The relationship between sphingomyelin and ceramide levels and soft neurological signs in ADHD

Attention deficit hyperactivity disorder (ADHD), characterized by attention deficit, hyperactivity, and impulsivity, has recently been associated with lipid metabolism. In particular, the roles of sphingomyelin, ceramide, andgalactosylceramidase in the pathophysiology of ADHD are being investigated. This study aims to explore the relationship between sphingolipid metabolism markers and soft neurological signs (SNS) in children diagnosed with ADHD who are not undergoing medication treatment. A cross-sectional analysis was conducted on 41 children and adolescents aged 7-12 years diagnosed with ADHD and 39 neurotypically developing controls. Plasma levels of ceramide, sphingomyelin, and galactosylceramidase were measuredusing Enzyme-Linked Immunosorbent Assay (ELISA). SNS were assessed using the Physical and Neurological Examination for Soft Signs (PANESS). Statistical analyses included Student's t-tests, Mann-Whitney U tests, and Multivariate Analysis ofCovariance (MANCOVA), along with logistic regression analysis. Plasma levels of ceramide and sphingomyelin in children with ADHD showed significant differences compared to the neurotypically developing control group; however, there were no significant differences in galactosylceramidase levels between the two groups. Positive correlations were found between plasma levels of ceramide and sphingomyelin and the PANESS subscales F1 (Total Gait and Station) and F3 (Total Dysrhythmia). Additionally, logistic regression analysis indicated that high ceramide levels were positively associated with ADHD. This study underscores a significant association between alterations in sphingolipid metabolism (specifically increased levels of ceramide and sphingomyelin) and the presence of SNS in children with ADHD. These findings elucidate the potential role of sphingolipid metabolism in the pathophysiology of ADHD and provide suggestions for future therapeutic research targeting sphingolipid metabolism in the treatment of ADHD.