Epigenetic Age in Children and Adolescents With ADHD — Wrigglesworth et al. (2025)

The question

Researchers asked whether children and adolescents with ADHD appeared biologically older or younger than children without ADHD when age was estimated from patterns of DNA methylation.

These estimates are sometimes called epigenetic clocks. They are statistical tools that compare age-related methylation patterns with a person's chronological age. They are not a diagnosis, a direct measure of brain maturity, or a complete measure of health.

What the researchers did

The primary sample came from the Neuroimaging of the Children's Attention Project in Australia.

• 169 participants contributed 293 saliva samples.
• 91 participants had ADHD symptoms.
• 75 were assessed at one time point.
• 94 were assessed two or three times.
• Assessments covered approximately ages 9 to 14.
• The researchers used three epigenetic clocks: PedBE, Horvath, and Skin & Blood.
• They compared the gap between estimated epigenetic age and chronological age in ADHD and comparison groups.
• They also examined whether that gap changed differently over time.
• They repeated the analyses in the independent Oregon ADHD-1000 cohort, which included 727 eligible participants, although only 16% contributed longitudinal data.

What the study found

The ADHD and comparison groups did not differ reliably in epigenetic age gap across the three clocks.

The groups also did not show reliably different rates of epigenetic aging over time. Results were consistent in the Oregon replication cohort.

One result involving the PedBE clock changed after adjustment for medication use, but it did not replicate consistently across clocks or in the second cohort. The authors appropriately treated it as uncertain rather than as evidence that ADHD medication changes biological aging.

The clearest interpretation

This study found no strong evidence that ADHD is associated with faster or slower epigenetic aging during the developmental period studied.

A more precise sentence is:

In these child and adolescent samples, the DNA-methylation clocks used in the study did not reliably distinguish participants with ADHD from participants without ADHD, either at one time point or in how the estimates changed over time.

What the study does not show

The results do not prove that:

• ADHD has no epigenetic features.
• lived experience, chronic stress, discrimination, sleep, medication, or environmental conditions have no biological effects;
• children with ADHD are biologically identical to children without ADHD in every way;
• these findings apply to adults or later-life aging;
• an individual person's “biological age” can be determined from this research.

The study also did not compare competing explanations for ADHD or for health differences associated with ADHD. A null result for epigenetic age does not make inflammation, the gut microbiome, mitochondrial function, sleep, diet, stress physiology, or any other proposed mechanism more likely. Each explanation requires its own evidence.

Strengths

• It included both cross-sectional and repeated assessments.
• It used three different epigenetic clocks.
• The PedBE clock was developed for pediatric buccal tissue and was the best-fitting clock for these samples.
• The researchers attempted replication in an independent cohort.
• They corrected for multiple comparisons and did not present an isolated nominal finding as conclusive.

Important limits

• The longitudinal portion of the primary sample was small, and only 30 participants completed all three waves.
• The replication cohort had only two time points, and just 16% contributed longitudinal data.
• The study may not have had enough power to detect small group differences.
• Saliva methylation estimates cannot be treated as direct measures of brain development or whole-body aging.
• The age range was limited and cannot answer questions about infancy, adulthood, menopause, or later-life health.
• Co-occurring mental-health conditions could not be accounted for.
• Medication dose and duration were not available.
• The primary sample was predominantly male, especially among those retained at the third wave. The study gives little specific information about girls and none about ADHD women.

Practical and clinical relevance

There is no clinical test, treatment decision, or accommodation recommendation that follows from this study.

Its value is mainly corrective: it does not support claims that children with ADHD are globally “biologically older,” globally “younger,” or aging at a different rate based on these epigenetic clocks.

For neurodivergent-affirming writing, avoid turning a group-level methylation estimate into a story about an ADHD child's body being damaged, delayed, or abnormal. The finding is about the limits of these measures in these samples—not about the legitimacy of ADHD experiences or the effects of living in environments that may not fit.

Source

Wrigglesworth, J., Fransquet, P. D., Ryabinin, P., Mooney, M. A., Craig, J. M., & Silk, T. J. (2025). Epigenetic age across development in children and adolescents with ADHD. Psychiatry Research, 345, 116373. https://doi.org/10.1016/j.psychres.2025.116373[1]