CORDIS - EU research results
CORDIS

An integrated hypothesis for cognitive and positive symptoms in schizophrenia

Project description

Improving quality of life with schizophrenia

Schizophrenia is a severe mental disorder characterised by extreme psychosis, hallucinations, delusions, impaired cognitive function and social behaviour. Currently, the only existing treatment – antipsychotics – targets specific symptoms, while the rest continue to affect patients. Under the common assumption that symptoms are caused by distinct pathophysiological mechanisms, the EU-funded INTEGRATE project aims to test the hypothesis that striatal hyperdopaminergia – an excess of the neurotransmitter dopamine in the central region of the brain commonly associated with psychosis – is caused by abnormal cortical inhibition. The project could lead the way to treatment that prevents psychosis and also address impaired cognitive function, thus significantly improving patients’ daily lives.

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.

Coordinator

UNIVERSITETET I OSLO
Net EU contribution
€ 208 400,40
Address
PROBLEMVEIEN 5-7
0313 Oslo
Norway

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Region
Norge Oslo og Viken Oslo
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 208 400,40