Is There a Genetic Link Between Melatonin and ADHD in Children?

ADHD (Attention Deficit Hyperactivity Disorder) is a complex neurodevelopmental condition influenced by multiple genetic and environmental factors. It is well established that genes related to dopamine regulation, neuronal development, and synaptic function contribute to ADHD risk.

Melatonin is a hormone primarily involved in the regulation of circadian rhythms and sleep. In recent years, researchers have begun investigating whether variations in genes affecting melatonin synthesis, secretion, or regulation may be associated with ADHD symptom severity or risk, particularly via effects on sleep and circadian regulation.

The evidence so far does not show a clear, simple “ADHD gene = melatonin gene” relationship. Rather, there are intriguing associations and hypotheses under active investigation.

Key Findings & Studies

Genetic Risk of Melatonin Secretion and ADHD Symptoms

A recent study published in ResearchGate titled Association between genetic risk of melatonin secretion and attention deficit hyperactivity disorder (2024) explored whether genetic variants that reduce melatonin secretion are linked to ADHD. 

• The study used polygenic risk scores (PRS) derived from genome-wide association studies (GWAS) for urinary melatonin metabolite levels (UMCR) and for ADHD. 
• They found a negative genetic correlation (r_g = –0.134, SE = 0.012, p < 0.001), suggesting that alleles associated with lower melatonin secretion are modestly correlated with greater ADHD risk. 
• In their sample of children, a higher PRS for reduced melatonin secretion was associated with more severe ADHD symptoms, and this effect was partially mediated via delayed sleep onset. 

This study is probably the strongest direct evidence so far linking genetic variation in melatonin regulation with ADHD traits.

A news summary in EurekAlert! notes the same findings: “children with genetic traits that reduce melatonin secretion at night exhibited more severe ADHD symptoms at age 8 to 9 years.”

However, these are associations and do not establish causation.

Animal Model Evidence

While human data are limited, there is some experimental animal work. A 2018 paper in Nature, titled, Melatonin inhibits attention-deficit/hyperactivity disorder caused by maternal sleep deprivation in offspring, reported that administering melatonin to rodents exposed to prenatal or perinatal stress reduced ADHD-like behaviours in offspring. 

Animal models can offer mechanistic insight, but translating these to human pathophysiology is always speculative.

Melatonin and ADHD in Children: Clinical and Sleep Studies

Though not strictly genetic, many studies look at melatonin levels or melatonin treatment in children with ADHD, which indirectly support the idea of melatonin dysregulation in ADHD.

• A review in PubMed Central (PMC) titled Melatonin in Neurodevelopmental Disorders: A Critical Literature Review, summarises multiple studies showing altered melatonin rhythms or lower melatonin levels in neurodevelopmental conditions, including ADHD. 

• A study in PMC titled “Low Doses of Melatonin to Improve Sleep in Children with ADHD” (PMC) showed that melatonin supplementation (1 mg) increased total sleep time in children and adolescents with ADHD, especially in those taking stimulant medication. 

• An earlier clinical trial in ScienceDirect looked at melatonin’s effect on behaviour and cognition in ADHD: “Effect of Melatonin on Sleep, Behavior, and Cognition in ADHD” suggested modest benefits on sleep but mixed results on behaviour and cognition. 

• Some genetic association work has examined circadian clock genes (e.g. PER, CLOCK, etc.) in relation to ADHD symptoms and sleep traits. ADxS (an ADHD expert site) notes that “a small number of genetic association studies reported links between polymorphisms in circadian clock genes and ADHD symptoms.” 

• A broader review of genetics and sleep disorders in children, published on the Frontiers website, mentions melatonin receptor genes (e.g. MTNR1B) as potential modifiers of sleep and circadian rhythm disorders in neurodevelopmental conditions. 

These clinical and observational data support the plausibility of melatonin system involvement in ADHD, particularly via its role in sleep and circadian regulation.

Biological Plausibility & Mechanisms

Here are some of the plausible biological pathways by which melatonin genetic variation might influence ADHD risk or symptom severity:

1. Circadian Regulation & Sleep Disruption
   Genetic variants reducing melatonin secretion or receptor sensitivity may lead to delayed or fragmented sleep. Sleep disruption is well known to worsen attention, executive function, and impulse control, which are core ADHD domains.

2. Mediation via Sleep Phenotypes
   In the same 2024 PRS study by ResearchGate, part of the link between melatonin genetics and ADHD symptoms was mediated by delayed sleep onset (i.e. genetic predisposition → delayed sleep → worse ADHD symptoms).

3. Neuronal and Synaptic Effects
   Melatonin has antioxidant, anti-inflammatory, and neuroprotective roles. Some hypotheses suggest that melatonin may influence synaptic plasticity and neuronal connectivity. Dysregulation in these areas is implicated in ADHD. (These mechanistic ideas are still speculative.)

4. Interaction with Other Genetic Risks
   Because ADHD is polygenic, melatonin‐related genes would likely interact with other ADHD risk genes (dopamine, synaptic, and neuronal development). The effect of melatonin genetics alone is probably small.

ALSO READ: Melatonin for Kids: What Parents Need to Know

Limitations & Caveats

• Association, not causation: Most findings are correlational. Even in the PRS study, causality is not proven.

• Modest effect sizes: The genetic correlation (r_g = –0.134) is small, indicating a weak association.

• Population specificity: The PRS and GWAS datasets used come from particular ethnic and geographic populations; associations might differ in other populations.

• Complex trait architecture: ADHD has many genetic and environmental contributors; melatonin genes would be just one component.

• Confounding and measurement: Sleep phenotypes are challenging to measure precisely, and residual confounding may bias results.

• Limited replication so far: Few studies to date have directly tested melatonin genetics in ADHD, so replication in independent cohorts is needed before strong conclusions can be drawn.

What Sleep/Medical Experts Recommend (Given Current Evidence)

Given the emerging nature of the evidence, sleep and paediatric experts generally frame this as “an interesting hypothesis, warranting further research” rather than fact. Some practical points:

• Clinicians may consider screening for sleep problems in children with ADHD, as sleep disruption can exacerbate symptoms or mimic them.

• Melatonin supplementation is sometimes used to address sleep onset delay in ADHD, but with caution and under medical supervision.

• Genetic testing for melatonin genes is not yet part of standard ADHD workups, given the limited and preliminary evidence.

• Future research (especially longitudinal and interventional studies) is needed to clarify causal direction and therapeutic implications.

Conclusion

While the idea of a genetic link between melatonin and ADHD in children is still nascent, recent polygenic analyses do suggest a small but statistically significant association between lower genetically predicted melatonin secretion and more severe ADHD symptoms (in part mediated by delayed sleep). Animal and clinical studies further support the plausibility of melatonin system dysregulation contributing to ADHD via sleep and neuronal pathways.

However, evidence remains preliminary. More replication, mechanistic studies, and controlled trials are needed before we can say that melatonin genetics are a robust risk factor for ADHD or that they should guide clinical practice.

Disclaimer: The information shared on BabyYumYum.com is provided for general knowledge and educational purposes only. It should not be taken as professional medical advice, diagnosis or treatment. Every child and family is different, so we encourage you to speak with your doctor, paediatrician, or another qualified healthcare professional if you have any concerns about your own health or your child’s wellbeing.