Exploratory research on the rapid neuroplastic effects of ketamine on healthy subjects using structural MRI analysis-a retrospective study

In the past decade, ketamine has emerged as a potent and rapid-acting antidepressant, with nearly 50\% of treated patients experiencing a significant reduction in symptoms at 24 hours from a single infusion. While the exact mechanisms behind ketamine's antidepressant effects remain unclear, preclinical studies suggest it enhances neuroplasticity and restores connectivity in brain regions involved in mood regulation. For this reason, magnetic resonance imaging (MRI) has been a valuable tool in investigating ketamine's short-term effects on brain structure and function. However, studies focusing on structural MRI have largely investigated gray matter volume (GMV), with findings often heterogeneous and pointing to limitations in traditional morphometric approaches such as voxel-based morphometry (VBM). This Thesis presents a retrospective study using longitudinal T1-weighted MRI data from 74 healthy subjects who received either ketamine alone, ketamine with lamotrigine pretreatment, or placebo, and were imaged before and 24 hours after a single administration. Neuroimaging softwares were used to process and extract region of interest (ROI) measurements from the raw T1-weighted MRI images; a GLM-based residual method was applied for data normalization, and repeated-measures ANOVA was used to detect significant time × treatment interactions. The study explores not only traditional measures of gray matter volume but also cortical thickness, volume of hippocampal subfields and sulcal morphometry as potential markers of short-term neuroplasticity. The results revealed regional volume decreases and changes in cortical thickness and sulcal depth in the ketamine groups compared to the placebo group. These findings are intriguing, as they may reflect potential short-term neuroplastic effects of ketamine; however, they require further validation through additional data and studies.