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Genetics Perspective on Schizotypy and Antisaccades

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Genetics Perspective on Schizotypy and Antisaccades AN IMAGING (BEHAVIOUR-) GENETICS PERSPECTIVE ON SCHIZOTYPY AND ANTISACCADES Dissertation der Graduate School of Systemic Neurosciences der Ludwig-Maximilians-Universität München Christine-Johanna Macare 6th June 2016 First Supervisor/Reviewer: Prof. Dr. Ulrich Ettinger Second Supervisor/Reviewer: Prof. Dr. Dan Rujescu Third Reviewer: Prof. Dr. Peter Falkai Examination committee: Prof. Dr. Ulrich Ettinger Prof. Dr. Stefan Glasauer Prof. Dr. Herman Müller Prof. Dr. Stefan Duschek Date dissertation sumitted: 14th November 2014 Date of defense: 30th April 2015 Date change requirement accepted: 6th June 2016 2 Acknowledgements This work would not have been possible without the support I was privileged to receive. I am thankful … … to Prof. Maximilan Reiser for supervising the research facilities in which the studies were conducted. … to my thesis advisory committee, i.e. Prof. Ulrich Ettinger, Prof. Dan Rujescu, Prof. Norbert Müller and Prof. Heiner Deubel for supervising, guiding and supporting my work and to the Graduate School of Systemic Neurosciences for their support. … to Prof. Ulrich Ettinger for his day-to-day supervision and his support as well as to our co- authors in particular Prof. Timothy Bates, Prof. Nicholas Martin and Prof. Dan Rujescu for feedback. … to the former Biological Psychology work force at the Department of Psychiatry at the Ludwig-Maximilians-University in Munich, specifically to Dr. Anna Costa, Dr. Désirée Aichert and to Nicola Woestmann for mental support and practical day-to-day help. “Thank you” to Ute Coates for helping with the scanning and to Prof. Thomas Meindl for providing access to the scanning facilities. … to Dr. Tianye Jia, Dr. Gabriel Robert and Dr. Barbara Ruggeri at the SGDP at King’s College London for mental support. Finishing this thesis would not have been possible without the support of Prof. Gunter Schumann. … to my friends and family. Thanks to Andy, Tomi, Ute, Judith and Jaqueline for encouraging me and supporting me during my time in Munich. Thanks to Sirka, Maximilian, Kira, Lucie and especially Anna, Ingo and Viktor for pleasant distractions from work. Thank you to my family for everything. 3 THIS THESIS IS DEDICATED TO MY GRANDMOTHER, MARIA. 4 Table of Contents LIST OF ABBREVIATIONS .............................................................................................................. 9 LIST OF FIGURES ............................................................................................................................ 13 LIST OF TABLES .............................................................................................................................. 15 ABSTRACTS....................................................................................................................................... 16 1. GENERAL INTRODUCTION ................................................................................................... 19 1.1. ENDOPHENOTYPES .................................................................................................................... 19 1.1.1. THE ENDOPHENOTYPE CONCEPT IN PSYCHIATRY ................................................................. 21 1.1.2. IMAGING GENETICS AND THE ENDOPHENOTYPE CONCEPT ................................................... 22 1.1.3. HERITABILITY ........................................................................................................................ 23 1.1.4. THE CLASSICAL TWIN DESIGN .............................................................................................. 24 1.1.5. STRUCTURAL EQUATION MODELLING .................................................................................. 30 1.1.6. SUMMARY ENDOPHENOTYPES ............................................................................................... 36 1.2. SCHIZOTYPY............................................................................................................................... 38 1.2.1. THE CONSTRUCT OF SCHIZOTYPY ......................................................................................... 38 1.2.2. THEORETICAL BACKGROUND TO SCHIZOTYPY ..................................................................... 39 1.2.3. THE MULTIDIMENSIONALITY OF SCHIZOTYPY ...................................................................... 43 1.2.4. ASSESSMENT OF SCHIZOTYPY ............................................................................................... 47 1.2.5. SCHIZOTYPY AND PERSONALITY ........................................................................................... 50 1.2.6. SCHIZOTYPY AND ITS HERITABILITY ..................................................................................... 52 1.2.7. SCHIZOPHRENIA SPECTRUM DISORDERS ............................................................................... 54 1.2.8. THE CONTINUUM MODEL ...................................................................................................... 58 1.2.9. THE SCHIZOPHRENIA SPECTRUM AND ITS NEURAL CORRELATES ........................................ 59 1.2.10. SUMMARY SCHIZOTYPY ........................................................................................................ 65 1.3. THE ANTISACCADE TASK .......................................................................................................... 66 1.3.1. DEFINITION OF ANTISACCADES ............................................................................................. 67 1.3.2. ANTISACCADE TASK DESCRIPTION ....................................................................................... 67 1.3.3. ANTISACCADES AS MEASURES OF OCULOMOTOR INHIBITION ............................................. 69 1.3.4. MEASURES OF ANTISACCADE TASK PERFORMANCE............................................................. 71 1.3.5. MODELS OF ANTISACCADE ERRORS ...................................................................................... 74 5 1.3.6. NEURAL CORRELATES OF ANTISACCADE TASK PERFORMANCE........................................... 75 1.3.7. ANTISACCADE PERFORMANCE ACROSS THE SCHIZOPHRENIA SPECTRUM ............................ 84 1.3.8. SUMMARY THE ANTISACCADE TASK .................................................................................... 88 1.4. FUNCTIONAL MAGNETIC RESONANCE IMAGING .................................................................... 90 1.4.1. INTRODUCTION TO FUNCTIONAL MAGNETIC RESONANCE IMAGING .................................... 90 1.4.2. IMAGING PARAMETERS ......................................................................................................... 93 1.4.3. THE BOLD SIGNAL ................................................................................................................ 95 1.4.4. PRE-PROCESSING ................................................................................................................... 99 1.4.5. EXPERIMENTAL DESIGNS .................................................................................................... 104 1.4.6. FMRI DATA ANALYSIS ........................................................................................................ 104 1.4.7. SUMMARY FUNCTIONAL MAGNETIC RESONANCE IMAGING ............................................... 107 1.5. OVERVIEW OVER THE CURRENT STUDIES ............................................................................. 108 2. SUBSTANTIAL GENETIC OVERLAP BETWEEN SCHIZOTYPY AND NEUROTICISM: A TWIN STUDY ................................................................................................ 110 2.1. INTRODUCTION ........................................................................................................................ 110 2.2. METHODS ................................................................................................................................. 112 2.2.1. SAMPLE ................................................................................................................................ 112 2.2.2. SCHIZOTYPY ........................................................................................................................ 113 2.2.3. NEUROTICISM ...................................................................................................................... 114 2.2.4. ZYGOSITY ............................................................................................................................ 114 2.2.5. DATA PREPARATION ............................................................................................................ 114 2.2.6. PRELIMINARY ANALYSES .................................................................................................... 115 2.2.7. QUANTITATIVE GENETIC MODELLING ................................................................................. 115 2.3. RESULTS ................................................................................................................................... 117 2.3.1. PCA OF SCHIZOTYPY ........................................................................................................... 117 2.3.2. PRELIMINARY ANALYSES .................................................................................................... 117 2.3.3. SAMPLE DESCRIPTION .......................................................................................................... 118 2.3.4. SEX-LIMITATION TWIN MODELLING .................................................................................... 118 2.3.5. PHENOTYPIC CORRELATIONS BETWEEN SCHIZOTYPY
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