Grant: Canada Postdoctoral Research Award (CPRA) program

Schizophrenia spectrum disorders (SSDs) are a series of debilitating mental disorders that affect approximately 1% of the population and significantly impair quality of life. Individuals with SSDs often suffer from other conditions such as diabetes, obesity, and high blood pressure, which can contribute to a decrease in lifespan of 15-20 years and lead to difficulties with thinking and memory (i.e., cognition). Antipsychotics are a common treatment for SSDs, but their use can be associated with a worsening of these physical health problems. However, a lack of understanding regarding how SSDs develop has made identifying new treatments difficult. Previous research has shown that problems with how the hormone insulin regulates blood sugar levels, known as 'insulin resistance', may be involved. Specifically, insulin resistance can damage the cells that line blood vessels in the brain, which can lead to a leaky blood-brain barrier (BBB). As the BBB controls the movement of substances into and out of the brain, damage to the BBB can permit the entry of unwanted proteins, potentially leading to brain inflammation. In previous studies, brain inflammation was associated with the development of disorders similar to SSDs, and reversing BBB leakage was associated with symptom improvement. Thus, this study will use a non-invasive brain imaging technique to explore whether (1) BBB leakage and insulin resistance are present in individuals experiencing first-episode psychosis when compared to healthy individuals, (2) BBB leakage can predict clinical, functional, and cognitive outcomes in patents with first-episode psychosis, and (3) persistent BBB leakage is associated with higher symptom severity and worse functional outcomes after three months of antipsychotic treatment. If we find support for these ideas, this could lead to the development of new treatments to help individuals suffering from SSDs.