Circadian rhythms and neuroendocrine dysregulation in ADHD: Therapeutic insights from omega-3 fatty acids
Abstract
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental condition often accompanied by circadian rhythm disturbances, particularly delayed sleep phase. These involve suprachiasmatic nucleus (SCN) dysregulation, altered melatonin secretion, and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be exacerbated by artificial light exposure. Genetic studies further implicate circadian mechanisms, linking ADHD with polymorphisms in clock genes such as PER and CLOCK. Nutraceuticals, particularly omega-3 polyunsaturated fatty acids (n-3 PUFAs), have been proposed as modulators of circadian rhythms. N-3 PUFAs are essential for brain health and may influence melatonin synthesis and sleep-wake regulation. Preclinical and clinical findings suggest that supplementation can improve cognitive and behavioral outcomes in ADHD, possibly through circadian pathways, though direct clinical evidence remains limited. This review integrates findings on melatonin and cortisol dysregulation in ADHD and evaluates n-3 PUFAs as potential non-photic zeitgebers. N-3 PUFAs may modulate circadian clock genes in the SCN, restore rhythm synchronization, normalize melatonin secretion, stabilize HPA axis activity, and reduce systemic inflammation. Future research should focus on well-designed trials to clarify the circadian effects of n-3 supplementation in ADHD.
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