Why Does Hypermobility Cause So Much Anxiety?
It’s not uncommon for people with hypermobility and EDS to feel anxious. Often deeply, chronically, sometimes inexplicably anxious. The kind of anxiety that doesn’t fully match the circumstances. The kind that flares when you stand up too quickly, or after a bad night’s sleep, or seemingly out of nowhere on a Tuesday afternoon when nothing particularly alarming has happened.
And if you’ve spent any time looking for answers online, you’ll already know what the standard advice looks like. Breathe deeply. Try meditation. Cut back on caffeine. Journaling. Therapy. All reasonable suggestions for anxiety in the general population. But if you’re hypermobile, there’s a very good chance you’ve tried most of these things and found them helpful only at the margins, because the anxiety you’re dealing with is not simply a psychological response to the stress of life. It is, at least in significant part, a direct product of what your nervous system, your connective tissue, and your body’s chemistry are doing every single day.
That distinction matters enormously. And it is almost entirely absent from existing advice.
So the purpose of this article is to go deep. Not surface level deep. Actually deep. We’re going to look at the real biological reasons why anxiety and hypermobility are so tightly linked, covering everything from the structure of your brain, to how your autonomic nervous system misfires, to the role of immune cells most people have never heard of. We’ll cover what the research actually says, how strong that research is, and what you can practically do about all of it. This is not a quick fix listicle. It is a thorough, honest account of one of the most underappreciated connections in the hypermobility world.
Fair warning: this is a very long article. Quite possibly the longest thing you’ve read this year about your own health. I haven’t written it yet as I type this sentence, but I already know it’s going to be something of a beast. The full spectrum of what hypermobility does to the body and nervous system spans so many interconnected systems that there’s genuinely no short version that does it justice.
Here’s also what we are NOT going to cover in depth, because this article has to stop somewhere: we won’t go into the full neurodivergence hypermobility overlap (that deserves its own article entirely), and we’ll only briefly touch on practical management before the full practical guide later in the article. So if you are a little nerdy and love absorbing knowledge, strap in.
The Quick Statistics (So We’re All on the Same Page)
Before we get into the biology, it’s worth establishing just how strong the link actually is, so nobody is in any doubt that we’re talking about a real, robust association rather than anecdotal pattern.
People with hypermobility are roughly four times more likely to be diagnosed with an anxiety disorder than non-hypermobile individuals [1]. One systematic review found anxiety prevalence of up to 51.2% across EDS cohorts [2]. A landmark 15 year prospective cohort study, the best quality evidence available on this question, found that hypermobile individuals had a relative risk of 22.3 for developing panic disorder or agoraphobia compared to non-hypermobile controls [3]. For context, that is not a small effect. That is an enormous one.
And these numbers aren’t generated by the anxiety of having a chronic illness, important as that psychological burden is. They appear in non-clinical populations. They appear in adolescents before the full weight of diagnosis and medical odyssey accumulates. They appear across multiple countries, multiple study designs, and multiple decades of research. This is not coincidence. Something structural and biological is driving it.
That something is what we’re here to understand.
The Numbers: How Common Is Anxiety in Hypermobility?
Let’s spend a moment with the evidence properly, because the numbers here are striking enough to deserve their own section. If you’ve ever felt like your anxiety was disproportionate to your circumstances, or wondered whether it was somehow connected to your body rather than your psychology, the research will likely feel quite validating.
The Bulbena Studies: Three Decades of Evidence
The person who arguably started all of this is a Spanish psychiatrist named Dr Antonio Bulbena. Back in 1993, he and his colleagues published what appears to be the first formal case-control study looking at anxiety in joint hypermobility syndrome. What they found was striking: roughly 70% of hypermobile rheumatology outpatients had some form of anxiety disorder, compared to 22% in non-hypermobile controls [4]. The exact sample size from this paper hasn’t been confirmed from the full text, as it’s abstract-only accessible, so treat the 70% figure as a ballpark rather than a precise estimate. But even as a rough figure, it announced something significant.
Five years later, the same research group turned the question around. Instead of starting with hypermobile patients and looking for anxiety, they started with anxiety patients and looked for hypermobility. The finding was equally striking: approximately 70% of people with panic disorder and/or agoraphobia had joint hypermobility syndrome, compared to just 10% of healthy controls [5]. Secondary sources suggest this represented a 16-fold increase in the odds of JHS in panic disorder patients compared to other outpatients after controlling for age and sex, though these exact figures should be treated with some caution as they come via review citations rather than direct full-text access.
These early studies raised the obvious question: is this just because having a painful, complex condition makes people anxious? A reasonable and important challenge. So in 2004, Bulbena’s group studied a non-clinical population, not patients in rheumatology or psychiatry clinics, but ordinary people in the community. And the relationship held: individuals with hypermobility scored significantly higher on state anxiety, trait anxiety, and social anxiety scales [6]. The anxiety-hypermobility connection was not simply a consequence of being ill.
The most methodologically rigorous study in this series came in 2011: a 15-year prospective cohort study starting with 158 participants aged 16 to 20 from a Spanish rural town. Of these, 29 had joint hypermobility syndrome. Anyone with anxiety at baseline was excluded, so the study was tracking who developed anxiety over the following 15 years, starting from a clean slate. The results are remarkable. By the 15-year follow-up, 41.4% of the hypermobile group had developed panic disorder or agoraphobia, compared to just 1.9% of controls. The relative risk was 22.3 (95% CI: 4.6-108.7, P<0.0001) [3].
Let that land for a moment. Hypermobile individuals were not just slightly more likely to develop anxiety. They were over twenty times more likely to develop panic disorder or agoraphobia compared to their non-hypermobile peers. The same study found nearly fourfold higher anxiolytic drug use in the JHS group, and significantly elevated rates of social phobia (relative risk 6.52) and simple phobia (relative risk 3.31).
Now, there are limitations. The sample was relatively small (only 29 people in the JHS group), drawn from a single Spanish rural town, which limits how confidently we can generalise. The dropout rates over 15 years weren’t fully reported. But the effect sizes are so large that even with these caveats, the finding is hard to dismiss.
The Latest Evidence
The more recent research has, if anything, strengthened the picture. In 2022, a systematic review by Kennedy and colleagues covering 23 studies found anxiety prevalence of up to 51.2% across EDS cohorts, making it one of the highest-prevalence psychiatric comorbidities in the condition [2]. For comparison, depression prevalence was reported at 30.2% in the same review.
A Swedish nationwide registry study by Cederlöf and colleagues, covering 1,771 people with EDS compared against 17,710 matched controls, found dramatically elevated risk ratios for a range of psychiatric conditions: ASD at 7.4 times the rate, ADHD at 5.6 times, and depression at 3.4 times [7]. It’s worth noting that this study did not specifically extract anxiety disorder data from the registry, which is a significant limitation for our purposes, but the broader psychiatric burden it documents is striking.
The most recent high-quality study, published in the British Journal of Psychiatry in 2024 by Kampoureli, Eccles and colleagues, used functional MRI to study 63 participants, finding that hypermobility was present in 60% of those with generalised anxiety disorder, compared to just 21.2% of non-anxious controls. The odds ratio for hypermobility in the anxious group was 4.39 [1]. And this study didn’t just confirm the association, it showed you the brain mechanisms driving it, which we’ll come to shortly.
There’s also a 2022 study by David, Eccles and colleagues that drew on data from over 3,000 adolescents in the AVON longitudinal cohort and found that. Joint hypermobility at around age 14 was associated with significantly elevated odds of developing anxiety disorder by age 18, with an adjusted odds ratio of 3.14 [8]. Critically, this relationship was mediated by autonomic factors, meaning the nervous system dysregulation was doing the work, not simply the psychological distress of being different or having pain.
What These Numbers Actually Mean for You
Here is the point that I want to be absolutely clear about, because it matters both practically and psychologically: if you are hypermobile and anxious, your anxiety is not a character flaw, not a sign of psychological weakness, and not simply a reasonable response to a difficult life situation. It is, in substantial part, a predictable consequence of the biology you were born with.
That does not mean psychology is irrelevant. It very much isn’t, and we’ll get to the psychological layers later. But it does mean that approaching anxiety in hypermobility purely as a psychological problem, treatable by psychological means alone, is likely to leave a lot of the picture unaddressed. Why anxiety is so disproportionately common in hypermobile individuals is not a mystery with a vague answer. It is a question with multiple specific, identifiable, biological answers. And those answers are what the next several sections are about.
Your Brain on Hypermobility: The Amygdala Connection
Of all the biological explanations for the hypermobility-anxiety link, the neurological one is perhaps the most fascinating, and in some ways the most unexpected. It turns out that hypermobile people’s brains are physically different from non-hypermobile brains, in a way that predicts higher anxiety vulnerability.
The Amygdala: Your Body’s Threat Detection System
The amygdala is a small, almond-shaped structure deep in the brain, one on each side, and it is your central threat-detection system. Think of it as the brain’s smoke alarm. Its primary job is to detect potential danger, trigger a fear response, and mobilise the body for protective action. When the amygdala fires, the heart rate goes up, breathing quickens, muscles tense, attention narrows, and adrenaline floods the system. In genuine danger, this is exactly what you want.
The problem comes when the smoke alarm is too sensitive. When it goes off not just for actual fires, but for burnt toast, for the smell of someone else’s cooking, for the idea of cooking. When the threshold for activation is low enough that the alarm is firing more or less constantly, the result is what we experience as chronic anxiety.
In 2012, Dr Jessica Eccles and colleagues published a structural MRI study of 72 healthy volunteers, 36 hypermobile and 36 non-hypermobile, matched for age and sex. They measured brain volumes using voxel-based morphometry, a technique that analyses regional grey matter density across the whole brain. What they found was that the hypermobile group had significantly larger bilateral amygdala volumes. The left amygdala showed a Cohen’s d of 0.80, and the right amygdala showed a Cohen’s d of 0.85 [9].
For reference, Cohen’s d of 0.80 is considered a large effect size in psychological and neuroimaging research. Effect sizes of this magnitude are comparable to, or larger than, those seen in clinical psychiatric populations. And crucially, this was a non-clinical sample: these were healthy volunteers, not people who had been diagnosed with anxiety disorders. Their amygdalae were structurally enlarged regardless of whether they were currently anxious.
This matters because it suggests the enlarged amygdala is not simply a consequence of living with anxiety. It appears to be a constitutional feature, something built into the hypermobile nervous system from the start, that then predisposes to anxiety. How exercise acts directly on the amygdala and anxiety circuits in hypermobility is one of the reasons why certain management strategies are more effective than others in this population, and we’ll return to that later in this article.
Why Bigger Doesn’t Mean Better
You might think a larger amygdala would be an advantage, a more powerful threat-detector. But this is one of those situations where more is not better. A larger, more reactive amygdala is essentially a hair-trigger alarm system. It detects threats earlier, more frequently, and with less provocation than a normally-sized one. The result is not enhanced protection from danger. The result is a chronically elevated state of threat readiness that, over time, becomes indistinguishable from anxiety.
The 2024 Kampoureli and Eccles fMRI study expanded on this with important new findings. In a group of 63 participants, they found that when the hypermobile group with generalised anxiety disorder was asked to process emotional stimuli, both the left amygdala and the right mid insula showed significantly amplified activity compared to all other groups [1]. The interaction between hypermobility and anxiety appeared to act multiplicatively on these brain regions, not just additively. Being hypermobile made the anxious brain more reactive than you’d expect from anxiety alone.
There’s also a useful analogy here that I find helps to make this concrete. Imagine a smoke detector that has been wired to be slightly more sensitive than the factory standard. In a normal house, this might occasionally cause an annoying false alarm when you make toast. But if that same detector is installed in a kitchen where the cooking fumes are heavier than average, the false alarms become constant. The amygdala in hypermobility is the oversensitive detector. The rest of this article is largely about what creates the heavier-than-average fumes.
The Insula and Interoception: Feeling Everything More Intensely
The amygdala doesn’t operate in isolation. It works closely with another region called the insula, particularly the anterior insula, which is the brain’s primary interoceptive cortex. Interoception is the brain’s ability to sense the internal state of the body: heartbeat, breathing, gut sensations, pain, temperature, muscle tension. Everything happening inside you, rather than outside you.
The insula takes in this constant stream of bodily signals, integrates them, and feeds them into your emotional experience. When your heart rate rises, the insula notices. When your stomach is unsettled, the insula notices. When your muscles are tense, the insula notices. And it passes all of this to the amygdala and the emotional processing centres to ask: what does this mean? Are we okay?
In people with hypermobility, the evidence suggests this interoceptive system is both more acute and more prone to generating anxiety-relevant signals. A 2014 study by Mallorquí-Bagué, Garfinkel, Eccles and colleagues, using a combination of psychophysiological measures and fMRI, found that interoceptive sensitivity mediated the relationship between hypermobility and state anxiety [10]. In other words, the more finely tuned the hypermobile person’s internal body sensing, the more anxious they were. The insula of hypermobile participants showed significantly greater reactivity to emotional stimuli: t=5.76 for the right insula, t=3.95 for the left insula, compared to non-hypermobile participants.
The Kampoureli 2024 study built on this finding, showing that the Beighton score (the measure of hypermobility) directly correlated with anterior insula activity in anxious individuals specifically [1]. The more hypermobile you are, the more reactive the anxiety-interoception circuit appears to become.
What does this look like in everyday life? It might look like this: your heart rate picks up slightly because you stood up too fast. A non-hypermobile person’s brain barely registers this. Your brain, with its amplified interoceptive system, notices the heartbeat change acutely. The insula sends the signal upward. The amygdala receives it and asks: is this dangerous? And in the absence of a clear external threat to point to, the brain’s answer is often: maybe. Better stay alert. The result is anxiety without apparent cause, which is one of the most common and distressing features of the hypermobile experience.
This is also where why interoceptive confusion can make anxiety harder to identify and manage becomes relevant: when your internal signals are amplified and sometimes difficult to interpret accurately, distinguishing between a genuine physiological event and an anxiety response becomes genuinely hard. We’ll return to this concept when we discuss POTS, which creates an almost perfect case study of this confusion.
There is a concept from neuroscience called predictive processing that is worth briefly introducing here, because it reframes the whole situation helpfully. The brain, according to this model, doesn’t simply receive sensory information and react. It constantly generates predictions about what it expects to sense, and then updates those predictions based on incoming data. Anxiety, in this framework, arises when the brain’s predictions about bodily safety don’t match the incoming sensory data, or when the incoming data is too ambiguous to generate a confident prediction. A nervous system that receives noisy, imprecise, hard-to-interpret body signals, which is what hypermobility appears to create, is a nervous system that will constantly struggle to generate confident predictions about whether the body is safe. The result is a background hum of unresolved threat that we experience as anxiety.
And here’s the part that really matters practically: none of this is a psychological failing. It is the predictable output of a nervous system architecture that processes body signals differently. Understanding anxiety as a physiological state, not just a psychological one is the essential reframe that makes most of the practical management strategies later in this article make sense.
Proprioception: When Your Body Can’t Find Itself in Space
From the amygdala and the insula, let’s move to a different but closely related mechanism: proprioception. This is, in my view, the most underappreciated explanation for anxiety in hypermobility, and the one that no competitor article has adequately covered. That’s a gap worth filling.
What Is Proprioception and Why Does It Matter?
Proprioception is your body’s position sense. It’s the ability to know where your limbs are in space without looking at them. Close your eyes and touch your nose: that’s proprioception doing the work. Reach into a dark bag and feel for your keys without being able to see them: proprioception again. Walk across an uneven surface without looking at your feet every step: proprioception, continuously, thousands of times a day.
It works through a network of specialised sensory receptors, primarily in the joints, muscles, and connective tissue, that constantly send signals to the brain about joint angle, muscle length, tension, and movement. These signals feed into the somatosensory cortex and, critically, into the cerebellum, which uses them to calculate and predict how the body is moving. The brain’s GPS, essentially, but for your own skeleton.
In a non-hypermobile body, this system is relatively reliable. The proprioceptive signals are consistent, the joint end-ranges are firm, and the brain can maintain a reasonably accurate moment-to-moment model of where the body is and what it is doing. There’s little uncertainty in the system, so there’s little threat signal generated by it.
In a hypermobile body, this system is compromised. The collagen that forms the joint capsules, ligaments, and tendons is more compliant than typical. Joint end-ranges are ill-defined. Joints can move further than the proprioceptive system is calibrated to handle, and often do so silently, without the usual warning signals. The mechanoreceptors in the joint structures may sit in tissue that is stretched, damaged, or simply structurally different, which affects the quality of the signals they generate.
A 2015 study by Jones, Henriques and Clayton tested proprioceptive precision directly in EDS patients versus healthy controls, using a task that required participants to judge felt hand position. EDS patients were significantly less precise in their proprioceptive estimates, and this deficit positively correlated with the severity of joint hypermobility [11]. The more hypermobile the joints, the less accurate the body’s internal position-sensing. The proprioception deficits that keep the threat response activated are a direct consequence of this architecture, and the knock-on effect on anxiety is considerable.
How Poor Proprioception Fuels Anxiety
Here’s where the proprioception-anxiety connection becomes clinically important: the brain requires a degree of certainty about body position to feel safe. Not perfect certainty, but enough confidence in its internal model to function without constant vigilance.
When proprioceptive signals are unreliable, that confidence is undermined. The brain cannot maintain a stable, trustworthy model of where the body is and what state it is in. This doesn’t just cause clumsy movements and a higher risk of sprains. It generates a continuous, low-grade threat signal, because from the brain’s perspective, a body it cannot reliably track is a body in an uncertain, and therefore potentially dangerous, state.
Think of it this way. Imagine you’re responsible for monitoring a complex system, like a power grid, but half your sensors are giving you noisy, unreliable readings. You can’t tell whether the unusual readings represent a real problem or just sensor noise. What do you do? You stay alert. You keep watching. You don’t relax your vigilance, because the cost of missing a real problem is worse than the cost of sustained alertness. That is, essentially, what the brain does when it receives poor proprioceptive information from hypermobile joints. It maintains a state of heightened readiness, because the alternative, assuming everything is fine based on unreliable data, feels risky.
This is exactly the mechanism proposed in a 2024 paper by Eccles, Quadt, Garfinkel and Critchley, published in the Philosophical Transactions of the Royal Society B. Their model proposes that imprecise proprioceptive signals in hypermobility generate elevated prediction error in the brain’s internal models, and that this prediction error, when combined with neurodivergent traits or anxiety vulnerability, produces emotional dysregulation [12]. In plain terms: poor joint sensing creates uncertainty in the brain’s model of the body, and that uncertainty gets experienced as anxiety or emotional lability.
The study found that variant connective tissue specifically determined whether proprioceptive error was linked to emotional dysregulation in neurodivergent individuals. This is a critical finding: it’s not just that hypermobile people are more sensitive or more anxious as a personality trait. It’s that the imprecision of their proprioceptive signals is driving the emotional dysregulation through a specific, identifiable neural mechanism.
Why This Matters More Than Most People Realise
I want to dwell on the practical implications of this for a moment, because they go beyond the purely neurological.
If your body’s position-sensing system is unreliable, your brain is going to allocate substantially more attentional resources to tracking your body. More vigilance to where your joints are. More monitoring of movement. More updating of body maps. This is cognitively expensive, and it happens largely below conscious awareness. The result is a background cognitive load that feels, from the inside, like low-level anxiety or general nervousness, even in situations where nothing externally threatening is happening.
It also creates what I’d call a movement-anxiety feedback loop, and it’s one of the more vicious cycles in hypermobility. Poor proprioception creates uncertainty about movement safety, which generates anxiety about moving, which creates muscle tension and guarding, which further disrupts the quality of proprioceptive signals (because tense muscles don’t transmit joint position information cleanly), which creates more proprioceptive uncertainty, which creates more anxiety about moving. And so on.
There’s also a falls-avoidance dimension. People who have experienced joint instability, subluxations, or unexpected collapses often develop a heightened fear of movement, which psychologists call kinesiophobia. This is entirely rational on one level: if your joints have let you down before, caution makes sense. But the cascade consequence is reduced movement, reduced loading of the proprioceptive system, further deconditioning of the joint sensors, and a worsening of the underlying proprioceptive deficit. The anxiety drives the deconditioning that makes the anxiety worse.
I appreciate this probably sounds grim. But it matters to understand this cycle clearly, because it means that some of the most effective anxiety interventions for hypermobile people are not primarily psychological at all. They are physical. Specifically, they involve the role of proprioceptive training in calming a sensitised nervous system: structured exercise and stability work that rebuilds the proprioceptive signals the nervous system is starving for. We’ll get to that later in this article.
For now, the key point is this: you may have been told your anxiety is in your head. And in a technical sense, all anxiety is processed in the brain. But the inputs driving it can come from the body, through mechanisms that are structural, measurable, and independent of your psychological state. The anxious proprioceptive loop is one of those mechanisms, and it is almost entirely ignored in standard anxiety treatment.
POTS, Dysautonomia, and the Anxiety Impersonator
If there is one section in this article that I could require every general practitioner to read before they next see a hypermobile patient complaining of anxiety, it would be this one.
Postural Orthostatic Tachycardia Syndrome, almost universally known as POTS, is a form of dysautonomia, meaning a dysregulation of the autonomic nervous system, the part of the nervous system that controls unconscious bodily functions like heart rate, blood pressure, digestion, and sweating. In POTS specifically, the problem is an excessive rise in heart rate when moving from lying or sitting to standing.
In adults, POTS is defined by a sustained heart rate increase of more than 30 beats per minute on standing, without a corresponding drop in blood pressure, within 10 minutes of upright position [13]. In teenagers, the threshold is 40 beats per minute. The mechanism, in simplest terms, involves blood pooling in the lower body on standing (particularly relevant in hypermobility because compliant vascular walls are part of the connective tissue picture), insufficient compensatory vasoconstriction, and a compensatory surge of adrenaline (noradrenaline) to try to maintain cardiac output.
It is that adrenaline surge that concerns us here.
When Your Nervous System Can’t Regulate Itself
The autonomic nervous system has two main branches: the sympathetic branch (fight-or-flight, acceleration) and the parasympathetic branch (rest-and-digest, deceleration). In a well-regulated nervous system, these two branches work in dynamic balance, deploying the accelerator when needed and applying the brakes when appropriate. In dysautonomia, this balance is disrupted. The autonomic nervous system becomes poorly regulated, spending too much time in sympathetic overdrive and not enough time in parasympathetic recovery.
This isn’t just physiologically uncomfortable. It is, from a subjective experience standpoint, almost indistinguishable from anxiety.
The adrenaline surge of a POTS episode creates: racing heart, chest tightness, breathlessness, dizziness, tremor, sweating, a feeling of impending doom or dread. Every single one of these is also a symptom of a panic attack. Not similar. Essentially identical. And because hypermobile individuals may have very few conscious reasons to be anxious at the time these episodes occur, the brain, desperately trying to make sense of the physiological state it finds itself in, will often construct an anxiety narrative to explain it. Something must be wrong. You must be anxious about something. What is it?
This is what researchers like Dr Eccles and colleagues have described as the “cardiac anxiety cycle”: palpitations generate catastrophisation, catastrophisation generates hyperventilation, hyperventilation generates more palpitations, and the whole thing spirals into what looks, from the outside and sometimes from the inside, like a full-blown panic attack [14]. The autonomic dysfunction that underlies both brain fog and anxiety in POTS patients is often the same mechanism driving both sets of symptoms simultaneously.
The prevalence of dysautonomia in hypermobility is significant. A 2022 study by Csecs and colleagues found that 50-51% of neurodivergent adults had hypermobility had symptoms meeting JHS criteria, and that joint hypermobility specifically mediated the relationship between neurodivergence and autonomic dysfunction [15]. A 2021 cross-sectional study by Eccles and colleagues found that 38% of mental health clinic patients had generalised joint laxity, compared to 19% in the general population (odds ratio 2.54), and critically, that symptoms of orthostatic intolerance mediated the relationship between hypermobility and anxiety disorder diagnosis [16]. Dysautonomia is not just a comorbidity of hypermobility. It is a mechanistic pathway between hypermobility and clinical anxiety.
Why POTS Gets Misdiagnosed as Anxiety
The symptom overlap between POTS and anxiety is so complete that misdiagnosis is the norm rather than the exception. Many hypermobile people spend years being told their palpitations, breathlessness, and panic-like episodes are anxiety, being prescribed anxiolytics and antidepressants that don’t address the underlying physiology, being referred to psychologists for problems that have a substantial autonomic component.
I have lost count of the number of people I have spoken with who were told, often for years, that their episodes were panic attacks, and who only discovered the POTS explanation when they happened to sit down, take their pulse while standing, and realise that their heart rate was climbing 40 or 50 beats per minute for no obvious psychological reason. That moment of recognition is often described as one of the most significant turning points in their understanding of their own body.
This is not a trivial problem. The damage from misdiagnosis is real and multifaceted. It delays appropriate treatment, obviously. But it also creates what researchers have called iatrogenic harm, harm caused by the healthcare system itself. Being told repeatedly that your physical symptoms are psychological, when they are not primarily psychological, erodes trust in both clinicians and in your own perception of your body. It creates a specific kind of anxiety: health anxiety driven by the fear of being dismissed again, hypervigilance to bodily symptoms born from the experience of those symptoms being repeatedly minimised. Why POTS symptoms so closely mimic a panic attack is explained in detail in our POTS guide, and it’s worth reading if any of this resonates.
There is also a structural brain difference associated with POTS worth knowing about. A 2015 MRI study by Umeda and colleagues found reduced grey matter volume in the left anterior insula in POTS patients, precisely the region we’ve already identified as central to interoceptive processing and the anxiety experience [17]. There were also significant negative correlations between left insula volume and both trait anxiety and depression scores. POTS does not merely generate anxiety symptoms. It appears to structurally alter the brain regions involved in processing and regulating those symptoms.
The picture that emerges from all of this research is that, in hypermobility, the distinction between POTS and anxiety is often artificial. They share mechanisms. They share symptoms. They feed each other. And treating anxiety while ignoring the autonomic dysfunction is like trying to reduce a smoke alarm’s sensitivity without addressing the source of the smoke.
The Adrenaline Paradox
One of the more counter-intuitive aspects of POTS-related anxiety is what I think of as the adrenaline paradox. POTS involves compensatory adrenaline surges precisely because the autonomic system is struggling to maintain adequate perfusion on standing. But those adrenaline surges then generate the very anxiety symptoms that make the hypermobile patient feel more stressed, which activates the sympathetic nervous system further, which worsens the autonomic dysregulation, which triggers more compensatory adrenaline.
It is a closed, self-reinforcing loop. And it is a loop that no amount of cognitive reframing will fully interrupt, because the adrenaline is real, physiologically real, not psychologically generated. This is one of the clearest examples of why low CO₂ creates anxiety-like symptoms from the inside out: the breathing pattern changes associated with POTS-driven adrenaline surges further alter blood chemistry in ways that amplify the anxiety state.
How do you know whether a particular episode of fast heart rate and dread is POTS or panic? There are some practical clues. POTS symptoms are typically positional: they worsen on standing and improve on lying down. A simple active standing test, where you measure heart rate lying down for five minutes and then immediately on standing, and for the following ten minutes, can give you a rough indication. A rise of more than 30 bpm (or more than 40 in teenagers) that is sustained and accompanied by the typical symptoms is suggestive. This is not a substitute for proper medical investigation, including a tilt-table test for formal POTS diagnosis. But it is a starting point for recognising that what you’re experiencing may have an autonomic dimension rather than a purely psychological one.
It is also important to note that POTS and genuine anxiety disorder are not mutually exclusive. Many hypermobile people have both. The POTS generates physiological anxiety symptoms, which then contribute to genuine anxiety disorder through the psychological mechanisms we’ll cover shortly (particularly the medical trauma and fear-avoidance sections). So the task is not to decide between POTS and anxiety, but to understand how much of each you’re dealing with, and to address both appropriately.
Mast Cells, Histamine, and the Chemical Side of Anxiety
There is a third biological driver of anxiety in hypermobility that gets almost no attention in standard discussions of the topic: the immune system. Specifically, mast cells and their primary mediator, histamine.
This section is going to sound like we’ve gone quite far from the world of joints and connective tissue. We haven’t. Bear with me.
The MCAS-Hypermobility-Anxiety Triangle
Mast cells are immune cells found throughout the body, particularly in tissues that come into contact with the external environment: the skin, the gut lining, the lungs, and, critically, throughout the brain and nervous system. They’re part of the first-line immune response, stationed like sentinels at the body’s borders and throughout its interior. When activated, they release a cascade of chemical mediators, the most well-known of which is histamine, but also including tryptase, prostaglandins, leukotrienes, interleukins, and various other inflammatory compounds.
In Mast Cell Activation Syndrome (MCAS), these cells activate too readily, releasing their mediators in response to triggers that would not normally cause a reaction: temperature changes, stress, certain foods, hormonal shifts, exercise, or even just standing up. We cover how mast cell overactivation fuels nervous system hyperreactivity in detail in our dedicated MCAS guide, but for the purposes of this section, the key point is the connection between mast cells, histamine, and the anxiety experience.
The overlap between hypermobility, POTS, and MCAS is well documented. A 2022 review by Monaco, Choi, Maitland and colleagues found that approximately 24% of EDS patients had a MCAS diagnosis [18]. Another study cited in the same review found that 66% of patients with both POTS and EDS had symptoms suggestive of mast cell disorder. Nearly one in three MCAS patients had comorbid hEDS in a sample of over 37,000 patients. These three conditions, hypermobility, POTS, and MCAS, form an overlapping triad so commonly seen together that researchers have started treating them as a connected clinical entity.
The question for our purposes is: how does mast cell activation produce anxiety?
How Histamine Directly Affects Your Brain
Histamine is not just an immune chemical. It is also a neurotransmitter. It acts in the brain through at least four receptor subtypes, with H1 and H3 receptors being most relevant here. H1 receptors in the brain are involved in wakefulness, attention, and emotional arousal. When histamine activates H1 receptors, it promotes wakefulness and heightened vigilance. This is why older antihistamines, which cross the blood-brain barrier easily, cause drowsiness. They are blocking histamine’s wake-promoting, vigilance-promoting effects in the brain.
Now consider what happens when mast cells are overactivating and releasing excess histamine. The brain is receiving an abnormally high histamine signal. The result, through H1 receptor activation, is hyperarousal, heightened vigilance, and a state of heightened alertness that is functionally indistinguishable from anxiety. Not metaphorically similar. Physiologically the same state.
Beyond direct receptor effects, histamine also promotes the release of corticotropin-releasing hormone (CRH), which activates the HPA axis (the hypothalamic-pituitary-adrenal axis, your stress response system), generating cortisol and adrenaline. Elevated mast cell activity is therefore not just creating histamine-driven hyperarousal. It is also activating the broader stress hormone cascade. The result is a body in a state of chemically-driven high alert, which maps onto the subjective experience of anxiety very neatly. How mast cells communicate directly with the nervous system through these inflammatory pathways is one of the reasons why the gut-brain immune picture is so clinically important in hypermobility.
The most striking evidence for mast cells as a driver of psychiatric symptoms comes from a 2023 case series by Weinstock, Nelson and Blitshteyn, published in the Journal of Personalized Medicine [19]. They described 8 patients, all previously diagnosed with psychiatric conditions only, who underwent mast-cell-directed treatment. The psychiatric diagnoses present at baseline included generalised anxiety disorder in 5, panic disorder in 4, and depression in 5. After treatment targeting mast cell activation, 6 out of 8 showed complete psychiatric response, meaning resolution of the anxiety, depression, and panic symptoms. The remaining two showed partial or marked improvement.
Now. This is a case series of 8 patients. There is no control group. It is retrospective. The treatments were heterogeneous and included multiple agents simultaneously. The MCAS diagnostic criteria used are themselves somewhat contested. I am not presenting this as definitive proof that MCAS causes psychiatric disease. I am presenting it as a signal, a clinically compelling signal, that in some subset of hypermobile individuals, the mast cell-histamine axis is a significant contributor to the anxiety experience, and that addressing it may produce psychiatric improvements that no amount of cognitive behavioural therapy would have achieved, because the source of the problem is chemical, not cognitive.
What This Means Practically
The practical implication here is not that everyone with hypermobility and anxiety has MCAS, or that antihistamines are the answer to anxiety in this population. Most people with hypermobility and anxiety will not find that H1 blockers resolve their mental health symptoms. But a meaningful subset will, and they are worth identifying.
The pattern to look for is anxiety that comes in waves, with a distinctly physical, inflammatory flavour: flush or heat, brain fog, itching or hives, gastrointestinal symptoms, widespread pain flares, and anxiety or panic episodes that seem to cluster with these other symptoms. Anxiety that is particularly triggered by known MCAS triggers (certain foods, temperature, stress, exercise) rather than by purely psychological stressors. Anxiety that responds unusually well, or unusually poorly, to standard treatments.
If any of this resonates, it may be worth discussing MCAS assessment with your doctor. This is not straightforward, because MCAS remains an area of genuine diagnostic controversy and the testing has significant limitations. But the connection is real enough that it deserves investigation in treatment-resistant cases. How stress hormones directly activate mast cells and drive physical symptoms is one of the feedback loops that makes this particularly relevant in high-stress periods.
The evidence base here is honestly quite small, and I want to be transparent about that. The Weinstock case series is n=8. The mechanistic reasoning for why histamine generates anxiety is solid. The MCAS-hypermobility overlap is well established. But the specific claim that treating MCAS will improve anxiety in hypermobility patients needs proper clinical trials before we can make it with confidence. What we can say is that if you’re not responding to standard anxiety approaches, the mast cell-histamine axis is a hypothesis worth investigating.
Central Sensitisation: When Your Nervous System Gets Stuck on High Alert
The final major biological mechanism before we move to the gut, medical trauma, and practical strategies is one that we’ve touched on implicitly throughout this article but haven’t addressed directly: central sensitisation.
Central sensitisation is what happens when the central nervous system, the brain and spinal cord, becomes chronically calibrated to amplify sensory signals. Think of it as the volume dial on your nervous system getting stuck at maximum. The dial still exists. You can try to turn it down. But it has a strong tendency to creep back up again because the system itself has been recalibrated towards amplification.
What Central Sensitisation Is and Why It Matters Here
In a typical nervous system, pain signals and threat signals are processed proportionally. A minor stimulus gets a minor response. A significant stimulus gets a significant response. The nervous system applies appropriate weighting to its inputs.
In central sensitisation, this proportionality breaks down. The threshold for responding is lowered. Existing pathways are made more efficient, so signals travel faster and more strongly. Inhibitory signals, the ones that would normally dampen down the response, are weakened. The result is amplified pain from stimuli that wouldn’t normally cause pain, or prolonged pain from stimuli that would normally cause only brief discomfort, or pain in areas distant from the original injury. This is a well-established mechanism in fibromyalgia and chronic pain conditions, and we cover it in depth when we look at how a sensitised nervous system drives both pain and anxiety.
But central sensitisation doesn’t just amplify pain. It amplifies all sensory and threat signals, including the ones that generate anxiety.
A 2024 case-control study by Söderpalm and colleagues, published in the European Journal of Pain, directly examined central sensitisation in adolescents with HSD and hEDS, using pressure pain threshold testing and exercise-induced hypoalgesia [20]. What they found was that the HSD/hEDS group had significantly lower pain thresholds across all tested muscle groups: the trapezius threshold was 2.06 kg/cm² in the hypermobile group versus 3.68 kg/cm² in controls. The tibialis anterior was 3.82 versus 5.31. Every single tested site showed significantly lower thresholds.
But the most diagnostically relevant finding was in exercise-induced hypoalgesia, the normal pain-reducing effect that exercise has in healthy people (this is partly what’s behind the “runner’s high”). In the HSD/hEDS group, exercise did not produce this pain-reducing effect. The hypoalgesia was absent, or diminished. This is a hallmark of defective descending pain inhibition, a specific feature of central sensitisation in which the brain’s own pain-control systems are no longer functioning properly.
And the same study found significantly elevated anxiety scores in the HSD/hEDS adolescents: a median HADS anxiety score of 5 compared to 2 in controls, with P=0.007 [20]. Anxiety and central sensitisation were going hand in hand, in adolescents, before decades of chronic illness experience had accumulated.
This matters because it points to a shared neural substrate. The same sensitised pathways that amplify pain signals also amplify anxiety signals. The same neuroimmune inflammatory processes that maintain central sensitisation (elevated glial activation, pro-inflammatory cytokines, altered NMDA receptor sensitivity) also influence the emotional processing systems that generate anxiety. When the nervous system amplifies everything, pain, sensation, and anxiety alike, it is not two separate problems happening simultaneously. It is one underlying state expressing itself in multiple domains at once.
The Sensitisation-Anxiety Feedback Loop
The relationship between central sensitisation and anxiety runs both directions, which is what makes it such a persistent and difficult problem to address.
Anxiety maintains and worsens central sensitisation through multiple pathways. Sustained anxiety keeps the sympathetic nervous system activated, which maintains the neuroinflammatory environment that keeps sensitisation in place. Anxiety-driven hypervigilance to sensory signals means the brain is constantly scanning for threats, which amplifies the gain on sensory processing. Anxiety disrupts sleep, and poor sleep is one of the most potent drivers of central sensitisation. We cover the sleep-anxiety relationship in hypermobility in considerable depth in our hypermobility and sleep guide, and the bidirectionality is particularly important there.
Conversely, central sensitisation maintains anxiety. An amplified sensory system generates more signals that could be interpreted as threatening. More pain signals. More interoceptive noise. More proprioceptive uncertainty. All of it feeds the amygdala and the insular cortex, which generates more anxiety, which worsens sensitisation. The cycle is genuinely self-reinforcing, and this is why how anxiety and stress physically trigger EDS flare-ups through multiple pathways is not just a theoretical concern. The sensitisation-anxiety loop is often the engine behind flare cycles.
This is also why single-factor interventions often fail in hypermobility-related anxiety. Addressing only the psychological component of anxiety while the proprioceptive noise, autonomic dysregulation, mast cell chemistry, and central sensitisation continue operating at full volume is like bailing out a boat without plugging the holes. You’ll achieve some improvement. But you won’t achieve stability.
Understanding this multi-factor picture is not meant to be discouraging. It is meant to be practically orienting. Once you can see all the components of the cycle, you can begin to address them strategically, targeting the points where you have the most leverage, rather than applying generic anxiety management strategies that weren’t designed with any of these biological mechanisms in mind.
The Gut-Brain Axis: Your Second Brain’s Role in Anxiety
If you’ve been reading the biological mechanisms above thinking “yes, but also my gut is absolutely terrible and I don’t know if that’s related,” then this section is going to connect some dots for you. And if you haven’t been thinking that, the statistics are about to be fairly hard to ignore.
GI Problems in Hypermobility: Far More Common Than You Think
Gastrointestinal problems are extraordinarily common in hEDS and HSD. Not just “a bit of bloating” common. Genuinely, strikingly common. A 2022 review by Thwaites, Gibson and Burgell, probably the most comprehensive analysis of GI disorders in hypermobility published to date, found that irritable bowel syndrome (IBS) affects 54% of people with hEDS compared to just 8% of controls [21]. Abdominal pain: 69% versus 27% in controls. Constipation: 73% versus 16%. Overall disorders of gut-brain interaction (the broader category that encompasses IBS, functional dyspepsia, and related conditions): 94% of people with hEDS versus 47% of controls [21]. Nearly everyone. If you’ve ever wondered why anxiety appears on nearly every list of EDS and HSD symptoms and not just the joint-related ones, the gut-brain connection is a large part of the answer.
And crucially, that same review found that GI dysfunction in hEDS was significantly associated with anxiety (odds ratio 2.26, P<0.001) and mood disorders [21]. These are not separate problems happening to the same person. They are connected problems, sharing mechanisms, feeding each other.
Why is GI involvement so prevalent in hypermobility? Several reasons, all of which trace back to connective tissue. The gut wall itself contains connective tissue, and compliant connective tissue throughout the GI tract means a predisposition to anatomical changes like hiatus hernia, visceroptosis (a drooping of the abdominal organs), and altered gut motility. The enteric nervous system, the network of neurons lining the gut that is sometimes called the second brain, is embedded in this tissue and is directly affected. Dysautonomia compounds this: reduced parasympathetic tone means slower gut motility, and POTS-related changes to splanchnic circulation (the blood supply to the gut) further disrupt normal GI function. Mast cell activation, as we covered earlier, adds intestinal inflammation and permeability changes to the mix. The gut in hypermobility is not just inconveniently uncomfortable. It is structurally and neurologically compromised in multiple ways simultaneously.
The Microbiome, Vagus Nerve, and Anxiety
Here’s the statistic that tends to surprise people most: approximately 95% of the body’s serotonin is produced not in the brain, but in the gut, by specialised cells in the gut lining called enterochromaffin cells [22]. Serotonin, the neurotransmitter most closely associated with mood regulation and anxiety, is predominantly a gut molecule. The brain makes a relatively small fraction of the total. This makes the gut’s functional state directly relevant to mood and anxiety, not just metaphorically, but biochemically.
The connection runs primarily through the vagus nerve, the tenth cranial nerve, which serves as the primary communication highway between the gut and the brain. Roughly 80% of the signals in the vagus nerve travel upward, from gut to brain, rather than downward. The gut is essentially reporting constantly to the brain about what is happening in the digestive system, and the brain responds to this information by adjusting autonomic tone, emotional state, and threat processing. The gut-brain-immune connection in fibromyalgia and hypermobility runs considerably deeper than most people realise, and the neuroinflammatory dimension of it matters considerably for anxiety.
When the gut microbiome, the vast community of bacteria, fungi, and other microorganisms inhabiting the GI tract, is disrupted (a state called dysbiosis), several things happen that are directly relevant to anxiety. Gut bacteria influence the production of short-chain fatty acids, which regulate peripheral serotonin production. Disrupted microbial populations alter GABA signalling (GABA being the brain’s primary inhibitory neurotransmitter, the one that applies the brakes on neural excitability). Dysbiosis promotes intestinal inflammation and increased gut permeability, which allows bacterial products to reach the circulation and ultimately influence neuroinflammatory processes in the brain [22]. Specific bacterial species, including Lactobacillus and Bifidobacterium, appear to produce GABA precursors and have been shown in animal models to reduce anxiety-like behaviour when their populations are healthy.
In hypermobility, the conditions for gut dysbiosis are practically built in. Slowed gut motility, which can affect up to 52% of hypermobile patients seen in GI clinics, creates conditions for small intestinal bacterial overgrowth. Mast cell activation causes intestinal inflammation and permeability changes. Dysautonomia disrupts the motility patterns that normally keep bacterial populations appropriately distributed along the GI tract. And the high rates of IBS in this population are likely both a cause and a consequence of the dysbiotic state. How diet and gut health influence the anxiety-inflammation connection in hypermobility is a genuinely complex picture, and one worth understanding practically, because it is one of the levers you actually have some control over.
What This Looks Like in Daily Life
The point I want to make here is an integrative one, because I think it’s the most clinically useful framing of the gut-brain relationship in hypermobility.
If you have hypermobility, anxiety, IBS, and brain fog, and many people reading this will have all four, the natural instinct is to treat these as a list of separate problems requiring separate solutions. Anxiety for the psychiatrist. IBS for the gastroenterologist. Brain fog for the neurologist. And each specialist, if you’re lucky enough to see them, treats their domain in isolation.
But these are not four separate problems. They are four expressions of the same underlying system being dysregulated in multiple directions simultaneously. The anxiety feeds the gut (the gut-brain axis is bidirectional, and psychological stress directly alters gut motility, permeability, and microbial composition through autonomic and neuroendocrine pathways). The gut feeds the anxiety (through serotonin dysregulation, vagal signalling, and neuroinflammation). The dysautonomia disrupts both. The mast cell activation inflames both. The central sensitisation amplifies all of it.
This is not a counsel of despair. It is actually, when you sit with it for a moment, a simplification. You’re not dealing with four problems. You’re dealing with one fundamentally dysregulated system that is expressing itself across four domains. Which means that interventions targeting the system, rather than chasing individual symptoms, are more likely to produce sustained improvement. We’ll come back to exactly what that looks like in practice.
Medical Trauma: The Anxiety That Doctors Created
This section is, if I’m honest, one of the most important in this entire article. And also one of the most uncomfortable to write, because it requires acknowledging something that most healthcare commentary is reluctant to name directly: the medical system, in its management of hypermobility and EDS, has caused significant and measurable psychological harm to a large proportion of the people it was supposed to help.
That is not an accusation aimed at individual clinicians. It is a structural observation about what happens when a condition that is primarily invisible, variable, and dismissed as psychological by default, meets a healthcare system that is trained to look for straightforward physical pathology and refer everything else to mental health services.
The Diagnostic Odyssey
The average time to diagnosis for hEDS is somewhere in the region of 10 years, with one large survey of 505 patients finding an average of 10.39 years [40], though many people report considerably longer. A decade, or more, of experiencing real, debilitating, life-altering symptoms and being told, in various ways and with varying degrees of kindness, that those symptoms either don’t exist, are exaggerated, are psychosomatic, are a manifestation of anxiety, or are simply not something any test can identify and therefore not something medicine can help with.
Consider what that experience does to a person’s nervous system over time. You come in with joint pain, fatigue, palpitations, gut dysfunction, and anxiety. You are told the investigations are normal. You are told to exercise more, stress less, consider therapy. You come back. Same thing. You see another doctor. Same thing. You start to internalise the message, as many people do, that you are somehow the problem: too anxious, too focused on symptoms, too sensitive. Or alternatively, you stop internalising it and start fighting for recognition, which is exhausting in its own right, and which often generates the very anxiety and hypervigilance about symptoms that the clinicians were pointing to as the problem.
A qualitative study by Halverson, Penwell and Francomano, published in 2023, interviewed 26 people with hEDS about their medical encounters [23]. What they found was a consistent pattern of what they called “clinician-associated traumatisation”: acute psychological distress arising directly from perceived hostility, dismissal, and disinterest from clinicians. Participants described PTSD-like responses to medical encounters. That is over a decade of repeated, cumulative traumatising interactions with the healthcare system.
Iatrogenic Harm and Health Anxiety
The concept of iatrogenic harm (harm caused by the act of medical treatment or, in this case, the repeated failure of medical engagement) is well established in medicine but is rarely applied to psychiatric consequences with the same rigour as physical ones. In hypermobility, the iatrogenic psychiatric harm is both specific and quantifiable.
A 2021 survey study by Lewis and colleagues, using what they termed the BITTEN framework to measure institutional betrayal in EDS patients, found that 48% of those reporting unmet mental health needs described experiencing institutional betrayal from healthcare providers [24]. Anxiety, stress, PTSD, and fear were reported in 59.6% of all respondents. Overall, trauma and mental health symptoms were coded in 91.4% of the sample [24]. These numbers are not primarily driven by the biological mechanisms we’ve covered up to this point, though those mechanisms are real and present. They are driven, in substantial part, by what the healthcare system did to these people over years of seeking help.
The specific form of anxiety that medical dismissal creates is worth distinguishing from general anxiety, because it has particular characteristics that matter for treatment. It is a hypervigilance about symptoms born from the experience of having symptoms dismissed. Every new symptom carries the weight of all the previous times you reported something and were not believed: is this real? Is it serious enough to present? Will I be dismissed again? Is it worth the emotional cost of another unhelpful appointment? This is not irrational catastrophising. It is an entirely rational adaptive response to an environment in which your body reports genuine problems that the gatekeepers of medical care have repeatedly declined to validate.
Likewise, how years of medical dismissal compound anxiety in EDS patients into a form that closely resembles PTSD is something we cover in our medical trauma guide in detail. If any of what I’ve just described is familiar, it is worth reading.
The cruel irony, and it genuinely is cruel, is that the health anxiety that the diagnostic odyssey creates then becomes evidence, in the clinician’s notes, that the patient has anxiety. Which becomes another reason not to investigate the physical symptoms thoroughly. The cycle is self-sealing. It is, in many ways, a perfect example of how anxiety and stress physically trigger EDS flare-ups through multiple pathways, except here the pathway runs entirely in the psychological domain, with the system reinforcing its own dysfunction.
Why This Matters for Treatment
There is a practical reason why the medical trauma section belongs in a discussion of anxiety management, and it is this: if a substantial part of your anxiety has its roots in medical trauma, as is the case for a large proportion of hypermobile people, then standard anxiety treatment delivered by an unfamiliar clinician in a clinical setting may actively retraumatise rather than help.
Cognitive Behavioural Therapy (CBT) is the frontline psychological treatment for anxiety, and it has evidence behind it in the hypermobility context, which we’ll cover in the management section. But CBT delivered without an understanding of hypermobility can inadvertently reinforce the message you’ve been receiving for years: that your physical symptoms are fundamentally a consequence of how you think and feel. When you’ve spent a decade being told this by people who didn’t believe your symptoms were physical, hearing it again from a therapist who doesn’t know your EDS history can feel like, and may actually be, a continuation of the same pattern.
The 2021 Lewis study found that patients who had experienced institutional betrayal had greater anger, greater negative healthcare expectations, and less likelihood of engaging with subsequent healthcare interventions [24]. This is not stubborn patient non-compliance. This is a predictable consequence of repeated institutional harm.
How early-life adversity primes the nervous system for chronic pain and anxiety compounds this further. Many hypermobile people arrive at their diagnostic odyssey already carrying a sensitised nervous system from earlier adverse experiences. The medical trauma doesn’t fall on a blank slate. It lands on a nervous system that is, in many cases, already primed for threat hyperreactivity.
What this means practically, which we’ll expand on shortly, is that trauma-informed approaches are not optional extras in managing anxiety in hypermobility. They are essential. The right therapist, with the right understanding, makes a difference that no amount of technique-based CBT will achieve if the foundational issue of trust has not been addressed.
What Can You Actually Do About It? A Practical Guide
Right. We’ve done the science. And I appreciate this has been a significant amount of science. But this is the section that actually matters in terms of what you do with your Monday morning.
A Note Before We Start
I want to be direct about something before we get into specifics. This is not a list of generic anxiety management tips that you will find plastered across every health website in slightly different fonts. I am not going to tell you to try mindfulness, sleep more, drink less caffeine, and hope for the best. These are not wrong suggestions. They are simply inadequate ones, because they address the surface expression of a problem whose roots, as we’ve spent considerable time establishing, are structural, biological, and in many cases directly physical.
Likewise, this is not a cure section. Hypermobility-related anxiety, when it has the number of contributing mechanisms we’ve described, is a management challenge, not a fixable event. What evidence-based management looks like is reducing the biological load from as many directions as possible, building resilience in the systems that are dysregulated, and addressing the psychological layers with approaches that are calibrated to what you’re actually dealing with.
Some of what follows will not be suitable for everyone. Some of it depends on where you are, what resources you have access to, and which of the contributing mechanisms are most dominant in your particular picture. The goal is not to do all of this at once. It is to understand the menu, and make intelligent choices about where to start.
Exercise and Proprioceptive Training
Let me lead with the intervention that the research most consistently supports, and which most hypermobile people are most confused about: exercise.
Exercise is one of the most potent anxiety interventions available, full stop. A large 2023 overview of systematic reviews covering 97 reviews, 1,039 trials, and 128,119 participants found that physical activity reduces anxiety with a median effect size of -0.42 [25]. That is a clinically meaningful effect, comparable to or larger than many pharmaceutical interventions, without the side effect profile. The mechanism is not mysterious: exercise acutely reduces cortisol and adrenaline, increases GABA, serotonin, BDNF (brain-derived neurotrophic factor, which promotes neural plasticity and resilience), and endocannabinoids. It activates frontal cortical regions that inhibit amygdala reactivity. It directly addresses the neurological substrate of the anxiety we’ve been describing.
But exercise for hypermobile people is not the same as exercise for people with neurotypical nervous systems and typical connective tissue. This is where most of the advice you’ll find online becomes actively unhelpful, because it assumes a body that responds to loading and progressive resistance in the way that most bodies do. Hypermobile bodies don’t, not initially, and not without specific modifications.
The first thing to understand is that proprioceptive training has to come before heavy loading. As we covered earlier, the proprioceptive system in hypermobility is impaired: the signals from joints, muscles, and connective tissue to the brain are noisier and less precise than in non-hypermobile bodies. Jumping straight into high-load resistance work without addressing this is like trying to navigate by a broken GPS. The brain doesn’t have good enough body-position information to recruit muscles efficiently, protect joints during loading, or generate confident predictions about movement safety. The result, typically, is injury, post-exertional malaise, and a reinforcement of the fear of movement that many hypermobile people have already developed. Why movement is one of the most evidence-based anxiety interventions for hypermobile bodies is something we cover in depth in the exercise guide, and it also covers the specific sequencing that makes exercise safe and effective for this population.
So what does proprioceptive training look like in practice? It means starting with exercises that give the nervous system clear, unambiguous feedback about joint position and muscle engagement, before progressing to higher loads or more complex movement patterns. Slow, controlled movements through full range. Isometric exercises (contracting a muscle without moving the joint), which load the joint without the proprioceptive challenge of dynamic movement. Exercises performed in front of a mirror initially, so that visual feedback can compensate for the imprecise proprioceptive signals. Work that targets the deep stabiliser muscles around the spine and major joints, because these muscles contain the highest density of proprioceptive receptors and their training directly improves the quality of position-sensing.
In terms of exercise type for anxiety specifically, the evidence in the general population favours both aerobic exercise and resistance training, with effect sizes roughly comparable [25]. For hypermobile people with significant POTS, horizontal or semi-recumbent aerobic work (recumbent cycling, swimming, rowing) is typically the safest starting point, because upright aerobic exercise, like running or cycling upright, will worsen orthostatic tachycardia and generate the very adrenaline-driven anxiety we’re trying to reduce. Starting horizontal and building gradually toward upright work as cardiovascular reconditioning improves is the standard approach for POTS rehabilitation, and it applies equally to the anxiety management rationale.
The other key principle is graded exposure. Many hypermobile people have developed movement avoidance, a perfectly understandable response to a history of pain, injury, and unpredictable joint behaviour. Movement avoidance feels protective but is counterproductive, because it further deconditions both the musculoskeletal system and the proprioceptive system, worsening the anxiety loop. Graded exposure means systematically and gradually reintroducing movements that have become feared, starting at levels that feel genuinely safe and building tolerance incrementally. This is not a push-through-the-pain approach. It is a deliberate, calibrated one. And it works, both for the anxiety and for the physical deconditioning.
A 2017 study by Scheper and colleagues found that proprioceptive inaccuracy confounded the relationship between muscle strength and activity limitations in hEDS patients: controlling for proprioception was more important than increasing sheer muscle strength alone [26]. This is a significant finding from a rehabilitation standpoint. You can build all the muscle you like, but if the brain’s body-mapping is unreliable, the muscle won’t be used effectively. Proprioceptive work first. Strength on top of it.
Breathing and Vagus Nerve Work
The vagus nerve is, in terms of practical anxiety management, one of the most important things to understand, because it is directly accessible and you can influence it right now without any equipment or professional involvement.
The vagus nerve is the primary parasympathetic nerve in the body: the one responsible for the rest-and-digest state that is the physiological opposite of fight-or-flight. It runs from the brainstem through the neck, chest, and abdomen, innervating the heart, lungs, and GI tract along the way. When vagal tone is high, the parasympathetic nervous system has effective control over the autonomic balance. When vagal tone is low, as it is in many people with POTS and hypermobility-related dysautonomia, the sympathetic nervous system has too much unopposed influence, generating the chronic low-grade adrenergic activation that contributes so heavily to the anxiety experience.
The good news is that vagal tone is not fixed. It is modifiable, and breathing is the most reliable way to do it.
Slow, diaphragmatic breathing at around six breaths per minute is the resonance frequency of the cardiovascular system. At this rate, your breathing cycles synchronise with your heart rate variability (HRV) in a way that maximally stimulates vagal afferents, the nerve fibres that carry signals from the heart and lungs back to the brainstem via the vagus nerve, increasing parasympathetic tone and reducing sympathetic arousal [27]. This isn’t alternative medicine. The mechanism is well established, and the evidence for HRV biofeedback, which uses this principle in a more formalised way, is genuinely good. A narrative review of the respiratory vagal stimulation model highlights growing evidence that breathing-based practices reduce anxiety and improve mood across multiple studies [27].
Six breaths per minute works out to a five-second inhale and a five-second exhale. Or, if you find the equal ratio difficult, a four-second inhale and a six-second exhale. The key is the length and smoothness of the exhale: the exhale specifically activates the vagus nerve via the baroreceptors in the aorta. A longer exhale relative to inhale produces a stronger parasympathetic response. The 4-7-8 breathing pattern (four seconds in, hold seven, exhale for eight), while slightly different from the resonance breathing rate, shares this extended-exhale principle and many people find it particularly effective for acute anxiety states.
A 2021 RCT by Bartlett and colleagues found that six-breaths-per-minute paced breathing increased HRV significantly more than a nature-video control condition in 96 participants [28]. This is not a dramatic effect size study. It is a proof of concept that the mechanism works acutely, consistently, and reliably.
For hypermobile people specifically, why HRV is a practical window into the anxiety-autonomic connection matters because it gives you a measurable marker of how your autonomic balance is doing, and whether your breathing and lifestyle interventions are actually shifting it. HRV tracking via a wearable device is more accessible than ever and can help you understand whether what you’re doing is making a difference at the autonomic level.
Cold water exposure, particularly cold water on the face or a brief cold shower, activates the dive reflex via the trigeminal nerve and vagal pathways, producing a rapid reduction in heart rate and sympathetic tone. This can be useful for acute anxiety management. However, if you have POTS, cold showers require caution: the sudden peripheral vasoconstriction can cause orthostatic problems, and some people with dysautonomia find cold exposure provocative rather than calming. Test this carefully and at your own pace.
A practical note here, because I’ve seen enough people in clinic: breathing exercises feel slightly absurd the first few times you do them. The urge is to dismiss them because they seem too simple relative to the complexity of what you’re dealing with. They are simple. That doesn’t mean they’re ineffective. The simplicity is the point: you are directly stimulating a cranial nerve via a mechanism you have continuous access to. The nervous system doesn’t know or care whether the intervention feels sophisticated. It responds to the stimulus.
Addressing the POTS Component
If POTS is a significant contributor to your anxiety experience, and from the biological picture we’ve built, it is worth at least investigating whether it is, then addressing the POTS directly is one of the highest-leverage anxiety interventions available. Treating anxiety while POTS-driven adrenaline surges continue unaddressed is, as I said earlier, like treating the smoke alarm sensitivity without dealing with the smoke.
The first-line non-pharmacological approaches to POTS management are worth knowing about regardless of whether you’ve had a formal POTS diagnosis. Increased sodium and fluid intake is the foundational step: higher blood volume means less compensatory adrenaline required when standing. The evidence supports 2–3 litres of water and 3–5 grams of sodium per day as a starting point for most adults, though this needs to be calibrated to your individual presentation and ideally discussed with a doctor. What the evidence actually says about managing POTS symptoms day-to-day includes a thorough breakdown of the salt and fluid evidence, and it is more nuanced than most sources suggest.
Compression garments, particularly abdominal binders and thigh-high compression stockings, reduce venous pooling on standing, again reducing the degree of compensatory adrenaline response. Elevating the head of your bed slightly (10-20 degrees) reduces overnight fluid redistribution and helps maintain blood volume in a more upright-accessible form. Avoiding prolonged standing, taking meals while sitting, and avoiding large meals (which divert blood to the gut and can trigger post-prandial POTS symptoms) are practical environmental modifications that reduce the number of adrenaline-triggering events per day.
For medication, beta-blockers (particularly low-dose propranolol) are among the most commonly used pharmacological approaches for POTS-related tachycardia. They work by blocking the effects of adrenaline on the heart, reducing heart rate on standing and thereby reducing the cascade of anxiety-like symptoms that an unchecked tachycardia produces [29]. Ivabradine, which selectively reduces heart rate without affecting blood pressure, is an alternative that some patients tolerate better. Fludrocortisone, a mineralocorticoid that promotes sodium and fluid retention, is used to expand blood volume. These are medical decisions, and they require a conversation with a doctor who understands POTS. But knowing they exist, and knowing the rationale for them, helps you ask better questions at that conversation.
Investigating MCAS
If your anxiety has the profile we described earlier, coming in waves with an inflammatory, physical flavour, clustering with flushes, GI disturbance, skin reactions, or widespread pain flares, and if it seems to respond better to antihistamines than to psychological interventions, MCAS is worth putting on your list of things to investigate.
MCAS assessment is not straightforward. The diagnostic criteria remain somewhat contested, and the standard testing (serum tryptase, 24-hour urine prostaglandin D2 and histamine metabolites) has significant sensitivity limitations. Tryptase is normal in many patients who clearly have mast cell symptoms. This is an area where a specialist who is genuinely familiar with the condition makes a considerable difference.
The initial management approach, if MCAS is suspected, typically starts with H1 antihistamines (the non-drowsy type, like cetirizine or loratadine, taken consistently rather than as-needed) and H2 antihistamines (ranitidine or famotidine, which block gastric and some CNS histamine receptors). Mast cell stabilisers, particularly cromolyn sodium (sodium cromoglicate) taken orally, can help reduce overall mast cell reactivity. A low-histamine diet trial, which reduces the histamine load coming in from food, is a practical first step that requires no prescription and gives useful diagnostic information: if reducing dietary histamine consistently reduces anxiety flares, that is meaningful signal.
The Weinstock 2023 case series, which we covered earlier, used a combination of H1/H2 blockers, quercetin (a natural mast cell stabiliser), low-dose naltrexone, and low-histamine diet to achieve complete psychiatric remission in 6 of 8 heavily treated psychiatric patients [19]. The evidence level is low. The signal is real enough to investigate if you’re treatment-resistant.
Therapy Approaches That Actually Work
CBT has the strongest evidence base for anxiety in the general population, and the evidence in the hypermobility-specific context, whilst limited, points in the same direction. A CBT-informed pain management programme studied by Rahman and colleagues found 15.1% improvement in anxiety scores (P<0.001) in people with hEDS and HSD, with gains sustained at five months [30]. That is a meaningful effect in a difficult population.
But here is what I want to say about CBT in this context, and it is something that most CBT resources won’t say themselves: standard CBT, as delivered to the general population, may be insufficient or actively counterproductive for hypermobile people with medical trauma, because it can inadvertently reinforce the message that physical symptoms are primarily driven by cognitive distortions. If your anxiety is substantially driven by POTS, MCAS, poor proprioception, and a decade of not being believed, the CBT framework of challenging “unhelpful thoughts” can feel dismissive of the very real biological experience you’re having. The right therapist, who understands hypermobility, who validates the biological reality of your experience before asking you to examine your cognitive responses to it, makes an enormous practical difference.
Acceptance and Commitment Therapy (ACT) is worth specifically mentioning here, because its model fits the hypermobility picture in a way that standard CBT does not quite capture. ACT doesn’t ask you to challenge or reframe thoughts. It asks you to change your relationship with them: to observe anxiety thoughts without being fused to them, and to commit to value-driven behaviour in the presence of discomfort rather than waiting until the anxiety resolves. For someone with a chronic condition, the goal of eliminating anxiety before engaging with life is both unrealistic and likely to produce life constriction. ACT, conceptually, is better suited to the long-term management of a condition that will not simply be fixed.
EMDR (Eye Movement Desensitisation and Reprocessing) and other trauma-focused therapies are specifically relevant for the medical trauma component. If your relationship with the healthcare system, and potentially with your own body, has been traumatised by years of dismissal, working with a therapist who specialises in EMDR or trauma-informed CBT addresses a layer of the anxiety that standard cognitive techniques will not reach. The PTSD-like responses that develop from chronic illness encountersin hEDS are well documented, and this is not a population that benefits from being referred to standard unsupported psychological services.
The ADAPT trial, the first randomised controlled trial specifically designed for anxiety in joint hypermobility, builds CBT together with interoceptive bio-behavioural training, using heartbeat tracking and discrimination tasks to directly retrain the interoceptive system [31]. The rationale is exactly what the neuroscience would predict: if interoceptive hyperreactivity is part of the mechanism driving anxiety in hypermobility, then training the interoceptive system to be more accurate and less reactive should directly address it. As of writing, the full results are not yet published, but the protocol is sound and the logic is tight.
The key practical point for all therapy approaches: the therapist needs to understand hypermobility. Not necessarily be an expert in it, but be willing to understand it, validate the biological complexity, and not interpret physical symptoms as evidence of anxiety disorder without first ruling out the mechanisms we’ve covered here. It is worth asking, before committing to a therapeutic relationship, how the therapist conceptualises the relationship between physical symptoms and anxiety in chronic illness.
Medication: What the Evidence Says
I want to be clear upfront: this section is informational, not prescriptive. Any medication decision needs to be made with your doctor, who knows your full medical picture. What I can offer here is the relevant evidence and the specific considerations that apply when you have hypermobility, POTS, and potentially MCAS, because these change the standard calculus in important ways.
SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the standard pharmacological first-line for generalised anxiety disorder and most anxiety disorders. They can be effective in the hypermobility context, but with caveats worth knowing about. GI side effects are common with SSRIs in the general population, and they tend to be more pronounced in people with already-disrupted GI function, including the IBS and dysmotility that are prevalent in hEDS. Starting at very low doses and titrating slowly is essential. Some SSRIs can also temporarily worsen anxiety in the first few weeks of treatment through their initial action on serotonin autoreceptors, and this early worsening can be particularly difficult to tolerate for someone whose anxiety has a strong physiological component.
SNRIs, which also target norepinephrine, carry the concern that the norepinephrine component may theoretically worsen POTS-related sympathetic overdrive, though clinical experience on this is mixed and not all patients with POTS experience this effect.
Beta-blockers, as mentioned in the POTS section, are relevant not just as POTS management but directly as anxiety medication. They reduce the peripheral manifestations of the fight-or-flight response (racing heart, tremor, sweating) without crossing the blood-brain barrier in meaningful quantities, which means they address the physiological expression of anxiety without sedating effects. For the specific subset of anxiety that is primarily generated by POTS-related adrenaline surges, low-dose propranolol can be more effective than SSRIs because it is addressing the actual source of the physiological symptoms.
Low-dose naltrexone (LDN) is increasingly discussed in the hypermobility and fibromyalgia community. The evidence for LDN is primarily in fibromyalgia pain, where a systematic review and meta-analysis found it effective versus placebo [32]. Its proposed mechanism, transient opioid receptor blockade leading to a rebound increase in endogenous opioids and anti-inflammatory effects on microglia, suggests it could reduce the central sensitisation and neuroinflammatory states that contribute to anxiety in hypermobility. However, there is no specific RCT evidence for LDN targeting anxiety in hEDS, and I want to be honest about that limitation. It is a hypothesis worth discussing with a knowledgeable clinician, particularly in treatment-resistant cases. What the evidence says about low-dose antidepressants in hypermobility conditions also covers the low-dose amitriptyline evidence, which has a different but sometimes useful pharmacological profile for anxiety, pain, and sleep in this population.
Benzodiazepines, the fast-acting anxiolytics like diazepam and lorazepam, are generally not recommended for long-term anxiety management in any population, due to tolerance, dependence, and rebound anxiety. In hypermobility specifically, there is also the concern that benzodiazepines, by relaxing muscle tone, could worsen joint instability. Short-term use in acute crisis situations is a different matter, but sustained use is something to approach with real caution.
Sleep: The Often-Overlooked Anxiety Amplifier
I want to close the management section with a brief but important note on sleep, because it is one of the most powerful levers in the anxiety picture and one of the most frequently neglected.
Sleep deprivation, even partial and cumulative, directly increases amygdala reactivity. A sleep-deprived amygdala is a more reactive amygdala. It responds to mild stressors with the intensity that a well-rested amygdala would reserve for significant threats. Given that the hypermobile amygdala is, as we established earlier, already structurally larger and more reactive than average, compounding this with poor sleep is genuinely adding fuel to an already active fire.
Conversely, anxiety disrupts sleep. Night-time nervous system activation, orthostatic tachycardia that continues even lying down in some POTS presentations, pain from joint positioning, and the hypervigilant mental state that anxiety generates all interfere with the architecture of restorative sleep. Why the anxiety-sleep cycle is particularly vicious in hypermobility is covered in our dedicated sleep guide, which goes into considerably more depth on this than I can here. But the short version is: addressing sleep is not optional in the context of anxiety management. It is one of the primary intervention targets, not an afterthought.
The anxiety interventions that most reliably improve sleep in this population are the ones that directly target autonomic regulation: slow breathing before bed, addressing POTS symptoms that worsen lying down, and, where relevant, reducing the histamine load that can cause night-time arousal in MCAS presentations.
Bringing It All Together: The Integrated Model
We’ve covered a lot of ground. So let me step back and give you the integrated picture, because the individual mechanisms are less important than the way they connect and reinforce each other.
The anxiety that hypermobile people experience is not one thing. It is the output of a biological system in which multiple dysregulations are operating simultaneously and synergistically.
You have a structurally enlarged amygdala with an amplified threat-detection threshold. You have an interoceptive system, centred on the insula, that processes body signals with heightened sensitivity and a tendency to flag ambiguous signals as threatening. You have proprioceptive inputs that are imprecise and noisy, which generates a continuous low-grade prediction error that the brain interprets as uncertainty, and therefore as a reason for vigilance. You have an autonomic nervous system that, in POTS, generates genuine adrenaline surges indistinguishable from panic, and which does so in response to something as mundane as standing up. You have mast cells that may be overactivating and flooding the brain with histamine, a neurochemical that directly produces hyperarousal and activates the stress hormone cascade. You have a gut that is producing serotonin in a disrupted environment, communicating upward through the vagus nerve in a state of inflammation and dysbiosis. You have a central nervous system that has been sensitised to amplify all of these signals. And layered on top of all of it, you have the psychological consequences of spending years in a healthcare system that didn’t believe you.
Any one of these would be enough to make someone anxious. Most hypermobile people are dealing with several of them at once, with varying degrees of each contributing at different times. This is why single-factor approaches fail so consistently. Treating the psychology without addressing the physiology leaves the biological drivers intact. Treating the POTS without addressing the central sensitisation leaves the amplification system running. Treating the anxiety without acknowledging the medical trauma leaves the psychological wound open.
The integrated model tells us something important about expectations: you are unlikely to eliminate anxiety in this context, because some of its drivers are structural and partially irreducible. What you are working toward is reducing the biological load from as many directions as you reasonably can, building resilience in the systems that will respond to that, and developing a relationship with your own nervous system that is characterised by understanding rather than panic when it does what its architecture makes it prone to do.
The research on all of these mechanisms is, by the standards of the medical literature on hypermobility generally, relatively recent. Dr Jessica Eccles and her colleagues at Brighton and Sussex Medical School have been producing the most substantive neuroscientific work on this, and the picture they’re building is one of the most clinically coherent models of anxiety causation in any chronic condition. The ADAPT trial, when its results are published, will likely be a landmark moment in demonstrating that targeting the interoceptive mechanism specifically can produce anxiety reduction beyond what standard CBT achieves.
That work is coming. In the meantime, you don’t need to wait for the perfect trial. The mechanisms are understood well enough to act on now.
Closing
We’ve covered, across this article, what is genuinely a comprehensive account of the hypermobility-anxiety relationship: the epidemiology, the brain structures, the autonomic mechanisms, the immune chemistry, the gut-brain connection, the psychological consequences of medical encounters, and the practical interventions that the evidence supports. That’s a beast of a read, and if you’ve made it this far, you now understand this subject better than the majority of clinicians you are likely to encounter.
The single most important thing I want you to take from this is the reframe. Your anxiety is not a character flaw. It is not weakness, or catastrophising, or being too sensitive. It is the predictable output of a nervous system that is, for specific biological reasons, wired toward a higher threat threshold, receiving noisier body signals, and, in many cases, further primed by experiences that would have destabilised anyone. That is not a counsel of hopelessness. It is the foundation of a rational management approach.
There is more that could be said here, inevitably. We haven’t gone deeply into the neurodivergence dimension of anxiety in hypermobility, which deserves its own article. We haven’t addressed paediatric presentations, or the particular considerations around anxiety in adolescents with hypermobility, beyond what the research touched on. And the medication picture will continue to evolve as more hypermobility-specific trials are conducted.
But you have more than enough here to have an informed conversation with your clinicians, to make sense of what your body is doing, and to start making targeted, evidence-based choices about where to put your energy.
Stay strong out there.
The Fibro Guy Team
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