Dysregulation of the orexin–leptin–ghrelin axis and its associations with chronotype and sleep disturbances in drug-naïve children with ADHD
Sleep Medicine, cilt.136, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 136
- Basım Tarihi: 2025
- Doi Numarası: 10.1016/j.sleep.2025.106839
- Dergi Adı: Sleep Medicine
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE, Psycinfo
- Anahtar Kelimeler: ADHD, Chronotype, Circadian rhythm, Ghrelin, Leptin, Orexin, Sleep disturbances
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder defined by inattention and behavioral dysregulation. Sleep disturbances are frequently reported in ADHD and strongly associated with circadian rhythms and sleep–wake regulation. Given the pivotal involvement of orexin, leptin and ghrelin systems in the modulation of cognitive, metabolic and circadian functions, this study aimed to investigate whether serum orexin-A, orexin-B, leptin and ghrelin levels are associated with chronotype and sleep disturbances in children with ADHD. Forty-five drug-naïve ADHD patients and 45 age and sex-matched healthy controls were assessed using validated measures of chronotype and sleep habits, and serum hormone levels were analyzed via two-site sandwich ELISA. Children with ADHD exhibited substantially higher eveningness chronotype, as well as markedly elevated bedtime resistance, sleep onset delay, night wakings and daytime sleepiness (all p < 0.001). Importantly, serum orexin-A (p < 0.001), orexin-B (p = 0.039) and leptin (p = 0.012) levels were significantly reduced in the ADHD group, whereas serum ghrelin levels were significantly increased (p < 0.001). Ghrelin levels showed strong positive associations with attention deficit scores, chronotype scores and total sleep disturbance scores (all p < 0.01), whereas orexin-A/B and leptin levels were negatively correlated with these parameters (all p < 0.05). Notably, children with an evening chronotype showed the highest ghrelin and lowest orexin/leptin levels. To our knowledge, these findings provide preliminary evidence of an association between disturbances in the orexin–leptin–ghrelin axis and chronotype-related circadian misalignment and sleep difficulties in childhood ADHD, suggesting that neurohormonal mechanisms may be relevant to the underlying pathophysiology.