Link between anxiety and joint hypermobility

Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility – May 2014

This study makes connections between the acute perception of our internal body states, which trigger excessive activation of our amygdala, with anxiety.

In lay terms, we are too sensitive and too responsive, thus unable to hold life’s rougher times at an arm’s distance. It’s as though we lack the protective barrier built into the “hardware” of most people to shield them from the extremes of their environment.

Objective: Anxiety is associated with increased physiological reactivity and also increased “interoceptive” sensitivity to such changes in internal bodily arousal.  

Joint hypermobility, an expression of a common variation in the connective tissue protein collagen, is increasingly recognized as a risk factor to anxiety and related disorders.

This study explored the link between anxiety, interoceptive sensitivity and hypermobility in a sub-clinical population using neuroimaging and psychophysiological evaluation.


Thirty-six healthy volunteers undertook interoceptive sensitivity tests, a clinical examination for hypermobility and completed validated questionnaire measures of state anxiety and body awareness tendency. Nineteen participants also performed an emotional processing paradigm during functional neuroimaging.


We confirmed a significant relationship between state anxiety score and joint hypermobility.

Interoceptive sensitivity mediated the relationship between state anxiety and hypermobility.

Hypermobile, compared to non-hypermobile, participants displayed heightened neural reactivity to sad and angry scenes within brain regions implicated in anxious feeling states, notably insular cortex.


Our findings highlight the dependence of anxiety state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common variant of collagen.

This was the abstract – annotations from the full text below:


Anxiety is associated with heightened physiological arousal and accompanying physical sensations.

Interoception (i.e., sensitivity to changes in the internal physiological state of the body) is considered to be fundamental to such emotional feelings (Damasio, 1994).

Interoceptive sensitivity is viewed as a constitutional trait that is stable over much of an individual’s lifespan. People who can judge their bodily signals (e.g., the timing of their heartbeats) to a high level of accuracy experience emotions more intensely (Wiens et al., 2000; Pollatos et al., 2007a,b) and, in both the general population and clinical populations, are more likely to experience higher levels of anxiety (Mor and Winquist, 2002; Domschke et al., 2010).

Neuropsychological and neuroimaging studies implicate a set of related brain regions in the expression of anxiety.

In particular, responses within

  • insula,
  • amygdala and
  • anterior cingulate cortex

are linked both to the development and maintenance of anxiety disorders (Damsa et al., 2009; Shurick and Gross, 2013).

Hyperactivity within these regions is coupled to exaggerated autonomic arousal responses (Critchley and Harrison, 2013) and occurs during anxiety symptom provocation (Holzschneider and Mulert, 2011).

People with joint hypermobility are vulnerable to anxiety disorders.

That’s now a scientifically proven fact, and you can print out the study and show it to your doctor. Doctors may not believe patients, but they have to believe the National Institute of Health (NIH) and studies registered in PubMed.

Joint hypermobility is a common inherited connective tissue condition that represents a qualitative variation in the fibrous structural protein collagen.

Collagen is a protein component of bone, cartilage, tendon, blood vessels, and other body constituents.

Hence joint hypermobility can present multiple clinical features which are associated with the collagen abnormality and can be either articular or extra-articular: widespread musculoskeletal pain, multiple soft tissue lesions and fragility of supportive connective tissue and skin (Ross and Grahame, 2011).

The estimated prevalence of joint hypermobility ranges between 10 and 20% in western countries and it is more frequent in women (3:1). Individuals with joint hypermobility often present autonomic abnormalities and stress-sensitive illnesses, including fibromyalgia, temporomandibular joint disorder and chronic fatigue syndrome (Smith et al., 2014).

The strong link between anxiety disorder and joint hypermobility was first established in 1988 (Bulbena et al.) and this finding has been widely replicated, confirming that joint hypermobility is associated with the heightened expression of anxiety symptoms (Garcia-Campayo et al., 2011; Bianchi Sanches et al., 2012; Smith et al., 2014) and represents a risk factor trait for developing anxiety disorders (Bulbena et al., 2011).

However, little is known about the underlying neural mechanisms through which joint hypermobility and anxiety symptoms interrelate. One neuroimaging study of healthy non-anxious individuals associated the expression of hypermobility to structural differences in emotional-processing brain regions; notably people with features of hypermobility manifest larger amygdala volume bilaterally compared to participants without any hypermobility (Eccles et al., 2012).

Interestingly, the same study shows that the hypermobile participants scored higher on questionnaire ratings of body awareness (an index of interoceptive sensibility) than non-hypermobile people.

The aim of the present study was to clarify the mechanistic relationship between anxiety, interoceptive sensitivity and joint hypermobility.

We combined the measurement of trait and state anxiety, interoceptive sensitivity (using established heartbeat detection methods) in participants from a non-clinical population, with and without hypermobility.

Further, we recorded neural responses during emotional processing using functional magnetic resonance imaging (fMRI). We tested the hypothesis that interoceptive sensitivity and its underlying neural substrates meditate the relationship between affective reactivity and hypermobility.


Clinical variables and questionnaire measures

Across the thirty-six non-clinical volunteers (16 male and 20 female) who participated in the study (Table ​(Table1),1), there were no significant differences in anxiety or body awareness scores between male and female participants.

Using “non-clinical” volunteers means they weren’t impaired by their hypermobility, and maybe didn’t even know they “qualified” for Joint Hypermobility Syndrome (JHS).

There were certainly no people with EDS involved in this study, yet it seems reasonable to assume the pronounced tissue laxity would also worsen the anxiety.

According to standardized cut-off points (≥5 for women and ≥4 for men), fourteen (38.9%) of the sample participants had joint hypermobility. Neuroimaging was undertaken on a subset of nineteen (9 male and 10 female) participants who performed the emotional processing task during fMRI.

Nine (42.1%) of this subsample met criteria for joint hypermobility. Hypermobile individuals scored significantly higher on measures of state anxiety than non-hypermobile individuals (rpb = 0.318, p = 0.029).

Open Table 1 in a separate window

No significant differences were found on the MAIA body awareness subscales when comparing hypermobile individuals to non-hypermobile.

Interoception accuracy data

When exploring the relationship between joint hypermobility, state anxiety and interoceptive sensitivity (by means of heartbeat mental tracking task); interoception was observed to mediate the association between joint hypermobility and state anxiety (Figure ​ 1)

An external file that holds a picture, illustration, etc. Object name is fpsyg-05-01162-g0001.jpg
Schematic showing the regression coefficients, with the coefficients (β) for the effect of hypermobility on state anxiety with the latter (when entering interoception into the model) in parentheses.

Functional imaging data

As in the larger group, hypermobile participants (n = 9) in the imaging subgroup (n = 19) showed significantly higher state anxiety scores (rpb = 0.387, p = 0.050) and a better performance in the mental tracking interoceptive sensitivity task (rpb = 0.438, p = 0.030) than non-hypermobile participants.

During the processing of anger vs. neutral images, a discrete set of brain regions also demonstrated enhanced activity within the hypermobile group including cerebellum, temporal cortices and thalamus(Table3).


Our findings link joint hypermobility to the presence of anxiety symptoms through the expression of enhanced interoceptive sensitivity.

Results also display heightened reactivity of brain regions notably “interoceptive” insular cortex during the processing of emotional stimuli in joint hypermobility.

Our findings highlight the dependence of emotional state on bodily context, and increase our understanding of the mechanisms through which vulnerability to anxiety disorders arises in people bearing a common heritable variant of collagen.

Our findings also suggest that maladaptive cognitions and appraisal tendencies toward body sensations may also be a determining factor: Not only did state anxiety correlate positively with objective measures of interoceptive sensitivity but in the questionnaire measure of body awareness, state anxiety correlated negatively with the attention regulation subscale (i.e., ability to control attention to body sensations) and the “trusting body sensations” subscale. These associations were amplified in individuals with greatest state anxiety.

These observations are noteworthy; our results confirm a primary hypothesis that increased interoceptive sensitivity is associated with increased likelihood of anxiety [and increased vulnerability to developing anxiety disorders (Domschke et al., 2010)]. 

Yet there is, a growing interest with empirical support (Parkin et al., 2014) in how enhancing awareness of bodily processes, e.g., through mindfulness approaches, may be used therapeutically for managing anxiety.

Our observations further highlight the relevance of “attributional models” wherein a capacity to control bodily changes is compromised in people with anxiety.

Thus, the concurrence of increased emotional reactivity and enhanced perceptual sensitivity to physiological arousal, with a diminished confidence in their interpretation and control, is characteristic of individuals with high-state-anxiety (Paulus and Stein, 2006). 

Hypermobile participants experienced significantly higher state anxiety than the non-hypermobile participants. The association between joint hypermobility and the clinical expression of anxiety is now robustly established (Bulbena et al., 2011; Bianchi Sanches et al., 2012).

In our non-clinical sample, hypermobile individuals demonstrated higher interoceptive accuracy when performing the heart beat detection task. Moreover, it was confirmed that interoceptive sensitivity particularly mediated the association between hypermobility and anxiety: this was suspected from an earlier observation of increased interoceptive sensitivity in individuals with hypermobile features (Eccles et al., 2012).

One potential mechanism is autonomic: In people with joint hypermobility, there is variant collagen in both joints and vasculature. Many hypermobile people develop autonomic symptoms (e.g., racing heartbeat) related to problems with orthostatic vasoconstriction. In more severe cases this is expressed as form of dysautonomia known as postural tachycardia syndrome (PoTS)

This uncontrolled increased cardiac response may result (through associative learning mechanisms) in increased interoceptive sensitivity (Pollatos et al., 2007a), which in turn may have emotional consequences.

Nevertheless, this account emphasizes heart rate changes and it is known that both the interoceptive sensitivity in hypermobile individuals (and the dysautonomia in PoTS) extends beyond the cardiovascular system (Mathias et al., 2011).

With regards to the functional neuroimaging paradigm, hypermobile individuals manifest stronger neural reactivity to affective stimulation within brain regions known to be involved in emotional processing, particularly in anxiety (i.e., insula, brainstem, thalamus), when compared to non-hypermobile participants. 

Specifically, hypermobile participants presented higher activation to sad scenes in areas implicated in interoceptive representation, feeling states and self-representation (i.e., insular cortex and inferolateral prefrontal cortex) as well as in areas implicated in encoding socially salient visual information (i.e., temporal cortices) and executive control processes (i.e., inferolateral prefrontal cortex) (Adolphs, 2001; Critchley and Harrison, 2013). 

Hypermobile participants also revealed enhanced activity to anger scenes within insula, inferotemporal cortex and thalamus.

the enhanced activity within the insular cortex likely supports the association between hypermobility and interoceptive sensitivity (high accuracy in heartbeat detection) and, by extension, its association to anxiety. Our findings show a tendency to greater affective reactivity among hypermobile participants within emotion-related

brain areas. Thus, hypermobile individuals do not only have greater interoceptive sensitivity but also higher emotional reactivity to visual stimuli with affective salience.

Higher affective reactivity is described in people with anxiety disorders, particularly social anxiety disorder, where patients also display hyper-reactivity within similar brain regions (Goldin et al., 2009).

To conclude, we present the first functional laboratory and neuroimaging study of the relationship between anxiety and hypermobility that also examines interoceptive sensitivity (heartbeat detection). The interactions observed between anxiety, hypermobility and interoception, as well as the differences in the activity of particular emotional brain regions; provide an essential basis for future research constitutional factors underpinning anxiety disorders. Moreover, our findings have the potential to inform innovation in therapeutic approaches.

2 thoughts on “Link between anxiety and joint hypermobility

  1. Pingback: Management of chronic pain in EDS – part 2 | EDS and Chronic Pain News & Info

  2. Pingback: hEDS Patients Face Many Physical and Mental Challenges | EDS and Chronic Pain News & Info

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