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Francesco Papaleo, Ph.D. - "A precision medicine genetic marker for core cognitive deficits in schizophrenia"

Genetics of Cognition Laboratory, Department of Neuroscience and Brain Technologies, Italian Institute of Technology (IIT), Genova, Italy
When Feb 27, 2018
from 12:00 PM to 01:30 PM
Where Tigem, Auditorium "Vesuvius"
Contact Name
Contact Phone 08119230659
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Abstract
Antipsychotics are the first-line and most widely used medications for the treatment of schizophrenia spectrum disorders. Clinical responses to these drugs are highly variable. However, predictors of individual responses to antipsychotic treatments have been elusive. Here we report a pharmacogenetics interaction related to a core cognitive dysfunction in patients with schizophrenia. In particular, genetic variations reducing dysbindin-1 expression differentiate individuals with better executive functions responses to antipsychotic drugs. Multilevel ex vivo and in vivo analyses in post mortem human brains, genetically modified mice, andDrosophilae melanogaster demonstrated that such antipsychotics-by-dysbindin-1 interaction is mediated by enhanced presynaptic dopamine D2 function within the prefrontal cortex (PFC). These findings provide a genetic indicator for a biological mechanism underlying cognitive disabilities in patients with schizophrenia, thus paving the way for the implementation of a precision medicine approach to treatment.

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