(FADS) Genetic Variants and Dietary Polyunsaturated Fatty Acid Intake: Associations with Negative Affect
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Fatty Acid Desaturase (FADS) Genetic Variants and Dietary Polyunsaturated Fatty Acid Intake: Associations with Negative Affect Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Liisa Hantsoo, M.A. Graduate Program in Psychology The Ohio State University 2012 Dissertation Committee: Janice K. Kiecolt-Glaser, Ph.D., Advisor Charles Emery, Ph.D. Ruchika Prakash, Ph.D. Copyrighted by Liisa Hantsoo 2012 Abstract Background: Depressive symptomatology has been associated with polyunsaturated fatty acid (PUFA) levels in diet and tissue. However, results have been mixed, and studies have failed to account for genetic factors that may influence such associations. Tissue PUFA levels are strongly influenced by elongase and desaturase activity, which are governed by the fatty acid desaturase (FADS) genes. Inefficient desaturase activity has been associated with depression. Further, FADS genotypes have been associated with neuropsychological phenotypes such as postpartum depression. Given these associations, the study of relationships among dietary PUFA intake, FADS genotype, and mood symptoms is warranted. Aims: The present study investigated associations among dietary intake of PUFAs, the rs174575 polymorphism of the fatty acid desaturase (FADS2) gene, and psychological outcomes. The primary aim was to determine if FADS2 genotype interacts with omega-3 (n-3) and omega-6 (n-6) PUFA dietary intake to influence associations with depressive symptoms, anxiety symptoms, anger, hostility, neuroticism, or optimism. Methods: A sample of 172 female undergraduate students provided genetic material from buccal cells, and completed a food frequency questionnaire and self-report measures including the Center for Epidemiological Studies Depression Scale, PROMIS Anxiety and Anger Scales, Cook Medley Hostility Scale, NEO Neuroticism Scale, and LOT-R Optimism Scale. Results: The main finding was that higher n-3 intake was associated with greater hostility. ii However, n-3 intake was not related to depressive symptoms, anxiety, anger, neuroticism, or optimism, nor was n-6 intake. Further, genotype did not interact with PUFA intake for any psychological outcomes. Conclusion: This study provided no evidence that the rs174575 fatty acid desaturase polymorphism influences associations between PUFA intake and mood. iii Dedication Dedicated to the mentors, friends, and loved ones who supported me along the way. iv Acknowledgments I would like to thank my advisor, Dr. Janice Kiecolt-Glaser, for her feedback and guidance. She encouraged my curiosity and supported my pursuit of this research project. I would also like to thank my co-advisor, Dr. Charles Emery, for his helpful feedback and support during my time in graduate school. I also appreciate the guidance of Dr. Ruchika Prakash, who has been a valuable member of my dissertation committee. A special thanks to my fellow lab members, Jean Philippe Gouin and postdoctoral fellows Jeannette Bennett and Christopher Fagundes, for providing feedback on statistical analyses and manuscript drafts. Finally, this project would not have been possible without the expert technical guidance provided by Min Chen and Bryon Laskowski of Dr. Ronald Glaser’s lab. Their patience and guidance, as I worked on the wetlab portion of my dissertation, was invaluable. I would also like to acknowledge the funding that I received to support this project; the American Psychological Association Division 38 Health Psychology Graduate Student Research Award, and the Ohio State University Critical Difference for Women Grant. The generous support of these agencies allowed this project to come to fruition, and I appreciate their support. v Vita 1979................................................................Born, Silver Spring, Maryland 2001................................................................B.A. Neuroscience, The Johns Hopkins University 2005................................................................M.L.A. Individualized, University of Pennsylvania 2007 …...........................................................University Fellow, The Ohio State University 2008................................................................Graduate Teaching Associate, Department of Psychology, The Ohio State University 2010................................................................M.A. Clinical Psychology, The Ohio State University Publications Kiecolt-Glaser, J.K., Gouin, J.P., Hantsoo, L. (2009). Close relationships, inflammation, and health. Neurosci. Biobehav. Rev, 35(1), 33-38. Wozniak, J., Mick, E., Waxmonsky, J., Kotarski, M., Hantsoo, L., Biederman, J. (2009). vi Comparison of open-label, 8-week trials of olanzapine monotherapy and topiramate augmentation of olanzapine for the treatment of pediatric bipolar disorder. J Child Adolesc Psychopharmacol,19(5), 539-45. Hanisch, L. H., Palmer S. C., Marcus, S. C., Hantsoo, L., Vaughn, D. J., & Coyne, J. C. (2009). Comparison of objective and patient-reported hot flash measures in men with prostate cancer. Journal of Supportive Oncology, 7(4), 131-135. Bennett, I.M., Palmer, S.C., Nicholson, J., Hantsoo, L., Rinaldi, J., Coyne, J. (2009). "One end has nothing to do with the other": Patient Attitudes Regarding Help Seeking Intention for Depression in Gynecologic and Obstetric Settings. Archives of Women's Mental Health, 12, 301–308. Gouin, J.P., Hantsoo, L., Kiecolt-Glaser, J.K. (2008). Immune Dysregulation and Chronic Stress Among Older Adults: A Review. Neuroimmunomodulation, 15(4-6), 251- 59. Hanisch, L., Hantsoo, L., Freeman, E., Sullivan, G., Coyne, J. (2008). Hot Flashes and Panic Attacks: A Comparison of Symptomatology, Neurobiology, Treatment, and a Role for Cognition. Psychological Bulletin, 134(2), 247-69. Kenen, R.H., Shapiro, P.J., Hantsoo, L., Friedman, S., Coyne, J. (2007). Women with vii BRCA1 or BRCA2 mutations renegotiating a post-prophylactic mastectomy identity: self-image and self-disclosure. Journal of Genetic Counseling, 16(6), 789-98. Wozniak, J., Biederman, J., Mick, E., Waxmonsky, J., Hantsoo, L., Best, C., Cluette- Brown, J. & Laposata, M. (2007). Omega-3 fatty acid monotherapy for pediatric bipolar disorder: A prospective open label trial. European Neuropsychopharmacology, 17(6-7), 440-7. Liang, J., Etheridge, A., Hantsoo, L., Rubinstein, A., Nowak, S., Halpern M.E. (2001). Asymmetric Nodal Signaling in the Zebrafish Diencephalon Positions the Pineal Organ. Development, 127, 5101-5112. Fields of Study Major Field: Psychology viii Table of Contents Abstract……………………...……………………………………………….……………ii Dedication………………...……...……………………………………………………….iv Acknowledgments…………………...………………………………………..……..…….v Vita…………………………………...………………………..………………………….vi List of Tables………………………………………………………………………..…….x List of Figures…………………………………………………………...………...……xxii Chapter 1: Introduction…………………………………………………………………....1 Chapter 2: Methodology………………………………………………………...……….43 Chapter 3: Results………………………………………………………...……………...62 Chapter 4: Discussion…………………………………………………………...…….…78 References…………………………………………………………...……………….…103 Appendix A: Tables and Figures…………………………………………………….…124 Appendix B: Recruitment Posting…………………………………………….……..…258 Appendix C: Measures……………………………………………..………………...…259 Appendix D: Abbreviations………………………………………………………….…277 ix List of Tables Table 1. Sociodemographic Characteristics of Participants............................................124 Table 2. rs174575 Genotypes …………………………………………...……………..125 Table 3. Self-Reported Diet and Health Characteristics..................................................126 Table 4. Nutritional Data from Food Frequency Questionnaire (Block FFQ)……..…..127 Table 5. Psychological Outcome Data.............................................................................128 Table 6. Psychological Outcome Data: Cutoff Scores.....................................................128 Table 7. Between Group Differences by Race………………………………….………129 Table 8. Between Group Differences by Academic Year…………………………..…..130 Table 9. Between Group Differences by Genotype.........................................................131 Table 10. Between Group Differences by Genotype.......................................................131 Table 11. Between Group Differences in CES-D Score……………………….……….132 Table 12. Between Group Differences in PROMIS Anxiety SF Score…………..….…133 Table 13. Between Group Differences in PROMIS Anger SF Score…..………………133 Table 14. Between Group Differences in Cook Medley Hostility Scale Score….……..134 Table 15. Between Group Differences in NEO Neuroticism Scale Score……..……….134 Table 16. Between Group Differences in LOT-R Scale Score……………………...….135 Table 17. Bivariate Correlation Table……………………….……………………...….136 x Table 18. Regression Table for Hypothesis 1 with CES-D Score as Outcome…….......137 Table 19. Regression Table for Hypothesis 1 with PROMIS Anxiety SF Score as Outcome………………………….……………………………………………..138 Table 20. Regression Table for Hypothesis 1 with PROMIS Anger SF Score as Outcome……………..………………………………………………………….139 Table 21. Regression Table for Hypothesis 1 with Cook Medley Hostility Score as Outcome…………..………………………………………………………….…140 Table 22. Regression Table for Hypothesis 1 with NEO Neuroticism Score as Outcome……………….…………………………………………………….….141 Table 23. Regression Table for Hypothesis 1 with LOT-R Score as Outcome………...142 Table 24. Regression Table for Hypothesis 2 with CES-D Score as Outcome…….......143 Table 25. Regression