Grant: Doctoral: Vanier Canada Graduate Scholarships

Schizophrenia affects about 1% of Canadians. Cognitive impairments are a core feature of schizophrenia that drives functional disability and socio-economic burden in this illness. Currently, there are no medications that significantly improve cognition in schizophrenia. A better understanding of the neurobiology of cognitive deficits in schizophrenia could guide the development of new pharmacological treatments. The cholinergic system of the brain is important for cognitive abilities and it has been proposed that dysfunctions in this system would underlie cognitive deficits in schizophrenia. However, this has not been tested yet. Here, we propose to study the cholinergic system with a positron emission tomography tracer that allows to quantify cholinergic innervation in the brain. The goals of the proposed study are to (1) establish whether individuals with schizophrenia show reduced cholinergic innervation compared to healthy individuals, (2) determine if reduced cholinergic innervation is related to less brain activation in schizophrenia and (3) to greater cognitive deficits in schizophrenia. We hypothesize that, in schizophrenia, cholinergic innervation is lower (goal 1) than in healthy individuals, that this is related to general cognitive dysfunction (goal 2) and abnormal brain activity (goal 3). We will also explore the effect of sex on cholinergic innervation. We will inform patients and family, clinicians, and pharmaceutical firms of our findings to have them translated into clinical practice. Results will be presented in international conferences and published in high-impact journals. As there are no drugs that alleviate cognitive impairments in schizophrenia, it is imperative to better understand the underlying neurobiology. This project will increase our understanding of the cholinergic system in schizophrenia and opens doors for breakthroughs in the development of new treatments.