Neurodevelopmental atypisms in the context of joint hypermobility, hypermobility spectrum disorders, and Ehlers-Danlos syndromes.

Joint hypermobility (JHM), defined as an increased range of joint motion, is a frequent somatic trait in the general population but also the hallmark of many of the hereditary disorders of connective tissue. Ehlers-Danlos syndromes (EDS) belong to this group of diseases and are characterized by tissue fragility, skin abnormalities, and JHM. Between JHM and EDS, there are the so-called hypermobility spectrum disorders (HSD), which is an umbrella term referring to people with symptomatic JHM who do not fulfill criteria for a syndromic connective tissue disorder such as EDS. Among the variety of clinical correlates of JHM/HSD/EDS, neurodevelopmental atypisms are common although often not screened for and identified in the clinical setting. This article reviews the pertinent literature concerning neurodevelopmental conditions for which there is some evidence of an association with JHM/HSD/EDS. These include hyperactivity and attention deficit, learning, communication, and motor problems including tic disorders such as Tourette syndrome and autism spectrum disorders. Underlying mechanism hypotheses for such interconnections are also reviewed. The coexistence of connective tissue-altered conditions and neurodevelopmental atypisms increases disability in patients from an early age. Thus, increased awareness among clinicians and researchers is necessary to promote assessment, diagnosis, and develop management strategies to meet the specific needs of those affected.

Updates on the psychological and psychiatric aspects of the Ehlers-Danlos syndromes and hypermobility spectrum disorders.

The field of the psychiatric and psychological aspects of Ehlers-Danlos syndromes (EDS) has been understudied and neglected for many years. People with EDS are often classified as "somatizers" by untrained clinicians. However, research on the biological basis of EDS is improving our understanding of the physiology and psychopathology of the disorder. In this article, we consider the literature on the psychopathological dimensions associated with EDS as well as the EDS symptoms in psychiatric conditions since our review in 2017. Literature confirms that psychological processes (i.e., fear, emotional distress, or negative emotions) in EDS have a significant impact on the outcomes of EDS. Common systemic associations are found between anxiety disorders and EDS as well as significant correlations with neurodevelopmental, eating, mood, and sleep disorders. There is limited but increasing evidence of an association between EDS and suicidal thoughts and behaviors, which should be further explored. The broad spectrum of human anxiety and associated somatic symptoms (beyond anxiety disorders) appears to be the core of the psychopathology in EDS and therefore, detecting and assessing EDS might be a new opportunity for psychiatric nosology to develop more inclusive phenotypes like the Neuroconnective Phenotype that include both somatic and psychological manifestations.

Gastrointestinal and eating problems in women with Ehlers-Danlos syndromes.

PURPOSE: Ehlers-Danlos syndromes (EDS) are a group of heritable conditions in which abnormal collagen synthesis leads to features such as joint hypermobility, skin abnormalities, and tissue fragility. Gastrointestinal (GI) symptoms are common among those affected. These may negatively impact eating behaviors, leading to weight/nutritional problems. We aimed to compare GI symptoms, disordered eating, and body mass index (BMI) between EDS patients and healthy controls, and to explore the link between these variables in EDS patients. METHOD: In this cross-sectional study, women with EDS and healthy controls responded to an online survey assessing GI symptoms (heartburn/regurgitations, early satiety, nausea/vomiting, bloating, abdominal pain, dysphagia), food allergies/intolerances, disordered eating, history of eating disorders (ED), and BMI. We performed intergroup comparisons as well as multivariate analyses to explore the associations between disordered eating, GI symptoms, and BMI in the EDS group. RESULTS: Sixty-six women with EDS and 39 healthy controls were included in the study. The EDS patients showed significantly more GI symptoms and food allergies/intolerances, increased prevalence of ED history, higher risk of current ED, and lower BMI than the controls. In the EDS group, the risk for ED was associated with GI symptoms; restricted eating was associated with GI symptoms, food allergies/intolerances, and dysphagia; uncontrolled eating was associated with GI symptoms; and BMI was associated with GI symptoms and food allergies/intolerances. DISCUSSION: Our results are concordant with that of previous reports highlighting the high level of GI problems and disordered eating in women with EDS. In addition, and for the first-time, the association between both is evidenced in this specific population. LEVEL OF EVIDENCE III: Case-control analytic study.

Study protocol of a multicenter randomized controlled trial of mindfulness-based intervention versus relaxation to reduce emotional exhaustion in medical students in France: the "Must prevent" study.

BACKGROUND: Medical students are exposed to an emotionally exhausting training/work environment and to stressful academic demands. Consequently, psychopathologies, burnout and suicidal ideation are frequent in this population. These factors can also affect their empathy and quality of care. Therefore, the development and implementation of programs to promote resilience to stress specifically in medical students and the evaluation of their efficiency are a priority. Here, we describe the protocol of the first French study to assess the long-term effectiveness and acceptability of a mindfulness-based intervention (MBI) compared with relaxation training (RT) to reduce emotional exhaustion in medical students. METHODS: This multicenter randomized controlled trial ("Must prevent") plans to enroll 612 students in the fourth and fifth year of medical studies from nine French universities. After inclusion, they will be assigned randomly to the MBI or RT group. Both interventions are structured around an 8-week program that includes one group class per week and daily at-home exercises. The primary endpoint is the emotional exhaustion score assessed with the Maslach Burnout Inventory at month 12 of the follow-up. Secondary endpoints include anxiety-depressive symptomatology, suicidality, psychoactive substance use, depersonalization, psychological and physical pain, empathy, emotional regulation, self-compassion, mindfulness, quality of life, and program acceptability. Evaluations will be done before and immediately after the 8-week intervention, and at month 6 and 12 of the post-intervention follow-up. DISCUSSION: If the proposed interventions are well accepted and useful to decrease negative emotions and/or increase wellbeing among medical students, they should be disseminated among this population and even included as part of the training on emotional skills needed for the routine medical practice. TRIAL REGISTRATION: This trial is registered under the number NCT04026594 (July 18, 2019).

[Effects of a standardized musical intervention on the management of pain and anxiety-state of sickle-cell adolescents]. / Effets d'une intervention musicale standardisée sur la gestion de la douleur et de l'anxiété-état des adolescents drépanocytaires.

The effect of a standardized musical intervention for adolescents with sickle cell disease was studied. Two groups were evaluated using the visual analog scale of pain and the anxiety-state inventory before and after a standardized musical intervention or breathing intervention. A significant decrease in scores was observed, most notably for the group benefiting from the standardized musical intervention. This intervention could be integrated into the overall management of adolescents with sickle cell disease.

Determinants of suboptimal medication adherence in patients with a major depressive episode.

BACKGROUND: Major Depression (MD) is often a chronic condition requiring a long-term pharmacologic treatment. Despite the efficacy of antidepressants, the medication adherence in those affected is usually very poor. In this scenario, further research concerning drivers of suboptimal adherence is needed. We aimed to explore medication adherence in patients with a MD episode, and to identify sociodemographic, clinical (psychiatric antecedents, comorbidities, medication, pain, and medication side effects), and psychosocial factors (negative life events, childhood trauma, and attitudes to medication) related to adherence status. METHOD: The Medication Adherence Rating Scale (MARS) was completed by 370 patients at hospital admission. Participants were divided into groups of optimal and suboptimal adherence based on the medication adherence behavior score (MARS's factor 1), and were compared with respect to the study variables. RESULTS: Twenty-nine percent of participants (n = 107) were found to be optimally adherents to their medication (score = 4/4). Compared to optimally adherents, suboptimally adherents (71%) presented a significantly higher depression severity, more psychiatric hospitalizations, suicidal ideation, physical pain, negative medication side effects, and antecedents of emotional maltreatment. Suboptimally adherents also had less favorable attitudes toward medication and were less in a relationship than optimally adherents. Multivariate analyses showed that depression severity, suicidal ideation, and physical pain increase the probability of belonging to the suboptimal adherent group. CONCLUSION: These results suggest a vicious circle in which more vulnerable patients are less adherent to medication, which could worsen the clinical picture maintaining, in turn, low adherence. More efforts are needed to develop interventions aiming to improve medication adherence in MD patients.

Low- and high-anxious hypermobile Ehlers-Danlos syndrome patients: comparison of psychosocial and health variables.

Despite the frequent co-ocurrence of hypermobile Ehler-Danlos syndrome (hEDS) and pathological anxiety, little is known about the psychosocial and health implications of such comorbidity. Our aim was to explore the association between high levels of anxiety and psychosocial (catastrophizing, kinesiophobia, somatosensory amplification, social support and functioning), health (pain, fatigue, BMI, tobacco/alcohol use, depression, diagnosis delay, general health), and sociodemographic factors in people with hEDS. In this cross-sectional study, 80 hEDS patients were divided into two groups according to self-reported anxiety levels: low and high. Psychosocial, sociodemographic and health variables were compared between the groups. Forty-one participants reported a high level of anxiety (51.2%). No differences were found in the sociodemographic variables between high-anxious and low-anxious patients. The percentage of participants with severe fatigue and high depressive symptomatology was significantly higher in the high-anxious group (80.5 vs 56.4; 26.8 vs 12.8%, respectively). High-anxious hEDS patients also showed significantly higher levels of pain catastrophizing, somatosensory amplification as well as a poorer social functioning and general health. Multivariate analyses showed that somatosensory amplification, pain catastrophizing and poor social functioning are variables that increase the probability of belonging to the high-anxious group. Despite limitations, this first study comparing high-anxious versus low-anxious hEDS patients with respect to health aspects, highlight the importance of considering the psychosocial factors (many susceptible to modification), to improve the adjustment to this chronic condition and provide support to those affected through a biopsychosocial approach.

Psychiatric and psychological aspects in the Ehlers-Danlos syndromes.

There is increasing amount of evidence pointing toward a high prevalence of psychiatric conditions among individuals with hypermobile type of Ehlers-Danlos syndrome (JHS/hEDS). A literature review confirms a strong association between anxiety disorders and JHSh/hEDS, and there is also limited but growing evidence that JHSh/hEDS is also associated with depression, eating, and neuro-developmental disorders as well as alcohol and tobacco misuse. The underlying mechanisms behind this association include genetic risks, autonomic nervous system dysfunction, increased exteroceptive and interoceptive mechanisms and decreased proprioception. Recent neuroimaging studies have also shown an increase response in emotion processing brain areas which could explain the high affective reactivity seen in JHS/hEDS. Management of these patients should include psychiatric and psychological approaches, not only to relieve the clinical conditions but also to improve abilities to cope through proper drug treatment, psychotherapy, and psychological rehabilitation adequately coupled with modern physiotherapy. A multidimensional approach to this "neuroconnective phenotype" should be implemented to ensure proper assessment and to guide for more specific treatments. Future lines of research should further explore the full dimension of the psychopathology associated with JHS/hEDS to define the nature of the relationship. © 2017 Wiley Periodicals, Inc.

Difficulty eating and significant weight loss in joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

Joint Hypermobility Syndrome, also known as Ehlers-Danlos Syndrome Hypermobility Type (JHS/EDS-HT), is a heritable disorder of connective tissue, common but poorly known by the medical community. Although generalized joint hypermobility and fragility of tissues have been described as core features, recent research highlights the multisystemic nature of JHS/EDS-HT, which presents with a wide range of articular and extra-articular symptoms. Among these, gastrointestinal problems, temporomandibular disorders, and smell and taste abnormalities are common among those affected, having significant implications for eating. The present work reviews the literature linking JHS/EDS-HT and eating problems. Two illustrative case reports, in which JHS/EDS-HT manifestations contribute to developing and maintaining disturbed eating behaviors and significant weight loss, are presented.

Joint hypermobility, anxiety and psychosomatics: two and a half decades of progress toward a new phenotype.

The strong association between a heritable collagen condition and anxiety was an unexpected finding that we first described in 1988 at the Hospital del Mar in Barcelona. Since then, several clinical and nonclinical studies have been carried out. In this paper, after summarizing the concept and diagnosis of joint hypermobility (hyperlaxity), we review case-control studies in both directions (anxiety in joint hypermobility and joint hypermobility in anxiety disorders) as well as studies on nonclinical samples, review papers and one incidence study. The collected evidence tends to confirm the strength of the association described two and a half decades ago. The common mechanisms that are involved in this association include genetics, autonomic nervous system dysfunctions and interoceptive and exteroceptive processes. Considering clinical and nonclinical data, pathophysiological mechanisms and the presented nosological status, we suggest a new Neuroconnective phenotype, which around a common core Anxiety-Collagen hyperlaxity, includes five dimensions: behavioral, psychopathology, somatic symptoms, somatosensory symptoms, and somatic illnesses. It is envisaged that new descriptions of anxiety disorders and of some psychosomatic conditions will emerge and that different nosological approaches will be required. The Neuroconnective model is a proposal that is under study and may be useful for clinical practice.

Ectomorphic somatotype and joint hypermobility are linked in panic and agoraphobic patients: a case-control study.

OBJECTIVE: To test whether there is an association between somatotype measures, joint hypermobility (JH), and panic and/or agoraphobia (PA). METHOD: Sociodemographic characteristics, somatotype, and JH status were assessed in 60 patients (30 men and 30 women) with PA and 60 non-clinical controls, matched by age and gender. RESULTS: Patients and controls categorized by gender did not differ in terms of age, educational degree, marital status, or labour situation. There were significant differences between mean somatotype groups both in men and women. Men and women somatotype patients were significantly less endomorphic and more ectomorphic than controls. Hypermobility was significantly more frequent in both male and female patients. In the entire sample, 38.3% of patients and 13.3% of controls were categorized as ectomorphic (χ(2) = 8.5, p = 0.004). After adjusting for age and sex, ectomorphic somatotype was independently related to JH status [OR = 3.25, 95% CI 1.35-7.8, p = 0.008]. CONCLUSIONS: Since PA may be associated with JH, it is suggested that the relationship found between panic and ectomorphic somatotype might be mediated through JH.

Joint hypermobility and sport: a review of advantages and disadvantages.

Joint hypermobility (JH) is a feature observed in several inherited conditions in which joints have a range of motion beyond normal limits. Such inherent flexibility makes it relatively easy for hypermobile people to perform certain physical activities, so this characteristic is particularly convenient for certain athletes. However JH also can carry some disadvantages: it has been associated to a higher risk of injury and to states of anxiety. The aim of this article is to provide an overview of the current evidence concerning the advantages and disadvantages of JH in the field of sport. We emphasize the importance of detecting JH in athletes in order to intervene appropriately through injury prevention programs, and emphasize how inherent anxiety may have a negative impact on sporting performance.

Joint Hypermobility and Fatigue Are Associated With Injuries in a Group of Preprofessional Ballet Dancers.

INTRODUCTION: Strenuous preprofessional ballet training places young students at an increased risk of injury. This represents a major concern for aspiring dancers since a link has been described between injury and dropping out. It is therefore important to identify physical and psychological factors related to injuries in dance for prevention purposes. METHODS: In this cross-sectional study, we explored the frequency and characteristics of injuries, as well as their physical and psychological determinants in preprofessional ballet dancers. Seventy-three participants (women = 75.6%; mean age = 13.7; SD = 1.8) were evaluated with the Beighton criteria for joint hypermobility and self-questionnaires assessing injuries in the last 18 months, fatigue, fear of injury, and motivation. RESULTS: Most of participants (61.6%) experienced injuries in the last 18 months, mainly in the lower limbs, and due to overuse. Multivariate analyses showed that joint hypermobility and fatigue predict injury status in this sample. CONCLUSION: These results confirm previous reports suggesting that physical factors such as fatigue and joint hypermobility, that are frequent in ballet dancers, should be taken into account in order to prevent injuries.

Are Palliative Care Volunteers Special People? A Comparative Observational Study Exploring Their Sociodemographic Profile and Psychological Resources.

BACKGROUND: Faced with rising needs for patient support, palliative care is shifting towards a more community-based approach. Yet the profile of volunteers in this field is poorly known. AIM: To explore psychosocial characteristics of palliative care volunteers, by comparing them to two groups, volunteers from the health and social sector without contact with palliative patients, and people from the general population without volunteer activity. DESIGN: Observational comparative study. Data were analyzed using descriptive statistics and logistic regression analysis. PARTICIPANTS: The 3 groups of participants were recruited in France between September 2020 and June 2021. They completed an online survey assessing sociodemographic characteristics and psychological resources (self-efficacy, hope, optimism, resilience, mindfulness, self-compassion, empathy, forgivingness, and gratitude). RESULTS: Data from 559 participants were analyzed. Palliative care volunteers had overall significantly higher levels of psychological resources than control groups. Multivariate analysis revealed, among sociodemographic and psychological characteristics that showed differences between groups at the univariate level, the most efficient predictors of group status. The best criteria to distinguish palliative care volunteers from health and social sector volunteers were older age, having received training, and lower levels of self-compassion. To distinguish palliative care volunteers from people with no volunteer activity, older age and non-active professional status were the best criteria. CONCLUSIONS: Palliative care volunteers displayed more psychological resources than controls. However, older age and being trained for volunteering, emerged as stronger factors for distinguishing palliative care volunteers from controls. Pursuing research about these volunteers should facilitate recruitment, training, and retention.

Association Between Activity Pacing and Negative Emotions in Patients With Chronic Pain: A Systematic Review.

OBJECTIVES: Chronic pain is a major health problem given its high prevalence and its multiple consequences on the physical and psychological functioning of patients. It is therefore important to determine the relationship between these consequences and pain management strategies such as activity pacing. This review aimed to examine the association between activity pacing and the level of negative emotions in chronic pain. A second objective was to explore sex differences in this association. METHODS: A systematic review of the literature was conducted following the PRISMA guidelines. Three independent reviewers used a combination of keywords within four databases to include studies examining the link between pacing and negative emotions in chronic pain. RESULTS: Pacing was associated with less negative emotions when measured using multidimensional tools, distinguishing it from avoidance, and highlighting the major components of pacing, such as maintaining a constant activity or conserving energy. Data did not allow examination of sex differences. DISCUSSION: Pacing is multidimensional and consists of various strategies of pain management which are not equally associated with negative emotions. It is important to use measures reflecting this conception to strengthen knowledges about the role of pacing in the development of negative emotions.

Adjustment to disease and quality of life in people with vascular Ehlers-Danlos and Loeys-Dietz syndromes: A mixed-method study.

Background: Vascular Ehlers-Danlos (vEDS) and Loeys-Dietz syndromes (LDS) are hereditary disorders of connective tissue having severe vascular complications (HDCTv) which lead to an increased risk of premature death. Little is known about the impact of the disease in patient's daily life. Method: Sixteen HDCTv patients (vEDS = 9 and LDS = 7), 16 age and sex-matched hypermobile Ehlers-Danlos syndrome patients (hEDS) and 18 healthy subjects (HS), responded to self-questionnaires assessing psychosocial adjustment, quality of life (QoL), anxiety, depression, pain, fatigue and sleep problems. Patients with HDCTv were also interviewed in order to explore qualitatively their experience with the disease. Results: Compared with HS, patients with HDCTv scored significantly higher on anxiety, depression, fatigue, sleep problems, and lower on QoL. Most HDCTv patients (93.8%) have optimal psychosocial adjustment. In addition, HDCTv patients scored higher on QoL and psychosocial adjustment, but lower in pain, fatigue, sleep problems, and depressive symptoms than hEDS patients. Four main themes were identified in qualitative analyses: living with HDCTv, knowledge/ignorance of the disease, health behaviors/self-care and coping strategies. Conclusion: Our results suggest that despite the negative impact of HDCTv on the patients' daily lives, overall, they present an optimal disease adjustment which points to appropriate coping strategies. More research in psychosocial aspects of people with these rare diseases are needed to confirm these results and better understand their needs.

«Digesting Crohn's Disease¼: The Journey of Young Adults since Diagnosis.

Crohn's disease affects 2.5 million people in Europe (more than 100,000 people in France) and often occurs between the ages of 15 and 30, a period marked by self-construction. However, few studies have focused on the experience of the diagnosis during this sensitive developmental stage. This study aimed to qualitatively explore the experience of Crohn's disease in young adults since their diagnosis. Fifteen young adults (18-35 years) diagnosed with Crohn's disease participated in a semi-directive interview. Narrative data were subjected to a thematic analysis, and thirty percent of the interviews were double-coded. The results revealed an evolution of four main themes since diagnosis: (1) course of care, (2) illness perceptions, (3) disease management and (4) self-perception. For most participants, the onset of the disease was difficult, marked by severe symptoms requiring hospitalization, numerous medical examinations and sometimes several consultations before diagnosis. This journey was more difficult when it was associated with negative relations with the medical staff, who were sometimes perceived as unsupportive. Thus, some people described this diagnostic period as an "ordeal", while others experienced it as a "relief" from their suffering. The announcement of the diagnosis was often a "shock", an "upheaval" or a "downfall", followed by phases of denial associated with a desire to maintain a "normal life" and not to be defined by the disease. Despite a difficult start, most participants grew from their experience with CD, with a sense of a personal development that was made possible by self-regulation processes that enabled them to draw on their own experience and resources to adjust to their illness. By highlighting positive possibilities for evolution, this study suggests the importance of supporting the psychological resources of young adults by proposing, at an early stage, psychological support or therapies focused on acceptance and engagement.

Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

Introduction: The link between anxiety disorders and joint hypermobility syndrome (now under hypermobility spectrum disorders, which include hypermobile Ehlers-Danlos syndrome) has been widely replicated over the past 30 years and has grown beyond the initial nosological limits. To integrate clinical and research progress in this field, a new neuroconnective endophenotype (NE) and its corresponding instrument, the Neuroconnective Endophenotype Questionnaire (NEQ), have been developed. This new clinical construct, created with the active participation of patients, includes both somatic and psychological dimensions and symptoms and resilience items. Methods: The NE includes five dimensions: (1) sensorial sensitivity, (2) body signs and symptoms, (3) somatic conditions, (4) polar behavioral strategies, and (5) psychological and psychopathological dimensions. The NEQ information is collected through four self-administered questionnaires (sensorial sensitivity, body signs and symptoms, polar behavioral strategies, and psychological characteristics) and a structured diagnostic part that should be completed by a trained observer. This hetero-administered part incorporates (a) psychiatric diagnoses (using structured criteria, e.g., MINI), (b) somatic disorders diagnosis, using structured criteria, and (c) assessment of joint hypermobility criteria. Results: In a sample of 36 anxiety cases with 36 matched controls, the NEQ obtained high scores for test-retest, inter-rater reliability, and internal consistency. As for predictive validity, cases and controls significantly differed in all five dimensions and hypermobility measurements. Discussion: We can conclude that the NEQ has achieved acceptable reliability and validity values and, therefore, is ready to be used and tested in different samples. This original and consistent construct including somatic and mental items may improve clinical specificity, the search for more comprehensive therapies, and their genetic and neuroimaging bases.

Corrigendum: Validation of the neuroconnective endophenotype questionnaire (NEQ): a new clinical tool for medicine and psychiatry resulting from the contribution of Ehlers-Danlos syndrome.

[This corrects the article DOI: 10.3389/fmed.2023.1039223.].