Hypermobility and Anxiety: Why Your Body Is Wired for It (And What to Do)

About
Latest Posts

Adam Foster is the founder of The Fibro Guy and one of the leading voices in hypermobility, EDS, and chronic pain rehabilitation. A former Reconnaissance Soldier, he developed chronic pain after an IED blast in Afghanistan and built his approach from the ground up when the medical system had no answers. Since 2009 he has worked with thousands of people across eight countries, drawing on pain neuroscience, motor learning, and sensorimotor rehabilitation. He co-authored "No Pain, No Pain" with trauma psychologist Dr Mairi Harper, directed the documentary "Invisible Monster," and has been featured in Forbes, BBC Radio 4, ITV News, LiveScience, and The Telegraph.

Who This Is Actually About

Before any of the mechanisms, it’s worth being precise about who we’re talking about here, as a lot of the confusion in this topic comes from three fairly different groups getting discussed as though they were one.

Generalised joint hypermobility is common. In European populations it sits at roughly one in ten, and in some other ethnic groups it’s been put as high as one in four, with the figure varying a great deal by age and sex as well ^[7]^[8]. In children the reported range is even wider, running from well under one in ten to more than a third depending on which criteria were used and who was being measured ^[9]. That spread tells you something on its own really, which is that we’re measuring a trait with a line drawn through it, rather than a disease with an edge.

Most of those people are absolutely fine. They’re hypermobile, they were good at gymnastics, they can do the party trick with their thumb, and nothing follows from it. The anxiety literature is not about them, or at least not much ^[10]^[11].

Hypermobile, HSD, hEDS, and Why the Labels Keep Moving

Generalised joint hypermobility on its own is a trait. Hypermobility spectrum disorder is the label for being hypermobile and symptomatic with it, where the symptoms can’t be explained by something else, and hypermobile Ehlers Danlos syndrome sits on top of that with a tighter checklist covering skin, family history and systemic involvement ^[12]^[13].

The awkward truth is that the boundary between those last two is drawn by agreement rather than by biology. There’s no blood test, no gene to check and no biological measure that separates hEDS from HSD, so where the line sits depends on which version of the criteria your clinician is working from and how thoroughly they looked ^[14]^[15]. Two people with practically identical bodies can end up with different labels, different referrals and different amounts of being believed.

Which matters a great deal for reading anything about anxiety, as what’s known about hEDS and what’s known about hypermobile people in general aren’t drawn from quite the same population, and the difference between those two populations is exactly the thing that predicts the anxiety in the first place ^[10]^[12].

What Variant Connective Tissue Actually Affects

The other thing worth getting straight early: connective tissue isn’t only in joints. It’s in blood vessel walls, in skin, in the gut wall, in the fascia that wraps and connects muscle, and in the structures that hold organs roughly where they’re supposed to be ^[16]^[17].

So when the tissue is more compliant than average, the consequences really aren’t confined to how far an elbow goes back. Vessels that are more distensible behave differently when you stand up, gut that’s more compliant moves things along differently, and fascia that’s more compliant transmits force differently and may well carry sensory consequences of its own, though the fascial side of this is an emerging idea rather than settled ground ^[17]^[16].

Which is why hypermobility stopped being treated as a rheumatological footnote and started being described as a multisystem phenotype, with psychiatric, autonomic, sensory and quality of life aspects to it ^[3]^[18]. That reframing is genuinely the most solid thing in this whole area.

How Strong the Link Actually Is

Start with the part that doesn’t wobble. Across everything that’s been pooled, adults with joint hypermobility have substantially higher odds of an anxiety disorder than adults without it, and the difference is around fourfold ^[1]. Hold on to that one, as almost everything else here is a good deal more tentative than it is.

The kind of anxiety most repeatedly tied to hypermobility isn’t generalised worry though, it’s panic and agoraphobia ^[1]^[19]. Among people attending rheumatology clinics in the early nineties, panic disorder, agoraphobia and simple phobia were all strongly associated with joint hypermobility syndrome, while generalised anxiety wasn’t, at least not in that group ^[19]. Coming at it from the opposite end, among people already diagnosed with panic disorder or agoraphobia and not yet treated for it, around two thirds turned out to be hypermobile, against roughly one in ten of the people they were compared with ^[20]. Two different doors into the same room.

Which Came First, and Why That’s So Hard to Answer

Turning up together only ever tells you that two things turn up together. It can’t tell you which came first, and in this field that objection gets raised constantly, usually by somebody who has already decided the anxiety came first and caused the rest.

Now, there’s one piece of evidence that gets round that, and it’s pretty much the backbone of this whole area. A group of young people in Spain were assessed in their late teens, and the hypermobile ones who had no anxiety whatsoever at the start were then followed for fifteen years ^[2]. By the end, panic or agoraphobia had appeared in a little over forty in every hundred of them, and in the people who weren’t hypermobile it was about two in a hundred ^[2]. That’s the difference between a common outcome and a rare one, and because the anxiety genuinely wasn’t there at the start, hypermobility looks like a risk trait rather than something anxiety causes ^[2]^[21].

Take it with the caution it deserves though, as it’s been done once, in one country, and nobody has repeated it over that kind of timescale. It’s still the single most useful thing anybody has measured here, and it points firmly in one direction.

At Both Ends of Life

The same pattern shows up in the old and in the very young. In older adults in Spain, anxiety disorders in the past year were roughly three times more common in the hypermobile group ^[22], and in children, generalised joint hypermobility has been linked to higher odds of separation anxiety, social phobia, panic and agoraphobia, and generalised anxiety ^[23]. Looked at from the other direction again, hypermobility turns up more often in children already being treated for anxiety disorders than you’d expect by chance ^[9].

None of that proves a mechanism, obviously. What it does mean is that the link isn’t an artefact of one age group, one clinic or one decade’s diagnostic fashion, which is more than you can say for a lot of findings in this space.

Hypermobility on Its Own, and Hypermobility With Symptoms

When the anxiety evidence is pulled together properly, anxiety is highest in people whose generalised joint hypermobility is symptomatic, lower in people who are hypermobile without symptoms, and lower again in everybody else ^[10]. In symptomatic groups the proportion sitting at clinical levels of anxiety can be very high indeed ^[10]. Among high performing young people who were hypermobile but not symptomatic, the real impairment clustered in those who had both hypermobility and anxiety, rather than in the hypermobility on its own ^[11].

So hypermobility by itself is a fairly weak predictor, and hypermobility plus symptoms is a much stronger one, which fits the general drift of the last decade, in that the interesting variable was never the range of motion, it was everything travelling alongside it ^[3]^[24].

Why It’s Panic Specifically

The fact that it’s panic and agoraphobia rather than generalised worry is a clue, and it’s a clue most summaries skip straight past.

Generalised anxiety is largely about thoughts, about anticipating and running through what might happen, whereas panic is about the body: heart, breath, chest, dizziness, the sense that something physical is happening right now and is about to get worse. Agoraphobia is what grows out of repeated panic, and it’s the perfectly reasonable avoidance of places where the next one would be difficult to manage ^[19]^[20].

So if hypermobility were producing anxiety purely through the stress of living with a difficult condition, you’d expect the excess to sit in generalised worry. Instead it sits in the anxiety type most tightly bound to bodily sensation, and that’s exactly what you’d predict if unusual bodily signalling were doing some of the driving ^[2]^[3]^[25].

That’s an inference, and we’d rather mark it as one than pretend the literature has stated it that plainly. It is, in our opinion, the most telling detail in the whole area, and it’s the reason the mechanistic work has concentrated where it has ^[5]^[26].

Why Clinic Numbers Read Higher Than They Should

You’ll see figures quoted for anxiety in hEDS that sit somewhere between half and four fifths of everybody attending, and those numbers are real, and they come from real specialist centres ^[27]^[28]^[29]. They’re also not what you’d find in the general population, and reading them as though they were is one of the commonest mistakes made with this topic.

People who reach a specialist hypermobility clinic are, more or less by definition, the ones whose symptoms got bad enough to justify the referral, the travel and the wait. That selects for severity, for multisystem involvement, and for exactly the kind of long medical history that generates anxiety all on its own. Step outside the clinic and look at whole national populations instead, and the rates of psychiatric diagnosis in EDS and hypermobility syndrome are still elevated, so the effect doesn’t vanish, it just gets smaller and rather more honest ^[30]^[31].

The Criteria Kept Moving Underneath It

One awkward detail runs through everything above, which is that the diagnostic labels changed underneath the research. The older work used Brighton criteria or the joint hypermobility syndrome label, the newer work uses hEDS and hypermobility spectrum disorder, and the two sets don’t map cleanly onto each other ^[12]^[13]^[24]. There’s still no blood test, no genetic marker and no biological measure that settles who has hEDS and who has HSD, so the boundary is drawn by a checklist that has itself been redrawn more than once ^[14]^[15].

Which means that when somebody tells you the anxiety link is established across forty years of research, the honest footnote is that “it” hasn’t been quite the same “it” the whole way through. The direction has stayed remarkably consistent anyway, both before the current criteria existed and after ^[7]^[32], and consistency across changing definitions is actually reassuring in a backhanded sort of way, as a finding that only appears under one exact definition usually turns out to be an artefact of that definition.

What a Fourfold Difference Does and Doesn’t Mean

One clarification, as raised odds get misread constantly, and in both directions.

Raised odds of anxiety in hypermobility don’t mean most hypermobile people are anxious. It means anxiety is considerably more common in that group than in the comparison group, and the comparison group’s rate was not zero ^[1]. Plenty of hypermobile people have no anxiety whatsoever, and plenty of people with crippling anxiety are as stiff as a board.

It also doesn’t mean your anxiety was caused by your connective tissue. An association of this size at group level tells you almost nothing about which individual case was caused by what, and that limit applies even where the mechanism is well understood, which here it very much isn’t ^[3]^[4].

What it does mean is that if you’re hypermobile and anxious, you are in an extremely well populated category, and it’s a perfectly reasonable thing to raise with a clinician as a connected picture rather than as two unrelated problems ^[1]^[2]^[24]. That’s a modest claim, and it’s the one the evidence actually supports.

What Else Is in the Room

Anxiety doesn’t arrive on its own here, and understanding what it travels with is most of the reason it’s so difficult to treat in isolation.

Depression, pain, fatigue, gut symptoms, migraine and poor quality of life all cluster together in hEDS and HSD with some consistency ^[29]^[33]^[34]^[35]. Look at very large medical record databases and the rates of anxiety and depression are raised, and look at specialist centres and the autonomic symptom burden and the quality of life scores are the sort that would be considered alarming in almost any other condition ^[33]^[28]^[36]. In adolescents, hypermobility measured at fourteen has been linked to depression and anxiety later on, so the clustering starts early rather than arriving after twenty years of pain ^[37]^[38].

That clustering is why single cause explanations keep falling over. Treat the anxiety and leave the orthostatic intolerance, the pain and the reflux exactly where they are, and you’re treating one output of a system with several inputs, which tends to produce a partial response that fades ^[3]^[39].

Now, there’s an inversion of this that does real harm, and it’s worth naming before we go any further. If anxiety is common in hypermobility, it becomes very easy for a clinician to read every symptom as anxiety, and that happens constantly. Dysautonomia and fatigue get read as anxiety, anxiety gets read as deconditioning, and genuine nerve involvement gets missed altogether ^[29]^[40]^[41]. Small fibre neuropathy, which is a measurable problem with the smallest sensory and autonomic nerve fibres, appears to be fairly common in hEDS, and it produces burning, tingling, temperature oddities and autonomic symptoms that have nothing whatsoever to do with mood ^[41]^[42].

The association cuts both ways then, as it’s a reason to take the anxiety seriously as a real and physiological thing, and it’s also the single biggest source of misdiagnosis in this population.

Depression, and the Half That Gets Discussed Less

Anxiety gets the attention in this topic, partly because the panic link is so striking and partly because panic is dramatic enough to be interesting. Depression is quieter and it’s at least as common.

Rates of depression are raised in EDS and hypermobility syndrome at national population level, so this isn’t a clinic artefact ^[30]^[31]. Within specialist settings, depression and anxiety run alongside each other with considerable overlap, and psychological distress and reduced quality of life get reported pretty consistently in hypermobility type EDS ^[28]^[29]^[34].

The developmental picture is worth sitting with for a minute. Hypermobility measured in mid adolescence has been associated with depression a few years later, and in that work resting heart rate carried part of the association, which is a physiological marker doing the explanatory work rather than a psychological one ^[37]^[38]. Symptomatic hypermobility in late adolescence has been associated with both anxiety and depressive disorder ^[37].

Now, none of that says the depression is caused by the connective tissue. Being in pain for years, sleeping badly, losing the ability to do things you used to do, and being disbelieved throughout are all perfectly sufficient causes of depression on their own, and they’re all more common here ^[43]^[44]^[34]. The honest position is that the biology and the circumstances are both present, both load the same system, and nobody has managed to weigh one against the other.

What’s clinically useful about it is a good deal narrower. If you’re being treated for anxiety alone and the low mood is being left as a secondary consequence that’ll lift when the anxiety does, that assumption has no particular evidence behind it in this population, and it’s worth saying so out loud ^[29]^[39].

Fatigue, and Why It Belongs in an Anxiety Article

Fatigue gets left out of anxiety discussions because it doesn’t sound like an emotional symptom, and leaving it out distorts the picture badly.

In fibromyalgia and ME or CFS clinics, a very large proportion of people turn out to meet hypermobility criteria, and how hypermobile somebody is predicts how symptomatic they are ^[45]. So a substantial number of people carrying a fatigue diagnosis are hypermobile and have never once been told ^[45]^[46].

The connection to anxiety runs through arousal and through load. Fatigue, pain and the cardiac autonomic picture independently predict how much central sensitisation somebody carries, while anxiety, put into the same model, doesn’t come out as an independent predictor ^[47]. Read that alongside the idea that physiological arousal rather than pure cognition is doing a lot of the work here, and the picture that emerges is of a body running a high symptom load, with anxiety as one of the things that falls out of it rather than the thing generating it ^[3]^[48].

That’s a framing rather than a proof, and it needs saying that way round. What it does do is explain why anxiety treatment that ignores the fatigue tends to underperform, and why being told to exercise your way out of it without any attention to the autonomic side so often makes everything worse for a fortnight ^[49]^[46].

Children and Teenagers, Because This Starts Early

Most of what gets written about hypermobility and anxiety is written about adults, which gives the impression that it’s something that develops after twenty years of symptoms. It doesn’t look that way at all.

Generalised joint hypermobility in children is associated with higher odds of separation anxiety, social phobia, panic and agoraphobia, and generalised anxiety ^[23]. Looked at from the other side, hypermobility appears more often among children already being treated for anxiety than you’d expect ^[9]. In children and adolescents attending hEDS services, anxiety is extremely common and poor sleep sits right alongside it, with worse sleep tracking with worse anxiety, worse mood and worse quality of life ^[27].

The sensory side turns up early too. In adolescents with HSD or hEDS, the pressure at which touch starts to hurt is lower across several muscle groups, and it comes with more fatigue and more cognitive and emotional difficulty ^[50]. So the amplification that gets described in adults with twenty years of pain behind them, is already measurable in teenagers.

Hypermobile Without Symptoms Is a Different Situation

This is the part that should reassure a parent reading this with a hypermobile eight year old.

Among high performing young people who were hypermobile but not symptomatic, the meaningful impairment sat in those who had both hypermobility and anxiety, not in hypermobility by itself ^[11]. Anxiety is highest in symptomatic hypermobility, lower where hypermobility is present without symptoms, and lower again elsewhere ^[10]. A hypermobile child who is otherwise well is in a different situation from a hypermobile child who is in pain, exhausted and dizzy on standing, and lumping the two of them together is how this topic frightens people unnecessarily.

What the Longitudinal Picture Suggests

Hypermobility measured in mid adolescence has been associated with depression a few years later, with resting heart rate carrying part of that association, and symptomatic hypermobility in late adolescence has been associated with both anxiety and depressive disorder ^[37]^[38]. Which means the window where something might be done, sits earlier than most services are set up to reach.

Take it as a direction rather than a prediction though, as this is one line of work in one country and nobody has tested whether intervening in adolescence changes any of it ^[37]^[38]. The practical version is modest and worth doing anyway: if a hypermobile teenager is anxious, that isn’t a separate problem to be handed to a different department, and if a hypermobile teenager is dizzy, tired and sore, the anxiety is not the obvious first explanation ^[27]^[40].

Neurodivergence Shows Up Here Too

Hypermobility is more common in autistic people and in people with ADHD or tic disorders, and it comes with more orthostatic intolerance and more musculoskeletal pain in those groups ^[51]^[52]. So a hypermobile, anxious, neurodivergent teenager is a very common combination rather than an unusual one, and each part of it tends to get assessed by a different service that doesn’t talk to the others.

That’s a reason to ask for the whole picture to be looked at together, rather than a reason to panic. The clustering is well described, the mechanism connecting the parts is not, and the current usefulness of knowing about it is mostly in how the case gets put together rather than in any specific treatment that follows from it ^[51]^[24].

The Amygdala Story, and Why “Wired for It” Overstates It

The brain scan version of this topic has escaped into the wild, and the wild version goes something like this: hypermobile people have a bigger fear centre, therefore they’re built for panic. It’s a tidy story, and it’s also a good deal more certain than what it came from.

What was actually measured is that bilateral amygdala volume is greater in hypermobile adults than in adults who aren’t hypermobile, and that showed up in healthy people who didn’t have an anxiety diagnosis at all ^[6]. Amygdala volume was the main structural thing separating the two groups, and the difference was a large one ^[6]. That’s genuinely interesting, and it’s the origin of very nearly every “bigger amygdala” headline you’ve read since.

Then it got more complicated, which is what usually happens next. Looking at people who were already in psychiatric care, amygdala volume scaled with how hypermobile somebody was, but only in the anxious ones ^[53]. In the people who weren’t anxious, that relationship wasn’t there at all ^[53], and insular volume was raised specifically in the anxious hypermobile group ^[53]. So the structural finding looks strongest in a hypermobility plus anxiety phenotype, rather than in hypermobility across the board.

What the Newer Imaging Actually Emphasises

The newer imaging moved the emphasis off size and onto behaviour. Watching what the brain does while somebody looks at emotional faces, the interaction between hypermobility and generalised anxiety shows up in left amygdala and mid insula activity, and how hypermobile somebody is tracks with anterior insula activity in the anxious group ^[5]. Connectivity between the amygdala and the precuneus is stronger too ^[5]. None of that says the amygdala is simply bigger in everybody who’s hypermobile, it says threat processing behaves differently when hypermobility and anxiety occur together ^[5].

That’s a subtler claim and honestly a more useful one, as it puts the weight on how bodily signals are being interpreted, rather than on a lump of tissue being a certain size.

Three Reasons to Keep the Brain Scan Story in Its Box

– The groups have been small: Almost all of the structural imaging here has been done in small groups of people, and small imaging findings have a habit of shrinking or disappearing altogether when somebody repeats them at scale. That isn’t a criticism of the work, it’s just what early imaging looks like in a condition nobody was funding properly ^[6]^[53].

– Some of it was analysed loosely: At least one of those structural results was run in a way that didn’t account for how many different places in the brain were being looked at, and that weakens how confident anyone can be about the precise anatomy involved ^[53]. It may well be right. It just hasn’t been nailed down yet.

– Amygdala size isn’t a general anxiety marker anyway: In other psychiatric conditions the amygdala findings go the other way, or don’t appear at all, so volume can’t be read as a measure of how anxious somebody is ^[54]^[55]^[56]. If bigger meant more anxious as a general rule, the rest of psychiatry would surely have noticed by now.

So What Is Fair to Say

A fair reading is this. Imaging points repeatedly at the amygdala and the insula, the findings converge, and they’re mechanistic clues rather than anything approaching a clinical test ^[5]^[53]^[6]. Nobody can scan you and tell you why you’re anxious, and nobody should be offering to.

The framing matters here a great deal more than the anatomy does. “Your brain is wired for anxiety” lands like a life sentence, and it isn’t supported. The defensible version is that variant connective tissue affects blood vessels, autonomic regulation, pain and the processing of body signals, and that those things together raise vulnerability to anxiety rather than deciding it ^[5]^[25]^[57]. Vulnerability is a very different word from destiny, and it’s the one the evidence supports.

Why the Wiring Language Does Actual Damage

We’d normally let a framing argument go, but this one has consequences worth spelling out.

Telling somebody her brain is built for anxiety hands her a fixed trait with no treatment implication attached whatsoever. It explains everything and suggests nothing. And it’s demonstrably not what the evidence says, as the structural findings sit most clearly in people who have both hypermobility and anxiety, rather than in hypermobility across the board ^[53]^[5].

It also quietly moves the problem out of the body and into the personality, which is precisely the move this population has spent decades on the receiving end of. A story about altered threat processing in the context of bodily signalling is a story about a body producing unusual signals, and that’s a very different conversation from one about a brain being inherently fearful ^[5]^[3]^[57].

The defensible claim is smaller and considerably more useful. Being hypermobile raises the odds, several body systems appear to contribute, which one matters most in you is currently unknown, and none of it is fixed in the way a wiring metaphor implies ^[3]^[4]^[24].

Explore the course

Interoception, and Why “You Feel Everything More” Needs Splitting In Two

Interoception is the sense of your own internal state. Heartbeat, breath, gut, bladder, temperature, the general hum of being a body. It’s built from signals arriving from inside you, and the insula is the main part of the cortex that represents them ^[58]^[57].

The idea that interoception sits between hypermobility and anxiety is one of the better developed ideas in this area. Interoceptive sensitivity has been shown to mediate the relationship between hypermobility and state anxiety, meaning the link between the two ran statistically through how strongly people registered their own bodily signals ^[25]^[39]. Across EDS and HSD, enhanced interoception, somatosensory amplification and altered body awareness keep being described as the plausible bridge ^[21]^[39]^[29].

Detecting a Signal, and What You Make of It

Now, this is where the popular version goes wrong, and it goes wrong in a way that changes what you’d actually do about it.

“Feeling everything more” is really two separate things that got collapsed into one phrase. The first is how accurately you detect an internal signal, so whether you can genuinely count your own heartbeats better than the next person can. The second is how much attention you pay to internal signals and how you evaluate them, so whether a flutter reads as neutral information or as something going badly wrong.

Pull the interoception and anxiety literature together and the evidence for the second is consistent, while the evidence for the first is decidedly mixed and depends heavily on how it was measured ^[4]. Anxiety is reliably linked to more negative, threat focused evaluation of bodily sensations, and objective accuracy at detecting them is a much messier picture ^[4]. That work isn’t hypermobility specific, so read it as the general backdrop rather than as a finding about you.

Why it matters practically: if the whole problem were detection accuracy, there’d be very little to do about it, whereas if a large part of it is how signals get attended to and evaluated, that’s considerably more workable, and it’s the part any psychological approach would actually be aiming at ^[4]^[39].

The Insula, and Why It Keeps Turning Up

Worth a short detour on the insula, as it appears in both halves of this article and it isn’t exactly a household name.

It’s the part of the cortex most involved in representing internal bodily state, and how much interoceptive awareness somebody has is associated with its anatomy ^[58]^[57]. It also turns up repeatedly in hypermobility imaging: greater volume in the anxious hypermobile group, and mid insula and anterior insula activity varying with hypermobility in anxious people looking at emotional material ^[53]^[5].

Which makes it the most likely meeting point for the two halves of this story, as signals from a body that behaves unusually arrive in a region that represents internal state, and that region is also involved in how emotional significance gets assigned ^[5]^[57]^[58].

That’s a satisfying account and it needs holding loosely, as it rests on small imaging studies and on a general interoception literature that isn’t specific to hypermobility ^[53]^[58]^[4]. Satisfying accounts are exactly the ones worth being suspicious of, as they stop people looking.

Where This Leaves the Mechanism

Honestly, interoception is a good hypothesis with real data behind it and no proof attached. The mediation comes from small groups, the general literature is mixed on half the idea, and nobody has shown that changing interoception in a hypermobile person changes their anxiety ^[25]^[4]^[39]. It’s a reason to suspect rather than a reason to believe, which is a phrase you’ll see a few times in this article, as it keeps being the right one.

Proprioception, and the Business of Not Quite Knowing Where You Are

Proprioception is the sense of where your joints are and what they’re doing, and it’s built from receptors in muscle, tendon, joint capsule and skin. It’s why you can touch your nose with your eyes shut, and why you can walk downstairs without watching your feet.

In hypermobility, that sense is measurably less precise. Joint position sense at the elbow and the knee is poorer in generalised joint hypermobility ^[59], lumbar proprioception is poorer, and so is stability, meaning how far somebody can shift their weight before they lose control of it ^[60]. Adults with joint hypermobility also sway more, recruit muscle differently, and very commonly carry a fear of falling, although most of what’s been done in that area is small and uses mixed definitions of hypermobility, so treat the overall picture as a strong hint rather than a settled number ^[61].

The Uncertainty Model, and Our Bias in Saying It

The proposed link to anxiety runs through uncertainty. If the signal coming up from the joints is less precise, the brain is making its predictions about your body on noisier information, and a nervous system that can’t predict its own body reliably has a pretty decent reason to stay on guard ^[8]^[62]. Pair that with heightened attention to internal signals and you’ve got a body that is both harder to read and being read more intently.

It’s a neat model, and we’ll say plainly that it’s the one our own work is built around, so treat us as biased on it. What it is not, is proven. Nobody has shown that improving proprioception in a hypermobile person reduces their anxiety, and the direct evidence here is much stronger for the sensorimotor problems themselves than for anything psychiatric ^[59]^[8]. In our opinion it’s the most likely place for a rehab approach to be doing its work, and that opinion is currently running some way ahead of what anyone has tested.

What It Looks Like When You’re Living In It

Now, the practical version of imprecise proprioception isn’t a laboratory measurement, it’s the accumulation of small surprises. A knee that gives way on a curb. A shoulder that goes somewhere it shouldn’t while you’re reaching into a cupboard. A foot that lands slightly wrong on ground you’d already looked at. Each one on its own is nothing much, but two hundred of them over a couple of years teaches a nervous system that the body isn’t entirely trustworthy, and that lesson is not irrational, it’s an accurate summary of the available data.

Which is the thing most reassurance gets wrong. Being told there’s no reason to feel on edge, by somebody who has never had a hip sublux while they were standing still, isn’t reassurance, it’s just being told you’ve misread your own experience.

How the Two Sensory Problems Interact

Proprioception and interoception get discussed separately because they’re studied separately, and in a living body they aren’t separate at all.

One is information about where you are, the other is information about what state you’re in. Put imprecise information about position together with heightened attention to internal state, and you have a system being asked to make confident predictions from material it can’t fully trust, while monitoring the results very closely ^[8]^[4]^[25].

That’s the shape of the proposed mechanism, and it’s the reason the model has been extended beyond anxiety into emotional regulation more broadly, including in neurodivergent groups ^[8]^[24]. It’s coherent, it makes predictions, and it hasn’t been tested as a whole. Individual pieces of it have support, the assembled version is a model rather than a finding ^[8]^[4].

We’d add one thing from working with people rather than from the literature, and we’ll mark it as exactly that. The order in which things improve tends to be signal first, strategy second, load third. Giving the brain clearer information about the joint, then a better way of controlling it, then adding load, rather than adding load to a joint the brain can’t locate properly and just hoping the strength sorts the rest out. That’s our working model and it’s an opinion, and the evidence behind it covers the sensorimotor deficits rather than the sequence we’ve built out of them ^[59]^[60]^[8].

Dysautonomia, POTS, and the Best Supported Route of the Lot

If you want the mechanism with the most evidence behind it, this is the one.

Autonomic symptoms are common in hEDS and HSD, POTS is a substantial part of that, and the burden is heavy enough to drag quality of life down on its own ^[36]^[3]. In hypermobile people with mental health or neurodevelopmental diagnoses, autonomic symptoms are reported more often, and orthostatic intolerance mediated the relationship between hypermobility and having an anxiety diagnosis ^[3]. Mediated is the important word there, as it means the link between hypermobility and anxiety ran, statistically, through the autonomic problem, rather than sitting alongside it doing nothing much at all.

The developmental version of the same finding is arguably more striking. In adolescents, resting heart rate mediated the link between hypermobility at fourteen and common mental illness later on ^[37]^[38]. A physiological measure, taken years earlier, carrying the association, which is genuinely difficult to explain as worry causing everything.

There’s a direct measurement behind it too. On standing, hypermobile people show greater heart rate reactivity, and in the anxious hypermobile group the amygdala and insula responses to emotional material are amplified ^[26]. Body and brain measured in the same people, pointing the same way.

What Dysautonomia Actually Is, In Plain Terms

The autonomic nervous system runs the things you don’t think about. Heart rate, blood pressure, blood vessel diameter, digestion, sweating, temperature, pupil size, bladder. It’s the part of the system doing the constant small adjustments that keep you upright and functioning while your attention is somewhere else entirely.

Dysautonomia is what you call it when those adjustments stop being reliable. Stand up and blood drops into your legs, and normally the vessels tighten and the heart adjusts and you don’t notice a thing. If the vessels are more distensible than average, more blood pools, the adjustment has to be bigger, and it often gets made by heart rate alone ^[49]^[16].

Which is why POTS and hypermobility sit together as often as they do. Connective tissue is in vessel walls, so more compliant tissue is a plausible reason for more pooling, and more pooling means a bigger compensatory response every single time you stand up ^[36]^[16]^[17].

The important bit for this article is what that compensatory response is made of, as it’s the same machinery that produces the physical experience of fear, and it’s being switched on several dozen times a day by nothing more alarming than getting off the sofa ^[49]^[26].

Why POTS Impersonates Anxiety So Convincingly

Palpitations. Shakiness. Dizziness. Breathlessness. Fatigue. Gut symptoms. Difficulty thinking straight. Now write that list on a referral letter without mentioning that it all happens on standing up, and see which department that letter lands in ^[49]^[63].

POTS is repeatedly misdiagnosed as chronic anxiety or panic disorder, and it’s so well recognised as a problem that it gets stated plainly in the clinical literature rather than hinted at ^[64]^[65]^[66]. The overlap isn’t superficial either, as both produce a tachycardia you can feel, both produce adrenaline symptoms, and both get considerably worse with heat, dehydration, poor sleep and standing in a queue.

Hyperadrenergic POTS adds another layer, as the catecholamine excess happens upright and can produce crisis like tachycardia and blood pressure spikes that look exactly like a panic attack from the outside ^[67]^[65]. And if the catecholamine testing gets done lying down, which it often is, the abnormality can be missed completely ^[67]. So somebody can be told their tests were normal, when the test was run in the one position where the problem doesn’t happen (which honestly happens a lot in this space).

– The practical consequence for you: If your worst symptoms are reliably tied to being upright, to heat, or to the twenty minutes after a big meal, that pattern is worth writing down and taking with you. Anxiety doesn’t usually keep a timetable like that ^[49]^[63].

– The practical consequence for the anxiety itself: Repeated adrenaline surges that arrive without an obvious cause are a perfectly reasonable way to build a fear of the surges. That’s a learned response to a real physiological event, and it doesn’t make the physiological event any less real ^[3]^[26].

Telling an Adrenaline Surge From a Panic Attack

Almost nobody gets taught the difference between these two, and it changes what you do next.

A panic attack, in the classic sense, has a psychological on ramp. Something is noticed, it’s interpreted as dangerous, arousal climbs, the arousal is itself interpreted as dangerous, and the whole thing loops. An adrenaline surge in dysautonomia often doesn’t work like that at all, as the physiology arrives first, unprompted, and the fear arrives afterwards as a perfectly sensible reaction to a heart doing something alarming without permission ^[49]^[67].

– Look at the order of events: If the racing heart reliably comes before the frightened thought rather than after it, that’s a pattern worth recording. It doesn’t rule anxiety out and it isn’t diagnostic on its own, but it’s the kind of detail that changes a consultation ^[49]^[65].

– Look at what precedes it: Standing up, heat, a hot shower, a large meal, a long queue, the first twenty minutes after getting out of bed. Those are orthostatic and postprandial triggers, and they don’t care what you were thinking about ^[49]^[63].

– Look at what it does to your legs: Blood pooling symptoms, colour change in the feet, an overwhelming need to sit or to put your legs up. Anxiety doesn’t usually produce those ^[49]^[63].

– Look at whether reassurance touches it: Being reassured that nothing is wrong does very little to a physiological surge, and in a purely cognitive panic loop reassurance usually does something. Neither result proves anything by itself ^[66]^[64].

Write the pattern down over a few weeks before an appointment. A description of what your body does, when, and in what order, is much harder to dismiss than a description of how you feel about it, and in a system where dysautonomia is so routinely read as anxiety, that difference is genuinely worth the effort ^[66]^[64]^[65].

And the reason this matters beyond the diagnosis: if you’ve had dozens of unexplained surges over several years, developing a fear of them is learning, not pathology, and treating the fear without addressing the surges leaves the curriculum running ^[3]^[49].

The Limit of This Explanation, Stated Honestly

Dysautonomia is the best supported bridge here. It is not the whole bridge.

The evidence supports association and partial mediation, not proof that autonomic dysfunction is the sole cause of anxiety in hypermobility ^[3]^[68]. Plenty of hypermobile people have significant anxiety and unremarkable autonomic testing, and plenty have florid POTS and no anxiety disorder at all. If dysautonomia were the whole story, those two groups wouldn’t exist in anything like the numbers they do.

It’s also worth saying that dysautonomia in this population isn’t only POTS, and it isn’t only heart rate. Autonomic involvement in hEDS appears to differ from what turns up in small fibre neuropathy on its own, which suggests the autonomic picture here has its own character, rather than being borrowed wholesale from a neighbouring condition ^[42]^[41].

Pain That Amplifies, and What That Does to a Nervous System

Central sensitisation is the process where the spinal cord and brain become more responsive to input, so that a given signal from the body produces more pain than it used to. It isn’t imagination and it isn’t a malfunction in the sense of something being broken, it’s a system that has adjusted its gain, and gain, once adjusted, tends to stay adjusted.

Among people with both pain and hEDS or HSD, evidence of central sensitisation is present in the very large majority ^[69]. In adolescents with HSD or hEDS, the pressure at which touch becomes painful is lower across several different muscle groups, alongside more fatigue and more cognitive and emotional difficulty ^[50]. So the sensitivity isn’t confined to the joints that hurt, it’s rather more general than that.

Now, the interesting recent wrinkle. When fatigue, pain, cardiac dysautonomia and anxiety are all put into the same model to see which independently predicts the central sensitisation burden, fatigue, pain and the cardiac autonomic picture come out as predictors and anxiety doesn’t ^[47]. Which suggests that where anxiety and sensitisation travel together, a good deal of the connection may run through the symptom load, rather than the anxiety directly driving the sensitisation ^[47].

That’s one analysis and it needs repeating before anyone leans hard on it. It’s a useful corrective though, as the assumption usually runs the other way, and the assumption usually has a great deal less behind it than this does.

What Sensitisation Feels Like From Inside It

The clinical description of central sensitisation is dry, and it undersells the experience considerably.

What it actually looks like is a waistband that becomes unbearable by lunchtime. A light touch on the arm that registers as unpleasant rather than neutral. Noise that stops being background. Being cold in a room everybody else is perfectly comfortable in. Pain that spreads to places that were never injured, which is the one that gets people told they’re catastrophising, when what they’re describing is a measurable lowering of the pressure at which touch becomes painful across multiple sites ^[50]^[69].

Now, the reason this belongs in an anxiety article rather than a pain one. A nervous system with the gain turned up is a nervous system for which ordinary daily life contains more aversive events, and more aversive events mean more reason to be braced. The anxiety and the sensitisation aren’t competing explanations, they’re two readings of the same increased responsiveness ^[69]^[50]^[47].

And it cuts against the idea that this is all a thinking problem, as you can measure it with an algometer on somebody’s thigh, and thinking differently about your thigh does not change what the algometer reads ^[50].

Where the Nerves Themselves Come Into It

Small fibre neuropathy appears to be common in hEDS, affecting the thin nerve fibres that carry temperature, some pain signalling and a large part of autonomic function ^[41]. It’s measurable on a skin biopsy, which matters a great deal, as it turns a set of symptoms that sound vague into something with a physical finding attached.

The sensory and autonomic involvement in hEDS also looks different from what you see in idiopathic small fibre neuropathy, so the two aren’t simply the same problem with different labels ^[42]. Nobody has shown that small fibre involvement causes the anxiety. What it does do is explain a chunk of the sensory strangeness that otherwise gets filed under nerves in the psychiatric sense, rather than nerves in the anatomical one ^[41]^[42].

The Gut, and the Route From It Upwards

Gut symptoms in hypermobility are a great deal better documented than most of the mechanisms in this article, and they’re much more common than most people expect.

At the point of hEDS diagnosis, the majority already have at least one gut symptom, and among those who then get tested for dysmotility, most turn out to have abnormal results ^[70]. Of everything that could be lined up against the dysmotility, the thing that independently predicted it was POTS ^[70], which is a fairly neat demonstration that the autonomic and gut stories here are really one story with two sets of symptoms.

Abdominal pain, feeling full very quickly after eating, constipation and diarrhoea are all significantly more common in HSD and hEDS than in people without either, and the underlying mechanism remains poorly understood and is probably several mechanisms rather than one ^[71]. Across very large matched record databases, the gut and non joint comorbidity profile in EDS is clearly elevated rather than marginally so ^[33].

How the Gut Connects to the Anxiety

Separate hEDS and HSD into groups by their gut pattern, and the group with upper gut disorders plus irritable bowel has higher anxiety, more autonomic symptoms, more POTS and worse quality of life than hEDS and HSD without that pattern ^[35]. So the gut burden isn’t just uncomfortable, it’s sitting alongside the worst of everything else.

The route from gut to mood is plausible and reasonably well mapped in general terms. Immune signalling, vagal signalling, the enteric nervous system and the microbiome all provide channels between the two, and the vagus in particular links mood, digestion and heart rate in the same circuit ^[72]^[73]. That general work isn’t hypermobility specific though, so what it gives you is a mechanism that could plausibly apply here, rather than one anybody has traced in this population.

– What it means in practice: If you’re anxious and you’re also spending a significant part of every day managing reflux, nausea, bloating or unpredictable bowels, treating the anxiety in isolation is asking an awful lot of it ^[35]^[71].

– What it doesn’t mean: Nobody has shown that fixing the gut fixes the anxiety, and the microbiome end of this in particular is a long way from anything you could act on with any confidence ^[72]^[35].

Why the Gut Symptoms Get Dismissed Too

So, gut symptoms in hypermobility follow the same unhappy path as everything else in this article. They’re common, they’re poorly explained, and being poorly explained gets read as being psychological.

The mechanism genuinely is not well understood, and it’s probably several mechanisms operating together rather than one ^[71]. That’s an admission of uncertainty about the biology, and it keeps being converted, somewhere between the literature and the consulting room, into a conclusion about the person. Meanwhile the dysmotility is measurable, the association with POTS is measurable, and the comorbidity profile across very large matched populations is clearly raised ^[70]^[33].

So if you’ve been told your gut symptoms are stress, the accurate version is that the mechanism hasn’t been worked out, that gut and autonomic function are demonstrably entangled here, and that stress is a hypothesis rather than a finding ^[70]^[71]^[74].

– What’s worth pursuing: Dysmotility is testable, and the strongest independent predictor of it in hEDS is POTS, so the autonomic and gut questions are worth asking in the same appointment rather than in two different departments a year apart ^[70]^[74].

– What’s worth expecting: Partial answers, unfortunately. Upper gut disorders and irritable bowel patterns cluster with the worst of everything else here, and that clustering is a great deal better documented than any treatment for it ^[35]^[71].

Mast Cells, Where the Evidence Is Thinnest and the Confidence Is Loudest

The hEDS, POTS and mast cell activation triad has become one of the most repeated ideas in this community, and it’s the part of this article where the gap between how certain people sound and how certain anyone should be, is at its very widest.

Start with what’s genuinely there. Overlap between mast cell activation syndrome, POTS and EDS has been reported, and it keeps being reported ^[75]. In specialist settings, a diagnosis of MCAS turns up in a meaningful minority of women with HSD or hEDS, and in roughly a quarter of those presenting with the full triad picture ^[36]. There are also descriptions of neuropsychiatric symptoms improving after treatment aimed at mast cells ^[76].

Now the part that gets left off the graphic. There’s currently no high quality evidence proving that mast cell activation syndrome is associated with dysautonomia, with hypermobility, or with both, despite the overlapping symptoms and despite some people clearly responding to treatment ^[77]. Reviews of the triad say much the same thing in rather more words: the associations are observed, the biological mechanism remains unclear, and the evidence quality is low ^[78]^[79]^[80].

A large part of the problem is definitional. What counts as MCAS varies between the criteria sets in use, the testing is awkward, mediators are unstable and the thresholds are argued about ^[80]^[77]. When two groups can look at the same person and disagree about whether she has the condition, prevalence figures stop meaning very much, and a prevalence figure that doesn’t mean much can’t support a causal claim about anxiety.

The current gastroenterology position on all of this is worth having, as it’s practical rather than polemical. It accepts that the observed associations between hEDS or HSD, POTS and MCAS exist, says the biological mechanisms remain limited and evolving, and recommends that POTS and MCAS testing is targeted at people whose presentation actually fits, rather than done as a matter of routine on everybody with hypermobile joints ^[74].

Histamine and the Brain, Honestly

Histamine does act as a neurotransmitter, and mediators released by mast cells can interact with microglia, astrocytes and cytokine signalling in the brain ^[76]^[81]. So there is a real biological route by which mast cell activity could plausibly affect mood and arousal.

Most of that though, is mechanistic, or has been shown in cells and in animals, and nobody has tested whether it holds as an explanation for anxiety in hypermobile people ^[81]^[82]. A plausible route and a demonstrated one are very different things, and this is a plausible route.

– What that means if antihistamines help you: Take the win. Something responding to treatment is information, and it doesn’t require the triad to be a proven biological entity ^[76].

– What that means if they do nothing: Also information, and not a personal failure. The overlap is reported in a minority, not in everybody, and there’s no good evidence you should expect it to work ^[77]^[78].

– What it means for testing: Targeted rather than routine, aimed at people whose symptoms genuinely fit the picture ^[74].

– What it means for the anxiety claim specifically: There are descriptions of neuropsychiatric symptoms improving with mast cell directed treatment, and that’s worth knowing about, but descriptions of improvement in a small number of people are a long way from evidence that mast cells explain anxiety in hypermobility ^[76]^[77].

And a general point that applies well beyond this section. The gap between how much is known about a mechanism and how confidently it gets talked about is, in this field, almost inversely proportional. The best evidenced route here is the autonomic one, and it’s the least marketed, while the least evidenced is the mast cell one, and it has all the infographics. That isn’t a coincidence, as an explanation that covers everything will always be more appealing than one that covers a third of it properly ^[3]^[77]^[80].

Why This One Gets Overclaimed So Reliably

Worth understanding the mechanics of it, as the same pattern will turn up in the next popular explanation too.

A symptom cluster that nobody can explain is intolerable to live with, and an explanation that covers everything at once is enormously relieving. The triad does exactly that. Hypermobile joints, dizziness, flushing, gut trouble, anxiety, food reactions, and a single unifying cause with a treatment attached. It’s a much better story than the accurate one, which is that several things are going on, they interact, and nobody has untangled them yet ^[78]^[80]^[3].

Add in that mast cell directed treatment genuinely does help some people, and you have a self reinforcing loop ^[76]. Responders tell other people, non responders assume they haven’t found the right protocol, and because the diagnostic criteria are contested and the testing is awkward, nobody can easily establish who was in which group in the first place ^[80]^[77].

None of that means the triad isn’t real. It means the confidence in it is currently coming from somewhere other than the evidence, and in a community that has been dismissed for decades, an explanation that finally explains everything is very hard to argue with ^[77]^[79]^[74].

Where Else This Turns Up, and What That Suggests

Hypermobility keeps appearing in places that have nothing obvious to do with joints, and the pattern is worth knowing about, partly because it may explain some of the anxiety and partly because it explains why so many people end up collecting several diagnoses.

In adults with autism, ADHD or tic disorders, hypermobility is more common, orthostatic intolerance is more common, and musculoskeletal pain is more common, with the number of hypermobile joints mediating the link to both the dysautonomia and the pain ^[51]^[83]. Across the autism literature specifically, the prevalence of hypermobility and related conditions is elevated ^[52]. In people with functional seizures, hypermobility is markedly more common, and that held independently of anxiety and depression ^[84]. In fibromyalgia and ME or CFS clinics, a very large proportion meet hypermobility criteria, and how hypermobile somebody is predicts how symptomatic they are ^[45]. There’s even an emerging line connecting hypermobility to bipolar affective disorder, with neurodivergent characteristics appearing to mediate part of it ^[85].

Take all of that as a pattern rather than as a set of proven links though, as most of it is observational, much of it is subgroup dependent, and the populations being compared vary a great deal ^[51]^[84]^[85].

Why It Might All Hang Together

The proposed common thread is emotional regulation built on unreliable body information. If proprioceptive and interoceptive signals are less precise, then the raw material for both emotional regulation and self modelling is noisier, which could plausibly show up as anxiety in one person, as sensory overwhelm in another, and as something that gets labelled functional in a third ^[8]^[24].

That’s a model, and a fairly elegant one, and it’s a long way from being demonstrated. It’s the kind of idea that either turns out to be the organising principle of the whole field, or turns out to be a story that fitted the data we happened to have. Both happen.

What it’s genuinely useful for right now is formulation. Recognising hypermobility changes how a psychiatric or general medical picture gets put together, and that change of framing is available today even though the targeted treatments aren’t ^[24]^[86].

The Functional Label, and Why This Matters For It

The functional seizure finding deserves its own paragraph, because of where it lands.

Hypermobility is markedly more common in people with functional seizures, and that held independently of anxiety and depression, which is the detail that matters ^[84]. If the hypermobility were simply a marker of being anxious, adjusting for anxiety should have removed the association. It didn’t.

Functional is a label that gets applied when the presentation doesn’t fit a recognised structural cause, and in practice it very often gets heard, and sometimes meant, as psychological. A physical trait turning up at elevated rates in that group, independently of mood, is a reason to be a great deal more careful with the label rather than less ^[84]^[24].

Same argument applies to the fatigue clinics. A very large proportion of people carrying a fibromyalgia or ME diagnosis turn out to be hypermobile, and how hypermobile they are predicts how symptomatic they are, which suggests a measurable physical characteristic is being routinely missed in populations who have already been told their condition is poorly understood ^[45]^[46].

None of that reclassifies anybody’s diagnosis, and it isn’t an argument that fibromyalgia is really hypermobility. It’s an argument for looking, as looking is cheap and the consequence of not looking is another person spending years in the wrong clinic ^[45]^[84].

The Years Before Anybody Believed You

There’s a mechanism in this article that requires no neuroimaging, no autonomic testing and no mast cell mediator assay, and it may well be the largest single contributor to anxiety in this population.

Getting an hEDS diagnosis confirmed takes, on average, about a decade, and the average number of other diagnoses collected along the way is roughly ten ^[87]. Larger recent surveys put the delay higher still, at somewhere between seventeen and twenty two years depending on whether it’s HSD or hEDS, alongside frequent dismissal and open scepticism from clinicians ^[43]^[44]. That isn’t a delay in treatment, that’s most of somebody’s early adulthood spent being told, by people with authority, that the thing happening to her body isn’t happening.

The consequences of that get described pretty consistently: mistrust of clinicians, doubt about one’s own perceptions, and in some accounts something that looks a great deal like medical post traumatic stress ^[39]^[44]^[88].

Why This Isn’t a Soft Point

It’s tempting to file this under psychological impact and move straight on to the biology, and that’s a mistake for two reasons.

The first is that health anxiety and body vigilance are learned, and this is exactly the curriculum that teaches them. If you have spent years having real symptoms dismissed, then paying very close attention to your body is not a distortion, it’s the strategy that eventually got you taken seriously. Asking somebody to stop doing that, without changing anything about the system that made it necessary, is asking her to give up the only thing that ever worked.

The second is that it contaminates the research as well as the person. Specialist clinic groups are made up of people who survived that process, which is part of why anxiety figures from those settings run so high ^[27]^[28]^[43]. Some proportion of the anxiety measured in hypermobility research is a measurement of what medicine did to those people, and there’s currently no good way to separate that out from the biology.

Now, the thing that makes this one worth naming out loud rather than burying in a list. It’s the only mechanism here that is somebody’s fault. The autonomic nervous system isn’t anybody’s fault. Twenty years of being told to try yoga and manage your stress is.

The Shape of the Delay, and Why It Does Specific Damage

It isn’t only the length of the wait, it’s what happens during it. Roughly ten alternative diagnoses get collected along the way, which means ten separate occasions of being given an explanation, adjusting to it, being treated for it, and then having it withdrawn ^[87]. Each of those is a small lesson in the unreliability of medical explanation, delivered by the very people whose explanations you most need to be able to trust.

The qualitative accounts of this are consistent and fairly grim, describing it as something people survive rather than something they attend ^[88]^[44]. Frequent dismissal and open scepticism from clinicians turn up in the larger surveys as a routine feature rather than an unlucky exception ^[43]^[44].

– It teaches symptom vigilance: Paying very close attention to your body is the behaviour that eventually produced enough detail to be taken seriously. Asking somebody to drop it, without changing anything about the system, is asking her to unlearn the only strategy that worked ^[44]^[39].

– It teaches pre emptive self doubt: After enough dismissals, people start filtering what they report before they even say it, which makes the next consultation worse and the delay longer ^[44]^[88].

– It makes ordinary appointments expensive: If a routine consultation carries a genuine risk of being disbelieved about something that matters, then avoiding appointments becomes rational, and avoidance then gets recorded as anxiety ^[44]^[43].

What This Means for How the Anxiety Gets Treated

Two things follow, and they’re both practical.

If a clinician treats the anxiety as the primary problem and the medical history as background, the treatment is aimed at the wrong target and the person in the chair knows it, and that mismatch is itself a reason treatment gets abandoned ^[39]^[89].

And if a clinician accepts the medical history as an obvious and sufficient cause, the biology gets ignored instead, which is the same error the other way round. Dysautonomia, nerve involvement and pain amplification are all present and all measurable, and none of them stops being real because somebody has also been badly treated ^[3]^[41]^[69].

The useful version holds both. The biology loads the system, the circumstances load the system, and the loading is additive rather than competitive ^[3]^[18]^[90].

Why the Standard Anxiety Advice Underperforms Here

Cut down on caffeine. Try meditation. Breathe from your diaphragm. Get some exercise. Keep a worry diary. All perfectly reasonable, all supported for anxiety in the general population, and all of it tends to produce a thin, disappointing result in this group, which then gets read as poor compliance.

There are three reasons for that, and none of them is that you didn’t try hard enough.

The first is that a fair amount of what’s being treated as anxiety is physiological and postural, so a technique aimed at thoughts is being pointed at something that didn’t start as a thought ^[49]^[66]^[3]. Breathing work does influence vagal activity, which is genuinely relevant, but influencing vagal tone and resolving orthostatic intolerance are not the same thing at all ^[73]^[91].

The second is that the advice assumes a steady starting point that stays put. Pain, fatigue, poor sleep and gut symptoms are all raised here, they fluctuate, and they independently load the same system the anxiety sits in ^[47]^[27]^[35]. Asking somebody to practise a calming technique consistently, while the inputs into the system change week to week, is asking for a result the design simply can’t deliver.

The third is that the psychological work with the best showing in this population isn’t standalone. Where improvements have been reported in EDS and HSD, the psychological component was usually sitting inside a broader programme alongside physiotherapy rather than running on its own ^[89]^[39], and generic advice is by definition standalone.

So the advice isn’t wrong. It’s underpowered for the situation it’s being applied to, and it’s being asked to do a job that ought to be shared out across several things at once ^[21]^[29]^[16].

What Actually Helps, and How Confident to Be About Each Bit

The evidence is at its thinnest exactly where you most want it to be thick, unfortunately, and there’s no honest way round that.

The one thing with decent support across the board is that care should be multidisciplinary. Physical, psychological and autonomic aware management together beats treating this as a purely musculoskeletal problem, and that recommendation shows up consistently ^[21]^[29]^[16]. Beyond that, almost everything below is either extrapolated from the general anxiety literature or supported by small work in hypermobility specifically, and we’ll say which is which as we go.

Movement and Rehab

Exercise is a central part of managing POTS, and it’s one of the few non drug approaches that holds up in that setting ^[49]^[74]. Given how much of the anxiety picture in hypermobility appears to run through the autonomic side, that alone is a decent reason to take it seriously ^[3]^[26].

Separately, the sensorimotor problems are real and measurable, so there’s something concrete to aim at. Joint position sense, balance and the strategies used to control a wobbly joint are all trainable in principle, and physical therapy for hypermobility has enough behind it to be considered the default conservative approach ^[59]^[92]^[93]^[94].

Where it gets thin is anxiety specifically. Nobody has properly tested whether proprioceptive training reduces anxiety in hypermobile people, and the direct evidence is much stronger for the sensorimotor outcomes than for anything psychiatric ^[59]^[8]. So the honest position is that exercise has good general support, a plausible mechanism, and no dedicated trial for this outcome in this population.

– Start below the level that provokes symptoms: The conservative evidence in hypermobility is broadly supportive of graded physical approaches, and the failure mode people describe most often is starting at an intensity the autonomic system can’t currently meet ^[94]^[92]^[49].

– Aim at control rather than range: The measurable deficits are in position sense, stability limits and how the body is controlled, not in how far it can stretch ^[59]^[60].

– Expect the rehab to be slower than you want: That isn’t evidence based so much as it’s what the conservative literature keeps showing in aggregate, which is real but modest benefit over time rather than anything quick ^[94]^[92].

What the Movement Side Actually Looks Like

Since “exercise” covers everything from a walk to a barbell, it’s worth being specific about what the evidence here points at, and equally specific about where we’re extrapolating.

The measured deficits are in joint position sense at individual joints, in lumbar proprioception, in how far somebody can shift their weight under control, in sway, and in how muscles get recruited ^[59]^[60]^[61]. Not in strength as such, and definitely not in range of motion, which is already generous by definition.

So the targets that follow from the evidence are about information and control. Slower positions where the joint has to be found rather than thrown into position, work in the middle of a range instead of at the end of it, and enough attention on what’s happening that the brain gets a usable signal back, which in practice means fewer repetitions done properly rather than more done on autopilot. That’s our reading of what the deficits imply and we’d rather say so than dress it up as a trial result ^[59]^[8].

The autonomic constraint sits on top of all of it. Exercise is central in POTS management, and it’s also the thing most likely to provoke symptoms if the starting intensity is wrong, so the progression has to be built around what the autonomic system can currently meet rather than around what the muscles could manage ^[49]^[74]^[94].

– Positions matter more than they should: Working on the floor, or seated, or with the upper body supported, removes most of the orthostatic load while leaving the sensorimotor work intact ^[49]^[92].

– Consistency beats intensity by a distance: The conservative evidence in hypermobility shows real but modest benefit accumulating over time, which is an argument for something small and repeatable rather than something ambitious and abandoned ^[94]^[92]^[93].

– Fear of falling is part of the problem to be treated: It’s very common in this group, and it changes how people move, which then changes what the nervous system learns ^[61]^[59].

Managing the Load Rather Than Just the Symptom

Something that falls out of the evidence rather than being tested directly, so treat it as a reading rather than a recommendation with a trial behind it.

Fatigue, pain and the cardiac autonomic picture independently predict how much sensitisation somebody is carrying, while anxiety doesn’t come out as an independent predictor in the same model ^[47]. Read that alongside the clustering of pain, fatigue, gut symptoms and poor sleep in this population, and the picture is of a system with several simultaneous loads on it ^[35]^[27]^[43].

Which suggests that anything reducing total load is doing anxiety work indirectly, even if it never once mentions anxiety. Fewer unexplained surges. Better sleep. Less pain. Fewer days spent running on a deficit and paying for it later. None of that has been tested as an anxiety intervention in hypermobility, and it follows from the mechanism rather than from a result ^[47]^[3]^[46].

The practical shape of it is deeply unglamorous. Working out what reliably costs you, and reducing the frequency rather than trying to become able to do all of it. That’s the bit of rehab nobody ever puts on a poster, and it’s usually where the first real improvement comes from.

Breathing and Vagal Work

Slow breathing genuinely does influence vagal activity, and vagal regulation is a real link between mood, digestion and heart rate, so the rationale here is sound ^[73]^[91].

The direct evidence is a good deal more modest than the enthusiasm. Diaphragmatic breathing practised properly has lowered anxiety scores and heart rate ^[95]. Biofeedback aimed at heart rate variability did raise the vagally mediated part of that variability, but it didn’t outperform the comparison on anxiety scores, which is the awkward result that rarely makes it into the infographics ^[96]. Neither of those was done in hypermobility, so what you have is general anxiety evidence plus a plausible autonomic rationale for why it might matter more here ^[95]^[96]^[73].

Our own view, stated as a view, is that breathing work is worth doing because it’s free, low risk and repeatable, and because of the CO2 tolerance and mechanical breathing side of things, rather than because anyone has shown it fixes anxiety in hEDS. Take that as opinion rather than as evidence.

Getting the Autonomic Side Actually Looked At

If your symptoms are reliably positional, this is worth pursuing properly rather than accepting anxiety as the explanation ^[49]^[64]^[66].

– Ask for the assessment that matches the symptom: Testing for POTS and for mast cell involvement should be targeted at presentations that genuinely fit rather than run as a blanket panel, and that’s the current specialist position rather than us being difficult ^[74].

– Positional testing matters for the catecholamine side: In hyperadrenergic presentations, the abnormality appears on standing, so a supine test can come back clean while the problem is entirely real ^[67]^[65].

– Treating the autonomic picture is a legitimate anxiety intervention: Not instead of psychological work, alongside it. Fewer unexplained adrenaline surges leave fewer things to become afraid of ^[3]^[49].

Psychological Therapy

Psychological work in EDS and HSD is genuinely promising and genuinely under evidenced, and those two statements belong in the same sentence.

What’s been done is mostly small, mostly not randomised and mostly low quality, with improvements reported for pain, fear, anxiety and quality of life, particularly where the psychological component sat inside a broader programme alongside physiotherapy ^[89]^[39]^[97]. That’s an encouraging signal and it isn’t proof, and there’s no large trial anybody can point you at ^[89]^[39].

Outside hypermobility, the ground is a fair bit firmer. Acceptance and commitment therapy improves pain related distress in chronic pain, including pain related anxiety, and across the wider chronic pain literature it produces small but real effects on anxiety ^[98]^[99]. Cognitive behavioural therapy has solid support in anxiety disorders generally, and adding exercise to it appears feasible and often helpful [100]. None of that is hypermobility specific though, so it’s a reason to expect these things to help, rather than a demonstration that they do here.

You’ll also see a targeted treatment for anxiety in hypermobility referred to as though it’s an established option. It’s a treatment concept with a published plan for testing it, not a result, and that distinction matters a great deal if somebody is selling it to you [101].

– What to look for in a therapist: Somebody who will work with the body symptoms as real physiological events, rather than as catastrophic thinking to be corrected. The evidence for embedding psychological work inside physical rehab is better than the evidence for it standing alone ^[89]^[39].

– What a reasonable target looks like: How bodily signals get evaluated and attended to, rather than whether they’re real. The consistent part of the interoception and anxiety evidence is about negative, threat focused appraisal, and that’s the part with something to work on ^[4]^[39].

– Why embedding it matters: Where improvements have been reported in this population, the psychological component usually sat inside a broader programme alongside physical rehab, which is also the shape the general recommendation takes ^[89]^[97]^[16].

– What to be wary of: Any approach that requires you to accept that the symptoms are generated by anxiety before treatment can start. Given how often dysautonomia and nerve involvement get misread as anxiety in this population, that’s a premise worth declining ^[40]^[41]^[66].

Medication

There are no anxiety medication trials specific to hypermobility, so everything here is borrowed from the general anxiety literature [102].

What that literature shows is that SSRIs and SNRIs work for anxiety disorders in adults, with no major difference in effectiveness between the two classes, and that dropping out because of side effects becomes more likely as the dose goes up [102]. That last part is well worth carrying into a conversation with a GP, as the instinct when a dose isn’t working is to raise it, and higher doses buy less additional benefit than people assume while reliably buying more side effects [102].

Whether those drugs behave differently in hypermobile people is an open question with no evidence attached either way. Plenty of people in this community report unusual medication sensitivity, and that observation currently has no research behind it that would let us tell you what to expect.

A Note on Medication Sensitivity

Worth separating two things that get run together, as the honest answer differs between them.

Whether SSRIs and SNRIs work for anxiety disorders is well established in adults generally, and the dose response picture is clear enough to be useful, in that going higher buys diminishing extra benefit while reliably buying more reason to stop [102]. That’s solid ground and it applies to everybody.

Whether hypermobile people metabolise or tolerate these drugs differently is a genuinely open question, and the honest answer is that nobody has looked properly. It’s reported constantly in this community and there is nothing in the evidence that would let us tell you what to expect, in either direction [102]. So if you’ve had an unusual response, that isn’t evidence you’re imagining it, and it also isn’t something a prescriber can currently plan around.

The practical middle ground is the same one that applies to most things here. Start low, change one thing at a time, keep a record, and treat an unexpected response as information rather than as a failure of the whole approach.

Sleep

Now, sleep gets treated as an afterthought and it really shouldn’t be. In children and adolescents with hEDS, poor sleep is common, and worse sleep tracks with worse anxiety, worse depression and worse quality of life ^[27]. In adults, sleep disturbance shows up as part of the broader multisystem burden that amplifies pain, fatigue and cognition ^[43].

Nobody has run proper sleep intervention trials in hEDS or HSD, so there’s no hypermobility specific protocol to hand you ^[27]. But the association is strong enough, and sleep is upstream of enough else, that it’s a perfectly reasonable place to put effort while the trials don’t exist.

Putting It in Some Sort of Order

None of the above tells you what to do on Monday, so here’s our reading of it, marked clearly as ours rather than as something the evidence dictates.

– Get the autonomic question answered first: Not because it’s the most important thing in every case, but because it’s the most misdiagnosed thing, the most treatable thing, and the thing most likely to be generating symptoms that are currently being filed as anxiety ^[3]^[49]^[66].

– Then the sleep: Sleep sits upstream of pain, fatigue, cognition and mood, the association in this population is strong, and improving it doesn’t require anybody to agree with you about mechanisms first ^[27]^[43].

– Then the movement, started lower than feels sensible: The sensorimotor deficits are the best measured thing in the whole article and the most obviously trainable, and the commonest failure is intensity rather than approach ^[59]^[60]^[94].

– Then the psychological work, embedded rather than standalone: What evidence there is favours psychological approaches sitting inside a broader programme rather than running on their own, and it also keeps the framing honest ^[89]^[39]^[97].

– Medication whenever it’s needed, without treating it as a last resort: The general evidence is decent, the hypermobility specific evidence doesn’t exist, and nobody has to earn the right to a prescription by failing at everything else first [102].

Taking It Into an Appointment

Now, most of the practical difficulty here isn’t choosing a treatment, it’s getting somebody to look at the right thing, and that is a skill rather than a personality trait.

– Lead with the pattern, not the feeling: A description of what your body does, when it does it, and in what order, is much harder to file under anxiety than a description of how frightening it is. Both are true. Only one of them survives contact with a ten minute appointment ^[66]^[64].

– Bring the positional detail: Symptoms that cluster around standing, heat, large meals and the first part of the morning point somewhere specific, and that’s the detail most likely to get you an autonomic assessment rather than a reassurance leaflet ^[49]^[63].

– Ask for testing that matches the presentation: Targeted testing is the current specialist position rather than a demand, so asking for an assessment that fits your symptoms is asking for standard care ^[74].

– Say what you’ve already tried and what it did: Not to prove you’ve earned it, but because a partial response to a general anxiety approach is itself useful information about which part of the picture is doing the driving ^[89]^[39].

– Don’t accept a normal supine result as the end of the hyperadrenergic question: If the problem happens upright, that’s where the measurement needs to be taken ^[67]^[65].

Two things not to do. Don’t take a printed stack of papers in with you, as it changes the register of the conversation and rarely goes well. And don’t go in having already decided which of the mechanisms in this article is yours, as none of us can tell you that yet, and arriving with a diagnosis makes the whole thing adversarial ^[3]^[4].

What We’d Be Careful About

– Anything sold as rewiring your nervous system: Targeted treatments built on these mechanisms are not proven, the mechanistic story is ahead of the intervention evidence by a considerable distance, and a confident programme built on an unproven mechanism is still an unproven programme ^[24]^[92]^[94].

– Any protocol that requires the triad to be settled biology: The overlap between hypermobility, POTS and mast cell activation is reported, the mechanism is unclear, the evidence quality is low, and testing should be targeted rather than routine ^[77]^[80]^[74].

– Anything offered on the basis of what your amygdala is doing: Imaging in this area is mechanistic and preliminary, nobody has a clinical test, and anyone claiming to normalise a brain structure they have never measured is selling a story ^[5]^[6]^[53].

– Stretching as a treatment for any of it: Nothing in this evidence supports more range of motion as the answer to a problem that appears to be about control and signal quality rather than about tightness ^[59]^[60]^[8].

The Biopsychosocial Bit, Said Properly

We work inside the biopsychosocial model and we’ll say so plainly, as it’s the dominant framework in pain science and it’s the right one. It also gets used badly often enough that the phrase has become a warning sign for a lot of people reading this, so it’s worth setting out what it actually means here.

Biology is present. Variant connective tissue, autonomic dysregulation, sensory imprecision, pain amplification, small fibre involvement and gut dysmotility are all measurable, and they’re all more common in this group ^[3]^[41]^[69]^[70].

Psychology is present. Threat focused evaluation of bodily signals, learned fear of surges, and vigilance built from years of unpredictability are all real processes, and they’re the parts most amenable to being worked on ^[4]^[39].

Circumstances are present. A decade of diagnostic delay, repeated dismissal, lost work, lost capability and a healthcare system that isn’t built for multisystem conditions all load the same system ^[87]^[43]^[44].

What goes wrong in practice is that the social gets quietly dropped and the psychological gets over weighted, until biopsychosocial becomes a polite route to saying somebody’s symptoms are psychological. That isn’t what the model says and it isn’t what the evidence here shows ^[3]^[40]^[18]. All three load the same nervous system, none of them makes anything less real, and the biology in this particular condition is unusually well documented compared with most places the model gets applied.

The practical upshot is a low bar and a useful one: any explanation that requires you to accept that the symptoms are generated by your mind before treatment can start has misused the framework, and you’re perfectly entitled to say so ^[40]^[41]^[66].

What Happens Later On

There’s very little written about hypermobility in older age, and what there is suggests the anxiety link doesn’t simply fade out.

In older adults, anxiety disorders in the past year were roughly three times more common in the hypermobile group than in the comparison group ^[22]. So whatever’s driving this isn’t purely a feature of young adulthood, and the common assumption that hypermobility settles down with age doesn’t extend neatly to the psychiatric side of it ^[22]^[90].

That’s about as much as anybody can tell you, as this has been looked at properly once, in one country, in one age group, so treat it as a hint rather than a finding ^[22]. It’s a genuine gap, and a strange one given how much attention the adolescent and young adult end has had ^[37][103].

What Nobody Knows Yet

Worth being blunt about the size of the hole, as a lot of what gets sold in this space depends on you not noticing it.

Nobody knows which mechanism matters most in which person. Autonomic dysfunction, interoception, pain sensitisation, immune signalling, gut symptoms and medical trauma are all in the frame, all have something behind them, and there’s no way at present to work out which is driving your anxiety ^[3]^[4]^[76].

Nobody can diagnose hEDS with a test. There’s no biomarker and no genetic marker, the criteria have changed and will probably change again, so the boundary between hEDS, HSD and generalised hypermobility is drawn by agreement rather than by biology ^[14]^[15]^[12].

Nobody has run the treatment trials. The descriptive and associative literature is decades ahead of the intervention literature, which is the normal shape of a field that only recently started being taken seriously, and it’s also why so much of the advice you’ll come across is confident about mechanisms and vague about outcomes ^[24][103]^[89].

And nobody has properly separated the biology from what medicine did to people. Some unknown proportion of the anxiety measured in hypermobility is the residue of a decade of dismissal, and there’s no clean way to subtract it ^[87]^[43]^[44].

The one genuinely settled shift is the framing. Hypermobility stopped being a benign joint finding and became a multisystem phenotype with measurable psychiatric, autonomic, sensory and quality of life correlates across childhood, adulthood and old age ^[3]^[18]^[23]^[22]. That’s the change that matters, and it’s the reason anybody is studying any of this at all ^[90].

There’s one more gap that gets very little attention and probably deserves a good deal more. Almost everything in this article describes groups, and treatment happens to individuals. Nobody has worked out how to tell, in the room, whether the person in front of you is mainly an autonomic case, mainly a sensitisation case, or mainly somebody who has been badly treated for fifteen years and is now understandably wary. The agreed research priorities in this field say much the same thing: the useful next questions are about who is at risk, by what mechanism, and which subgroup responds to which treatment [103]^[24].

Until somebody answers that, the sensible approach is the unglamorous one. Address the parts that are measurable, treat the things that have evidence behind them, be honest about which bits are guesses, and change the plan when it doesn’t work rather than deciding the person didn’t try ^[89]^[94][102].

The Fibro Guy

References

[1] Smith, T.O., Easton, V., Bacon, H., Jerman, E., Armon, K., Poland, F. et al. (2013) ‘The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis’, Rheumatology. https://doi.org/10.1093/rheumatology/ket317

[2] Bulbena, A., Gago, J., Pailhez, G., Sperry, L., Fullana, M.A. and Vilarroya, O. (2011) ‘Joint hypermobility syndrome is a risk factor trait for anxiety disorders: a 15-year follow-up cohort study’, General Hospital Psychiatry. https://doi.org/10.1016/j.genhosppsych.2011.03.004

[3] Csecs, J.L.L., Dowell, N.G., Savage, G.K., Iodice, V., Mathias, C.J., Critchley, H.D. et al. (2021) ‘Variant connective tissue (joint hypermobility) and dysautonomia are associated with multimorbidity at the intersection between physical and psychological health’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31957

[4] Clemente, R., Murphy, A. and Murphy, J. (2024) ‘The relationship between self-reported interoception and anxiety: A systematic review and meta-analysis’, Neuroscience & Biobehavioral Reviews. https://doi.org/10.1016/j.neubiorev.2024.105923

[5] Kampoureli, C.N., Rae, C.L., Gould Van Praag, C., Harrison, N.A., Garfinkel, S.N., Critchley, H.D. et al. (2025) ‘Neural processes linking joint hypermobility and anxiety: key roles for the amygdala and insular cortex’, The British Journal of Psychiatry. https://doi.org/10.1192/bjp.2024.259

[6] Eccles, J.A., Beacher, F.D.C., Gray, M.A., Jones, C.L., Minati, L., Harrison, N.A. et al. (2012) ‘Brain structure and joint hypermobility: Relevance to the expression of psychiatric symptoms’, British Journal of Psychiatry. https://doi.org/10.1192/bjp.bp.111.092460

[7] Garcia-Campayo, J., Asso, E. and Alda, M. (2010) ‘Joint Hypermobility and Anxiety: The State of the Art’, Current Psychiatry Reports. https://doi.org/10.1007/s11920-010-0164-0

[8] Eccles, J.A., Quadt, L., Garfinkel, S.N. and Critchley, H.D. (2024) ‘A model linking emotional dysregulation in neurodivergent people to the proprioceptive impact of joint hypermobility’, Philosophical Transactions of the Royal Society B: Biological Sciences. https://doi.org/10.1098/rstb.2023.0247

[9] Javadi Parvaneh, V., Modaress, S., Zahed, G., Rahmani, K. and Shiari, R. (2020) ‘Prevalence of generalized joint hypermobility in children with anxiety disorders’, BMC Musculoskeletal Disorders. https://doi.org/10.1186/s12891-020-03377-0

[10] van Die-de Vries, J.E., Rameckers, E., Calders, P., Engelbert, R.H., Ramaekers, S.P., Goossens, M.E. et al. (2025) ‘Role of Anxiety in Individuals with Generalized Joint Hypermobility: A Systematic Review’, Archives of Rehabilitation Research and Clinical Translation. https://doi.org/10.1016/j.arrct.2025.100467

[11] de Vries, J., Verbunt, J., Stubbe, J., Visser, B., Ramaekers, S., Calders, P. et al. (2021) ‘Generalized Joint Hypermobility and Anxiety in Adolescents and Young Adults, the Impact on Physical and Psychosocial Functioning’, Healthcare. https://doi.org/10.3390/healthcare9050525

[12] Malfait, F., Francomano, C., Byers, P., Belmont, J., Berglund, B., Black, J. et al. (2017) ‘The 2017 international classification of the Ehlers–Danlos syndromes’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31552

[13] Castori, M., Tinkle, B., Levy, H., Grahame, R., Malfait, F. and Hakim, A. (2017) ‘A framework for the classification of joint hypermobility and related conditions’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31539

[14] Forghani, I., See, J. and McGonigle, W.C. (2025) ‘Hypermobile Ehlers–Danlos Syndrome: Diagnostic Challenges and the Role of Genetic Testing’, Genes. https://doi.org/10.3390/genes16050530

[15] Gensemer, C., Burks, R., Kautz, S., Judge, D.P., Lavallee, M. and Norris, R.A. (2020) ‘Hypermobile Ehlers‐Danlos syndromes: Complex phenotypes, challenging diagnoses, and poorly understood causes’, Developmental Dynamics. https://doi.org/10.1002/dvdy.220

[16] Malfait, F., Castori, M., Francomano, C.A., Giunta, C., Kosho, T. and Byers, P.H. (2020) ‘The Ehlers–Danlos syndromes’, Nature Reviews Disease Primers. https://doi.org/10.1038/s41572-020-0194-9

[17] Wang, T.J., Stecco, A., Hakim, A.J. and Schleip, R. (2025) ‘Fascial Pathophysiology in Hypermobility Spectrum Disorders and Hypermobile Ehlers–Danlos Syndrome: A Review of Emerging Evidence’, International Journal of Molecular Sciences. https://doi.org/10.3390/ijms26125587

[18] Sinibaldi, L., Ursini, G. and Castori, M. (2015) ‘Psychopathological manifestations of joint hypermobility and joint hypermobility syndrome/ Ehlers–Danlos syndrome, hypermobility type: The link between connective tissue and psychological distress revised’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31430

[19] Bulbena, A., Duró, J.C., Porta, M., Martín-Santos, R., Mateo, A., Molina, L. et al. (1993) ‘Anxiety disorders in the joint hypermobility syndrome’, Psychiatry Research. https://doi.org/10.1016/0165-1781(93)90008-5

[20] Martín-Santos, R., Bulbena, A., Porta, M., Gago, J., Molina, L. and Duró, J.C. (1998) ‘Association Between Joint Hypermobility Syndrome and Panic Disorder’, American Journal of Psychiatry. https://doi.org/10.1176/ajp.155.11.1578

[21] Bulbena, A., Baeza‐Velasco, C., Bulbena‐Cabré, A., Pailhez, G., Critchley, H., Chopra, P. et al. (2017) ‘Psychiatric and psychological aspects in the Ehlers–Danlos syndromes’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31544

[22] Bulbena‐Cabré, A., Rojo, C., Pailhez, G., Buron Maso, E., Martín‐Lopez, L.M. and Bulbena, A. (2017) ‘Joint hypermobility is also associated with anxiety disorders in the elderly population’, International Journal of Geriatric Psychiatry. https://doi.org/10.1002/gps.4733

[23] Jari, M. and Alesaeidi, S. (2025) ‘Association Between Generalized Joint Hypermobility and Anxiety Disorders in Children: A Case-Control Study’, Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders. https://doi.org/10.1177/11795441251365672

[24] Sharp, H.E.C., Critchley, H.D. and Eccles, J.A. (2021) ‘Connecting brain and body: Transdiagnostic relevance of connective tissue variants to neuropsychiatric symptom expression’, World Journal of Psychiatry. https://doi.org/10.5498/wjp.v11.i10.805

[25] Mallorquí-Bagué, N., Garfinkel, S.N., Engels, M., Eccles, J.A., Pailhez, G., Bulbena, A. et al. (2014) ‘Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility’, Frontiers in Psychology. https://doi.org/10.3389/fpsyg.2014.01162

[26] Eccles, J., Owens, A., Harrison, N., Grahame, R. and Critchley, H. (2016) ‘Joint hypermobility and autonomic hyperactivity: an autonomic and functional neuroimaging study’, The Lancet. https://doi.org/10.1016/s0140-6736(16)00427-x

[27] Hertel, A.K., Jones, J.T., Lytch, A., Cramer, E., Schroeder, A. and Black, W.R. (2025) ‘Prevalence of psychiatric and sleep disorders and their impact on quality of life in children with hypermobile Ehlers-Danlos syndrome: an observational study’, Rheumatology International. https://doi.org/10.1007/s00296-025-05836-0

[28] Slepian, P.M., Axenova, K., McCarthy, M., Siegal, R., Gobin, K., Weinrib, A. et al. (2025) ‘Rates of mental health concerns among individuals assessed at the GoodHope Ehlers-Danlos Syndrome Clinic’, Orphanet Journal of Rare Diseases. https://doi.org/10.1186/s13023-025-03550-5

[29] Henning, M., Hock, M., Shukri, A., Löw, V., Kernich, N., Rauterberg, J. et al. (2026) ‘Prevalence and management of mental health comorbidities in a German cohort of patients with Ehlers-Danlos syndromes and a generalized hypermobility spectrum disorder’, Orphanet Journal of Rare Diseases. https://doi.org/10.1186/s13023-026-04242-4

[30] Cederlöf, M., Larsson, H., Lichtenstein, P., Almqvist, C., Serlachius, E. and Ludvigsson, J.F. (2016) ‘Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers–Danlos syndrome or hypermobility syndrome and their siblings’, BMC Psychiatry. https://doi.org/10.1186/s12888-016-0922-6

[31] Demmler, J.C., Atkinson, M.D., Reinhold, E.J., Choy, E., Lyons, R.A. and Brophy, S.T. (2019) ‘Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case–control comparison’, BMJ Open. https://doi.org/10.1136/bmjopen-2019-031365

[32] Bianchi Sanches, S.H., Osório, F.D.L., Udina, M., Martín-Santos, R. and Crippa, J.A.S. (2012) ‘Anxiety and joint hypermobility association: a systematic review’, Revista Brasileira de Psiquiatria. https://doi.org/10.1590/s1516-44462012000500005

[33] Alsakarneh, S., Al Ta’ani, O., Madi, M.Y., Syn, W., Ruffle, J.K., Aziz, Q. et al. (2025) ‘Comprehensive Risk Profile of Gastrointestinal and Extra Articular Comorbidities in Ehlers–Danlos Syndrome: A Propensity‐Matched Analysis of 118,256 Individuals’, Alimentary Pharmacology & Therapeutics. https://doi.org/10.1111/apt.70506

[34] Orenius, T., Kautiainen, H., Louhi, M., Montin, L., Bulbena, A. and Lindgren, K.A. (2022) ‘Health-Related Quality of Life and Psychological Distress in Patients With Hypermobility Type Ehlers-Danlos Syndrome’, Sage Open. https://doi.org/10.1177/21582440221091237

[35] Choudhary, A., Fikree, A., Ruffle, J.K., Takahashi, K., Palsson, O.S., Aziz, I. et al. (2024) ‘A machine learning approach to stratify patients with hypermobile Ehlers‐Danlos syndrome/hypermobility spectrum disorders according to disorders of gut brain interaction, comorbidities and quality of life’, Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.14957

[36] Collins Hutchinson, M.L., Liang, E., Fuster, E. and Blitshteyn, S. (2025) ‘Autonomic symptom burden, comorbidities and quality of life in women with Hypermobility Spectrum Disorders and hypermobile Ehlers-Danlos syndrome’, Autonomic Neuroscience. https://doi.org/10.1016/j.autneu.2025.103356

[37] Eccles, J.A., Quadt, L., McCarthy, H., Davies, K.A., Bond, R., David, A.S. et al. (2022) ‘Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case–control study’, BMJ Open. https://doi.org/10.1136/bmjopen-2022-066130

[38] Eccles, J.A., Scott, H.E., Davies, K.A., Bond, R., David, A.S., Harrison, N.A. et al. (2020) ‘Joint hypermobility and its relevance to common mental illness in adolescents: a population-based longitudinal study’. https://doi.org/10.1101/2020.09.14.20191130

[39] Song, J.Z., Luong, D., Feldman, E.C.H., Tran, S., Perrier, L., Eubanks, K. et al. (2023) ‘Psychological interventions for individuals with Ehlers-Danlos syndrome and hypermobility spectrum disorder: a scoping review’, Orphanet Journal of Rare Diseases. https://doi.org/10.1186/s13023-023-02799-y

[40] Blitshteyn, S. (2025) ‘Dysautonomia: a common comorbidity of systemic disease’, Immunologic Research. https://doi.org/10.1007/s12026-025-09661-2

[41] Igharo, D., Thiel, J.C., Rolke, R., Akkaya, M., Weis, J., Katona, I. et al. (2022) ‘Skin biopsy reveals generalized small fibre neuropathy in hypermobile Ehlers–Danlos syndromes’, European Journal of Neurology. https://doi.org/10.1111/ene.15649

[42] Dell’Aversana, D., Provitera, V., Trinchillo, A., Masciarelli, F., Tozza, S., Caporaso, G. et al. (2026) ‘Distinct sensory and autonomic involvement in hypermobile Ehlers–Danlos syndrome compared with idiopathic small fiber neuropathy: a multimodal study’, Scientific Reports. https://doi.org/10.1038/s41598-026-60461-6

[43] Daylor, V., Griggs, M., Weintraub, A., Byrd, R., Petrucci, T., Huff, M. et al. (2025) ‘Defining the Chronic Complexities of hEDS and HSD: A Global Survey of Diagnostic Challenges, Life-Long Comorbidities, and Unmet Needs’, Journal of Clinical Medicine. https://doi.org/10.3390/jcm14165636

[44] Hill, J.C., Cascante, D.C. and Breazeale, J. (2025) ‘Surviving their stripes: the diagnostic odyssey and impact of life with hypermobile Ehlers-Danlos syndrome’, BMJ Connections Clinical Genetics and Genomics. https://doi.org/10.1136/bmjccgg-2025-000044

[45] Eccles, J.A., Thompson, B., Themelis, K., Amato, M.L., Stocks, R., Pound, A. et al. (2021) ‘Beyond bones: The relevance of variants of connective tissue (hypermobility) to fibromyalgia, ME/CFS and controversies surrounding diagnostic classification: an observational study’, Clinical Medicine. https://doi.org/10.7861/clinmed.2020-0743

[46] Eccles, J.A. and Davies, K.A. (2021) ‘The challenges of chronic pain and fatigue’, Clinical Medicine. https://doi.org/10.7861/clinmed.2020-1009

[47] Montemayor Zarazúa, A.P., Elizondo Solis, C.V., Ayala García, C., Pacheco Estrella, D.J., Ilizaliturri Guerra, O., Arana Guajardo, A.C. et al. (2026) ‘Linking central sensitization to multisystemic manifestations in hypermobile Ehlers-Danlos syndrome’, Frontiers in Pain Research. https://doi.org/10.3389/fpain.2026.1799439

[48] Eccles, J.A., Owens, A.P., Mathias, C.J., Umeda, S. and Critchley, H.D. (2015) ‘Neurovisceral phenotypes in the expression of psychiatric symptoms’, Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2015.00004

[49] Fedorowski, A. (2018) ‘Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management’, Journal of Internal Medicine. https://doi.org/10.1111/joim.12852

[50] Schubert‐Hjalmarsson, E., Fasth, A., Ickmans, K., Söderpalm, A. and Lundberg, M. (2024) ‘Exploring signs of central sensitization in adolescents with hypermobility Spectrum disorder or hypermobile Ehlers‐Danlos syndrome’, European Journal of Pain. https://doi.org/10.1002/ejp.4754

[51] Csecs, J.L.L., Iodice, V., Rae, C.L., Brooke, A., Simmons, R., Quadt, L. et al. (2022) ‘Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain’, Frontiers in Psychiatry. https://doi.org/10.3389/fpsyt.2021.786916

[52] Baeza-Velasco, C., Vergne, J., Poli, M., Kalisch, L. and Calati, R. (2025) ‘Autism in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers–Danlos syndromes: A systematic review and prevalence meta-analyses’, Autism. https://doi.org/10.1177/13623613251328059

[53] Eccles, J., Tung, J., Harrison, N., Mathias, C. and Critchley, H. (2017) ‘Joint Hypermobility Syndrome and Anxiety Disorder: Structural Brain Correlates’, European Psychiatry. https://doi.org/10.1016/j.eurpsy.2017.01.2246

[54] Hoogman, M., Bralten, J., Hibar, D.P., Mennes, M., Zwiers, M.P., Schweren, L.S.J. et al. (2017) ‘Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis’, The Lancet Psychiatry. https://doi.org/10.1016/s2215-0366(17)30049-4

[55] Angelescu, I., Brugger, S.P., Borgan, F., Kaar, S.J. and Howes, O.D. (2021) ‘The magnitude and variability of brain structural alterations in bipolar disorder: A double meta-analysis of 5534 patients and 6651 healthy controls’, Journal of Affective Disorders. https://doi.org/10.1016/j.jad.2021.04.090

[56] Schulze, L., Schmahl, C. and Niedtfeld, I. (2016) ‘Neural Correlates of Disturbed Emotion Processing in Borderline Personality Disorder: A Multimodal Meta-Analysis’, Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2015.03.027

[57] Bonaz, B., Lane, R.D., Oshinsky, M.L., Kenny, P.J., Sinha, R., Mayer, E.A. et al. (2021) ‘Diseases, Disorders, and Comorbidities of Interoception’, Trends in Neurosciences. https://doi.org/10.1016/j.tins.2020.09.009

[58] Fermin, A.S.R., Sasaoka, T., Maekawa, T., Chan, H.L., Machizawa, M.G., Okada, G. et al. (2023) ‘Insula neuroanatomical networks predict interoceptive awareness’, Heliyon. https://doi.org/10.1016/j.heliyon.2023.e18307

[59] Akaras, E., Deniz, G., Eymir, M. and Sönmez, M. (2025) ‘The effects of joint hypermobility on strength, proprioception, and functional performance’, Scientific Reports. https://doi.org/10.1038/s41598-025-24199-x

[60] ALMohiza, M.A. and Reddy, R.S. (2025) ‘Exploring the dynamics of stability and lumbar proprioception in hypermobility syndrome: a comparative and mediation analysis’, Journal of Orthopaedic Surgery and Research. https://doi.org/10.1186/s13018-025-05683-6

[61] Wang, Y., Strutton, P.H. and Alexander, C.M. (2025) ‘Falls and balance impairment; what and how has this been measured in adults with joint hypermobility? A scoping review’, BMC Musculoskeletal Disorders. https://doi.org/10.1186/s12891-025-08318-3

[62] Bulbena, A., Rosado, S., Cabaleiro, M., Martinez, M., Baeza-Velasco, C., Martin, L.M. et al. (2023) ‘Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers–Danlos syndrome’, Frontiers in Medicine. https://doi.org/10.3389/fmed.2023.1039223

[63] Shaw, B.H., Stiles, L.E., Bourne, K., Green, E.A., Shibao, C.A., Okamoto, L.E. et al. (2019) ‘The face of postural tachycardia syndrome – insights from a large cross‐sectional online community‐based survey’, Journal of Internal Medicine. https://doi.org/10.1111/joim.12895

[64] Gunning, W.T., Kvale, H., Kramer, P.M., Karabin, B.L. and Grubb, B.P. (2019) ‘Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G‐Protein Coupled Receptor Autoantibodies’, Journal of the American Heart Association. https://doi.org/10.1161/jaha.119.013602

[65] Andrew J Muzyk, B.B.K. (2015) ‘Manifestations of Anxiety Explaining Tachycardia and Hypertension in a Patient with POTS’, Family Medicine & Medical Science Research. https://doi.org/10.4172/2327-4972.1000153

[66] Kesserwani, H. (2020) ‘Postural Orthostatic Tachycardia Syndrome Misdiagnosed as Anxiety: A Case Report with a Review of Therapy and Pathophysiology’, Cureus. https://doi.org/10.7759/cureus.10881

[67] Kanjwal, K., Saeed, B., Karabin, B., Kanjwal, Y. and Grubb, B.P. (2011) ‘Clinical presentation and management of patients with hyperadrenergic postural orthostatic tachycardia syndrome. A single center experience’, Cardiology Journal. https://doi.org/10.5603/cj.2011.0008

[68] Westerman, M., Kafkas, A., Parry-Jones, A., Strong, S., Retzler, C. and Hallam, G. (2025) ‘Neurobiological and neuropsychological disturbance in EDS’, Frontiers in Neurology. https://doi.org/10.3389/fneur.2025.1648702

[69] Desai, M.J., Brestle, M. and Jonely, H. (2024) ‘Evidence for central sensitization as classified by the central sensitization inventory in patients with pain and hypermobility’, Pain Practice. https://doi.org/10.1111/papr.13411

[70] Alomari, M., Hitawala, A., Chadalavada, P., Covut, F., Al Momani, L., Khazaaleh, S. et al. (2020) ‘Prevalence and Predictors of Gastrointestinal Dysmotility in Patients with Hypermobile Ehlers-Danlos Syndrome: A Tertiary Care Center Experience’, Cureus. https://doi.org/10.7759/cureus.7881

[71] Thwaites, P.A., Gibson, P.R. and Burgell, R.E. (2022) ‘Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know’, Journal of Gastroenterology and Hepatology. https://doi.org/10.1111/jgh.15927

[72] Cryan, J.F., O’Riordan, K.J., Cowan, C.S.M., Sandhu, K.V., Bastiaanssen, T.F.S., Boehme, M. et al. (2019) ‘The Microbiota-Gut-Brain Axis’, Physiological Reviews. https://doi.org/10.1152/physrev.00018.2018

[73] Breit, S., Kupferberg, A., Rogler, G. and Hasler, G. (2018) ‘Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders’, Frontiers in Psychiatry. https://doi.org/10.3389/fpsyt.2018.00044

[74] Aziz, Q., Harris, L.A., Goodman, B.P., Simrén, M. and Shin, A. (2025) ‘AGA Clinical Practice Update on GI Manifestations and Autonomic or Immune Dysfunction in Hypermobile Ehlers-Danlos Syndrome: Expert Review’, Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2025.02.015

[75] Wang, E., Ganti, T., Vaou, E. and Hohler, A. (2021) ‘The relationship between mast cell activation syndrome, postural tachycardia syndrome, and Ehlers-Danlos syndrome’, Allergy and Asthma Proceedings. https://doi.org/10.2500/aap.2021.42.210022

[76] Weinstock, L.B., Nelson, R.M. and Blitshteyn, S. (2023) ‘Neuropsychiatric Manifestations of Mast Cell Activation Syndrome and Response to Mast-Cell-Directed Treatment: A Case Series’, Journal of Personalized Medicine. https://doi.org/10.3390/jpm13111562

[77] Grattan, C.E.H. (2020) ‘Mast Cell Activation Syndrome (MCAS)’, Postural Tachycardia Syndrome. https://doi.org/10.1007/978-3-030-54165-1_21

[78] Kucharik, A.H. and Chang, C. (2019) ‘The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS)’, Clinical Reviews in Allergy & Immunology. https://doi.org/10.1007/s12016-019-08755-8

[79] Monaco, A., Choi, D., Uzun, S., Maitland, A. and Riley, B. (2022) ‘Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature’, Immunologic Research. https://doi.org/10.1007/s12026-022-09280-1

[80] Castells, M., Giannetti, M.P., Hamilton, M.J., Novak, P., Pozdnyakova, O., Nicoloro-SantaBarbara, J. et al. (2024) ‘Mast cell activation syndrome: Current understanding and research needs’, Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2024.05.025

[81] Lauritano, D., Mastrangelo, F., D’Ovidio, C., Ronconi, G., Caraffa, A., Gallenga, C.E. et al. (2023) ‘Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines’, International Journal of Molecular Sciences. https://doi.org/10.3390/ijms24054811

[82] Aitella, E., Neri, L., Azzellino, G., Romano, C., De Martinis, M., Roncone, R. et al. (2026) ‘Role of Mast Cells and Neuroinflammation in Neuropsychiatric Disorders of the Developmental Period’, Biomolecules. https://doi.org/10.3390/biom16040530

[83] Csecs, J.L.L., lodice, V., Rae, C.L., Brooke, A., Simmons, R., Dowell, N.G. et al. (2020) ‘Increased rate of joint hypermobility in autism and related neurodevelopmental conditions is linked to dysautonomia and pain’. https://doi.org/10.1101/2020.09.14.20194118

[84] Koreki, A., Eccles, J., Garfinkel, S., Critchley, H., Cope, S., Agrawal, N. et al. (2022) ‘Hypermobility in patients with functional seizures: Toward a pathobiological understanding of complex conditions’, Epilepsy & Behavior. https://doi.org/10.1016/j.yebeh.2022.108710

[85] Bucknill, E., Quadt, L., Dew, R., Colasanti, A., Muller-Pollard, C.S., Critchley, H.D. et al. (2026) ‘Embracing complexity: connecting bipolar affective disorder, joint hypermobility and neurodivergence’, The British Journal of Psychiatry. https://doi.org/10.1192/bjp.2025.10483

[86] Eccles, J., Harrison, N. and Critchley, H. (2011) ‘Psychiatric manifestations’, BMJ. https://doi.org/10.1136/bmj.d998

[87] Halverson, C.M.E., Cao, S., Perkins, S.M. and Francomano, C.A. (2023) ‘Comorbidity, misdiagnoses, and the diagnostic odyssey in patients with hypermobile Ehlers-Danlos syndrome’, Genetics in Medicine Open. https://doi.org/10.1016/j.gimo.2023.100812

[88] Halverson, C.M.E., Clayton, E.W., Garcia Sierra, A. and Francomano, C. (2021) ‘Patients with Ehlers–Danlos syndrome on the diagnostic odyssey: Rethinking complexity and difficulty as a hero’s journey’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31935

[89] Clark, N.L., Kainth, G.S., Johnson, M., Rangan, A., Kottam, L. and Swainston, K. (2023) ‘Psychological interventions to improve pain, fatigue, anxiety, depression, and quality of life in children and adults with hypermobility spectrum disorders and Ehlers-Danlos syndrome: a systematic review’, Rheumatology International. https://doi.org/10.1007/s00296-023-05503-2

[90] Bulbena, A., Pailhez, G., Bulbena-Cabré, A., Mallorquí-Bagué, N. and Baeza-Velasco, C. (2015) ‘Joint Hypermobility, Anxiety and Psychosomatics: Two and a Half Decades of Progress Toward a New Phenotype’, Advances in Psychosomatic Medicine. https://doi.org/10.1159/000369113

[91] Giorgi, F. and Tedeschi, R. (2025) ‘Breathe better, live better: the science of slow breathing and heart rate variability’, Acta Neurologica Belgica. https://doi.org/10.1007/s13760-025-02789-w

[92] Garreth Brittain, M., Flanagan, S., Foreman, L. and Teran-Wodzinski, P. (2023) ‘Physical therapy interventions in generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome: a scoping review’, Disability and Rehabilitation. https://doi.org/10.1080/09638288.2023.2216028

[93] Engelbert, R.H.H., Juul‐Kristensen, B., Pacey, V., de Wandele, I., Smeenk, S., Woinarosky, N. et al. (2017) ‘The evidence‐based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome’, American Journal of Medical Genetics Part C: Seminars in Medical Genetics. https://doi.org/10.1002/ajmg.c.31545

[94] Palmer, S., Davey, I., Oliver, L., Preece, A., Sowerby, L. and House, S. (2020) ‘The effectiveness of conservative interventions for the management of syndromic hypermobility: a systematic literature review’, Clinical Rheumatology. https://doi.org/10.1007/s10067-020-05284-0

[95] Chen, Y.F., Huang, X.Y., Chien, C.H. and Cheng, J.F. (2016) ‘The Effectiveness of Diaphragmatic Breathing Relaxation Training for Reducing Anxiety’, Perspectives in Psychiatric Care. https://doi.org/10.1111/ppc.12184

[96] Saito, R., Yoshida, K., Sawamura, D., Watanabe, A., Tokikuni, Y. and Sakai, S. (2024) ‘Effects of Heart Rate Variability Biofeedback Training on Anxiety Reduction and Brain Activity: a Randomized Active-Controlled Study Using EEG’, Applied Psychophysiology and Biofeedback. https://doi.org/10.1007/s10484-024-09650-5

[97] Bohling‐Davis, E., Khan‐Lodhi, B., Jenkinson, E., Tremblett, M. and Meyrick, J. (2025) ‘Quality of Life With Ehlers‐Danlos Syndrome/Joint Hypermobility Syndrome: A Systematic Review of Psychosocial Interventions’, Musculoskeletal Care. https://doi.org/10.1002/msc.70070

[98] Wetherell, J.L., Afari, N., Rutledge, T., Sorrell, J.T., Stoddard, J.A., Petkus, A.J. et al. (2011) ‘A randomized, controlled trial of acceptance and commitment therapy and cognitive-behavioral therapy for chronic pain’, Pain. https://doi.org/10.1016/j.pain.2011.05.016

[99] Ye, L., Li, Y., Deng, Q., Zhao, X., Zhong, L. and Yang, L. (2024) ‘Acceptance and commitment therapy for patients with chronic pain: A systematic review and meta-analysis on psychological outcomes and quality of life’, PLOS ONE. https://doi.org/10.1371/journal.pone.0301226

[100] Frederiksen, K.P., Stavestrand, S.H., Venemyr, S.K., Sirevåg, K. and Hovland, A. (2021) ‘Physical exercise as an add-on treatment to cognitive behavioural therapy for anxiety: a systematic review’, Behavioural and Cognitive Psychotherapy. https://doi.org/10.1017/s1352465821000126

[101] Davies, G., Csecs, J.L.L., Ball, H., Dare, J., Bremner, S., Hosking, R. et al. (2021) ‘Altering Dynamics of Autonomic Processing Therapy (ADAPT) trial: a novel, targeted treatment for reducing anxiety in joint hypermobility’, Trials. https://doi.org/10.1186/s13063-021-05555-4

[102] Jakubovski, E., Johnson, J.A., Nasir, M., Müller-Vahl, K. and Bloch, M.H. (2018) ‘Systematic review and meta-analysis: Dose-response curve of SSRIs and SNRIs in anxiety disorders’, Depression and Anxiety. https://doi.org/10.1002/da.22854

[103] Habibian, S., Pacey, V., Chan, C., Hakim, A.J. and Williams, C.M. (2025) ‘Priority Musculoskeletal Health Research Questions for People With Generalized Joint Hypermobility: An International Delphi Study’, Arthritis Care & Research. https://doi.org/10.1002/acr.25501