Serum metabolites and inflammation predict brain functional connectivity changes in Obsessive-Compulsive disorder

Currently, our understanding of the metabolic and immune pathways involved in obsessive-compulsive disorder (OCD), as well as the precise mechanisms by which metabolism and immunity impact brain activity and function, is limited. This study aimed to examine the alterations in serum metabolites, inflammatory markers, brain activity, and brain functional connectivity (FC) among individuals with OCD and investigate the relationship between these factors. The study included 55 individuals with moderate-to-severe OCD (either drug-naïve or not taking medication for at least eight weeks) and 54 healthy controls (HCs). The High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) technique was used to detect serum metabolites, whereas the enzyme-linked immunosorbent assay (ELISA) was utilized to identify inflammatory markers. The FC of the brain was investigated using resting-state functional magnetic resonance immaging(rs-fMRI). The findings demonstrated that individuals with OCD exhibited significant alterations in 11 metabolites compared to HCs. In particular, 10 of these metabolites exhibited an increase, while one metabolite displayed a decrease. Additionally, individuals with OCD experienced a marked elevation in the levels of five inflammatory factors (TNF-α, IL-1β, IL-2, IL-6, and IL-12). Rs-fMRI analysis revealed that individuals with OCD exhibited atypical FC in various brain regions, such as the postcentral gyrus, angular gyrus, and middle temporal gyrus. These specific brain areas are closely associated with sensory-motor processing, cognitive control, and emotion regulation. Further stepwise multiple regression analysis revealed that serum metabolite levels, particularly phosphatidylcholine, and inflammatory markers such as IL-1β could predict alterations in brain FC among individuals diagnosed with OCD. In summary, this study uncovered that individuals with OCD exhibit alterations in serum metabolites, inflammatory markers, brain activity, and FC. The findings suggest that these metabolites and inflammatory markers might play a role in the development and progression of OCD by affecting brain activity and the FC of neural networks.