Genetics of Schizophrenia and Cognition

The etiology of neurodevelopmental behavioral disorders such as schizophrenia is complex and largely unknown, with both genetic and environmental contributing factors. While several potential schizophrenia-susceptibility genes have been identified, effect sizes are very small and replication is inconsistent, likely because of the complexity of human polymorphisms, genetic and clinical heterogeneity and the potential impact of gene-gene and gene-environment interactions. In this context, mutant mice bearing targeted mutations of schizophrenia-susceptibility genes are unique tools to elucidate the neurobiological basis of this devastating disorder. Using genetically modified mice for genes relevant to schizophrenia, we then employ a combined approach beginning at the behavioral level and culminating at the cellular and molecular levels. Cognitive abnormalities are core enduring symptoms in schizophrenia, dramatically contribute to poor functional outcomes in patients and currently represent a great “unmet therapeutic need”. We then mainly focus our work on behavioral cognitive analyses and relative neuronal correlates (e.g. using in vivo electrophysiology, magnetic resonance imaging, microdialysis, gene and protein expression analyses). New hope for preventing and curing schizophrenia-related symptoms and its cognitive deficits can come from early detection and early intervention. Thus, to develop effective tools for detecting high-risk individuals and prodromal stages we also characterize neurobehavioral features of our genetically modified mice during critical developmental periods. In particular, we study ages in mice equivalent to human ages spanning from embryonic stages to adolescence/young adulthood (when schizophrenia often appear), up to adulthood. For direct translational purposes we also analyze specific genetic polymorphisms in patients with schizophrenia and matched controls. In these individuals we then examine psychopathological/neurocognitive profiles and structural/functional brain measures in collaboration with clinical research centers.

TESI SPERIMENTALI IN “BEHAVIORAL GENETICS AND NEUROPSYCHOPHARMACOLOGY”

Il progetto di ricerca riguarda lo studio dei fattori genetici alla base dello sviluppo di disturbi cognitivi e patologie psichiatriche quali la schizofrenia.