The Chronic Constellation – The collection of co-occurring conditions that we see common in the hypermobile and autistic community.
The Chronic Constellation- the Double Trifecta of Co-morbid Conditions
Bendy Bodies and Minds
Because, as I’ve noticed after serving my local houseless neighbors for the last four plus years in southeast Portland, Oregon, many of my outside friends have signs of the Chronic Constellation as I call this lousy collection of issues (bendy bodies plus “bendy” minds — ADHD, autism, OCD, bipolar, borderline, more) that disable so many of us.
And many of them agree with me. Some have even almost cried with relief to know they’re not crazy, just not recognized yet, as they struggle to even find that day’s food while in so much pain. (And you have trouble sleeping in your cushy bed — imagine on the ground. It’s hard!)
Why else EDS is not rare. Just rarely diagnosed. | by Jan Groh | Medium
Neurodivergence has been established as associated with a significant number of co-occurring physical conditions, particularly for autistic individuals who are at risk for increased pain, hypermobility (including Ehlers-Danlos Syndrome) and gastrointestinal problems. However, data, so far, has been focused on adults and generally limited to discussions of condition prevalence alone.
Full article: Co-Occurring Physical Health Challenges in Neurodivergent Children and Young People: A Topical Review and Recommendation
The research into the relationship between neurodivergent conditions and hypermobility found that more than 50% of participants with a diagnosis of Autism, attention deficit hyperactivity disorder (ADHD) or tic disorder (Tourette syndrome) demonstrated elevated levels of hypermobility, compared with just 20% of participants from the general population.
Neurodivergent participants also reported significantly more symptoms of pain and dysautonomia (eg, dizziness on standing up) than the comparison group and this was related to the number of hypermobile joints.
I believe this study is further proof of the link between neurodivergence and physical health issues, demonstrating a direct relationship between hypermobility and increased pain and dysautonomia.
The curious connection between hypermobility and neurodivergence
Led by Brighton and Sussex Medical School (BSMS) and funded by the MRC, MQ Mental Health Research and Versus Arthritis, the research found that more than 50% of participants with a diagnosis of Autism, attention deficit hyperactivity disorder (ADHD) or tic disorder (Tourette syndrome) demonstrated elevated levels of hypermobility, compared with just 20% of participants from the general population.
Neurodivergent participants also reported significantly more symptoms of pain and dysautonomia (eg, dizziness on standing up) than the comparison group and this was related to the number of hypermobile joints.
Dr Jessica Eccles, Lead Author and Clinical Senior Lecturer and MQ Versus Arthritis Fellow at BSMS, said: “This study is further proof of the link between neurodivergence and physical health issues, demonstrating a direct relationship between hypermobility and increased pain and dysautonomia.
Neurodivergent people more likely to experience pain, due to hypermobility – BSMS
This resource is intended as an introductory primer for primary care clinicians who are beginning to consider whether apatient’s component conditions are part of a larger constellation. The relationship between Autism/ADHD and these conditions is well-established in the literature, and is linked throughout this resource. There is also literature identifying sub-clusters amongst these conditions, including hypermobility, dysautonomia, chronic pain, neurodivergence (Csecs et al2022); hypermobility, dysautonomia, GI, allergic conditions (Brooks et al 2021), and hypermobility, dysautonomia,mast celldysfunction (Wang et al 2021). We expect that this resource may be useful for many of your non-Autistic/ADHD patients.
Clinician Guide: Constellation of Chronic Medical Conditions Commonly Seen in Autistic & ADHD Adults
It is clear from current evidence there is a co-occurring physical health disparity in neurodivergent adults. For example, neurodivergent adults display a higher expression of joint hypermobility and pain compared to neurotypical adults (Csecs et al., Citation2020). Furthermore, autistic women with generalised joint hypermobility (GJH) experience higher immune- and endocrine-conditions than autistic women without GJH (Casanova et al., Citation2018). However, it is vital to understand physical health in neurodivergent CYP (aged up to 25 years (National Institute for Health and Care Excellence (NICE), Citation2020)). Neurodivergent CYP experience worsened physical health conditions than neurotypical CYP (McLeod et al., Citation2019).
Full article: Co-Occurring Physical Health Challenges in Neurodivergent Children and Young People: A Topical Review and Recommendation
The Trifecta/Triad
Hopefully you’ve heard of “The Trifecta” by now – that is, the relatively common trio of issues we find comorbid in the Ehlers-Danlos community of any form of EDS (or the newly recognized, less visible or well known diagnosis of Hypermobility Spectrum Disorders since March 2017) plus Mast Cell Diseases (now, MCDs) in any form (whether forms of Mastocytosis or Mast Cell Activation Syndrome or HaTS) and finally Dysautonomia which all have to some degree. Many hypermobile patients will have the specific subset known as POTS.
The Chronic Constellation- the Double Trifecta of Co-morbid Conditions
hEDS, POTS, and MCAD together as a trifecta syndrome present as a complex and multisystemic disorder and may result in severe health conditions that may alter the patient’s quality of life. The major challenge in identifying this trifecta syndrome is an accurate diagnosis, as evidenced by this patient’s long‐term diagnostic process. A multidisciplinary approach should be encouraged and utilized regarding patient care, disease classification, clinical diagnosis, and the therapeutic approaches for disease management for persons with such a trifecta.
Idiopathic osteoporosis, Ehlers–Danlos syndrome, postural orthostatic tachycardia syndrome, and mast cell activation disorder in a 27‐year‐old male patient: A unique case presentation – PMC
We have a pattern here, as many of you know. More than 70 percent of our practice has this constellation of immune, connective tissue, and neurovascular differences that are resulting in significant disability.
While we knew about the co-occurrence of things like dysautonomia, hypermobility, spectrum conditions, we knew about this as it relates to neurodivergence, it’s in the literature. We really did not expect the pattern to be so striking and so widespread. And in fact, 95% of our neurodivergent patients have has this particular presentation.
Even when we look at this sub-population of Autistic patients for example, average life expectancy is 36 to 54 years. That is striking because they’re not dying from autism. They’re dying from premature cardiovascular disease and suicide.
Constellation of Related Medical Conditions Impacting Autistic & ADHD Adults: All Brains Belong VT – YouTube
Conversely, since befriending several autistics and autistic cousins in the local autistic support groups in past years, I found the reverse to be true as well: almost all showed signs of bendiness (hypermobility) to varying degrees, and complained of many of the same health issues I’ve had all my life including heavy allergies or at least sensitivities among other things. (Autoimmune diseases, fibro, IBS, more.)
This is turning into one heck of a coincidence in my book and I’m dying to see a study correlating hypermobility and autism. Dr. Theoharis Theoharides has correlated autism with the highly comorbid Mast Cell Actviation Diseases since 2013 though meanwhile. Edited to add in September 2021: there are increasing numbers of studies showing this correlation you can find on my Autism Resources page now.
I also find the following neuro-divergent and psychiatric constellation really common in our group as well, on the spectrum or not: anxiety, depression, ADD/ADHD, OCD, SPD, PTSD, mixed mood disorders, Bipolar, Borderline Personality Disorder, Narcissistic Personality Disorder and any and all variations thereupon you can find. Dual diagnosis anyone? Try “Hexa diagnosis” in some. And no, I’m not kidding, they’ve voluntarily shared their diagnoses with me in some cases even without my asking.
We really must stop trying so hard to classify people into single boxes with our short sighted views; further, I’ve personally observed people’s conditions and mental health and neurology to change over time – and diagnoses to change or resolve, frankly. Yes I speak from experience in at least one case.
Of course, we are often quite loathe to admit to any of this not only from the social stigma all too sadly attached to having mental illness or neurodivergence of any kind despite how common it truly is, but because way too many of our doctors proceed to write off all of our very real pain and physiological issues to “just anxiety” or depression, sadly.
The Chronic Constellation- the Double Trifecta of Co-morbid Conditions
In neurodivergent adults, there is a strong link between the expression of joint hypermobility, dysautonomia, and pain, more so than in the comparison group. Moreover, joint hypermobility mediates the link between neurodivergence and symptoms of dysautonomia and pain. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties in neurodivergent people, including co-occurring physical symptoms, and guide service delivery in the future.
Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain – PubMed
Results: The percentage of MCAS within the group of POTS and EDS was 31% in comparison with 2% within the non-POTS and EDS group. The 95% confidence interval calculated for the MCAS in the POTS and EDS group did not overlap with 2%, which showed a statistically significant result. The odds ratio between the two groups was found to be 32.46. Conclusion: There was a marked percentage of MCAS among the patients with diagnoses of POTS and EDS.
The relationship between mast cell activation syndrome, postural tachycardia syndrome, and Ehlers-Danlos syndrome – PubMed
In neurodivergent adults, there is a strong link between joint hypermobility, dysautonomia, and pain.
The curious connection between hypermobility and neurodivergence
You’ve got to look at the whole person.
Dr. Leonard Weinstock
The Pentad
The Pentad:
- Autoimmune Disease
- Dysautonomia
- Ehlers Danlos Hypermobility Syndrome
- Mast Cell Activation Syndrome
- Gastrointestinal Dysmotility
Central Sensitivity Syndromes
Research has shown that autistic people are more vulnerable to physical ill health than non-autistic people, including chronic health conditions known as “central sensitivity syndromes” (CSSs), including fibromyalgia, irritable bowel syndrome (IBS), migraine, and myalgic encephalomyelitis (ME/CFS). These conditions are all though to include central sensitisation as a core component, that is a state of “hyperexcitation” of the central nervous system (CNS) in which sensory input, particularly pain, is amplified.
Autistic people without a diagnosed CSS reported significantly more CSS symptoms than the comparison group, with a mean score above the clinical cut-off. Non-autistic participants with a CSS had significantly more autistic traits than the comparison group. Autistic people with a CSS reported the most sensory sensitivity, with autism only and CSS only groups reporting similar levels of sensory sensitivity and all diagnostic groups reporting more sensory sensitivity than the comparison group. Sensory sensitivity, anxiety, autistic traits, age and gender were all significant predictors of CSS symptoms. The overlap in symptoms between autistic individuals and those with CSS suggests diagnostic overshadowing and possible under-diagnosis or misdiagnosis. Furthermore, these symptoms may exacerbate or mask one another.
Hypermobility
There are strong links between neurodivergence and symptomatic hypermobility, and this is an exciting area of research we are supporting. It is likely that connective tissues are different than the general population in some of these neurodivergences.
FAQ | SEDSConnective
Everyone I meet with EDS seems to either be on or at least related or even married to an autistic person. Or alternatively experiencesADHD I’ve since realized (updated 2021).
The Chronic Constellation- the Double Trifecta of Co-morbid Conditions
This self-reported small case-control study confirms the association of fibromyalgia, hypermobility and neurodivergence, and suggests that close relatives also exhibit this association.
The Association Between Fibromyalgia, Hypermobility and Neurodivergence Extends to Families: Brief Report – Article (Preprint v5) by Clive Kelly | Qeios
Autism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social, and emotional processes. Increased likelihood of chronic physical symptoms, including fatigue and pain, are also recognized. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts susceptibility to psychological symptoms alongside recognized physical symptoms.
Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain – PubMed
The neurodivergent group manifested elevated prevalence of hypermobility (51%) compared to the general population rate of 20% and a comparison population (17.5%). Using a more stringent age specific cut-off, in the neurodivergent group this prevalence was 28.4%, more than double than the comparison group (12.5%). Odds ratio for presence of hypermobility in neurodivergent group, compared to the general population was 4.51 (95% CI 2.17-9.37), with greater odds in females than males. Using age specific cut-off, the odds ratio for GJH in neurodivergent group, compared to the comparison group, was 2.84 (95% CI 1.16-6.94). Neurodivergent participants reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. The number of hypermobile joints was found to mediate the relationship between neurodivergence and symptoms of both dysautonomia and pain.
Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain – PubMed
GI, cardiovascular, autonomic and allergic manifestations are significantly more prevalent in EDS patients compared with hospitalized patients without EDS. Physicians should consider EDS in patients with unexplained GI, cardiovascular, autonomic and allergic conditions and exercise precautions when treating EDS patients in a hospital setting.
Prevalence of gastrointestinal, cardiovascular, autonomic and allergic manifestations in hospitalized patients with Ehlers-Danlos syndrome: a case-control study – PubMed
There are strong links between neurodivergence and symptomatic hypermobility, and this is an exciting area of research we are supporting. It is likely that connective tissues are different than the general population in some of these neurodivergences.
FAQ | SEDSConnective
Neurodivergent people are more than twice as likely as the general population to have hypermobile joints and are far more likely to experience pain on a regular basis, according to new research.
Neurodivergent people more likely to experience pain, due to hypermobility – BSMS
Fibromyalgia
The Association Between Fibromyalgia, Hypermobility and Neurodivergence Extends to Families: Brief Report – Article (Preprint v5) by Clive Kelly | Qeios
- Many patients presenting with fibromyalgia have features of neurodivergence
- This combination is strongly associated with the presence of joint hypermobility
- The relatives of these patients also report an increased prevalence of all three conditions
Fibromyalgia (FM) has an estimated lifetime prevalence in the west of 0.2-6.8% . Clinical experience suggests patients are presenting to rheumatology specialists with the combination of FM and symptomatic hypermobile Ehlers-Danlos syndrome (hEDS) at a younger age than a decade ago. Case studies prompted interest in the potential overlap between fibromyalgia (FM) and attention deficit hyperactivity disorder (ADHD) over a decade ago and high rates of prior ADHD were reported among women who later presented with features of FM . The term ’neurodivergence’ incorporates conditions such as ADHD, autism and Tourette’s syndrome and further observations confirmed that a quarter of people with neurodivergence had FM , commensurate with a report that the prevalence of ADHD was raised in Dutch women with FM . This association was soon confirmed by van Rensburg who demonstrated that 45% of FM patients also had ADHD . Both conditions are associated with lower circulating levels of dopamine, with evidence of an overlap in the gene coding for dopamine receptor function, which is thought to explain some of the personality traits associated with each condition .
A Spanish study highlighted the overlap between autism, hEDS and FM and suggested that neurodivergent conditions in general were associated with both chronic pain and hEDS . A high prevalence of joint hypermobility was recorded among women with ADHD , and hEDS itself was linked to the presence of several of the personality traits described among both people with chronic musculoskeletal pain and those with ADHD . Eccles et al demonstrated that brain structure was different among people with hEDS and suggested that this explained many of the psychiatric features which mirrored those observed in neurodivergent conditions .
Psychological distress in early life was suggested as a predisposing factor for chronic pain, especially if adverse childhood experiences (ACE) included lack of parental support or validation which were also associated with personality traits seen in neurodivergence . Considering mechanisms by which these diagnoses may occur, Khalil suggested that ADHD may trigger FM via central sensitisation, consequent upon ACEs , and that this might explain the pain and motor distress seen in FM. Stimulants given for ADHD have been described as both reducing pain and improving cognitive dysfunction, the latter being a hallmark of FM (‘fibrofog’) . A French study emphasised the extensive co-occurrence associated with ADHD and the overlap with both widespread musculoskeletal pain and personality disorders. They also noted that fatigue was a major aspect of ADHD, and that associated sleep disturbance was common . They suggested that the prevalence and severity of co-occurring conditions increased with age, and this was supported by Asztely who demonstrated that 77% of neurodivergent women developed chronic musculoskeletal pain in later life . Although most literature on the overlap between FM and neurodivergence has come from Europe, there is evidence that the relationship between these conditions also applies to populations in the Far East .
More recently, hypermobility was observed in over half of a neurodivergent group with an odds ratio of 4.5 compared to a comparison group. The extent of hypermobility mediated the relationship between neurodivergence and both dysautonomia and musculoskeletal pain . Casanova et al. reviewed the evidence linking neurobehavioral and pain syndromes with dysautonomia and dysregulation of the immune system. They reported significant genetic overlap between each of neurodivergence, hEDS and FM, suggesting that hypermobility and pain may even be considered as aspects of autism .
Clinical experience has revealed that many patients presenting with FM and hEDS also report symptoms of chronic pain and mental health issues among their family members. Although the links between these conditions are now recognised among patient populations, we are unaware of any previous studies of the frequency with which they occur within families of those affected. An increased prevalence within close relatives might be expected given the genetic overlap between these disorders. Our objective was to investigate the incidence of diagnosed FM, hEDS and neurodivergence within first-and second-degree relatives of index cases with both FM and hEDS to assess whether this is greater than that observed within a comparison group of index cases attending the same clinical service but with a different musculoskeletal diagnosis.
The Association Between Fibromyalgia, Hypermobility and Neurodivergence Extends to Families: Brief Report – Article (Preprint v5) by Clive Kelly | Qeios
The incidence of diagnosed neurodivergent conditions within first-and second-degree relatives of index cases with both FM and hypermobility was significantly greater than that observed within a comparison group of relatives. We included OA patients and their families as appropriate comparator controls as many immune disorders are increased in prevalence among neurodivergent people. In addition, the incidence of both FM and hypermobility were also increased among close relatives of those with these conditions, with the rates highest among neurodivergent relatives. This supports previous findings of overlap between these disorders and strongly suggests that neurodivergent people are at much greater risk of developing FM .
Neurodivergent conditions are present from birth and therefore predate the onset of both HSD and FM. However, symptoms arising from these conditions are very varied and may not be recognised as being due to neurodivergence until adult life. This is more often the case for females than males, and within trans and non-binary people, which may increase their psychological distress and promote anxiety. Overlapping psychological features are described among females with FM and ADHD females . Chronic pain may be consequent upon central sensitisation, which can develop in more than three-quarters of women with ADHD over time and this study suggests that similar trends are found among their close relatives.
The presence of hypermobility may mediate the relationship between neurodivergence and chronic pain in FM . Psychological distress in early life is suggested as a predisposing factor for chronic pain, especially if adverse childhood experiences (ACEs) included lack of parental support or validation which may produce personality traits resembling those seen in neurodivergence . As the present study demonstrated, females are disproportionately overrepresented within these pain populations, in contrast to the distribution of neurodivergent conditions in the community where diagnosis in males is more common, perhaps due to underdiagnosis in younger females. Many females obtain their diagnosis of neurodivergence during their teenage years or in early adulthood, while males are often diagnosed at an earlier age. Further research should focus on screening for neurodivergent conditions among patients referred to services for the management of chronic pain so that appropriate support and intervention can be offered. The association between FM and neurodivergent conditions is under-appreciated by many clinicians working in these areas and the promotion of greater awareness and understanding of the overlap between these conditions would benefit patients and clinicians alike. This study is very relevant to today’s society where many young people are struggling with their identity. Pain in all its manifestations can be associated with this process, and it is important for health-care professionals to recognise this. Understanding how best to respond to young people’s emotional and social issues is fundamental to providing an efficient and cost-effective health system.
Power calculations prior to the study were performed and the results used to guide the study design. Despite small numbers, the results were highly significant, supporting the validity of this approach. However, we acknowledge that this is a small study with significant limitations which include the fact that all data relied on self-reporting and that reported diagnoses were not independently verified. The lack of an objective determination of each diagnosis limits the results’ internal and external validity. This could have led to an overestimate of the prevalence of neurodivergence, FM or hypermobility because of greater awareness of these conditions within affected families. By contrast, it is also possible that the reported prevalence estimates may be an underestimate, as not all relatives would have undergone diagnostic assessment for their symptoms, which may not have yet evolved in younger family members.
An overlap of genes coding for neurodivergence and for symptomatic hEDS has been reported . This may explain some of relationship between the three conditions although further research is needed to confirm the extent of this association . However, it is becoming evident that the relationship between FM and neurodivergent traits is not confined to patient populations. Recent work has shown a strong correlation between FM and autistic traits in a large, self-selected adult community population , mediated by a combination of hypermobility and food intolerance . Clearly, more work is needed to assess the risk factors for chronic musculoskeletal pain among neurodivergent people both in diagnosed populations and in the community if we are to learn how to intervene early and effectively. It is essential that the voices of neurodivergent people are listened to and that their input to this process is sought .
The Association Between Fibromyalgia, Hypermobility and Neurodivergence Extends to Families: Brief Report – Article (Preprint v5) by Clive Kelly | Qeios
This study confirmed a high prevalence of neurodivergence among patients presenting to a hospital clinical with features of FM and hEDS. Furthermore, close relatives of these patients’ self-reported increased levels of neurodivergence, FM and hypermobility among themselves. Those relatives who reported a diagnosis of neurodivergence also reported higher percentages of diagnosed FM and hypermobility.
The Association Between Fibromyalgia, Hypermobility and Neurodivergence Extends to Families: Brief Report – Article (Preprint v5) by Clive Kelly | Qeios
