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Purpose <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月7日

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  • Hurşit Ferahkaya,
  • Ayşegül Tuğba Hira Selen,
  • Şeyma Tezer,
  • Ömer Faruk Akça,
  • Abdullah Akkuş,
  • İbrahim Kılınç,
  • Fatma Coşkun

摘要

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.