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

Uncovering novel clinical characteristics, risk factors and brain phenotypes across the spectrum of adolescent psychosis.

Alternative title: Sammenhenger mellom miljø og risikofaktorer, kliniske observasjoner og hjernefenotyper hos ungdommer med psykoselidelser.

Awarded: NOK 9.6 mill.

Project Manager:

Project Number:

334326

Application Type:

Project Period:

2023 - 2026

We study psychotic disorders among adolescents aged between 12 and 18 years and who have an early disease onset. At this early age, psychosis is a relatively rare but severe condition, often with lifelong need for care for the child, and with consequences for family members and for society. The causes of psychosis development are unknown and it is important to find the biological disease mechanisms to develop new and better treatment and find preventive measures. In our adolescent psychosis studies, we have previous findings of smaller brain volumes on magnetic resonance imaging (MRI) brain investigation while some of the central brain nuclei show larger volumes, which we do observe in patients with an adult age-of onset. Some of the brain features can be unique signatures for adolescent psychosis disorders, particularly schizophrenia, and keys to understanding disease development and medication effects on the brain. From adult studies, we know that birth asphyxia is related to smaller brain area, and we now study how brain findings in adolescent psychosis are related with birth asphyxia, genetic risk, and other risk factors for psychosis development. We study patients with schizophrenia or bipolar spectrum disorders, youth at clinical high risk for psychosis development, and healthy controls, of both genders, initially over 3 years. They are investigated for brain phenotypes and brain connectivity, cognition, blood markers, clinical symptomatology and functioning. We study how risk factors; prenatal adversities, immune function, infections exposure, genetic risk, and given medication are related to the brain findings. We coordinate studies of international cohorts of adolescent psychosis. In Norway, we can use information from birth cohorts and registry data. We expect to find predictive markers psychosis development at this young age and to make a contribution regarding psychosis etiology, disease prevention and treatment improvement for these children.

Early-onset psychosis disorders (EOP) are mental diseases in youth with unknown cause and poor differentiation. The topic is important given the poor treatment response and clinical outcome, the stronger genetic load and brain abnormalities, a life-long need for pharmacological treatment, and possibility for new discoveries. In EOP, we find smaller intracranial volumes and large basal brain nuclei, which we cannot reproduce in adult-onset samples. The small brain and yet undiscovered brain features can be unique signatures for EOP, particularly schizophrenia, and keys to understanding disease development. Birth asphyxia is related with smaller brain volume, lower IQ and white matter microstructure disarrays. We characterize adolescent patients aged 12-18 years with schizophrenia or bipolar spectrum disorders, youth at clinical high risk for psychosis development, and healthy controls, both genders, initially over 3 years. Large samples are needed and we expand to include neurodevelopmental disorders and birth cohorts. We coordinate international EOP samples. By combining methods from computational psychiatry, registry data and advanced neuroimaging, gene and biomarkers, the project will yield novel knowledge about clinical characteristics, risk factors and brain phenotypes across the spectrum of adolescent psychosis. From MRI, we quantitate brain phenotypes: Cortical structures, white matter, network connectivity and myelin mapping. We study how risk factors; prenatal adversities, infections exposures, immunity and genetic risk, converge upon the EOP phenotype. We use in-depth phenotypic characterization and whole genome sequencing in large-scale collaborations. We expect to find predictive markers for youth at high risk for psychosis and to unravel aspects of the patophysiology of psychosis. Translational and interdisciplinary approaches make for diagnostic distinction and stratification, for better treatments and prevention.

Funding scheme:

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

Funding Sources