Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain

Abstract

Objectives: Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms. Here, we tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 adults with neurodevelopmental condition diagnoses.

Methods: Rates of generalized joint hypermobility (GJH, henceforth hypermobility) in adults with a formal diagnosis of neurodevelopmental conditions (henceforth neurodivergent group, n = 109) were compared to those in the general population in UK. Levels of orthostatic intolerance and musculoskeletal symptoms were compared to a separate comparison group (n = 57). Age specific cut-offs for GJH were possible to determine in the neurodivergent and comparison group only.

Results: The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17-9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16-6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain.

Conclusions: In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future.

Keywords: Ehlers-Danlos syndrome; Tourette syndrome; attention deficit hyperactivity disorder (ADHD); autism; autonomic dysfunction; joint hypermobility; neurodevelopmental conditions; pain.

Figure 1

Percentage of individuals in each group who had generalized joint hypermobility according to both JHS criteria (Beighton score ≥4) and 2017 hEDS criteria (age specific cut-off). Error bars show 95% CI.

Figure 2

(A) Percentage of individuals in each group and within each sex who had generalized joint hypermobility according to JHS criteria (Beighton score ≥4). (B) Percentage of individuals in each group and within each sex who had generalized joint hypermobility according to 2017 hEDS criteria (age specific cut-off). Error bars show 95% CI.

Figure 3

Difference in orthostatic intolerance symptom score (A); musculoskeletal symptom score (B) and Beighton score (C) between neurodivergent and comparison group. Graphic is a data rain cloud illustrating raw data, median and interquartile range, and probability density for each variable in each group. Mean and standard error are visualized also.

Figure 4

Graph showing the relationship between orthostatic intolerance symptom score and Beighton score with line of best fit. Error bars show ±1 standard error of the mean.

Figure 5

Graph showing the relationship between musculoskeletal symptom score and Beighton score with line of best fit. Error bars show ±1 standard error of the mean.

Figure 6

Hypermobility as a mediator of predictor relationship between neurodivergent status and (A) orthostatic intolerance score; (B) musculoskeletal score. The confidence interval for the indirect effect is a bootstrapped confidence interval based on 1,000 samples.