Connective issues

When we think of neurodivergence, our focus understandably lands on brain and behaviour, and the intersection of those with wider society. But what of the interface between the two – our bodies?

Psychologists and physicians have recognised for many years now that neurodivergent people experience physical symptoms at a rate higher than the general population. Many will be quick to bring to mind research linking autism and gut issues, or perhaps the fact that those with ADHD experience everything from metabolic disorders to migraine more often than their neurotypical peers.

However, researchers have more recently become aware of a mediating factor linking neurodivergence in many individuals to these more widespread chronic physical conditions - hypermobility.

What is hypermobility?

Conditions affecting connective tissue are often associated with overly flexible joints and not much else. Those with connective tissue disorders such as Ehlers Danlos Syndrome (EDS) or hypermobility spectrum disorder (HSD) have joints which overextend beyond typical ranges, may dislocate easily, and can frequently slide into awkward positions which fall short of full dislocations (known as subluxations).

But that's not the whole story. Connective tissue – which provides support in skin, tendons, ligaments, blood vessels, organs and bones – is found throughout the body. This means symptomatically hypermobile people often experience a whole suite of multisystemic physical conditions beyond simply being bendy – migraines, heart problems, gynaecological troubles, and/or autoimmune issues, to name just a few.

Overly flexible tissue can also not only result in significant amounts of chronic pain, but may also produce dysautonomia (dysregulation of autonomic functions, such as maintaining appropriate blood pressure upon standing), proprioceptive issues, and anxiety. As anyone who has dealt with these conditions in isolation can attest to, managing symptoms alongside day-to-day functioning can be stressful and frustrating, and present many practical barriers to everyday life. Experienced in conjunction with one another, the physical and psychological load of hypermobility can be intense. 

Beyond the mental health aspect of dealing with multiple chronic conditions, however, evidence is emerging of a strong association between hypermobility and neurodivergence.

Bendy brains

In 2012, Dr Jessica Eccles of Sussex University and colleagues were investigating the brain structure of hypermobile individuals, after noticing that many autistic people presenting to their clinic showed signs of hypermobility. The team performed MRI scans on 72 volunteers without clinical anxiety and collected objective measures of hypermobility (using the Beighton Scale), anxiety, and interoceptive ability. Through this, they determined that 36 participants scored above 1 on the Beighton Scale, indicating some degree of hypermobility.

Those in the hypermobile group also scored significantly higher on measures of interoceptive sensitivity, while falling slightly short of being significantly more anxious than controls. Upon inspecting the volume of these participants' amygdalae, and comparing them with non-hypermobile controls, it became apparent that the volume of the amygdala was significantly larger in the hypermobile group.

Not only that, but results showed that participants' degree of hypermobility correlated with the volume of several brain areas. Of particular note was a negative correlation with the volume of the right superior temporal cortex, an area involved in processing social and emotional signals, which is also found to be atypical in the brains of autistic individuals.

To the team, these differences suggested a few things. Firstly, differences in the amygdala may indicate that hypermobile individuals may be more sensitive to pain (or the threat of it), and/or that their autonomic functions were disrupted – an aspect Dr Eccles is currently investigating.

Results showing higher interoceptive sensitivity also suggested that the hypermobile participants may have a 'more finely tuned sensory representation of internal body signals'. The team took particular note of findings in the superior temporal cortex, speculatively concluding that perhaps 'processes compromising function in neurodevelopmental conditions may occur in individuals with hypermobility.'

Surprisingly prevalent

Encouraged by various smaller reports suggestive of a link, as well as larger positive indications from a Swedish cohort in 2016, Dr Eccles and colleagues undertook a study to uncover the prevalence of symptomatic hypermobility in neurodivergent people.

In 2022, the Sussex-based team published findings showing that within their sample of 109 UK-based adults with diagnosed autism, ADHD, or Tourette's Syndrome, 51 per cent of neurodivergent participants showed evidence of hypermobility, compared to just 20 per cent of neurotypical controls. Even with stricter cut-off points for connective tissue problems, the neurodivergent participants were still twice as likely to show symptoms of hypermobility than neurotypicals, with female participants more likely to be hypermobile than males.

These findings are echoed by similar papers, such as a recent study from Professor Sir Simon Baron-Cohen and team at the University of Cambridge which broadened the list of physical conditions associated with autism. The paper, published in 2023 in Molecular Autism, illustrated evidence of increased risk of physical disease across all organ systems and stated that hypermobility is more likely to occur among autistic women than allistic women.

While research in this area is still emerging, models illustrating a possible interplay between symptoms of hypermobility and neurodivergent behaviour have been proposed. Carolina Baeza-Velasco of the University of Paris and colleagues' review paper which presented said models – themselves adaptations of previous work – looked at the sparse existing literature on psychological factors linked to pain and disability in both joint hypermobility and EDS.

Distilling the findings of the 118 relevant works included in their analyses, the team found suggestions that many behaviours associated with neurodivergence could be employed as strategies to mitigate pain, dysautonomia, proprioceptive impairment, and anxiety symptoms in those with symptomatic hypermobility.

While it's certain that many neurodivergent behaviours will not be explained by a relationship with hypermobility, future iterations and more contemporary research (particularly those using patient voice) are likely to refine the proposed interactions within such models.

Connecting the dots

Increasing professional and public awareness of these connections may allow psychologists and other health professionals to develop new, personalised treatment approaches, and to provide support to neurodivergent people in a more timely manner.

Currently, clinical awareness of the relationship between connective tissue, neurodivergence, and chronic physical conditions lags behind academia. Few healthcare professionals have a working knowledge of how these symptoms manifest, in part due to the highly variable and individual ways in which facets of each condition overlap. This variability is so extensive, in fact, that it's given rise to a common phrase used to foster awareness in clinicians: 'If you can't connect the issues, think connective tissues!'

Jane Green MBE, the Founder and Chair of SEDSConnective (a UK-based charity which raises awareness of the challenges of hypermobility and neurodivergence), emphasises that this lack of public awareness can lead to worse outcomes for hypermobile individuals. Drawing from her own lived experiences, her work often emphasises the impact of unrecognised physical challenges on neurodivergent students.

In conversation with Research Digest, Green shared one example of how this might play out: 'Schools are required to check with medical practitioners if there is a reason for school absence. But often the medical practitioner will not know [about physical symptoms related to neurodivergence] and diagnose "anxiety". The student is then either marked as engaging in Emotional Based School Avoidance or given unauthorised absence coding.'

Such dynamics can set children on troublesome paths – feeling unseen and unheard, suspected of lying about troublesome symptoms by the adults surrounding them, and labelled as somewhat delinquent for missing school for what has been determined to be a 'minor reason'. Green also points out that this effect has been exacerbated by long-Covid; research in progress is investigating hints that hypermobile individuals may be more at risk for developing the condition.

But it doesn't have to be that way. In fact, knowing about the connection between neurodivergence and connective tissue could offer opportunities to improve neurodivergent students' access to support. SEDSConnective recommends screening hypermobile children for signs of neurodivergence, and vice versa, in the belief that such an approach would be able to successfully identify neurodivergent individuals early – even those from traditionally underdiagnosed groups (e.g. girls), or high-masking individuals.

Such an approach could allow kids in need of specialised psychological and physical health support to access it earlier in life, and mitigate risks associated with their condition(s) further down the line. Would wider hypermobility screening, beyond those already suspected to be neurodivergent, be similarly productive? That remains to be seen, but it may be a fruitful avenue for future research.

Research in this area is still emerging, but we may soon reach a tipping point at which these connections will inform both symptom management options for neurodivergent populations and wider medical understanding.