# Circadian rhythms and neuroendocrine dysregulation in ADHD: Therapeutic insights from omega-3 fatty acids

## TL;DR

This paper explores how circadian rhythm disruptions in ADHD may be addressed with omega-3 fatty acids, which could help regulate sleep and brain function.

## Contribution

The paper introduces omega-3 fatty acids as potential non-photic zeitgebers to modulate circadian dysregulation in ADHD.

## Key findings

- Omega-3 fatty acids may influence melatonin synthesis and sleep-wake regulation in ADHD.
- N-3 PUFAs could modulate circadian clock genes in the SCN and normalize HPA axis activity.
- Supplementation with n-3 PUFAs may improve ADHD outcomes through circadian pathways, though clinical evidence is limited.

## 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.