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  1. JA Eccles,
  2. V Iodice,
  3. NG Dowell,
  4. A Owens,
  5. L Hughes,
  6. S Skipper,
  7. Y Lycette,
  8. K Humphries,
  9. NA Harrison,
  10. CJ Mathias,
  11. HD Critchley


Objective To test the hypothesis that Joint hypermobility and autonomic dysfunction are over-expressed within neurodevelopmental disorders. Joint hypermobility is a widespread poorly recognized connective tissue condition with affected individuals overrepresented among panic and anxiety disorders, irritable bowel syndrome, fibromyalgia, and chronic fatigue. The relevance of hypermobility to neuropsychiatric disorders of developmental origin is currently unknown, despite anecdotal case reports and clinical suspicion of a link. Autonomic nervous system dysregulation, typically postural tachycardia syndrome is often found in hypermobile individuals. Interestingly, differences in amygdala and superior temporal cortex anatomy have been reported in hypermobile populations and functional abnormalities in patients with autism.

Method Thirty-seven adults with neurodevelopmental disorder, 205 patients attending general psychiatric clinics without neurodevelopmental diagnosis and 29 healthy controls were recruited. Hypermobility was assessed using the Beighton scale (BS) and autonomic symptoms using the Autonomic Symptoms and Quality of Life Score (ASQoLS: orthostatic, gastrointestinal, bladder, secretomotor, sudomotor and sleep domains.

Results The neurodevelopmental cohort had a mean age of 34.6 years (27 male). Nineteen had Attention Deficit Hyperactivity Disorder (ADHD), 4 Autistic Spectrum Disorder (ASD), 1 Tourette Syndrome (TS) and the remainder combinations of ADHD, ASD and TS. Nine had co-morbid affective disorder. Eighteen patients (48.6%) were classified as hypermobile (BS>=4) compared to 67/204(32.7%) in the general psychiatric group (p=0.048) and 3/29(10.3%) in healthy controls (p=0.007) and this prevalence was also significantly higher that reported in a large general population cohort (1156/6022, 19.19%, p=<0.001). Mean autonomic dysfunction score was significantly higher in the neurodevelopmental cohort compared to controls (mean±SEM: neurodevelopmental disorder patients, 45.8±4.86; controls, 8.5±1.62). This effect was seen across all sub-scales of the ASQoLS. Total autonomic dysfunction score did not differ significantly between neurodevelopmental cohort and the general psychiatric group, however neurodevelopmental disorder patients had significantly higher scores on orthostatic and gastrointestinal disturbance subscales.

Conclusion We demonstrate for the first time that rates of hypermobility and symptoms of autonomic dysfunction are particularly high in adults with neurodevelopmental diagnoses. It is likely that the importance of hypermobility and autonomic dysfunction to the generation and maintenance of psychopathology in neurodevelopmental disorders is poorly appreciated. Work underway(autonomic testing, fMRI) will test the hypothesis that autonomic reactivity and interoceptive sensitivity predispose to the expression of psychiatric symptoms, particularly anxiety. It is further hypothesized that inefficient neural co-ordination of efferent autonomic drive with imprecise interoceptive representations may be amplified in hypermobile individuals. In hypermobility, this mechanism might explain increased vulnerability to stress sensitive and developmental neuropsychiatric conditions.

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