Correlation of White Matter Abnormalities with Glutamate Levels in Patients with Obsessive--Compulsive Disorder

• Grant number: 25/05329-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Marcelo Queiroz Hoexter
• Grantee: Giulia Faria Zima
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric condition characterized by intrusive thoughts and repetitive behaviors that significantly interfere with daily life. Research has linked OCD to structural and neurochemical changes in the brain, which can be studied using neuroimaging techniques such as Diffusion Tensor Imaging (DTI) and Magnetic Resonance Spectroscopy (¹H-MRS). DTI studies have identified alterations in white matter (WM) integrity in OCD, including lower fractional anisotropy (FA), lower fractional anisotropy of cellular tissue (FAt), and higher free-water (FW) levels. These findings suggest that neuroinflammation may play a role in the disorder's pathology. Additionally, previous research has reported reduced glutamate levels in the ventromedial prefrontal cortex (VMPFC) of OCD patients, supporting a connection between glutamate dysregulation and neuroinflammation, as glutamate is involved in cognition, learning, and inflammatory processes. Despite advances in neuroimaging, no previous studies have simultaneously used both DTI free-water imaging and ¹H-MRS glutamate measurement to investigate OCD. This study aims to bridge that gap by examining the relationship between WM microstructure and glutamate levels in OCD patients. Neuroimaging data were collected from 135 participants, including 83 OCD patients and 52 control subjects. We hypothesize that higher glutamate levels will correlate positively with FA and negatively with FW, indicating a potential link between WM integrity and neuroinflammation. This relationship is not expected in control subjects, highlighting the need for further research into the role of neuroinflammation in OCD.