Differential Ceramide Metabolism in Autogenous and Reactive Obsessions: A Biomarker Perspective in OCD

Objective: This study aimed to compare the levels of ceramide pathway metabolites between autogenous and reactive subtypes of patients with obsessive-compulsive disorder (OCD) and healthy controls (HC). Methods: Targeted lipid analyses of ceramide C24:1, hydroxy-ceramide (C24:0 and C18:0), sphingomyelin (SM 16:0), and sphingosine-1-phosphate (S1P) were performed in 52 OCD patients and 27 HC. Patients with OCD group were divided into subgroups based on their primary obsessions: autogenous obsession (AO) and reactive obsession (RO). Sphingolipid species of three groups were compared. Serum samples of ceramide pathway metabolites were analysed by liquid chromatography-mass spectrometry. Results: C18:0 hydroxy-ceramide and S1P levels were significantly higher in patients with OCD than in the HC (p ＜ 0.001). The levels of C24:1 ceramide in the OCD patients with AO were significantly higher than in the OCD patients with RO (p = 0.013) and in the HC group (p ＜ 0.001). In patients with OCD, significant positive correlations were found between C24:1 ceramide levels and C24:0 hydroxy-ceramide levels (r = 0.326, p = 0.019), between C24:0 hydroxy-ceramide levels and C18:0 hydroxy-ceramide (r = 0.569, p ＜ 0.001) and S1P (r = 0.619, p ＜ 0.001), and between C18:0 hydroxy-ceramide levels and S1P (r = 0.652, p ＜ 0.001). Conclusion: The finding of significantly higher C24:1 ceramide levels in OCD patients with AO may be a novel bio-marker that highlights the heterogeneous nature of OCD and the specific neurobiological differences between autoge-nous and reactive subtypes. This study highlights the role of ceramide pathway metabolites in the pathophysiology of OCD and provides new insights into its underlying mechanisms.