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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Mind the gap: fusing brain imaging and genetics data to reveal mechanisms underlying psychiatric disorders

Alternative title: Mind the gap: Å kombinere hjerneavbildning og genetiske data for å forstå de underliggende mekanismene til psykiatriske lidelser

Awarded: NOK 12.0 mill.

Psychiatric disorders are among the main contributors to morbidity and disability globally. While the past few decades have provided first insights, our understanding of the biological processes underlying the disordered brain is still limited. BRAINGAP seeks to build up a mechanistic understanding from the gene level of how these disorders manifest in the brain across life. In other words, we want to understand which gene variants affect the brain, as well as where in the brain and when in life. To find out, we will conduct a series of advanced statistical analyzes on a large sample of brain imaging and genetic data. A study of this size is made possible by the recent shift towards open research (Open Science) and data sharing. With this project, we hope to close the knowledge gap between the neural and genetic mechanisms that underlie the development of psychiatric disorders.

Psychiatric disorders are among the main contributors to morbidity and disability globally, yet our understanding of the pathophysiology is still limited. The past few decades of brain imaging research have provided insights into brain structural and functional aberrations associated with the disorders, however, it is now clear that there are no single brain phenotypes with strong effects. Instead, we observe largely heterogeneous patterns spread across the brain, with life transition period playing a critical role. In our view, this complexity can only be disentangled if we build up a mechanistic understanding of the spatiotemporal dynamics from the gene level. That is, we need to understand which gene variants, along with where, when and how together these affect the brain. In BRAINGAP, we will uncover neuro-genetics as a time- and space-varying system, implementing a series of advanced statistical analyses on unprecedented large sample sizes. BRAINGAP aims to reveal the genetic architecture underlying brain structure and function (“where?”), determine when in life genes differentially affect the brain (“when?”), and to investigate the neuro-genetic mechanisms underlying the multifaceted nature of psychiatric disorders (“how?”). The project targets psychiatric disorders using a multidimensional common-signs-common-pathways approach that cuts across diagnostic boundaries, including the study of variation in mental health in the general population. The BRAINGAP approach has only now become possible with the recent move toward open science and data sharing that has allowed us to compile a large collection of imaging genetics data through public resources and our network of international collaborators. This unique data, together with BRAINGAP’s novel high gain concept allows us to study neuro-genetics as an integrated unit that accounts for spatiotemporal dynamics, closing the current transfer gap between the neural and genetic underpinnings of psychiatric disorders.

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FRIMEDBIO-Fri prosj.st. med.,helse,biol

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