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Polymorphic Regions of the Estrogen Receptor, Androgen Receptor and Serotonin Transporter Genes and Their Association with Mood Variability in Young Women

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Polymorphic Regions of the Estrogen Receptor, Androgen Receptor and Serotonin Transporter Genes and Their Association with Mood Variability in Young Women Lakehead University Knowledge Commons,http://knowledgecommons.lakeheadu.ca Electronic Theses and Dissertations Retrospective theses 2006 Polymorphic regions of the estrogen receptor, androgen receptor and serotonin transporter genes and their association with mood variability in young women Richards, Meghan A. http://knowledgecommons.lakeheadu.ca/handle/2453/3361 Downloaded from Lakehead University, KnowledgeCommons Polymorphic Regions 1 Ruimmg head: GENETIC POLYMORPHISMS AND MOOD Polymorphic Regions of the Estrogen Receptor, Androgen Receptor and Serotonin Transporter Genes and their Association with Mood Variability in Young Women Meghan A. Richards M.A. Thesis Lakehead University Supervisor: Dr. Kirsten Oinonen copyright © Meghan Richards, 2006 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Library and Bibliothèque et 1^1 Archives Canada Archives Canada Published Heritage Direction du Branch Patrimoine de l'édition 395 Wellington Street 395, rue Wellington Ottawa ON K1A 0N4 Ottawa ON K1A 0N4 Canada Canada Your file Votre référence ISBN: 978-0-494-21539-5 Our file Notre référence ISBN: 978-0-494-21539-5 NOTICE: AVIS: The author has granted a non­ L'auteur a accordé une licence non exclusive exclusive license allowing Library permettant à la Bibliothèque et Archives and Archives Canada to reproduce,Canada de reproduire, publier, archiver, publish, archive, preserve, conserve,sauvegarder, conserver, transmettre au public communicate to the public by par télécommunication ou par l'Internet, prêter, telecommunication or on the Internet,distribuer et vendre des thèses partout dans loan, distribute and sell theses le monde, à des fins commerciales ou autres, worldwide, for commercial or non­ sur support microforme, papier, électronique commercial purposes, in microform,et/ou autres formats. paper, electronic and/or any other formats. The author retains copyright L'auteur conserve la propriété du droit d'auteur ownership and moral rights in et des droits moraux qui protège cette thèse. this thesis. Neither the thesis Ni la thèse ni des extraits substantiels de nor substantial extracts from it celle-ci ne doivent être imprimés ou autrement may be printed or otherwise reproduits sans son autorisation. reproduced without the author's permission. In compliance with the Canadian Conformément à la loi canadienne Privacy Act some supporting sur la protection de la vie privée, forms may have been removed quelques formulaires secondaires from this thesis. ont été enlevés de cette thèse. While these forms may be includedBien que ces formulaires in the document page count, aient inclus dans la pagination, their removal does not represent il n'y aura aucun contenu manquant. any loss of content from the thesis. Canada Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Polymorphic Regions 2 Abstract The present study examined whether genetic polymorphisms on the estrogen receptor, androgen receptor, and serotonin transporter genes affect mood reactivity or mood variability in women. A total of 279 women from the university community completed a screening questionnaire (phase 1) for the study. During phase two, 146 women provided a buccal swab which was analyzed for Variable Number Tandem Repeat (VNTR) polymorphisms on the aforementioned genes. They also participated in an anxiety- inducing task. The Positive and Negative Affect Scale Expanded (PANAS-X), the Pleasantness-Unpleasantness Scale, as well as the Beck Anxiety Inventory (BAI) were completed prior to and following the completion of the mood induction task in order to assess mood reactivity. Mood variability was assessed in the third phase of the study where 62 women completed the PANAS and the Pleasantness-Unpleasantness Scale at eight one-hour intervals over the course of one 24-hour period. It was hypothesized that women’s mood variability, either during the laboratory mood manipulation or over the 8- hour period, would differ based on number of repeats of (1) the 17 base pair element within intron 2 of the Serotonin transporter gene (5-HTT), (2) CAG repeat numbers on the Androgen Receptor (AR) gene, or (3) number of TA repeats on the Estrogen Receptor a (ERa) gene. Women’s emotional variability did not differ significantly as a function of genotype. However, with respect to emotional reactivity, the following trends were observed: (1) a greater amount of overall mood change and PA change for the homozygous long group of the ERa allele, (2) a greater amount of NA change for the heterozygous group of the ERa allele, and (3) a greater amount of PA change for the 8/10-9/10 allele group of the 5-HTT gene. Additional predictors of affect are discussed. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Polymorphic Regions 3 Acknowledgements I would like to thank my advisor, Dr. Kirsten Oinonen, first of all for her patience, guidance and expertise. I would also like to thank her for the example she has set at both the personal and professional level. Thanks also to Dr. Dwight Mazmanian of Lakehead University for his comments and suggestions on the proposal and final thesis and to Dr. Tara Perrot-Sinal of Dalhousie University for sharing her ideas and recommendations regarding the final thesis. Thanks to Jessica Bird for her help with the data collection and entry. Finally, I would like to extend thanks to my family and fiiends, especiallv Nicholas, for their support and encouragement. Portions of this work were funded by a Canadian Institute of Health and Research (CIHR) grant awarded to Dr. Kirsten Oinonen. Additional scholarship funding was provided by an Ontario Graduate Scholarship and a Lakehead University Graduate Fellowship. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Polymorphic Regions 4 Table of Contents Abstract ...................................................................................................................................... 2 Ackno wl edgements ................................................................................................................... 3 Table of Contents ..................................................................................................................... 4 List of Tables .............................................................................................................................7 Introduction ............................................................................................................................... 8 Serotonin (5-HT) ..........................................................................................................9 The Serotonin Transporter (5-HTT) and the Serotonin Transporter Gene .......................................................................................12 Estrogen and the Estrogen Receptor Gene ................................................................17 Androgens and the Androgen Receptor ................................................................... 20 Mood Versus Affect ................................................................................................... 21 Measurement of Affect .............................................................................................. 24 Studies Measuring Affect ..........................................................................................27 Affect Induction Procedures ......................................................................................30 The Present Study .......................................................................................................33 Method ..................................................................................................................................... 34 Participants... .............................................................................................................34 Measures..................................................................................................................... 35 Screening Questionnaire ............................................................................... 35 Mental Rotations Test ....................................................................................36 Laboratory Mood Questionnaires ................................................................ 38 Beck Anxiety Inventory ............................................................................... 38 Pleasantness-Unpleasantness Scale ............................................................. 39 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Polymorphic Regions 5 Positive and Negative Affect Scale Expanded ............................................ 39 Hourly Mood Questionnaire .........................................................................40 Positive and Negative Affect Scale .............................................................. 41 Genotyping ..................................................................................................... 41 Procedure ................................................................................................................................ 42 Screening Phase ......................................................................................................... 42 Laboratory Phase ......................................................................................................
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