Lower Posterior Cingulate Cortex Glutathione Levels in Obsessive-Compulsive Disorder

Abstract

BackgroundSeveral lines of evidence support the hypothesis that lower cerebral levels of glutathione (GSH), associated with increased oxidative stress, may contribute to obsessive-compulsive disorder (OCD). However, no studies to date have investigated brain GSH levels in individuals with OCD. MethodsTwenty-nine individuals with OCD and 25 age-, sex-, and race-matched comparison individuals without OCD underwent single-voxel, two-dimensional J-resolved proton magnetic resonance spectroscopy (MRS) to examine GSH levels in the posterior cingulate cortex (PCC). MRS data were analyzed using LCModel and a simulated basis set. Group metabolite differences referenced to total creatine (Cr), as well as relationships between metabolite ratios and symptom severity as measured by the Yale-Brown Obsessive-Compulsive Scale, were analyzed using linear regression with adjustment for age, sex, and race. ResultsOne OCD participant failed to produce usable PCC MRS data. We found significantly lower PCC GSH/Cr in OCD participants compared with non-OCD participants (β = −.027; 95% confidence interval: −.049 to −5.9 × 10−3; p = .014). PCC GSH/Cr was not significantly associated with total Yale-Brown Obsessive-Compulsive Scale score in the OCD group (β = 5.7 × 10−4; 95% confidence interval: −4.8 × 10−3 to 5.9 × 10−3; p = .83). ConclusionsLower PCC GSH/Cr may be indicative of increased oxidative stress secondary to hypermetabolism in this brain region in OCD. Future MRS studies are warranted to investigate GSH levels in other brain regions that comprise the cortico-striato-thalamo-cortical circuit thought to be abnormal in OCD.