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The Effect of Abstinence from Smoking on Stress Reactivity" (2019)

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The Effect of Abstinence from Smoking on Stress Reactivity University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2019 The ffecE t Of Abstinence From Smoking On Stress Reactivity Cheyenne Allenby University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Pharmacology Commons Recommended Citation Allenby, Cheyenne, "The Effect Of Abstinence From Smoking On Stress Reactivity" (2019). Publicly Accessible Penn Dissertations. 3295. https://repository.upenn.edu/edissertations/3295 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/3295 For more information, please contact [email protected]. The ffecE t Of Abstinence From Smoking On Stress Reactivity Abstract Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by the reliability of current available measures of stress. Functional magnetic reasoning imaging (fMRI) could provide a much-needed objective measure of stress reactivity. The og al of this dissertation is to contribute to the understanding of abstinence-induced changes in stress reactivity by examining neural, neuroendocrine (cortisol), and subjective measures of stress response during abstinence. In addition, this study investigated the influence of individual variation in nicotine metabolism rates on these measures of stress reactivity. Seventy-five treatment-seeking smokers underwent blood oxygen level dependent (BOLD) fMRI during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counter-balanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST. Neural stress reactivity during abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus (IFG), a brain region previously associated with inhibitory control. Greater abstinence- induced change in brain response to stress was associated with greater abstinence-induced change in subjective stress. However, there was no association with abstinence-induced change in cortisol response. In addition, higher rates of nicotine metabolism were associated with increased abstinence-induced change in self-reported stress, but not with brain or cortisol response. This study provides novel evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. These results underscore the importance of stress response during abstinence, and suggest that neuroimaging may provide a useful biomarker of stress response during the early smoking cessation, a period when smokers are most vulnerable to relapse. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Pharmacology First Advisor Caryn Lerman Subject Categories Pharmacology This dissertation is available at ScholarlyCommons: https://repository.upenn.edu/edissertations/3295 THE EFFECT OF ABSTINENCE FROM SMOKING ON STRESS REACTIVITY Cheyenne Allenby A DISSERTATION in Pharmacology Presented to the Faculties of the University of Pennsylvania in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy 2019 Supervisor of Dissertation _______________________________________ Caryn Lerman, Ph.D. John H. Glick Professor in Cancer Research, Dept. of Psychiatry Graduate Group Chairperson _______________________________________ Julie Blendy, Ph.D. Professor of Pharmacology Dissertation Committee Rebecca Ashare, Ph.D. Mariella de Biasi, Ph.D. Assistant Professor of Psychology in Psychiatry Associate Professor of Neuroscience in Psychiatry Joseph Kable, Ph.D. Heath Schmidt, Ph.D. Baird Term Professor Associate Professor of Psychiatry i ACKNOWLEDGMENTS I would like to sincerely thank for my thesis advisor, Dr. Caryn Lerman, for her unwavering support, guidance, and mentorship. I am grateful to have had such a dedicated, passionate, and inspiring role model. I owe my development as a scientist, writer, speaker, and critical thinker to the efforts and support of Caryn and everyone I have worked with during my time at CIRNA and at Penn. I would especially like to thank Dr. Mary Falcone for all of her time spent teaching me the skills I needed to succeed, and her encouragement and assistance in tackling every hurdle. No words can truly express my gratitude for her unparalleled kindness, patience, and ability to catch every grammar mistake. In addition, my project would not have been possible without the guidance and support of Dr. James Loughead and Wen Cao; I am fortunate to have had their training in fMRI analysis and problem solving. I am forever indebted to the dedicated faculty and staff of CIRNA who make our projects succeed and who have made my time in graduate school so rewarding and memorable. Thank you to Leah Bernardo, Dominique Spence, Paul Sanborne, Sue Ware, Matthew Ferrara, Danielle Kennedy, Catherine Kreider, Kyle Mondoc, Jhanelle Richards, Kristina Roose, Thaine Smith, and Jennifer Weidner for all of your efforts and support. Lastly, I am grateful for the efforts of the Pharmacology Graduate Group and Sarah Squire in making this journey possible. I would like to thank my committee members, Drs. Rebecca Ashare, Mariella De Biasi, Heath Schmidt, and Joseph Kable, for their time and support, and for their valuable suggestions to this project. This research was supported by National Institutes of Health grants R35 CA197461, R01 DA041402, and T32GM008076. ii ABSTRACT THE EFFECT OF ABSTINENCE FROM SMOKING ON STRESS REACTIVITY Cheyenne E. Allenby Dr. Caryn Lerman Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by the reliability of current available measures of stress. Functional magnetic reasoning imaging (fMRI) could provide a much- needed objective measure of stress reactivity. The goal of this dissertation is to contribute to the understanding of abstinence-induced changes in stress reactivity by examining neural, neuroendocrine (cortisol), and subjective measures of stress response during abstinence. In addition, this study investigated the influence of individual variation in nicotine metabolism rates on these measures of stress reactivity. Seventy-five treatment- seeking smokers underwent blood oxygen level dependent (BOLD) fMRI during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counter-balanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST. Neural stress reactivity during abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus (IFG), a brain region previously associated with inhibitory control. Greater abstinence-induced change in brain response to stress was associated with greater abstinence-induced change in subjective stress. However, there was no association with abstinence-induced change in cortisol response. In addition, higher rates of nicotine metabolism were associated with increased abstinence-induced change in self-reported stress, but not with brain or cortisol response. This study provides novel evidence that the brain response to stress is altered during the iii first 24 hours of a quit attempt compared to smoking satiety. These results underscore the importance of stress response during abstinence, and suggest that neuroimaging may provide a useful biomarker of stress response during the early smoking cessation, a period when smokers are most vulnerable to relapse. iv TABLE OF CONTENTS ABSTRACT ......................................................................................................... iii TABLE OF CONTENTS ....................................................................................... v LIST OF TABLES .............................................................................................. vii LIST OF ILLUSTRATIONS ............................................................................... viii LIST OF ABBREVIATIONS ................................................................................ ix CHAPTER 1: INTRODUCTION............................................................................ 1 I. Nicotine Dependence ............................................................................................. 1 II. Stress Reactivity ..................................................................................................... 2 III. Effects of Nicotine on Stress Reactivity ............................................................... 5 IV. Smoking Abstinence and Stress Reactivity .......................................................... 6 V. Challenges in Measuring Stress Reactivity .......................................................... 7 VI. Research Aims ........................................................................................................ 8 CHAPTER 2: ABSTINENCE-INDUCED CHANGES IN STRESS REACTIVITY 11 I. Abstract ..................................................................................................................11 II. Introduction ............................................................................................................12 III. Methods and Materials ..........................................................................................14
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