# Hypothalamic–pituitary–adrenal axis activity and neurotrophic factors in drug-naive children and adolescents with attention-deficit/hyperactivity disorder

## TL;DR

This study found that children with ADHD have higher levels of certain brain-related proteins and stress hormones compared to healthy children, suggesting altered brain development and stress responses in ADHD.

## Contribution

The study identifies altered neurotrophic and HPA axis markers in drug-naive ADHD children, suggesting potential biological pathways in ADHD pathophysiology.

## Key findings

- ADHD children had higher serum levels of BDNF, GDNF, VEGF, ACTH, and cortisol compared to healthy controls.
- No significant correlation was found between neurotrophic factors, HPA axis hormones, and ADHD symptom severity scores.
- The findings suggest parallel and partially independent mechanisms involving neurotrophic and HPA axis systems in ADHD.

## Abstract

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a complex and not fully understood etiology. Increasing evidence suggests that neurotrophic factors involved in neurodevelopment and synaptic plasticity, as well as hormones of the hypothalamic-pituitary-adrenal (HPA) axis that regulate the stress response, may contribute to the pathophysiology of ADHD.

This cross-sectional study aimed to compare children diagnosed with ADHD and healthy controls with respect to serum levels of brain-derived neurotrophic factor (BDNF), glial cell line–derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), neurotrophin-3 (NT-3), adrenocorticotropic hormone (ACTH), and cortisol. A total of 80 children aged 6–18 years with a diagnosis of ADHD and 81 healthy controls were included in the study. The severity of ADHD symptoms was assessed using the Conners’ Parent Rating Scale–Short Version (CPRS-SV). Serum levels of biochemical parameters were measured using commercially available electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay kits.

Compared with the healthy control group, the ADHD group exhibited significantly higher serum levels of BDNF, GDNF, VEGF, ACTH, and cortisol, whereas NT-3 levels did not differ between the groups. These group differences remained statistically significant after controlling for potential confounding variables. Correlation analyses revealed no significant associations between neurotrophic factors, hypothalamic–pituitary–adrenal (HPA) axis hormones, and CPRS-SV subscale scores.

The present findings indicate that neurotrophic factors and hormones related to the hypothalamic–pituitary–adrenal (HPA) axis are altered in medication-naïve children and adolescents with ADHD. The absence of a direct correlation between neurotrophic factors and HPA axis hormones suggests that these systems may contribute to the pathophysiology of ADHD through parallel yet partially independent and complex mechanisms. Future longitudinal and multimodal studies are warranted to elucidate the dynamic interactions between stress-related neuroendocrine processes and neurodevelopmental pathways in ADHD.