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Genetic and Environmental Risk Factors Associated with Obsessive-Compulsive Disorder and Its Symptom Dimensions: a Twin Study

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Genetic and Environmental Risk Factors Associated with Obsessive-Compulsive Disorder and Its Symptom Dimensions: a Twin Study Genetic and Environmental Risk factors associated with Obsessive-Compulsive Disorder and its symptom dimensions: A twin study Clara López Solà ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indicar el nom de la persona autora. ADVERTENCIA. La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR (www.tdx.cat) y a través del Repositorio Digital de la UB (diposit.ub.edu) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y puesta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB. No se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR o al Repositorio Digital de la UB (framing). Esta reserva de derechos afecta tanto al resumen de presentación de la tesis como a sus contenidos. En la utilización o cita de partes de la tesis es obligado indicar el nombre de la persona autora. WARNING. On having consulted this thesis you’re accepting the following use conditions: Spreading this thesis by the TDX (www.tdx.cat) service and by the UB Digital Repository (diposit.ub.edu) has been authorized by the titular of the intellectual property rights only for private uses placed in investigation and teaching activities. Reproduction with lucrative aims is not authorized nor its spreading and availability from a site foreign to the TDX service or to the UB Digital Repository. Introducing its content in a window or frame foreign to the TDX service or to the UB Digital Repository is not authorized (framing). Those rights affect to the presentation summary of the thesis as well as to its contents. In the using or citation of parts of the thesis it’s obliged to indicate the name of the author. Research Line:Clinical andExperimentalNeuroscience Research Group:Psychiatry andMentalHealth Department ofClinicalSciences Univ Doctorate inMedicine School ofMedicine ersity ofBarcelona 2015 GENETIC AND ENVIRONMENTAL RISK FACTORS ASSOCIATED WITH Clara OBSESSIVE-COMPULSIVE DISORDER AND ITS SYMPTOM DIMENSIONS: A TWIN STUDY López Solà 6FKRRORI0HGLFLQH 8QLYHUVLW\RI%DUFHORQD 'HSDUWPHQWRI&OLQLFDO6FLHQFHV 'RFWRUDWHLQ0HGLFLQH 5HVHDUFK/LQH&OLQLFDODQG([SHULPHQWDO1HXURVFLHQFH 5HVHDUFK*URXS3V\FKLDWU\DQG0HQWDO+HDOWK GENETIC AND ENVIRONMENTAL RISK FACTORS ASSOCIATED WITH OBSESSIVE-COMPULSIVE DISORDER AND ITS SYMPTOM DIMENSIONS: A TWIN STUDY DOCTORAL THESIS CLARA LÓPEZ SOLÀ SUPERVISORS Ben J. Harrison José M. Menchón JULY 2015 L'ignorance affirme ou nie; Sciences doute (“La ignorancia afirma o niega rotundamente; La ciencia duda” François Marie Arouet (Voltaire) It would be possible to describe everything scientifically, but it would make no sense; it would be without meaning, as if you described a Beethoven symphony as a variation of wave pressure. (“Sería posible describir todo científicamente, pero no tendría ningún sentido; Carecería de significado describir la sinfonía de Beethoven como una variación de la presión de la onda auditiva”) Albert Einstein 3URIHVVRUV%HQ-+DUULVRQDQG-RVp00HQFKyQFHUWLI\WKDWWKH\KDYHVXSHUYLVHG DQGJXLGHGWKHGRFWRUDOWKHVLVHQWLWOHG³*HQHWLFDQG(QYLURQPHQWDO5LVN)DFWRUV $VVRFLDWHGZLWK2EVHVVLYH&RPSXOVLYH'LVRUGHUDQGLWV6\PSWRP'LPHQVLRQV$ WZLQVWXG\´SUHVHQWHGE\&ODUD/ySH]6ROj7KH\KHUHE\DVVHUWWKDWWKLVGRFWRUDO WKHVLVIXOILOOVWKHUHTXLUHPHQWVWREHGHIHQGHG 6XSHUYLVRUV $VVRFLDWH3URIHVVRU%HQ-+DUULVRQ 0HOERXUQH1HXURSV\FKLDWU\&HQWUH'HSDUWPHQWRI3V\FKLDWU\7KH8QLYHUVLW\RI 0HOERXUQH9LFWRULD$XVWUDOLD $VVRFLDWH3URIHVVRU-RVp00HQFKyQ ,',%(//%HOOYLWJH%LRPHGLFDO5HVHDUFK,QVWLWXWH 'HSDUWPHQWRI3V\FKLDWU\%HOOYLWJH8QLYHUVLW\+RVSLWDO &OLQLFDODQG([SHULPHQWDO1HXURVFLHQFHV8QLYHUVLW\RI%DUFHORQD TABLE OF CONTENT ACKNOWLEDGMENT...................................................................................................ϵ LIST OF TABLES............................................................................................................1ϭ LIST OF FIGURES..........................................................................................................1ϯ LIST OF ABBREVIATIONS..............................................................................................1ϱ LIST OF PUBLICATIONS................................................................................................ϭϳ CHAPTER 1: INTRODUCTION......................................................................................ϭϵ 1.1. Obsessive-Compulsive Disorder (OCD). An Introduction to the Multidimensional Approach.................................................................................2ϭ 1.2. Obsessive-Compulsive and Related Disorders (OCRDs).................…..............2ϰ 1.3. Obsessive-Compulsive Disorder as an Anxiety Disorder (AD)………………..…….Ϯϴ 1.4. Twin Studies……………………………………………………………………………………………….ϯϬ 1.4.1. The Value of Twin Studies in Psychiatry…………………………………………..3Ϭ 1.4.2. Twin Studies in OCD with other Anxiety Disorders…………………………..3ϭ 1.4.3. Twin Studies in Obsessive-Compulsive and Related Disorders...........3Ϯ 1.5. Summary........................................................................................................3ϯ CHAPTER 2: GENERAL AIMS & HYPOTHESIS.............................................................3ϱ CHAPTER 3: METHODS……………................................................................................4ϭ 3.1. Participants…………………………………………………………………………………………………….4ϯ 3.2. Psychometric Measures………………………………………………………………………………….4ϰ 3.ϯ. Statistical Analysis…………………………………………………………………………………………..ϰϲ CHAPTER 4: RESULTS…………………………………………………………………………………………….ϰϵ STUDY 1..........................................................................................................ϱϯ STUDY 2..........................................................................................................7ϭ STUDY 3........................................................................................................1Ϭϵ CHAPTER 5: DISCUSSION & CONCLUSIONS............................................................14ϱ 5.1. Summary of Key Findings.................................................................................1ϰϳ 5.2. General Discussion and Implications for Future Research...............................1ϰϵ 5.2.1. Implications for Genetic Research in OCD, ADs and OCRDs……………1ϰϵ 5.2.2. Implications for Research on Environmental Risk Factors……………...15ϱ 5.2.3. Gene-by-Environmental Interaction Factors…………………………………..1ϱϲ 5.2.4. Nosological Implications…………………………………………………………………16ϭ 5.2.5. Clinical Implications………………………………………………………………………..16Ϯ 5.3. Limitations.........................................................................................................16ϰ 5.4. Conclusions........................................................................................................16ϱ CHAPTER 6: SUMMARY IN SPANISH…………………………………………………………………….1ϲϳ CHAPTER 7: REFERENCES……………………………………………………………………………………..18ϭ $&.12:/('*(0(176$*5$'(&,0,(1726$*5$Í0(176 Y aquí, debajo de un árbol grande y frondoso de un pueblecito de l’Alt Empordà, Calabuig, y envuelta por el calor agradable del mes de mayo, me dedico a escribir los agradecimientos de esta tesis. Echo la vista atrás y me remonto a aquel enero de 2010 en Melbourne. Nunca pensé que aquella aventura de 4 meses daría lugar a lo que hoy defiendo como mi tesis doctoral, creo que nunca llegué a ser 100% consciente de lo que se iniciaba en aquel momento de cambio personal. I can’t start the acknowledgments without saying a big thank you to my supervisor, Professor Ben Harrison. Professor Harrison has shown me how to write and organise a paper, to communicate clearly and succinctly, to discriminate between what is relevant and what is not, and to be creative and much more. You’ve always been there, although separated by thousands of miles. Thank you for helping during this long process, for trusting me in critical moments and, for motivating me to keep on with this project when everything seemed impossible. It was worth it! I’ve learnt a lot in this experience with you. You have shown me how to set up a successful research project and what it takes to do research in psychiatry. Words cannot describe the overwhelming gratitude I have for you. It’s been a pleasure for me to work under your supervision. Without you, none of this would have been possible. I would also like to thank to the ATR (especially Jenny and Shaie), John Hopper, Minh Bui, and Leo for all your interest and dedication from the beginning of the process and to all the 2,495 Australian twins that dedicated time and effort to answer our survey. Thank you so much! Lastly,
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