Hata_2026_J.Psychiatr.Res_204_8

OBJECTIVES: Soluble epoxide hydrolase (sEH) is involved in regulating neuroinflammation implicated in autism spectrum disorder (ASD) pathophysiology. However, the relevance of perinatal sEH levels to later ASD symptoms remains unclear. This study aimed to examine the association between umbilical cord blood sEH concentrations and pediatric ASD symptoms. METHODS: Data were obtained from the Hamamatsu Birth Cohort for Mothers and Children, a prospective birth cohort study. Enzyme-linked immunosorbent assay was used to measure sEH concentrations in umbilical cord serum. Monocyte chemoattractant protein-1 (MCP-1) concentrations were also measured to examine sEH-related inflammatory signaling pathways. ASD symptom severity was assessed at 6 years of age using the autism diagnostic observation schedule (ADOS). RESULTS: This study included 854 children. Overall, higher sEH concentrations were significantly associated with lower ADOS calibrated severity scores (CSS) after adjustment for confounding factors. In boys, higher sEH concentrations were significantly associated with lower restricted and repetitive behavior, social affect, and CSS scores. In both the overall sample and boys, sEH concentrations negatively correlated with MCP-1 levels. No significant associations were observed in girls. Furthermore, MCP-1 levels were not significantly associated with ADOS scores. CONCLUSIONS: Higher sEH concentrations in umbilical cord blood were associated with lower ASD symptom severity. Thus, sEH-related lipid metabolism may be associated with neurodevelopmental processes linked to ASD symptoms. However, given the observational design of the study, causal relationships remain unclear. Further longitudinal and mechanistic studies are warranted to clarify the role of sEH-related lipid pathways in neurodevelopment.