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 biomarker that highlights the heterogeneous nature of OCD and the specific neurobiological differences between autogenous 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.