Genetic and phenotypic architecture of the ontogenetic determinants of severe mental illness
About the project
Mental illness is the largest contributor to years lived with disability worldwide. 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.
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.
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.
The project is financed by the Research Council of Norway (FRIMEDBIO - Young Researcher Talents) 2016 - 2020.
Department of Psychology and Norwegian Centre for Mental Disorders Research (NORMENT).
- Aldo Còrdova Palomera; Tobias Kaufmann; Karin Persson; Dag Alnæs; Nhat Trung Doan; Torgeir Moberget; Martina Jonette Lund; Maria Lage Barca; Andreas Engvig; Anne Brækhus; Knut Engedal; Ole Andreas Andreassen; Geir Selbæk & Lars Tjelta Westlye (2017). Disrupted global metastability and static and dynamic brain connectivity across individuals in the Alzheimer's disease continuum. Scientific Reports. ISSN 2045-2322. 7, s 1- 14
- Tobias Kaufmann; Dag Alnæs; Christine Lycke Brandt; Nhat Trung Doan; Karolina Kauppi; Francesco Bettella; Trine Vik Lagerberg; Akiah Ottesen Berg; Srdjan Djurovic; Ingrid Agartz; Ingrid Melle; Torill Ueland; Ole Andreas Andreassen & Lars Tjelta Westlye (2017). Task modulations and clinical manifestations in the brain functional connectome in 1615 fMRI datasets. NeuroImage. ISSN 1053-8119. 147, s 243- 252
- Lars Tjelta Westlye; Tobias Kaufmann; Dag Alnæs; Ingunn Riise Hullstein & Astrid Bjørnebekk (2017). Brain connectivity aberrations in anabolic-androgenic steroid users. NeuroImage: Clinical. ISSN 2213-1582. 13, s 62- 69
- Nhat Trung Doan; Andreas Engvig; Karin Persson; Dag Alnæs; Tobias Kaufmann; Jaroslav Rokicki; Aldo Còrdova Palomera; Torgeir Moberget; Anne Brækhus; Maria Lage Barca; Knut Engedal; Ole Andreas Andreassen; Geir Selbæk & Lars Tjelta Westlye (2017). Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer's disease spectrum. Scientific Reports. ISSN 2045-2322. 7:45131
- Torgeir Hellstrøm; Tobias Kaufmann; Nada Andelic; Helene L. Søberg; Solrun Sigurdardottir; Eirik Helseth; Ole Andreas Andreassen & Lars Tjelta Westlye (2017). Predicting outcome 12 months after mild traumatic brain injury in patients admitted to a neurosurgery service. Frontiers in Neurology. ISSN 1664-2295. 8:125, s 1- 12
- Tobias Kaufmann; Dag Alnæs; Nhat Trung Doan; Christine Lycke Brandt; Ole Andreas Andreassen & Lars Tjelta Westlye (2017). Delayed stabilization and individualization in connectome development are related to psychiatric disorders. Nature Neuroscience. ISSN 1097-6256. 20, s 513- 515
- Nhat Trung Doan; Andreas Engvig; Krystal Zaske; Karin Persson; Martina Jonette Lund; Tobias Kaufmann; Aldo Còrdova Palomera; Dag Alnæs; Torgeir Moberget; Anne Brækhus; Maria Lage Barca; Jan Egil Nordvik; Knut Engedal; Ingrid Agartz; Geir Selbæk; Ole Andreas Andreassen & Lars Tjelta Westlye (2017). Distinguishing early and late brain aging from the Alzheimer's disease spectrum: Consistent morphological patterns across independent samples. NeuroImage. ISSN 1053-8119. 158, s 282- 295
- Torgeir Hellstrøm; Lars Tjelta Westlye; Tobias Kaufmann; Nhat Trung Doan; Helene L. Søberg; Solrun Sigurdardottir; Wibeke Nordhøy; Eirik Helseth; Ole Andreas Andreassen & Nada Andelic (2017). White matter microstructure is associated with functional, cognitive and emotional symptoms 12 months after mild traumatic brain injury. Scientific Reports. ISSN 2045-2322. 7
- Nhat Trung Doan; Tobias Kaufmann; Francesco Bettella; Kjetil Nordbø Jørgensen; Christine Lycke Brandt; Torgeir Moberget; Dag Alnæs; Gwenaëlle Douaud; Eugene Duff; Srdjan Djurovic; Ingrid Melle; Torill Ueland; Ingrid Agartz; Ole Andreas Andreassen & Lars Tjelta Westlye (2017). Distinct multivariate brain morphological patterns and their added predictive value with cognitive and polygenic risk scores in mental disorders. NeuroImage: Clinical. ISSN 2213-1582. 15, s 719- 731
- Erlend Solberg Dørum; Dag Alnæs; Tobias Kaufmann; Geneviéve´ Richard; Martina Jonette Lund; Siren Tønnesen; Markus Handal Sneve; Nina Christine Mathiesen; Øyvind Rustan; Øivind Gjertsen; Sigurd Vatn; Brynjar Fure; Ole Andreas Andreassen; Jan Egil Nordvik & Lars Tjelta Westlye (2016). Age-related differences in brain network activation and co-activation during multiple object tracking. Brain and Behavior. ISSN 2162-3279. 6