CANADA: DEVELOPING BEHAVIOURAL PET PARADIGMS TO STUDY DOPAMINERGIC FUNCTION FOR USE IN SCHIZOPHRENIA

Severe mental disorders are characterized by the presence of psychosis and schizophrenia is the most common psychotic disorder. The disease is a major cause of disability worldwide and rank as one of the most costly disorders to afflict humans. The etiolo gy remains elusive, but schizophrenia is now regarded as a multifactorial disorder. This means that both genetic and environmental factors play a role, which is the case with most common diseases from diabetes to cancer. The lack of biological mechanisms makes the development of new drugs difficult, but all antipsychotic drugs are dopamine antagonists and its generally accepted that abnormalities of dopamine neurotransmission of some form is present in schizophrenia. Furthermore, it has been hypothesized that a dysfunctional dopaminergic reward system resulting in disturbed response to motivational stimuli could explain several aspects of the clinical picture of schizophrenia. We have in previous studies shown that the mesolimbic dopaminergic reward syste m is implicated in salient events, both appetitive and aversive. Further, we have shown that this system is aberrant in schizophrenia and may be implicated in the pathophysiology of the illness. However, all these evidence are indirect since we used funct ional Magnetic Resonance Imaging. This BILAT application aims to develop behavioural Positron Emission Tomography (PET) experiments. This technique can be used to measure changes in dopamine levels in response to behavioural tasks in humans more directly. In a final grant application, we will include a stipend for a PhD student in Oslo to work in the project to conduct behavioural PET paradigms both in healthy controls and subsequently with patient with schizophrenia. Hopefully, this will facilitate an es tablishment of a research group dedicated to brain research at the PET Centre in Oslo.