ADVERTIMENT. Lʼaccés Als Continguts Dʼaquesta Tesi Queda
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ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en Doctorate in Psychiatry Department of Psychiatry and Forensic Medicine Faculty of Medicine DOCTORAL THESIS ANXIETY & JOINT HYPERMOBILITY: CONNECTING MIND AND BODY Ph.D. Dissertation presented by Andrea Bulbena-Cabré to obtain the degree of International Doctor by the Universitat Autonoma de Barcelona. Director: Prof. Thomas Wise M.D John Hopkins School of Medicine Tutor: Prof. Antonio Bulbena Vilarrasa M.D., M.Sc. (Cantab), Ph.D. Universitat Autonoma de Barcelona New York, 2017 *Cover image: “Drawing hands” by M.C. Escher. Professor Thomas Wise (director) and Professor Antonio Bulbena Vilarrasa (tutor) certify that they have supervised and guided this doctoral thesis presented by Andrea Bulbena-Cabre “Anxiety & Joint hypermobility: connecting mind and body”. They hereby assert that this doctoral thesis fulfils the requirements to be defended. Prof. Thomas N. Wise M.D. Prof. Antonio Bulbena M.D., M.Sc., Ph.D Thesis Director Thesis Tutor Andrea Bulbena Cabre M.D., M.Sc. AKNOWLEDGMENTS My deep gratitude goes first to Prof. Wise and Prof. Bulbena, whom expertly advised me throughout my training and not only provided prudent and pointed guidance but also gave me warm and sincere support. Their unwavering enthusiasm stimulated my interest in the area of psychosomatic medicine, where the mind and body meet creating a fascinating universe. Their inspiring instruction made me think outside the box and ultimately made this thesis possible. Since I started my path in the medical field, I received mentorship from many different outstanding professionals at Universitat Autonoma de Barcelona, Universidad de Monterrey, New York Medical College, Yale University and now at the Icahn School of Medicine at Mount Sinai. My gratitude is extended to all the mentors and colleagues who inspired me, I treasure all the knowledge and wisdom you have shared with me. I also want to extend my gratitude to all the co-authors of the research projects; your support, encouragement, and warm and generous company during this doctoral thesis has been crucial for its success. A very special gratitude and love goes to my family for their unfailing support. You helped me understand that our greatest glory is not in never falling, but in rising every time we fall. Javi, por muchas más victorias juntos. A la meva meravellosa familia, per ser però sobretot per estar. TABLE of Contents 1 ABSTRACT ................................................................................................................................... 9 1.1 ENGLISH VERSION ......................................................................................................................... 11 1.2 SPANISH VERSION ......................................................................................................................... 13 2 INTRODUCTION ........................................................................................................................ 15 2.1 ANXIETY ......................................................................................................................................... 17 Epidemiology .......................................................................................................................................... 17 Anxiety in the elderly population ........................................................................................................... 17 Rediscovering the concept of “neurosis” ................................................................................................ 18 2.2 THE JOINT HYPERMOBILITY SYNDROME ....................................................................................... 20 Background ............................................................................................................................................ 20 Associated features ................................................................................................................................ 21 Diagnosis ................................................................................................................................................ 23 2.3 ANXIETY AND THE ROLE OF THE CONNECTIVE TISSUE .................................................................. 30 Background ............................................................................................................................................ 30 Underlying mechanisms ......................................................................................................................... 33 3 AIMS AND HYPOTHESIS ............................................................................................................ 35 3.1 JOINT HYPERMOBILITY IS ALSO ASSOCIATED WITH ANXIETY DISORDERS IN THE ELDERLY POPULATION .............................................................................................................................................. 37 Main Aim ................................................................................................................................................ 37 Specific Aims .......................................................................................................................................... 37 Hypothesis .............................................................................................................................................. 37 3.2 BODY PERCEPTION IN A SAMPLE OF NONCLINICAL YOUNGSTERS WITH JOINT HYPERMOBILITY 38 Main Aim ................................................................................................................................................ 38 Specific Aims .......................................................................................................................................... 38 Hypothesis .............................................................................................................................................. 38 4 METHODS ................................................................................................................................. 39 1 4.1 STUDY 1 & 2: PSYCHIATRIC AND PSYCHOLOGICAL ASPECTS IN THE EHLERS-DANLOS SYNDROMES & JOINT HYPERMOBILITY, ANXIETY AND PSYCHOSOMATICS: TWO AND A HALF DECADES OF PROGRESS TOWARD A NEW PHENOTYPE. ................................................................................................................... 41 4.2 STUDY 3: JOINT HYPERMOBILITY IS ALSO ASSOCIATED WITH ANXIETY DISORDERS IN THE ELDERLY POPULATION ................................................................................................................................ 42 Study details and sample characteristics ............................................................................................... 42 Instruments ............................................................................................................................................ 42 Statistical analysis .................................................................................................................................. 43 4.3 STUDY 4: BODY PERCEPTION IN A SAMPLE OF NONCLINICAL YOUNGSTERS WITH JOINT HYPERMOBILITY ......................................................................................................................................... 44 Study details and sample characteristics ............................................................................................... 44 Instruments ............................................................................................................................................ 44 Statistical analysis .................................................................................................................................. 45 5 RESULTS .................................................................................................................................... 47 5.1 STUDY 1 & 2: PSYCHIATRIC AND PSYCHOLOGICAL ASPECTS IN THE EHLERS-DANLOS SYNDROMES & JOINT HYPERMOBILITY, ANXIETY AND PSYCHOSOMATICS: TWO AND A HALF DECADES OF PROGRESS TOWARD A NEW PHENOTYPE. ................................................................................................................... 49 The Neuro-Connective Phenotype .......................................................................................................... 56 Therapeutic approaches ......................................................................................................................... 58 5.2 STUDY 3: JOINT HYPERMOBILITY IS ALSO ASSOCIATED WITH ANXIETY DISORDERS IN THE ELDERLY POPULATION ................................................................................................................................ 59 5.3 STUDY 4: BODY PERCEPTION IN A SAMPLE OF NONCLINICAL YOUNGSTERS WITH JOINT HYPERMOBILITY ........................................................................................................................................