From autism to schizophrenia: Study of the genetic mechanisms underlying brain dysfunction and structural phenotypes in schizophrenia and autistic spectrum disorders / AUSZ
Schizophrenia (SCZ) and autistic spectrum disorders (ASD), two severe disorders, share symptomatology and neurocognitive conditions. Distributed structural brain abnormalities are described in both disorders, involving cortical and sub-cortical anomalies, suggesting that they could reflect ?dysconnectivity? within cortical networks. We propose an integrative approach combining comprehensive cognitive assessments and complementary high-resolution genetics and brain imaging analyses with a translational approach in mouse models. Our objectives are: i) to compare developmental clinical features, brain anatomy and neurocognitive functions in a large sample of patients with early- and adult-onset SCZ or ASD and their respective relatives and controls; ii) to study the variant of genes involved in brain development in relation to brain structural variations. The analyses will focus on candidate genes that codetermine white matter architecture, myelination, connectivity, cortex morphology and gyrification; iii) to explore rare genetic variations in genome wide scans for Copy Number Variations and de novo mutations in sporadic cases; iv) to study novel animal models with genetic defects of myelination for developmental abnormalities of the subcortical white matter and clinical features of SCZ and ASD. This project will improve the identification of the biological basis of these disorders and, in turn, therapeutic interventions in mental and cognitive disorders.
cellular and genetic approaches, Schizophrenia and psychotic disorders, Imaging techniques, Molecular, Animal models
2011 - 2014
Marie-Odile Krebs (Coordinator)