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An integrated hypothesis for cognitive and positive symptoms in schizophrenia

Objective

An integrated hypothesis for cognitive and positive symptoms in schizophrenia:

Schizophrenia is a complex developmental brain disorder with three main clusters of symptoms: (i) positive (psychosis, delusions and hallucinations), (ii) negative (reduced motivation and social withdrawal), and (iii) cognitive (memory and executive function deficits). For the last 50 years, the only effective treatment has consisted of antipsychotics targeting dopamine receptors. Yet, antipsychotics control mostly the positive symptoms and are largely ineffective at treating other deficits.

It is frequently assumed that distinct pathophysiological mechanisms underlie different symptoms. Psychosis is associated with striatal hyperdopaminergia, probably due to abnormal activity of midbrain dopaminergic neurons. Yet cognitive deficits seem to arise from cortical excitation/inhibition unbalance. I propose to test, in a mice model, the hypothesis that striatal hyperdopaminergia results from dysfunctional cortical inhibition. If verified, this would suggest that normalizing cortical activity in schizophrenia might both restore cognitive function and prevent psychosis.

Field of science

  • /medical and health sciences/clinical medicine/psychiatry/schizophrenia

Call for proposal

H2020-MSCA-IF-2017
See other projects for this call

Funding Scheme

MSCA-IF-EF-ST - Standard EF

Coordinator

UNIVERSITETET I OSLO
Address
Problemveien 5-7
0313 Oslo
Norway
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 208 400,40