Contribution of lipid Peroxidation to Social Behaviors in individuals with autism spectrum disorders

Abstract Lipid peroxidation contributes to the development of autism spectrum disorders (ASD). Omega-3 and omega-6 polyunsaturated fatty acids undergo lipid peroxidation, and conversion to malondialdehyde (MDA). The MDA further react with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). MDA-LDL is known as a marker of lipid peroxidation. However, the association between PUFAs and MDA-LDL in the pathophysiology of ASD is unclear. We studied this association in 18 young individuals with ASD and 8 age- and sex-matched normal healthy controls. Social behaviors were assessed using the Social Responsiveness Scale (SRS). To overcome the small sample size, three measures were conducted: firstly, use of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, estimation of coefficient of variation for an appropriate variable selection; and finally, appropriate variables were selected. Plasma MDA levels and DHA/omega 6 PUFA arachidonic acid ratio were significantly higher, whereas plasma levels of superoxide dismutase were significantly lower in the ASD group than in the control group. Total SRS scores were significantly higher in the ASD group than in the control group. Multiple linear regression and adaptive Lasso revealed that plasma DHA/ARA ratio were significantly associated with total SRS scores. Plasma levels of the antioxidant enzyme superoxide dismutase were significantly decreased and plasma MDA-LDL levels were significantly increased. These findings firstly revealed that the plasma DHA/ARA ratio may be associated with social behaviors. Decreased plasma SOD levels and increased plasma MDA-LDL levels may be caused in relation to lipid peroxidation. These neurological bases may contribution to social impairment.