Using computational modelling to investigate excitatory and inhibitory cell dysfunction in schizophrenia

Schizophrenia is a severe psychiatric disorder and the eighth highest cause of disability-adjusted life years in young adults worldwide. Dopamine 2 receptor blockers - the only drug class available for the treatment of schizophrenia - decrease psychosis in around 70% patients, but they fail to substantially improve cognitive and motivational deficits. Extensive pre-clinical and clinical evidence points to NMDA receptors as an alternative therapeutic target, but it is unclear whether receptor subtypes located preferentially on excitatory or inhibitory cells are more dysfunctional. We will use dynamic causal modeling of magnetoencephalography (MEG) data to investigate how interacting excitatory and inhibitory cell (dys)function contributes to psychotic symptoms as well as cognitive and motivational impairments in schizophrenia. It is hoped that this will help inform glutamatergic treatment selection and guide future drug development.