelopmental markers. In addition to improving current brain-based models of mental illness, our genetic dissection provides novel clues about the fundamental architecture of the brain, the dynamic lifespan alterations, and the perturbations underlying neurodevelopmental disorders.
Financing
The project is financed by the Research Council of Norway (FRIMEDBIO - Young Researcher Talents) 2016 - 2020.
Cooperation
Department of Psychology and Norwegian Centre for Mental Disorders Research (NORMENT).