The idea that autism (ASD) and ADHD might occur alongside disorders of the body’s connective tissue has circulated among clinicians and researchers for years, built largely on small clinical samples and case reports.1,2 Connective tissue disorders are a broad group of conditions affecting the tissues that support and connect the body, and they include:
- Heritable structural disorders such as Ehlers-Danlos syndrome (which affects collagen and can cause fragile skin and unstable joints) and Marfan syndrome (which affects the fibers that support the body’s organs and can involve the heart and blood vessels)
- Hypermobility spectrum disorders (in which joints move beyond their normal range)
- Autoimmune conditions such as lupus.
We studied more than 117 million U.S. adults and adolescents aged 15 and older who had an outpatient visit between January 2017 and April 2026. We grouped patients by neurodevelopmental diagnosis into those with ASD but not ADHD, ADHD but not ASD, and co-occurring ASD and ADHD, and matched each of those patients with patients who had no neurodevelopmental diagnosis based on age, sex, and how often they used health care. For each group, we measured the proportion of patients with a connective tissue disorder diagnosis in one of several categories. We also looked at kidney stones, a condition we would not expect to share any biological link with neurodivergence. This helps gauge whether any apparent association simply reflects that neurodivergent patients tend to have more thoroughly documented charts.
Across all three neurodevelopmental groups, connective tissue disorders were consistently more common than in comparison patients and were most likely for patients who were diagnosed with ASD and ADHD. Patients with both ASD and ADHD had a 438% higher likelihood of a heritable structural connective tissue disorder and 340% higher likelihood of a hypermobility spectrum disorder compared with matched patients who had no neurodevelopmental diagnosis. The ASD-only group showed a 311% higher likelihood of heritable structural disorders and a 203% higher likelihood of hypermobility spectrum disorders, while the ADHD-only group showed a 170% and 148% higher likelihood, respectively. Associations were present but smaller for autoimmune and inflammatory connective tissue disorders, ranging from a 41% higher likelihood in the ADHD-only group to a 93% higher likelihood in the co-occurring group.
Connective tissue disorders remained rare in absolute terms even where the relative differences were large: heritable structural disorders were documented in roughly 12 per 1,000 ASD-only patients and 21 per 1,000 co-occurring patients, compared with 3 and 4 per 1,000, respectively, among comparison patients.
The negative-control outcome supported this interpretation only partially: kidney stones were no more common among ASD-only patients but were modestly elevated in the ADHD and co-occurring groups (19% and 9% higher likelihood, respectively). Because patients who see clinicians more often tend to accumulate more diagnoses of all kinds, this pattern suggests the connective tissue associations are partly, but not entirely, explained by more thorough documentation rather than a true difference in underlying rates.
