Concurrent Assessment of Neurotrophic Factors and HPA-Axis Hormones in Early Childhood Autism Spectrum Disorder

PURPOSE: Neurotrophic pathways and hypothalamic-pituitary-adrenal (HPA) axis regulation have been implicated in autism spectrum disorder (ASD), yet peripheral findings-particularly in early childhood-remain inconsistent. We examined peripheral neurotrophic factors and HPA-axis hormones in medication-naïve young children with ASD and evaluated their associations with clinical severity. METHODS: This cross-sectional study included 45 medication-naïve children with ASD (18-72 months) and 52 age-matched healthy controls. ASD diagnosis was established per DSM-5, supported by the Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (ABC). Morning samples (08:30-09:30) were assayed for serum BDNF, GDNF, NT-3, VEGF, cortisol, and plasma ACTH. Group comparisons used ANCOVA adjusted for age, sex, and BMI-for-age z score (BAZ), with Benjamini-Hochberg false discovery rate (FDR) correction. Within-ASD associations were tested using covariate-adjusted partial Spearman correlations. RESULTS: BDNF was significantly lower in ASD than controls and remained significant after covariate adjustment and FDR correction. No between-group differences were observed for GDNF, NT-3, VEGF, ACTH, or cortisol. Within the ASD group, lower BDNF correlated with higher CARS total scores and higher ABC relating, social and self-help, and total scores. No significant correlations were found between neurotrophic factors and ACTH/cortisol. CONCLUSIONS: In medication-naïve children with ASD aged 18-72 months, peripheral BDNF is reduced and relates to symptom severity and adaptive/social difficulties, whereas other neurotrophic factors and basal HPA-axis hormones do not differ from controls. Longitudinal studies incorporating standardized sampling and diurnal/stress-reactivity indices are needed to clarify developmental dynamics and clinical implications.