TYPE Editorial PUBLISHED 12 December 2022 DOI 10.3389/fpsyt.2022.1109515 Editorial: Neurodevelopmental, OPEN ACCESS neuropsychiatric and psychosocial correlates of joint EDITED AND REVIEWED BY Stephan Zipfel, University of Tübingen, Germany *CORRESPONDENCE Vincent Guinchat hypermobility and related vincent.guinchat@unil.ch SPECIALTY SECTION disorders This article was submitted to Psychological Therapy and Psychosomatics, Vincent Guinchat1*, Carolina Baeza-Velasco2,3,4 , a section of the journal Frontiers in Psychiatry Antonio Bulbena5,6 and Marco Castori7 RECEIVED 27 November 2022 1 Psychiatric Section of Mental Development, Psychiatric University Clinic, Lausanne University ACCEPTED 02 December 2022 Hospital, Lausanne, Switzerland, 2 Laboratoire de Psychopathologie et Processus de Santé, PUBLISHED 12 December 2022 Université Paris Cité, Boulogne-Billancourt, France, 3 Department of Emergency Psychiatry and CITATION Acute Care, CHU Montpellier, Montpellier, France, 4 Institute of Functional Genomics, University of Guinchat V, Baeza-Velasco C, Montpellier, CNRS, INSERM, Montpellier, France, 5 Department of Psychiatry and Forensic Medicine, Bulbena A and Castori M (2022) Universitat Autonoma de Barcelona, Barcelona, Spain, 6 Anxiety Unit, Hospital del Mar, Institute Editorial: Neurodevelopmental, Neuropsychiatry and Addictions, Barcelona, Spain, 7 Division of Medical Genetics, Fondazione neuropsychiatric and psychosocial IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy correlates of joint hypermobility and related disorders. Front. Psychiatry 13:1109515. KEYWORDS doi: 10.3389/fpsyt.2022.1109515 joint hypermobility, Ehlers-Danlos syndromes, neurodevelopmental disorders, COPYRIGHT psychopathology, psychology © 2022 Guinchat, Baeza-Velasco, Bulbena and Castori. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other Editorial on the Research Topic forums is permitted, provided the Neurodevelopmental, neuropsychiatric and psychosocial correlates original author(s) and the copyright owner(s) are credited and that the of joint hypermobility and related disorders original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which This Research Topic is concerned with the intriguing overlap between apparently does not comply with these terms. separated aspects of human variability: congenital contortionism (a.k.a. generalized joint hypermobility; GJH) on one hand, and neurodevelopmental disorders (NDD) and neuropsychiatric conditions (NC) on the other hand. Literature in this area is still sparse, and we are excited to gather new empirical data. As treated by two separate fields of Medicine, the concurrence of these conditions run under recognized for a long time. Accordingly, individuals seemingly manifesting these features (i.e., GJH plus NDD and/or GJH plus NC) are difficult to address to adequate services and likely to be excluded from the mainstream research. GJH, NDD, and some NC (e.g., anxiety disorders, and depression) are frequent in the general population. So, why an association between GJH and NDD, or GJH and NC should be worth of attention? Is their concurrence in the same individual a casual association or rather the effect of some pre-existing etiopathogenetic relationship? At this point, we can conceive three cooperating explanations: Frontiers in Psychiatry 01 frontiersin.org Guinchat et al. 10.3389/fpsyt.2022.1109515 - Firstly, while GJH is often a harmless trait, it may not address the criteria for hEDS. For these individuals the predict the development of a range of musculoskeletal background diagnosis are the hypermobility spectrum disorders and neuromotor manifestations including bodily pain, (HSD) (3). Asymptomatic GJH, HSD, and hEDS are currently motor delay, coordination troubles and fatigue (i.e., conceived as expressions of a unique spectrum of phenotypes. symptomatic GJH). Therefore, one could hypothesize Accordingly, HSD and hEDS are “spectrum disorders,” while that the neurodevelopmental and neuropsychiatric co- asymptomatic GJH represents the harmless extreme of such morbidities are the cognitive and behavioral correlates of a spectrum, which, in turn, is intermingled with normal the physical complaints, which in turn are directly related variability (3). Individuals with HSD and hEDS often present to the congenital nature of GJH. a range of associated non-musculoskeletal and neuromotor - Secondly, GJH, NDD, and NC, involve a physical comorbid attributes which include and are not limited to cardiovascular burden, and share some frequent associated disorders (e.g., dysautonomia, gastrointestinal functional disorders, bladder immune dysregulation, dysautonomia, and irritable bowel dysfunction, and psychiatric co-morbidities (4). Among the syndrome). Some of these disorders may not only mediate most studied psychiatric co-morbidities there are anxiety and the relationship between GJH, NDD, and NC, but also can depression (5). More recently, an association with eating trigger, mimic, or aggravate psychiatric conditions such as disorders was put forward (6). In addition, as GJH is a congenital depression and ultimately worsen physical disability. In this trait, some preliminary evidence suggests a relationship with perspective, GJH should be considered as a warning sign to simple motor delay, speech disorders (7), developmental explore more carefully the presence of impairing physical coordination disorders (8, 9), and attention deficit/hyperactivity symptoms in NDD and NC. disorders (10). - Thirdly, practice and scientific evidence support a high In this regard, the body-mind interconnections observed in hereditary burden for GJH, NDD, and some NC. Therefore, the context of GJH, HSD, and hEDS and supported by several we can assume that, at least in specific circumstances, the studies [e.g., (11, 12)], are illustrated to some extend in the concurrence of GJH, NDD/NC is the result of pleiotropy, model called “Neuroconnective endophenotype” (13). This which defines the capability that a single gene has to affect model integrates the somatic and psychological characteristics the development and functions of different tissues and presented by people with spectrum disorders (i.e., GJH without organs at the same time. In this scenario, we recognize musculoskeletal complaints, HSD, and hEDS) and anxiety, by that an increasing number of genes that have been and organizing them in five dimensions: (1) sensorial sensitivity will be associated with Mendelian variants of NDD as a (e.g., altered sensitivity concerning body awareness components result of a primary defect of developing brain, equally affect such as interoception), (2) body sign and symptoms such as the mesodermal derivatives contributing to joint formation dislocations, easy bruising, and dysautonomia. (3) Somatic and, hence, cause GJH. conditions including irritable bowel syndrome, chronic fatigue, fibromyalgia among others. (4) Polar behavioral Both symptomatic GJH and NDD show some continuity strategies (e.g., supercontrol-uncontrol and avoidance- with normal variability. Mendelian hereditary connective intrusion), and (5) psychological and psychopathological tissue disorders, such as the rare variants of Ehlers-Danlos dimensions (e.g., anxiety and depression). This theoretical syndromes (EDS; i.e., all subtypes except for hypermobile proposal highlights the need to evaluate patients with HSD EDS—hEDS), are currently considered the most common and hEDS who are seen in rheumatological and medical monogenic disorders featuring GJH (1). This could generate genetics settings as well as individuals primarily assessed by the the false impression that rare EDS subtypes are the most psychiatrist/clinical psychologist from an integrated perspective common diagnoses among individuals with symptomatic GJH. (somatic and psychological). Currently, most individuals who are referred to specialized We hope that the following articles, which compose clinics for symptomatic GJH are not affected by a monogenic this Research Topic, will contribute to add elements to the hereditary connective tissue disorder. They usually present disentanglements of these complex clinical situations, and a specific phenotypes of GJH with one or more associated reduce the delays for their recognition and management. musculoskeletal and/or neuromotor manifestations, but they do Ishiguro et al.’s paper will first offer an updated critique not have any causative mutation in the disease-genes currently of the current data available demonstrating an association in linked to monogenic hereditary connective tissue disorders. various NND and NC (autism, attention deficit/hyperactivity On the contrary, they are affected by hEDS, which is an disorder, anorexia nervosa, addiction, anxiety disorders, attenuated syndromic presentation resembling the other rarer mood disorders, and personality disorders) in people with EDS variants and ascertained by the application of the criteria spectrum disorders. Whether these symptoms are secondary published in the 2017 International Classification of EDS and to the psychological burden of chronic pain, fatigue, physical related disorders (2). Nevertheless, presumably no <50% of restriction, aesthetic stigma, or adverse life experience due to people with a specific phenotypes of symptomatic GJH do GJH (parental overprotection, bullying experience, and social Frontiers in Psychiatry 02 frontiersin.org Guinchat et al. 10.3389/fpsyt.2022.1109515 incomprehension), remain an open question but the therapeutic controls, assessed for HSD, ADHD, and physical comorbid implications are discussed. symptoms. They confirm an association between ASD and GJH Lamari et al. assess the psychosocial correlates of the that seems primarily driven by a comorbid ADHD, whereas a functional limitations of movements related to the severity stronger association is between ASD and symptomatic GJH. of joint hypermobility. Authors used data obtained through All these papers add elements on our understanding of analyses of descriptive and inferential crossings of 482 medical the far-reaching manifestations of GJH on human normal and records for an observational, quantitative, and cross-sectional abnormal variability. The authors focused of the wide range study. They show GJH consequences on body mechanics and of possible associations in the fields of neurodevelopment, motor performance in daily, instrumental, recreational, sports, cognition and behavior. The study of the psychiatric and and occupational activities leading to social stigmata. They also psychological relationships of GJH seems to offer a privileged corroborate the impact of pain and fatigue since childhood, as scenario for exploring the body-mind connections that exist unrecognized features of JH leading to suboptimal management. at the basis of human development and disease. The authors By screening 53 adults with Eating Disorders (ED; mostly pointed the necessity of future well-designed researches to more with anorexia nervosa), Baeza-Velasco et al. show that 41% deeply explore the etiology, pathogenesis and management of are positive for GJH (comparing with 20% in the general psychiatric, cognitive and behavior manifestations in individuals population). Moreover, the comparison between ED + GJH with GJH. patients and ED only patients indicated a clinical ED subtype In conclusion, the identification of GJH in people with that differ with respect to cognitive style: less cognitive rigidity NDD and some NC may represent a clue for suspecting a or control and restricting behaviors in the group ED + wider phenotype with intricate pathophysiological intersections GJH. This may mirror a distinct causal pathway leading between neurodevelopment and body habitus. In this category to eating symptoms probably mediated by gastrointestinal of people usually referred for a previous diagnosis or a suspicion problems (e.g., cramps, trouble swallowing, and food allergies) of NDD, prompt identification of GJH might help in early and sensorial anomalies that may impact the body image. diagnosing concurrent musculoskeletal manifestations which In this group “ED is probably secondary to the connective may contribute to, or worsen the leading medical issue. The tissue problems rather than attributable to the premorbid findings presented in these papers, together with the previous perfectionism and rigid cognitive style classically described and literature, are opening the path to explore the connections requires a specific management.” between GJH, the neurodevelopment and psychopathology with Csecs et al. followed a “Neurodivergent approach,” that the final aim to offer a tailored and, hence, more effective admits a frequent diagnostic overlap in NDD. They postulated treatments to our patients. a transnosographic effect of symptomatic GJH on development and tested for increased prevalence of joint hypermobility, autonomic dysfunction, and musculoskeletal symptoms in 109 Author contributions adults with neurodevelopmental condition diagnoses and a All authors listed have made a substantial, direct, comparison group. Odds ratio for presence of hypermobility and intellectual contribution to the work and approved it in neurodivergent group, compared to the general population for publication. was 4.51 (95% CI: 2.17–9.37), more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than the comparison group. Moreover, the GJH severity mediate the Acknowledgments relationship between neurodivergence and symptoms of both dysautonomia and pain. Thanks to the authors and to the Frontiers team that made Alternatively, Bejerot et al. in a case-control study including this Research Topic possible. 105 participants, found no differences in GJH between three groups: a group of children with pediatric acute-onset neuropsychiatric syndrome (an umbrella term describing acute Conflict of interest psychiatric episodes probably linked to inflammation and The authors declare that the research was conducted in the associated with postural orthostatic tachycardia syndrome), absence of any commercial or financial relationships that could individuals with any mental disorders, and healthy controls. be construed as a potential conflict of interest. These preliminary results tend to guide future studies toward the subgroup of patients with developmental traits, rather than acute disorder. 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