BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by abnormal functions of neuroendocrine systems with circadian rhythm, especially for the hypothalamic-pituitary-adrenal (HPA) axis and the melatonin-N-acetylserotonin (MEL-NAS) system and the interactions within and between them. However, the specific neuroendocrine mechanisms underlying ADHD remain poorly understood. This might be partly due to the clinical heterogeneity of the disorder and the inherent fluctuations of traditional acute biomarkers from biofluids, which fail to reflect long-term physiological homeostasis.
METHODS: This study utilized a cross-sectional design and recruited 106 Chinese children with ADHD (age: 6-12 years) diagnosed by physicians according to DSM-IV criteria. Cortisol (F), cortisone (E), melatonin (MEL), and N-acetylserotonin (NAS) in hair and their ratios were employed as the biomarkers of the two systems and the interactions within and between them. The ADHD symptoms were assessed with the SNAP-IV scale that includes inattention, hyperactivity/impulsivity, and oppositional symptoms and filled by children's parents. The 1-cm hair strands closest to the scalp were collected for the analysis of the four hormones with liquid chromatography-tandem mass spectrometry.
RESULTS: Oppositional symptoms showed significantly positive association with the MEL/NAS ratio (p < 0.05). After demographic variables and oppositional symptoms were controlled, hyperactivity/impulsivity showed significantly positive association with the F/NAS and E/NAS ratios (ps < 0.05), but it was not observed for inattention.
CONCLUSION: The clinical heterogeneity of ADHD core symptoms is underpinned by distinct neuroendocrine network imbalances. There was the function dominance of stress-related signaling over the NAS-mediated neuroprotection underlying the hyperactivity/impulsivity. Additionally, there was a disturbance in circadian metabolic homeostasis underlying the oppositional symptoms.
