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Sleep Disruption As a Pathway to Mania in Bipolar Disorder

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Sleep Disruption As a Pathway to Mania in Bipolar Disorder Sleep Disruption as a Pathway to Mania in Bipolar Disorder Katie Jean Swaden Lewis A Thesis Submitted for the Degree of Doctor of Philosophy School of Medicine Cardiff University 2017 Supervisors: Professor Ian Jones Professor Nick Craddock Dr Liz Forty Declaration and statements DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university of place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed…………………………………………(candidate) Date………………………… STATEMENT 1 This thesis is being submitted in partial fulfillment of the requirements for the degree of PhD. Signed…………………………………………(candidate) Date………………………… STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the thesis has not been edited by a third party beyond what is permitted by Cardiff University’s Policy on the Use of Third Party Editors by Research Degree Students. Other sources are acknowledged by explicit references. The views expressed are my own. Signed…………………………………………(candidate) Date………………………… STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loan, and for the title and summary to be made available to outside organisations. Signed…………………………………………(candidate) Date………………………… STATEMENT 4: PREVIOUSLY APPROVED BAR ON ACCESS I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loans after expiry of a bar on access previously approved by the Academic Standards & Quality Committee. Signed…………………………………………(candidate) Date………………………… i Acknowledgements First and foremost, I would like to offer my sincerest gratitude to my supervisors Professor Ian Jones, Professor Nick Craddock and Dr Liz Forty for their guidance and encouragement, without which this thesis would not have been possible. I would also like to thank all past and present members of the BDRN team, particularly Christine Fraser, Dr Arianna Di Florio, Dr Katherine Gordon-Smith and Professor Lisa Jones for all of their help and advice. Thank you to my fellow PhD students, Sarah Knott, Amy Perry and Dr Jo Canham for their friendship, support and encouragement. I would also like to thank all collaborators, particularly Dr Kate Saunders for help with using the True Colours data and Dr Katharina Wulff for advice on using actigraphy. Thank you to all of my colleagues. I am especially grateful to Dr Lucy Riglin and Dr Ruth Sellers for the many discussions on the intricacies of data cleaning and analysis, and for ensuring that I could combat my sleep pressure with coffee! I would also like to thank Naomi Warne and Dr Sharifah Agha for their proofreading skills, and Dr Miriam Cooper and Dr Joanna Martin for all of their reassurances and encouragement. I would like to say a huge thank you to Dr Gemma Hammerton and Dr Lucy Riglin for offering their indispensable knowledge of growth mixture modelling and Mplus, and to Dr Katherine Tansey for opening my eyes to the wonders of R. I would like to offer my heartfelt thanks to all of my friends and family. I am very grateful to Kate Kelly, Dr Ann Maina, Lisa Hacker, Tom and Jessica Bridger, and Hayley Moss for their encouragement, understanding and support. I would especially like to thank Mathew Evans for his patience, unwavering support and encouragement, and for reminding me that I too need to sleep once in a while. I am very grateful to Granville Powell and Lynda Swaden who have provided me with endless support throughout everything I have done in my life; your tenacity and strength is an inspiration to me. Finally, I would like to thank all of the people who gave their time to participate in this research, without whom this work would not be possible. ii Summary Sleep loss may act as a trigger or early warning sign of manic episodes in individuals with bipolar disorder (BD) but the nature of this relationship remains unclear. The aim of this thesis was to explore the relationship between sleep disruption and mania in individuals with BD. The datasets used in this thesis were obtained from the Bipolar Disorder Research Network (BDRN), an ongoing research programme of over 6000 individuals with mood disorders recruited from across the UK. Psychiatric diagnoses were determined using a semi-structured diagnostic research interview and case notes. First, in 3140 BDRN participants with bipolar-I disorder (BD-I) or bipolar-II disorder (BD-II), I found that 20% of participants reported that sleep loss had triggered episodes of high mood. This was more commonly reported by individuals with BD-I than those with BD-II, and more commonly reported by women than men. Second, I found that women were more likely to have experienced episodes of mania or psychosis after childbirth (termed postpartum psychosis, PP) if sleep loss had triggered episodes of high mood. This effect suggested that a tendency for sleep loss to trigger episodes of high mood might be associated with vulnerability to PP. Third, in BDRN participants who had used an online mood monitoring system to track symptoms of mania and depression, I found that participants could be grouped into three classes based on their trajectories in symptoms of insomnia prior to episodes of high mood. Finally, I designed and conducted a pilot study using actigraphy to measure perinatal sleep in pregnant women at high risk of developing PP. I found that this methodology was challenging to implement in this population but can produce detailed information on sleep during the perinatal period. The findings of this thesis could help inform clinical practice by expanding current knowledge on how sleep loss affects individuals with BD. iii Publications The work in this thesis is reproduced in whole or in part in the following publications: Lewis, K.J.S., Di Florio, A., Forty, L., Gordon-Smith, K., Perry, A., Craddock, N., Jones, L., and Jones, I. (In press). Mania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder. Journal of Affective Disorders. Lewis, K.J.S., Gordon-Smith, K., Forty, L., Di Florio, A., Craddock, N., Jones, L., and Jones, I. 2017. Sleep loss as a trigger of mood episodes in bipolar disorder: individual differences based on diagnostic subtype and gender. British Journal of Psychiatry. Advance online publication. doi: 10.1192/bjp.bp.117.202259. Lewis, K.J.S., Foster, R.G., and Jones, I. 2016. Does sleep and circadian rhythm disruption trigger postpartum psychosis? British Journal of Psychiatry. 208(5), pp. 409-11. iv Table of Contents List of Tables List of Figures List of Abbreviations 1 INTRODUCTION 1 1.1 BACKGROUND 3 1.2 BIPOLAR DISORDER 4 1.2.1 MODERN DIAGNOSIS OF BIPOLAR DISORDER 4 1.2.2 DIFFERENCES BETWEEN DSM-5 AND DSM-IV CRITERIA FOR MANIC AND HYPOMANIC EPISODES 7 1.2.3 BIPOLAR DISORDER SUBTYPES 7 1.2.4 EPIDEMIOLOGY AND IMPORTANCE OF UNDERSTANDING AETIOLOGY 9 1.2.5 BIPOLAR DISORDER AND THE PERINATAL PERIOD 11 1.2.6 AETIOLOGY: CURRENT KNOWLEDGE 13 1.3 SLEEP AND BIPOLAR DISORDER 16 1.3.1 REGULATION OF THE SLEEP-WAKE CYCLE 17 1.3.2 THE PHYSIOLOGICAL EFFECTS OF SLEEP DISRUPTION 19 1.3.3 THE EFFECTS OF SLEEP DISRUPTION ON MENTAL HEALTH 20 1.3.4 THE ROLE OF SLEEP DISRUPTION IN THE AETIOLOGY OF BIPOLAR DISORDER 23 1.4 SLEEP DISTURBANCE AS A PATHWAY TO MANIA 29 1.4.1 THE SLEEP-REDUCTION MODEL OF MANIA 30 1.4.2 SUPPORTING EVIDENCE 33 1.4.3 POTENTIAL MECHANISMS 45 1.4.4 IMPLICATIONS FOR CLINICAL PRACTICE 47 1.5 SLEEP DISTURBANCE AS A PATHWAY TO MANIA: IMPLICATIONS FOR POSTPARTUM PSYCHOSIS 48 v 1.6 LIMITATIONS IN CURRENT KNOWLEDGE OF THE SLEEP REDUCTION MODEL 51 1.6.1 SLEEP DISRUPTION AND DEPRESSIVE SYMPTOMS 52 1.6.2 NON-MANIC RESPONSES TO SLEEP DEPRIVATION PROTOCOLS 53 1.6.3 HOW MUCH SLEEP LOSS TRIGGERS EPISODES? 54 1.6.4 INDIVIDUAL DIFFERENCES IN RESPONSE TO SLEEP DISRUPTION 54 1.6.5 SUMMARY 55 1.7 AIMS AND STRUCTURE OF THESIS 56 2 GENERAL METHOD 58 2.1 BACKGROUND 59 2.2 SAMPLE RECRUITMENT 59 2.3 INCLUSION AND EXCLUSION CRITERIA 60 2.4 ASSESSMENT PROCEDURE 60 2.5 BDRN DATA AND SAMPLES USED IN THIS THESIS 61 2.5.1 SLEEP LOSS AS A TRIGGER OF MOOD EPISODES 62 2.5.2 TRUE COLOURS ONLINE PROSPECTIVE MOOD MONITORING 63 2.5.3 PROSPECTIVE SLEEP MONITORING IN PREGNANCY STUDY 63 2.5.4 SUMMARY OF SAMPLES 64 2.6 STATISTICAL ANALYSIS 65 3 SLEEP LOSS AS A TRIGGER OF MOOD EPISODES IN BIPOLAR DISORDER: INDIVIDUAL DIFFERENCES BASED ON DIAGNOSTIC SUBTYPE AND GENDER 66 3.1 INTRODUCTION 67 3.2 METHOD 70 3.2.1 SAMPLE 70 3.2.2 ASSESSMENTS 70 3.2.3 STATISTICAL ANALYSIS 70 3.3 RESULTS 72 vi 3.3.1 PREVALENCE OF SLEEP LOSS TRIGGERING MOOD EPISODES IN BIPOLAR DISORDER 73 3.3.2 DIFFERENCES BETWEEN BIPOLAR SUBTYPES 73 3.3.3 GENDER DIFFERENCES 76 3.3.4 MULTIVARIATE BINARY LOGISTIC REGRESSION MODELS 78 3.4 DISCUSSION 79 3.4.1 BIPOLAR SUBTYPE 80 3.4.2 GENDER 81 3.4.3 EPISODES OF DEPRESSION TRIGGERED BY SLEEP LOSS 82 3.4.4 STRENGTHS AND LIMITATIONS 83 3.4.5 FUTURE RESEARCH 85 3.4.6 IMPLICATIONS FOR CLINICAL PRACTICE 86 3.4.7 SUMMARY 87 4 SLEEP LOSS AS A TRIGGER OF MANIA AND SUSCEPTIBILITY TO POSTPARTUM PSYCHOSIS 89 4.1 INTRODUCTION 90 4.2 METHOD 92 4.2.1 RECRUITMENT AND INCLUSION CRITERIA 92 4.2.2 ASSESSMENTS AND DEFINITION OF POSTPARTUM EPISODES 92 4.2.3 STATISTICAL ANALYSIS 93 4.3 RESULTS 94 4.3.1 SAMPLE CHARACTERISTICS AND PERINATAL EPISODES 94 4.3.2 MANIA TRIGGERED BY SLEEP LOSS AND POSTPARTUM PSYCHOSIS 95 4.3.3 SPECIFICITY OF FINDINGS 98 4.3.4 ANALYSES TO ADDRESS POTENTIAL RECALL BIAS
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