Exploring the link between fatty acids, FADS2 expression, and ADHD using structural equation modeling

Fatty acids have been linked to attention-deficit/hyperactivity disorder (ADHD), but the biological basis of this association remains unclear. This study examined dietary and plasma fatty acid profiles and fatty acid desaturase-2 (FADS2) in children with ADHD. This cross-sectional study included 85 children with ADHD and 85 controls aged 6-12 years. ADHD symptoms were assessed using the Conners' Parent Rating Scale-Revised: Short Form (CPRS-R: S). Dietary fatty acid intake was estimated from three non-consecutive 24-hour recalls. Plasma fatty acids were measured by GC-MS. Plasma FADS2 protein levels were quantified by ELISA, and FADS2 mRNA expression was assessed by real-time PCR. Principal component analysis (PCA) was used to derive fatty acid components, followed by structural equation modeling (SEM) to evaluate associations with ADHD symptom severity. Children with ADHD showed a greater relative dietary contribution of omega-6 fatty acids and total PUFAs, higher plasma LA levels and omega-6/omega-3 ratio, and lower plasma MUFAs, GLA, and docosanoic acid than controls. Plasma FADS2 protein levels were numerically higher but not significantly different, whereas relative FADS2 mRNA expression was lower in the ADHD group. In SEM, greater ADHD symptom severity was associated with a PCA-derived component characterized by higher LA and omega-6/omega-3 ratio together with lower nervonic acid. Children with ADHD differed from controls across multiple dietary, plasma, and FADS2-related fatty acid measures, particularly those related to omega-6 balance. ADHD symptom severity was also associated with a multivariable fatty acid profile.