Psychological interventions for individuals with Ehlers-Danlos syndrome and hypermobility spectrum disorder: a scoping review

Purpose To identify the nature and extent of the evidence on psychological interventions among individuals with Ehlers-Danlos Syndrome (EDS) and Hypermobility Spectrum Disorder (HSD). Materials and methods Eligible studies reported on psychological interventions for individuals of all ages with EDS and/or HSD. All studies published in English were included, with no restrictions to publication year or status. MEDLINE, CINAHL, EMBASE, and PsycINFO were searched. Two reviewers independently screened studies and abstracted data. Results This scoping review included 10 studies reporting on EDS, HSD, or both. Only cohort studies and case studies were identified. Four studies investigated Cognitive Behavioural Therapy (CBT), one investigated Dialectical Behavioural Therapy (DBT), two investigated psychoeducation, two investigated Intensive Interdisciplinary Pain Treatment (IIPT), and one investigated Acceptance Commitment Therapy (ACT). Interventions targeted pain management, self-destructive behaviours, and related psychological issues (e.g., depression/anxiety). Sample sizes were small (n < 50) for most studies and interventions were generally poorly described. Conclusions There is a critical need for high-quality research surrounding psychological interventions for individuals with EDS/HSD. Psychological interventions for these individuals are understudied and existing studies lack validity. Researchers should investigate psychological interventions for individuals with all types of EDS/HSD with high-quality studies to validate findings from the existing studies. Supplementary Information The online version contains supplementary material available at 10.1186/s13023-023-02799-y.


Background
Ehlers-Danlos Syndrome (EDS) comprises a group of rare hereditary connective tissue disorders characterized by several shared clinical features such as joint hypermobility and hyper-extensible skin [1].EDS is estimated to affect between 1 in 2500 and 1 in 5000 people globally [2].Many individuals with EDS have frailty of soft tissue and blood vessels among other conditions which may contribute to chronic and severe disabilities, greatly affecting their quality of life and mortality [1].While some individuals are asymptomatic for their entire lives, many others experience multi-systemic and multi-factorial complications, including neurological, gastrointestinal, and cardiovascular complications, breathing difficulties, organ rupture, joint dislocation, and chronic pain [2][3][4][5].Currently, thirteen subtypes have been officially recognized, all of which are caused by different gene variants and have different manifestations [2,6].The six predominant types of EDS are classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis.Classical, hypermobile and vascular EDS are the most prevalent, accounting for 79% of the EDS population [6], while hypermobile EDS (formerly EDS type III) is the most common subtype overall [7].
Hypermobility Spectrum Disorder (HSD), formerly known as Joint Hypermobility Syndrome (JHS), is diagnosed in individuals with generalized joint hypermobility, fatigue, and chronic pain [8].HSD/JHS is occasionally classified as a milder variant of hypermobile EDS by health authorities because the two conditions share many clinical features, although this classification is not widely used [9].The condition is prevalent in at least 3% of the general population and it is diagnosed only after other conditions, including any of the EDS subtypes, have been excluded [9].Patients with HSD are often predisposed to soft tissue injury as well as slow and incomplete healing [10].Complications associated with HSD may inlude central and peripheral nervous system abnormalities; for example, many experience increased pain, resistance to local anesthetics, and gastrointestinal complications [10].
There is no known cure for EDS or HSD, and they are often difficult to diagnose since clinical presentation may vary greatly between patients and there is a lack of specific genetic tests [11].Many symptoms of EDS and HSD are also shared with other diagnoses, such as chronic fatigue syndrome, Marfan syndrome, and osteogenesis imperfecta [12,13].These difficulties often lead to a greater time to diagnosis compared to other diagnoses with similar symptom profiles (e.g., Marfan syndrome), which may be easily identified clinically and genetically [14,15].In a qualitative study of adults with EDS, it was revealed that many had shown symptoms as children that were overlooked and misdiagnosed by their families and healthcare professionals [16].This makes EDS and HSD of concern from a lifespan perspective, as lifelong health complaints are rarely investigated but are important to address throughout a person's development.In the qualitative study, those who were diagnosed as adults experienced unbearable pain and fatigue as their unaddressed symptoms worsened during their development into adulthood [16].

Psychiatric burden of EDS and HSD
In addition to the physiological impairments mentioned above, psychiatric disorders and psychosocial impairment are also common among individuals with EDS and HSD.Specifically, EDS and HSD have been associated with increased risk of conditions such as depression and anxiety as well as interpersonal issues when compared to the general population [17][18][19][20][21].In a cohort study of 106 patients with hypermobility-type EDS, Hershenfeld et al. [22] determined that psychiatric disorders were found in 42.5% of the cohort, with 22.7% of patients affected with 2 or more psychiatric diagnoses.Anxiety and depression were the most reported, with frequencies of 23.6% and 25.5%, respectively.This is notably higher compared to 17.6% of psychiatric disorders in the general population [23].Moreover, the presence of any pain symptom was associated with nearly 10 times greater odds of having a psychiatric disorder.
The exact reasons for the high rates of psychiatric disorders are unclear, but it is likely that the aforementioned physical symptoms (e.g., chronic pain and other medically unexplained symptoms) play a major role [20].Notably, the high prevalence of chronic pain in the EDS population is one of the many contributing factors that are hypothesized to be associated with high rates of psychosocial impairment [19].For example, many patients are misdiagnosed for years or accused of malingering, leading to mistrust of the medical/health care system and self-doubt [19].Furthermore, previous research has demonstrated that individuals with joint hypermobility have an altered sense of body awareness, which may play a role in emotional response and has been shown to mediate the relationship between joint hypermobility and anxiety [21].For example, Mallorquí-Bagué et al. [24] found that hypermobile individuals experienced significantly higher state anxiety compared to those who were not hypermobile and that this relationship was mediated by interoceptive sensitivity (i.e., enhanced body awareness).

Importance of psychological interventions
EDS may be managed with a variety of treatment options including physical therapy, nonsteroidal anti-inflammatory drugs, acetaminophen, opioid medications, and surgery, as well as non-traditional or complementary modalities including acupuncture and massage [25].However, previous studies by Rombaut and colleagues [26] and Grahame [27] highlighted limitations of common pharmacological and physical interventions, noting that analgesics, nonsteroidal anti-inflammatory drugs, psychotropics, and physiotherapy are often ineffective to address pain among individuals with EDS.In addition, individuals with EDS experience increased side effects of pain medications [28]; orthopedic procedures are indicated for pain relief in only selected patients [29].Thus, it has been suggested that psychological approaches [30,31], particularly to address chronic pain observed among individuals with EDS, may be helpful for recovery and rehabilitation.In a pilot study of 12 women with EDS, Bathen and colleagues [32] investigated a multidisciplinary rehabilitation program combining physical and cognitive behavioural therapy (CBT).Decreases in self-perceived pain were reported as well as increased participation in daily life.Such findings parallel those seen in patients with chronic pain [33], suggesting that such interventions may be readily adapted to meet the needs of patients with EDS and HSD.

Gaps in research on psychological interventions
Despite these promising outcomes, it has been suggested that more research is needed on relevant psychosocial strategies for individuals with EDS [31].Rombaut and colleagues [26] also emphasized the need for evidencebased recommendations for the optimal management of EDS, which includes psychological follow-up.Similarly, there is a lack of high-quality clinical guidelines for managing the psychosocial complexities associated with pain in EDS, limiting evidence-based practice [34].Furthermore, patient partners have been previously recognized as important contributors to developing (psychosocial) treatment options in EDS, but their expertise has not been leveraged to date [34].Overall, our study aims to examine the nature and extent of the current evidence on psychological interventions for individuals with EDS and HSD, identifying any gaps in research and providing suggestions for future research areas.

Design and search strategy and information sources
This review used the Joanna Briggs Institute methodological framework for the current scoping review with reference to Arksey and O'Malley's framework as well [35,36].These frameworks outline six main stages involved in a scoping review: (1) identifying the research question; (2) identifying relevant studies; (3) selecting studies; (4) charting the data; (5) collating, summarising and reporting the results; and (6) consulting with relevant stakeholders.Scoping reviews are conducted to determine the nature of existing evidence and to analyze and identify knowledge gaps, rather than to provide a detailed appraisal and assessment of the quality of the literature [35].Thus, a critical appraisal of the included studies is not required.The last stage of our project will be achieved via ongoing consultation with our integrated knowledge translation (iKT) Advisory Group, consisting of individuals with EDS and HSD.The overall project uses a collaborative iKT approach that engages all relevant knowledge users and stakeholders (i.e., researchers, clinicians, and patient partners) in the full spectrum of research activities such as setting the objectives and methods and implementation of the research [37].Our patient partners also contributed to informing our search strategy development and interpretation of results.The PRISMA-ScR checklist guided the reporting of this review [38].

Eligibility criteria
Studies involving the use of psychological interventions for individuals with EDS and/or HSD were included.We defined psychological interventions as those that aim to enhance coping strategies (e.g., for pain and resiliency) and address stress or low mood, either alone or in combination.This definition was previously used for a Cochrane systematic review and meta-analysis on psychological interventions for coronary heart disease [39].Examples of psychological interventions include cognitive behavioural therapy (CBT), motivational interviewing, acceptance and commitment therapy (ACT), and mindfulness.We only included studies where the psychological interventions were delivered by health care professionals who had been trained in their delivery (including both individuals who hold a clinical degree and those whose training was described within the study).Studies with participants of all ages were included.Our scoping review included experimental studies (randomized controlled trials (RCTs), cluster RCTs, quasi-randomized trials, and controlled clinical trials), quasi-experimental studies (including interrupted time series and controlled before and after studies), observational studies, and qualitative studies.We included studies regardless of publication status, including the grey literature.Our search strategy included English-language studies only and had no restrictions with respect to publication year.

Search strategy and information sources
Literature search strategies using subject headings and text words related to psychological interventions for individuals with EDS and/or HSD were developed from two systematic reviews [39,40], as well as the search strategy used by our research team on psychological interventions for adults with cerebral palsy, childhood-onset acquired brain injury, and spina bifida [41].A sample search strategy from CINAHL can be found in Additional file 1.A librarian with extensive experience in conducting systematic and scoping reviews conducted all of the literature searches in consultation with the research team.Experts in the field of EDS and HSD, including members of our research team, were consulted to ensure that all relevant data was obtained.A comprehensive literature search was run in Ovid MEDLINE, Ovid MEDLINE Daily, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, OVID EMBASE, OVID PsycINFO, and EBSCOhost CINAHL on March 28, 2021.Duplicates were removed using Zotero's duplicate identification strategy as well as manually.Appropriate wildcards were used in the search to account for plurals and variations in spelling.A grey literature search was performed by searching targeted websites (i.e., Ehlers-Danlos Society, Ehlers-Danlos Support UK, Marfan Foundation) as recommended by members of our research team.The team developed inclusion and exclusion criteria screening questions and forms for the title and abstract screening (level 1 screening), fulltext screening (level 2 screening), and abstraction.

Selection of articles and data abstraction
To increase the reliability of screening among reviewers, a pilot test of a pre-defined screening form based on the eligibility criteria was performed on a random 1% sample, and reviewers reported 90% agreement or higher before moving on to full screening.The inclusion and exclusion criteria were discussed and clarified to promote the consistent application of the selection criteria if necessary.All title and abstract screening (i.e., level 1 screening) identified by the literature search were performed independently, in duplicate.The full text of the potentially relevant articles was acquired and screened to determine final inclusion (i.e., level 2 screening).Level 2 screening was performed independently and in duplicate.Discrepancies were resolved by discussion or by a third reviewer, if necessary.Studies excluded during the screening phase were documented along with an explanation for exclusion.
Data abstracted from the publications included study characteristics (e.g., author names, year of publication, country of study conduct, study design, sample size, setting characteristics), participant characteristics (e.g., EDS and/or HSD, age, sex, race, etc.), psychological intervention characteristics, and outcome results.We used the Template for Intervention Description and Replication (TIDieR) checklist and guide [42] to inform the data abstraction on the psychological interventions.This guide includes how, when, where, and how much the intervention was delivered, as well as whether any modifications or tailoring were made/are recommended [43].The data abstraction form was pilot-tested and modified accordingly.Data abstraction was performed independently and in duplicate.Discrepancies were resolved by discussion or by a third reviewer, if necessary.The data from this scoping review were summarised quantitatively using numerical counts and as well as qualitatively using content analysis.Data are organized in the tables by type of psychological intervention.

Results
MEDLINE, EMBASE, PsychINFO, and CINAHL retrieved 727, 4164, 128, and 331 studies, respectively.Our grey literature search found two unpublished reports from Ehlers-Danlos Support UK and one unpublished report from Ehlers-Danlos Society; the authors were contacted but we were unable to obtain the full reports.A flowchart of the results of the study selection process is provided in Fig. 1.The initial search yielded a total of 5350 articles; after duplicates were removed, 4420 articles underwent initial (level 1) screening.Subsequently, 30 articles were eligible for full-text screening, of which 20 were excluded, leaving 10 studies for data abstraction.

Participant characteristics
There were 258 total participants in the ten studies included in our review.Sample sizes ranged from 1 (case report) to 95 (cohort study), with participants ranging in age from 9 to 51 years (note that some studies only provided a mean age, rather than an age range).Most studies (80%) had a small sample size (n < 50), which may be partly attributed to the study types (i.e., many were case studies).Nine of the ten studies included a higher proportion of female participants (90-100%) compared to males, with only one case study featuring a male patient.The ten studies included participants with EDS (hypermobile [32,44,48,51,52], classic [45], vascular [47], or unspecified [46,50,52] subtype) and/or JHS [32,44,49,51].JHS would be presently referred to as HSD.Three of the studies reported including individuals with comorbid conditions (i.e., Cornelia de Lange syndrome [45], Emotionally Unstable Personality Disorder (EUPD) [46], and Postural Orthostatic Tachycardia Syndrome (POTS) [47]) while the other seven did not indicate whether patients with mental or physical health comorbidities were excluded from participation.

Intervention characteristics
Table 2 describes the characteristics and results of the interventions.Nine of the ten studies described multidisciplinary interventions (i.e., interventions which administered more than one treatment modality) to treat EDS/JHS (all except Knowlton et al. [47]).Most of the studies (n = 8) aimed to provide patients with tools and techniques to manage pain independently and overcome functional limitations associated with their conditions, while the other studies (n = 2) focused on minimizing disruptive and harmful behaviours (i.e., self-harm) [45,46].CBT was a common psychological treatment used in the included interventions (n = 4) [32,44,46,49].Half (n = 5) of the studies used a combination of pharmacotherapy (e.g., medications) with some form of psychotherapy (e.g., CBT) [44-46, 51, 52].The multidisciplinary interventions (n = 9) used a combination of psychological therapy along with physiotherapy, occupational therapy, and/or physical exercise programming.For example, Henry et al. [46] used a combination of Dialectical Behavioural Therapy (DBT), pharmacotherapy, occupational therapy, and physiotherapy.
Interventions were administered by a multidisciplinary team for most of the studies (n = 8) [32,44,46,[48][49][50][51][52], while one study did not clearly describe the administrators [45] and one study had only one administrator (postmaster's clinical psychology Ph.D. student) [47].For all ten studies, the administrator of the psychological intervention specifically was not clearly described, although it could be assumed that the psychologists and therapists

None
JHS would be presently known as HSD were the administrators for those interventions which listed these professionals as part of the team.All interventions were administered in person; six interventions were administered on an in-patient basis (in clinic or in hospital) [32, 44-46, 48, 50], three interventions were administered on an out-patient basis [47,49,51], and one study did not describe whether the intervention was delivered on an in-patient or out-patient basis [52].
The duration of the interventions ranged from 5 days to 21 months for nine studies, while one study did not clearly describe the length of the intervention [52].The intensity of the interventions was not clearly described for seven studies [32, 44-46, 48, 49, 52]; the intensity of the other three interventions ranged from 45 min to 6 h in length per day [47,50,51].
In terms of outcome measures, two of the studies did not outline clear outcome measures [44,45], while the other eight listed multiple outcome measures which included at least one that measured pain levels.All the interventions resulted in some improvements in outcome measures from admission to follow-up (i.e., decrease in pain, decrease in depression), although two studies did not report significant results [44,46].Three of the interventions received modifications and/or tailoring before or during their administration: Chaleat-Valayer et al. [48] altered the program to be 5 days of hospitalization instead of 5 half-days at a day hospital (reasoning unclear; the decision was made following initial evaluation of the sessions), Revivo et al. [51] individuated treatment plans based on patient need (details not provided), and Rahman, Daniel, and Grahame [49] tailored the daily program design to accommodate the needs of each group of patients receiving treatment over the years (details not provided).

Psychological treatment component characteristics
Four of the studies included treatments using CBT techniques as the psychological intervention, one study investigated a DBT approach, two of the studies investigated programs focused on psychoeducation, two of the studies applied an intensive interdisciplinary pain program (IIPT), and one study used an ACT approach.

Cognitive behavioural therapy (CBT)
CBT is a form of psychotherapy that is commonly used to address pain management, disability, and other mental health challenges in individuals with chronic illness by providing the patient with tools to identify and cope with these challenges [32].Bathen et al. 's cohort study [32] investigated a program that used a CBT approach for all intervention components (e.g., exercise groups, pain management groups, and lectures) which were aimed at providing participants with EDS hypermobility type (EDS-HT) and JHS with tools to manage pain and activity limitations.Additional details about the approach were not provided.The rehabilitation program took place over the course of 2.5 weeks and session lengths ranged from 30 to 120 min.It was followed by a 12-week at-home exercise program.The program resulted in a significant change in the perceived performance of daily activities, a significant increase in muscle strength and endurance, and a significant reduction in kinesiophobia.
Branson et al. 's case report [44] investigated a 21-month two-phase program consisting of regular psychologist appointments along with other treatment sessions (e.g., physiotherapy and medication) to manage pain and nonacute joint events in patients with EDS-HT and JHS.The participant was taught pain management and CBT methods (i.e., breathing techniques, positive self-talk, and distraction).Session lengths and intensity were not clearly described.After the first five months of inpatient treatment, the participant continued to receive outpatient psychological treatment.The participant was ultimately able to manage her pain competently using CBT techniques in conjunction with pain medications (mirtazapine, gabapentin, and acetaminophen and naproxen, as needed).
Rahman, Daniel, and Grahame's cohort study [49] investigated a 6-week multidisciplinary pain management program that used CBT techniques for individuals with JHS-related pain.The program consisted of psychology sessions as well as physiotherapy and multidisciplinary sessions over 8 full days (42 h in total).Psychologists and physiologists both used CBT principles and worked closely with each other in sessions, although the principles were not specified in the study.Ultimately, participants had statistically significant improvements in all outcome measures (i.e., self-efficacy, depression, anxiety, frustration, impact of pain, average pain intensity, and pain catastrophizing) between baseline and 1-month follow-up, most of which were sustained at 5-month follow-up.
Zhou, Rewari, and Shanthanna's two case reports [52] investigated a 6-session pain management program for individuals with EDS.Both patients were treated using a multidisciplinary program, daily medications, pain and self-management sessions, CBT, graded exercises, coping, and relaxation strategies by a multidisciplinary team of pain physicians, nurses, pain psychologists, and kinesiologists.In addition to the above, the patient in case report 1 was provided education about postural awareness and improved body mechanics during work and relaxation, and the patient in Case 2 was also provided with tools for physical and mental relaxation (e.g., mindfulness).Session intensity and lengths were not described.Ultimately, both patients had significantly improved pain control and improvement in daily living post-intervention.

Dialectical behavioral therapy (DBT)
DBT is a type of CBT that uses strategies such as mindfulness, distress tolerance, and emotion regulation to improve the patient's quality of life [46].Henry et al. 's case report [46] investigated a year-long inpatient treatment program (Springbank Treatment Programme) aimed at reducing self-harm and promoting independence in a patient with EUPD, as well as comorbid EDS (unspecified type) and Functional Neurological Disorder.The program consisted of DBT as the psychological treatment along with pharmacotherapy, occupational therapy, and physiotherapy.The DBT portion of the treatment included emotional regulation and mindfulness techniques to reduce self-harm tendencies.The participant is noted to have completed two cycles of DBT skills training along with 12 months of one-on-one sessions, but intensity and frequency were not described further than that.The participant saw improvements in all nine outcome measures assessing symptomology, quality of life, mindfulness, and recovery at discharge which persisted at 6-month follow-up.It is notable that the DBT was used primarily to reduce self-harm behaviours associated with the participant's comorbid severe EUPD, while her EDS-related mobility problems were primarily targeted by physiotherapy.

Psychoeducational programs
Psychoeducation, also known as therapeutic patient education, helps patients with chronic diseases manage their lives effectively through education about their disease and treatment [48].Chaleat-Valayer et al. 's cohort study [48] investigated a therapeutic education program (PrE-duSED) for patients with hypermobile EDS that consisted of 10 workshops.Each workshop was structured around a unique objective (e.g., to teach relaxation, to educate about EDS) and the program took place over 5 days.The program was designed for both the patients with EDS as well as their relatives.Overall, patients saw a significant improvement in knowledge/skills, body image, and relationships but no significant changes were seen in terms of quality of life or pain coping strategies.Relatives had a significant improvement in skills and knowledge at the 6-month follow-up.
Cravero et al. 's case report [45] featured a psychoeducational treatment aimed at correcting challenging and disruptive behaviours causing bodily injury in patients with Cornelia de Lange Syndrome with comorbid EDS (classic type).This was administered in conjunction with medications to manage symptoms.This program took place over the course of 3 months during which the patient was hospitalized.The exact duration and intensity of the program were unspecified.The psychoeducational component of treatment involved a functional analysis of disruptive behaviours (i.e., identifying variables that influence challenging behaviours) and reinforcement of desired behaviours.Overall, significant clinical improvements were seen after 3 months of hospitalization; in the 2 years following discharge, the patient had a reduction in emergency room visits.

Intensive interdisciplinary treatment programs (IIPT)
IIPT treats chronic pain using a biopsychosocial model of health and illness and involves coordinated psychological and physical care.It may include nutrition, recreation, and expressive art therapies in addition to physical/ occupational/CBT therapies [50].Randall et al. 's cohort study [50] investigated an IIPT ranging from 3 to 6 weeks of daily therapy for patients with EDS and other pain disorders (e.g., Complex Regional Pain Syndrome).The psychological aspect consisted of psychotherapy (individual and group) for the patient (ages 8-19) and psychoeducational training for parents (not described).Other aspects of the program included individual/group physical therapy and occupational therapy.Details about the sessions were not provided beyond this description.Patient sessions (all aspects of the program) occurred over the course of 6 h daily while educational sessions for parents occurred over the course of 2 h per week.All outcome measures were measured at 5 years post-treatment.Ultimately, there was a statistically significant decrease in functional disability and clinically significant improvement was found for pain and function.Nearly 80% of respondents reported having no functional difficulties at follow-up, and 89% graduated high school on schedule.
Revivo et al. 's cohort study [51] also investigated an IIPT lasting 4-8 weeks that aimed to help patients with hypermobile type EDS and JHS with pain management.The program consisted of psychological counselling along with physical therapy, occupational therapy, and medication management.The psychological counselling included discussions of self-management strategies for pain and stress (e.g., coping self-statements) and relaxation techniques.Participants had 1-2 sessions per week lasting approximately 3-4 h each.Overall, participants saw a statistically significant reduction in average pain intensity ratings, improvements in physical and social daily functioning, and reductions in depression and painrelated anxiety.Almost all (97%) participants returned to school and most patients returned to valued activities (i.e., music, sports, etc.).

Acceptance and commitment therapy (ACT)
ACT is used to treat chronic pain and is a promising alternative for those who do not respond to CBT.It focuses on psychological flexibility and emphasizes accepting what's out of one's control and engaging in actions that will allow for a fulfilling life [47].Knowlton et al. 's case study [47] investigated an 8-month program called More to Life, which utilized an ACT approach for a patient with vascular type EDS.The program aimed to encourage patients to engage in actions that allow for a fulfilling life in face of disability by increasing psychological flexibility.This study was the only one to describe and evaluate a single discipline intervention.In this case study, the participant was taught ACT techniques over the course of 18 therapy sessions, lasting 45-50 min each.Each session focused on a different area of mindfulness and psychological flexibility (e.g., acceptance, core skills exercise, etc.).Ultimately, the participant saw clinically significant improvements in depression, psychological inflexibility, and flexibility related to pain.

Discussion
The purpose of this scoping review was to identify the nature and extent of studies investigating psychological interventions for individuals with EDS and HSD (formerly known as JHS).This review included five cohort studies, four case reports, and one study with two case reports.All included studies evaluated psychological interventions for patients with EDS and/or HSD.The most reported intervention was CBT.Notably, majority of participants were female across all studies.This is aligned with the prevalence of EDS and HSD in males and females; a UK cohort study showed that out of 6021 individuals diagnosed with EDS or HSD, roughly 70% were women [53].We also found that the majority of the treatment paradigms for EDS and/or HSD were multidisciplinary.It should be noted that the psychological components of the treatment plans were poorly described; many of the studies did not provide information detailing the intensity, duration, and/or frequency of interventions.Additionally, the results of case studies may not be generalizable to others within the cohort, and many of the cohort studies had relatively small sample sizes (n < 50).Overall, our findings show that there is a lack of high-quality research on psychological interventions for individuals with EDS and HSD.This is especially problematic because of the high prevalence of psychiatric disorders among individuals with EDS and HSD, which is becoming increasingly evident [54,55].Our review adds to the existing commentary about the significance of psychological burden for these individuals while emphasizing the alarming lack of research in this area despite a critical need for appropriate treatments.

Notable psychological interventions within included studies
Most included studies reported significant improvements for their respective interventions in terms of pain, reduction of destructive behaviours, and/or other outcome measures including anxiety, depression, and quality of life.However, these results are inconclusive due to the lack of high-quality research surrounding psychological interventions for individuals with EDS and HSD (e.g., small sample sizes, study types with poor validity/reliability, lack of RCTs, etc.).Some interventions identified in our review have been previously explored in similar patient populations and are thus recommended for further investigation in patients with EDS and/or HSD.
Four of our included studies investigated a CBT approach.Notably, Bathen et al. 's cohort study [32] reported significant improvements in activity performance, performance satisfaction, physical strength and endurance, self-reported pain intensity, and a decrease in kinesiophobia.Rahman, Daniel, and Grahame's cohort study [49] reported significant improvements in pain and depressive symptoms.In accordance with these results, several meta-analyses and reviews have demonstrated the efficacy of CBT for managing pain and improving daily functioning and independence in patients with chronic pain disorders [56,57].For example, a review by Knoerl et al. [58] investigated CBT for adults with chronic pain associated with fibromyalgia and arthritis.The CBT treatment reduced pain intensity significantly in 43% of the included RCTs, and significant improvements in other outcomes such as depression and anxiety were also noted in over 50% of the trials testing these outcomes.However, it should be noted that many trials on CBT for individuals with chronic pain have not compared CBT groups to another active control group.Williams et al. 's systematic review [59] demonstrated that when compared with active controls, some small improvements were observed for CBT in terms of pain, disability, and distress for adults with chronic pain, but these improvements were not significant.While we cannot conclude the efficacy of CBT based on our study results due to a lack of high-quality research, CBT may be further investigated as a method of improving pain and daily functioning of patients with conditions such as EDS or HSD which also cause chronic pain and disability.
Two studies investigated a psychoeducational program.Notably, Chaleat-Valayer et al. 's cohort study [48] found significant improvements in the patients' self-image as well as the knowledge and skills of patients and their relatives.A 2021 systematic review by Gómez-de-Regil [60] on psychoeducational interventions for patients with fibromyalgia revealed that interventions were able to significantly improve patients' pain intensity, fatigue, sleep quality, depression, anxiety, functional ability cognitive impairment, and quality of life.These results are supported by studies investigating psychoeducation for individuals with chronic pain [61,62].While we cannot conclude the efficacy of psychoeducational programs for those with EDS/HSD due to a lack of high-quality research, research on similar patient populations shows that psychoeducational programs may be worth investigating to improve the knowledge and skills of individuals who live with chronic pain and disability (e.g., patients with EDS and their families).
Two studies investigated an IIPT program.Randall et al. 's cohort study [50] found significant decreases in functional disability from admission to follow-up, as well as significant improvements in pain and function.Revivo et al. 's cohort study [51] found significant improvements in average pain intensity, patient/parent functioning, daily functioning, depression, and pain-related anxiety.These findings are consistent with results from a systematic review investigating IIPTs for children with chronic pain [63], which found IIPTs may significantly improve pain symptoms as well as disability short-term; however, the review revealed that there is a lack of well-designed clinical trials investigating IIPT efficacy, so these conclusions may not be reliable.An observational study published by Zernikow et al. [64] investigated IIPTs for adolescents and children with chronic pain.The authors found that participants had a significant reduction in pain-related and psychological (anxiety, depression, pain catastrophizing) outcome measures, which were sustained at the four-year follow-up.Overall, previous studies investigating IIPTs for the management of pain and other symptoms have yielded promising results for the chronic pain population.Although we again cannot conclude the efficacy of IIPT for those with EDS/HSD, this intervention warrants further investigation with highquality studies for this population.

Potential psychological interventions not explored in our included studies
It is notable that some psychological interventions studied in chronic pain populations, which have demonstrated significant improvements in outcomes such as pain, depression, and anxiety, have not been studied in individuals with EDS and/or HSD, or at least were not identified in this review.For example, Motivational Interviewing (MI) is a technique focusing on resolving an individual's ambivalence toward behavioural change by strengthening their commitment and motivation to change [65].MI has been previously investigated for individuals struggling with chronic pain; a systematic review and meta-analysis by Alperstein and Sharpe [65] on MI for individuals with chronic pain identified that MI was able to significantly increase short-term adherence to prescribed treatment plans and significantly reduce pain in the short-term.While more research is required to validate these results, future studies may explore MI as a psychological approach for improved pain management and adherence to treatment plans for individuals with EDS and HSD.
Mindfulness-Based Stress Reduction (MBSR) is another promising psychological intervention for individuals with EDS/HSD.MBSR promotes a nonjudgemental approach to pain where the physical and psychological aspects of pain are uncoupled [66].This is typically achieved through meditation and mindfulness practices in which the patient increases their awareness of body signals and breath.Some of the studies in our review briefly outlined mindfulness techniques (e.g., relaxation), but none of the programs clearly identified or described mindfulness as the main psychological component.MBSR has been previously investigated as a treatment for pain in individuals with chronic lower back pain, headache, and fibromyalgia [66].A 2011 systematic review [67] found that MBSR may significantly decrease anxiety, stress, and depression while improving the quality of life of patients with diseases such as cancer as well as chronic pain disorders.Another systematic review by Abbott et al. [68] found similar results for patients with vascular disease in that MBSR was effective in improving depression, anxiety, and psychosocial stress.Thus, future studies should explore MBSR in treating psychological symptoms associated with EDS and HSD as well.

Notable gaps in existing research and future direction
Our review yielded only ten studies that investigated psychological interventions for individuals with EDS and/or HSD.Of these ten, half were single case reports; the remaining were retrospective cohort studies.Consequently, study results may not be generalizable to the overall cohort.RCTs should be conducted to reliably evaluate the effectiveness of these psychological interventions.Qualitative studies were also not identified in our review but may be a meaningful addition to the literature (i.e., to provide insight into patient experience).While it is encouraging that the existing research has focused on individually tailored programs given that research has shown the importance of tailored treatment plans in the successful management of chronic pain, future studies should investigate the efficacy of tailored treatment plans on a larger cohort for increased validity and reliability [69].Similarly, small sample sizes may affect the reliability of the cohort study outcomes.Two of the studies [32,51] explicitly recommended future studies use larger sample sizes to validate the results.Another notable limitation among included studies was the lack of validated outcome measures used in some studies.Branson et al. 's case report [44] relied on the patient's self-report and physical symptoms, while Cravero et al. 's case report [45] relied on physical signs.Future studies should use standardized outcome measures for increased validity of findings.Lastly, one case report [46] included in our study focused heavily on the patient's other comorbidity (EUPD) rather than their EDS, which may confound its findings (i.e., Henry et al. 's [46] intervention may be better suited for individuals with EUPD rather than EDS).
An important finding among our included studies is that the psychological interventions were often not well-described.Many of the interventions mentioned the underlying psychological methods in general terms (e.g., CBT techniques), but failed to describe the treatment details.It was thus often unclear where and how the technique was applied.For instance, Rahman, Daniel, and Grahame [49] stated that the administrators in their study applied principles of CBT in their interventions, but the authors did not provide further details regarding which principles were used and how those principles were integrated into the treatment plan.Furthermore, in many of the studies, the administrators of the psychological interventions were not clearly identified (e.g., described as a "multidisciplinary team") and it was also unclear what type of training these administrators received to provide these interventions.Future studies should outline the psychological interventions in greater detail in terms of their principles, how those principles were applied to the treatment plan, and who the treatment administrators were.Similarly, many studies did not provide details on participant demographics.The race/ethnicity of participants was provided for only four of the ten studies, and all participants were white/ Caucasian.Future studies should include a more detailed demographic profile of its participants to establish the external validity of the treatments for a diverse population (e.g., determine if an intervention is suitable for individuals of different ethnicities).

Strengths and limitations
To our knowledge, this is the only existing scoping review that examines the literature on psychological interventions for individuals with EDS/HSD and identifies various gaps in existing research.It is strengthened by using an experienced information specialist to conduct an exhaustive literature search, as well as multiple reviewers to conduct screening and data extraction independently, in duplicate.The multidisciplinary expertise of our research team (e.g., EDS content experts, methodology experts) helped to strengthen the review, as well as our lifespan approach (e.g., we broadened our search and inclusion criteria to investigate individuals of all ages, rather than just adult or pediatric patients).We also acknowledge some limitations.Since this review included English-language studies only, there may have been a bias toward the inclusion of studies from English-speaking countries.Additionally, we limited our grey literature to three websites (Ehlers-Danlos Society, Ehlers-Danlos Support UK, and Marfan Foundation) on the recommendation of the research team; consequently, we may have excluded important and relevant studies from other sources.Another possible limitation is the search of only MEDLINE, CINAHL, EMBASE, and PsycINFO databases; a wider array of databases may have yielded more articles for inclusion.Additionally, our literature search was conducted on March 28, 2021; thus, we were only able to include articles that had been published by this date, all of which happened to investigate in-person psychological interventions.We acknowledge that we may have missed interventions that were subsequently conducted and published, such as the online RCT by Kalisch and colleagues [70].It should also be noted that nine of the ten studies were multidisciplinary, meaning that the psychological intervention was only one part of the treatment plan.As a result, it is impossible to ascertain that the outcomes of the treatments were a result of the psychological interventions alone, meaning that the included studies in our review may not accurately reflect the effectiveness of psychological interventions (e.g., the outcomes may have been more influenced by other components of the treatment such as medication or physiotherapy).Overall, more studies are needed that focus on individuals with EDS/HSD to verify the effectiveness of such interventions.

Conclusion
This scoping review on psychological interventions for individuals with EDS and/or HSD identified a lack of high-quality research for this population.Only cohort studies and case reports were identified, and most of the participants were diagnosed with EDS hypermobility type or JHS/HSD.CBT, IIPT, and psychoeducation may be worth investigating further with high-quality studies, but no conclusions about their efficacy can be made presently.MI and MBSR are psychological interventions that may be effective in treating pain and symptoms associated with pain (e.g., depression, anxiety).These may be further investigated for individuals with EDS and HSD.Future studies should also investigate psychological interventions with participants with other forms of EDS, as well as with larger sample sizes and higher quality studies (e.g., RCTs).Furthermore, many of the studies included in our review lacked sufficient detail surrounding demographic information (i.e., race/ ethnicity) and description of the intervention (i.e., how the principles of CBT were applied to the treatment plan).This information should be provided in future studies to account for demographic variables in determining the efficacy of a treatment plan and to provide a clearer understanding of effective psychological techniques.Ultimately, many patients with EDS and HSD experience heightened psychological distress from their conditions, yet there is a lack of high-quality research investigating psychological interventions for these individuals, both alone and as a component of a multidisciplinary treatment plan.The results of our study may guide future researchers in designing high-quality studies to determine the most effective interventions for the rehabilitation of individuals with EDS and HSD, which may later be useful in guiding clinical practice.

Fig. 1
Fig. 1 Articles yielded from the literature search, title and abstract screening, and full-text screening.Diagram adopted from PRISMA

Table 1
Description of included studies and study participants

Table 1 (
continued) JHS would be presently known as HSD

Table 2
Description of Interventions for Individuals with EDS and/or HSD