Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain

Abstract

ObjectivesAutism, 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.MethodsRates 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.ResultsThe 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.ConclusionsIn 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.

Food Intolerance and Sensitivity are Associated with Chronic Musculoskeletal Pain in A Self-Selected Community Population

“…Studies also confirm a higher prevalence of fibromyalgia and hypermobility among autistic females than in autistic males [26][27][28][29][30], with one estimate suggesting over three quarters of female autistic females develop MSK pain [31]. A risk ratio of 4.5 for hypermobility was reported in neurodivergent females [32], and it was proposed that hypermobility might mediate the relationship between fibromyalgia and neurodivergence [33]. In support of this, the risk ratios for ASD and ADHD are 7.4 and 6.0 respectively among hypermobile people [33].…”

“…Recent work has confirmed that patients with fibromyalgia and other forms of chronic pain are more likely to be neurodivergent [28,30] and that autistic people often develop chronic musculoskeletal pain [29,31]. This relationship also extends to close relatives [62], and hypermobility may mediate the association between fibromyalgia and autistic features [32], especially among symptomatic individuals [36,40]. Most young females with autism or ADHD who also had hypermobility reported the development of chronic pain in adulthood [39,41].…”

Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case–control study

“…Nevertheless, symptomatic hypermobility (hEDS /HSD/JHS) is considered to be an autosomal dominant trait with incomplete penetrance, variable expressivity and influenced by sex, since joint hypermobility is more common in females 43. However, despite this female preponderance, joint hypermobility is also associated with neurodivergence44 (including Fragile X syndrome, ADHD and autism), which is more commonly diagnosed in males. Importantly, however reported co-occurrences are potentially skewed by underdiagnosis of neurodivergence in females 45.…”

Autistic Traits Correlate with Chronic Musculoskeletal Pain: A Self-Selected Population Based Survey

“…In one study, 49% of a neurodivergent cohort had confirmed hypermobility [35], while Cederlof et al [36] reported a heightened risk ratio of 7.4 for ASD and 6.0 for ADHD in a large population-based case control study of people with 8hEDS/HSD. Recent studies confirm markedly increased rates of hypermobility among neurodivergent populations [32,37,38,39]. Csecs et al [39] reported a risk ratio for having generalised joint hypermobility of 4.5 in individuals with ASD, showed that MSK symptoms were the predominant form of chronic pain among neurodivergent people and suggested that joint hypermobility mediated much of the relationship between neurodivergence and pain in this population, with a marked genetic component.…”