Plasma polyunsaturated fatty acids and amino acids in children with attention-deficit hyperactivity disorder: correlations with clinical and cognitive features.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, characterized by inattention, hyperactivity and impulsivity. Metabolic profiles of polyunsaturated fatty acids (PUFAs) and amino acids have been linked to neurodevelopmental processes associated with ADHD. This cross-sectional study aimed to compare plasma levels of PUFAs and amino acids between medication-naive children with ADHD and typically developing (TD) children, after adjusting for multiple confounding factors, and explore their correlations with clinical symptoms and cognitive function. METHODS: A total of 102 medication-naive children with ADHD and 91 TD children were enrolled. Plasma concentrations of four PUFAs and seven neuroactive amino acids were measured using liquid chromatography-tandem mass spectrometry. Group comparisons were performed using analysis of covariance adjusted for age, gender, body mass index (BMI), paternal education level, maternal education level, family annual income, only child status, and main caregiver of children. Correlation analyses and multiple testing corrections were also conducted. RESULTS: After adjustment for confounding factors, ADHD group had higher plasma glutamate (Glu) (median: 103.08 vs. 102.25 µmol/L, P=0.043). Tryptophan (Try) was positively correlated with the Swanson, Nolan, and Pelham rating scale version IV (SNAP-IV) inattention scores (r=0.209, P=0.03). γ-aminobutyric acid (GABA) was negatively correlated with full scale intelligence quotient (IQ) (r=-0.198, P=0.04), and eicosapentaenoic acid (EPA) was negatively correlated with Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) processing speed (r=-0.212, P<0.05). Glu and arachidonic acid (ARA) levels differed significantly across groups defined by hyperactivity-impulsivity severity (H=6.695, P=0.04; H=8.616, P=0.01). Boys had higher WISC-IV verbal comprehension (P=0.04). CONCLUSIONS: This study provides exploratory evidence of weak but significant correlations among plasma PUFAs, amino acids, clinical symptoms, and cognitive function in medication-naive children with ADHD. These preliminary findings support further investigation of peripheral metabolic profiles as potential phenotypic correlations rather than established biomarkers for ADHD.