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

Parsing the developmental and genetic architecture of risk and resilience in the adolescent brain

Alternative title: Kartlegging av utviklingsmessige og genetiske kjennetegn til sårbarhet og motstandsdyktighet i ungdomshjernen

Awarded: NOK 12.0 mill.

Adolescence is a period in life associated with great physical, social and psychological changes. The adolescent brain is plastic, which enables fast development from childhood to adulthood. This period is, however, also associated with increased risk of developing mental disorders. Indeed, 50% of patients experience symptoms before 14 years of age and 75% before the age of 24. Thus, the onset of most mental disorders co-occur with profound neurodevelopmental changes and transitions to new life-roles during adolescence. However, the mechanisms underlying risk and resilience in the adolescent brain are largely unknown, seriously impeding the development of useful tools for early detection, individual clinical prediction and treatment. My providing neuroimaging data from a large number of children and adolescents in the Mother, father and child (MoBa) study cohort we will investigate the interactions between genetic, neurological, and environmental/social variables, both to understand and map normal brain development, as well as to uncover how abnormal development is associated with symptoms of mental illness throughout formative life phases. We will combine data from brain imaging, measures of cognition and mental health, and biological measures. In the long run, the results from this study will contribute to prevention, detection, and treatment of mental disorders. The project is a collaboration between the University of Oslo, Oslo University Hospital, and researchers in Trondheim, Bergen, Tromsø and Stavanger.

In contrast to most major somatic and neurological conditions, whose incidence and prevalence increase with advancing age, mental disorders primarily affect children, adolescents, and young adults. Indeed, 50% of patients experience symptoms before 14 years of age and 75% before the age of 24. Thus, the onset of most mental disorders co-occur with profound neurodevelopmental changes and transitions to new life-roles during adolescence. However, the mechanisms underlying risk and resilience in the adolescent brain are largely unknown, seriously impeding the development of useful tools for early detection, individual clinical prediction and treatment. Our main hypothesis is that sensitivity to external demands is a sine qua non for individual adaptation to dynamic environments, but comes at the cost of increased susceptibility when facing poor environmental conditions. Differential (between-subject) and dynamic (within-subject) susceptibility to mental illness are mediated by individual differences and temporary fluctuations in brain plasticity during childhood and adolescence. Such mechanisms influence the extent to which the environment is able to act on the brain, thus serve as critical modulators of gene-environment interactions during formative teen years. In order to test this hypothesis, our interdisciplinary and international team will combine existing large-scale brain imaging genetics databases (n>50,000) with a novel brain imaging effort of the genotyped and richly phenotyped MoBa cohort (n ~5000, followed from birth), thus constructing a unique openly available resource for the international research community. By defining the mechanisms and boundaries of brain plasticity as our Archimedean point, we will leverage these resources to pursue our fundamental aim of parsing the heterogenous neurodevelopmental architecture during adolescence, its environmental and neurogenetic modulators, focusing on mechanisms of risk and resilience in the adolescent brain.

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

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