Anxiety symptoms are elevated among people with joint hypermobility. The underlying neural mechanisms are attributed theoretically to effects of variant connective tissue on the precision of interoceptive representations contributing to emotions.

To investigate the neural correlates of anxiety and hypermobility using functional neuroimaging.

We used functional magnetic resonance neuroimaging to quantify regional brain responses to emotional stimuli (facial expressions) in people with generalised anxiety disorder (GAD) (N = 30) and a non-anxious comparison group (N = 33). All participants were assessed for joint laxity and were classified (using Brighton Criteria) for the presence and absence of hypermobility syndrome (HMS: now considered hypermobility spectrum disorder).

Participants with HMS showed attenuated neural reactivity to emotional faces in specific frontal (inferior frontal gyrus, pre-supplementary motor area), midline (anterior mid and posterior cingulate cortices) and parietal (precuneus and supramarginal gyrus) regions. Notably, interaction between HMS and anxiety was expressed in reactivity of the left amygdala (a region implicated in threat processing) and mid insula (primary interoceptive cortex) where activity was amplified in people with HMS with GAD. Severity of hypermobility in anxious, compared with non-anxious, individuals correlated with activity within the anterior insula (implicated as the neural substrate linking anxious feelings to physiological state). Amygdala-precuneus functional connectivity was stronger in participants with HMS, compared with non-HMS participants.

The predisposition to anxiety in people with variant connective tissue reflects dynamic interactions between neural centres processing threat (amygdala) and representing bodily state (insular and parietal cortices). Correspondingly, interventions to regulate amygdala reactivity while enhancing interoceptive precision may have therapeutic benefit for symptomatic hypermobile individuals.

Intriguingly, autism spectrum disorders (ASD) and symptomatic generalised joint hypermobility (S-GJH) (e.g. hypermobility spectrum disorders and Ehlers Danlos Syndrome) share several clinical manifestations including motor difficulties, sensory hypersensitivity and autonomic dysfunction. Moreover, many syndromic forms of ASD manifest a hypermobile phenotype. Despite the increased interest in the area, few systematic studies are available.

This large cross-sectional comparative study aimed to examine the association between S-GJH and ASD in adults.

We assessed GJH by physical examination using the Beighton Scoring System (BSS) and collected data on musculoskeletal symptoms and skin abnormalities amongst 156 adult patients with ASD and 413 adult community controls. A proxy for S-GJH was created by combining a positive BSS with at least one additional musculoskeletal symptom or skin abnormality.

The prevalence of S-GJH was significantly higher amongst patients with ASD than amongst controls (16.7% vs 4.8%, p< .001). A logistic regression model, adjusting for candidate covariates of GJH (age, sex, race), revealed a significant influence of ASD on S-GJH with adjusted odds ratio of 5.4 (95% CI 2.8-10.5, p< .001).

ASD and S-GJH are associated in adults. If recognised, musculoskeletal complications related to S-GJH can be relieved by physiotherapy. Clinicians should be familiar with that symptoms frequently occurring in GJH such as pain, fatigue and orthostatic intolerance may mimic or aggravate psychiatric symptoms (e.g. depression, anxiety). Knowledge about comorbidities may provide clues to underlying aethiopathological factors. Future research to clarify the mechanisms behind this association and to evaluate how comorbid S-GJH affects ASD outcome is warranted.

No significant relationships.

There is growing evidence that generalised joint hypermobility (GJH) is associated with several psychiatric conditions. There are no previous studies on adult ADHD.

To evaluate, in a large Swedish sample, if generalised joint hypermobility and adult ADHD are associated.

431 adults with ADHD and 417 controls were included. GJH was assessed by the Beighton Score, a physical examination, and the 5PQ, a self-report screening tool. Exploratively, reported musculoskeletal symptoms and abnormal skin manifestations suggestive of symptomatic GJH (e.g. Ehlers-Danlos syndrome), were assessed to differentiate this group from the general GJH group. Logistic regressions determined the influence of an ADHD diagnosis and known covariates (age, sex and ethnicity) on GJH and symptomatic GJH respectively.

ADHD was associated to GJH, as defined by the Beighton Score and the 5PQ, with adjusted odds ratios of 4.65 (CI 95% 3.01-7.18, p<.005) and 1.86 (CI 95% 1.39-2.48, p<.005), respectively. Likewise, ADHD and symptomatic GJH were associated with adjusted odds ratios of 6.94 (CI 95% 4.05-11.89, p<.005) and 2.66 (CI 95% 1.94-3.66, p<.005).

GJH and adult ADHD are associated conditions. Symptomatic GJH, defined as additional symptoms of pain and/or skin manifestations, has a considerably stronger link to adult ADHD than unspecific GJH has. GJH may represent a marker of an underlying systemic disorder with physical manifestations in connective tissue as well as behavioural manifestations including hyperactivity, impulsiveness and inattentiveness. Future studies should investigate if this represents a novel subtype of ADHD and if symptomatic GJH affects the ADHD management.

No significant relationships.