Effects of Antipsychotics on Brain Insulin Action in Females: A Randomised Placebo-Controlled, Crossover Neuroimaging Study

What this Trial Is About

Females treated with antipsychotics often experience higher rates of metabolic problems compared to males, and this study aims to understand how brain insulin resistance differs in females during different phases of their menstrual cycle. Researchers are investigating how the antipsychotic drug olanzapine affects brain insulin action in healthy young females, focusing on the follicular and luteal phases of the cycle. This study uses brain imaging and intranasal insulin to explore these effects and provides new insights into why females might be more affected by these metabolic side effects. Participants will receive four treatment conditions combining intranasal insulin or placebo with oral olanzapine or placebo in a randomized, crossover design. Each treatment period lasts three days, with olanzapine or placebo given on days 0 and 1, followed by cognitive tests and MRI scans on day 2. Visits occur twice during the follicular phase (days 4-10) and twice during the luteal phase (days 16-22 or near the next expected menses), with menstrual cycle phases confirmed by hormone measurements. During each visit, brain insulin action is assessed using two MRI scans following either intranasal insulin or placebo. Researchers will also collect fasting blood samples to measure glucose, insulin, and olanzapine levels. Cognitive functions such as visuospatial memory and processing speed are tested between scans. Participants are monitored for safety and complete four visits over five to six months. The primary outcome is brain connectivity measured by functional MRI, with secondary outcomes including cognitive performance.

Effects of Antipsychotics on Brain Insulin Action in Females