Likely neurodivergence and variant connective tissue in patients with chronic pain/chronic fatigue: a case-control study

Neurodivergent traits are frequently observed in individuals with chronic pain and/or chronic fatigue (CP/CF), yet the underlying mechanisms remain unclear. This study investigated the proportion of likely autism and attention deficit hyperactivity disorder (ADHD) in patients with CP/CF and examined whether joint hypermobility-a marker of variant connective tissue-mediated this relationship. We conducted a case-control study using an online survey. Eighty-three adults with CP/CF and 91 adults from a non-clinical comparison group completed validated screening measures for autism, ADHD, and joint hypermobility. Odds ratios (ORs) and 95% confidence intervals (CIs) for likely neurodivergence were calculated using binary logistic regression. Mediation analysis tested whether joint hypermobility explained the association between likely neurodivergence and CP/CF. Participants with CP/CF had markedly higher odds of likely autism (adjusted OR 14.3 95% CI [6.5, 31.5]) and likely ADHD (adjusted OR 12.9 95% CI [5.0, 26.7]) than the comparison group. The presence of joint hypermobility significantly mediated the relationship between neurodivergent traits and CP/CF (indirect effect: b = 1.6 95% CI [1.2, 2.1]). Our findings reveal a trans-diagnostic pattern of major clinical importance. In patients with CP/CF, routine screening for neurodivergence should be considered to optimise fair access to appropriate support for improved quality of life.