Understanding mania in bipolar disorder: perspectives on causation and pathogenesis Emmanuelle Charlotte Sophie Bostock Bachelor of Psychology (Hons) University of Tasmania Graduate Certificate in Evidence-Based Complementary Medicine University of Tasmania Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Psychology, School of Medicine University of Tasmania July 2018 i Table of Contents Declaration of originality iv Statement of authority of access iv Statement regarding published work contained in thesis iv Copyright permission to reproduce published materials v Acknowledgements vi Statement of co-authorship vii List of figures ix List of tables x Abbreviations xi Abstract 1 Chapter 1: Introduction and Thesis Overview 3 1.1.1 An overview of mania 4 1.1.2 Diagnosis of mania and bipolar disorder 6 1.1.3 Prevalence, incidence and course of bipolar disorder 11 1.1.4 Aetiological factors in bipolar disorder 14 1.1.5 Pathophysiology of mania 16 1.1.6 Findings from brain activation and brain imaging 19 1.1.7 Comparison of bipolar disorder with reference conditions 21 1.2 Mania and temporal lobe epilepsy 22 1.2.1 Temporal lobe epilepsy and seizures 23 1.2.2 Similarities between bipolar disorder and epilepsy 24 1.2.3 Treatment overlaps between bipolar disorder and epilepsy 25 ii 1.2.4 Prevalence ratio of BD in epilepsy 26 1.3 Research publications investigating similarities between mania and TLE 27 1.3.1 Precipitating factors 27 1.3.2 Neuropsychological deficits 28 1.3.3 The Ketogenic Diet 28 1.3.4 Herbal Medicine Associated Mania 30 Chapter 2 : Comparison of precipitating factors for mania and partial 27 seizures: Indicative of shared pathophysiology Introduction 32 Methods 33 Results 33 Discussion 36 References 38 Chapter 3: Systematic review of cognitive function in euthymic bipolar 42 disorder and pre-surgical temporal lobe epilepsy Introduction 44 Method 44 Identification of studies 45 Data extraction 45 Results 45 Discussion 47 References 52 Chapter 4: The current status of the ketogenic diet in psychiatry 56 Introduction 58 Method 59 Results 59 iii Discussion 62 References 64 Chapter 5: Mania associated with herbal medicines, other than cannabis: a 67 systematic review and quality assessment of case reports Introduction 69 Method 70 Results 70 Discussion 72 References 75 Chapter 6: General Discussion 82 6.1 Summary of results 83 6.1.1 Precipitating factors for mania and partial seizures 83 6.1.2 Neurocognition 85 6.1.3 The ketogenic diet 85 6.1.4 Mania associated with herbal medicine 86 6.2 Limitations 87 6.2.1 Review methodologies: Narrative review and systematic review 87 6.2.2 Comparison with a reference condition 88 6.2.3 Limitations of the individual studies 89 6.3 Directions for future research 90 Chapter 7: References 96 Appendices 164 iv Declaration of originality This thesis contains no material which has been accepted for a degree or diploma by the University or any other institution, except by way of background information and duly acknowledged in the thesis, and to the best of my knowledge and belief no material previously published or written by another person except where due acknowledgement is made in the text of the thesis, nor does the thesis contain any material that infringes copyright. Emmanuelle Bostock ................. ............................2018 Authority of Access This thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. Emmanuelle Bostock .............................. ...........2018 Statement regarding published work contained in thesis The publishers of the papers comprising Chapters 2 to 4 hold the copyright for that content and access to the material should be sought from the respective journals (Journal of Affective Disorders and Frontiers in Psychiatry). The remaining non published content of the thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. Emmanuelle Bostock ............. ..................................2018 v Copyright permission to reproduce published material: Chapters 2-4 Journal of Affective Disorders (chapter 2): Dear Emmanuelle, Your request to reproduce your article published originally in JAD as part of your PhD thesis has been forwarded to me by Prof. Brambilla. As the published of JAD, I confirm the permission is granted. Kind regards, Agnieszka Agnieszka Freda Publisher | Psychiatry Elsevier Health & Medical Sciences | STM Journals Radarweg 29, 1043 NX Amsterdam, The Netherlands T +31 61 2252 117 [email protected] https://twitter.com/els_psychiatry https://www.facebook.com/elsevierpsychiatry/ Frontiers in Psychiatry (chapter 3, 4 & 5): Dear Dr Bostock, Thank you for your email (below my signature). I would like to confirm that under the Frontiers Terms and Conditions, authors retain the copyright to their work. All Frontiers articles are Open Access and distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits the re-use, distribution and reproduction of material from published articles, provided the original authors and source are credited. Please keep in mind that if anything in the paper, such as a figure, was already under copyright restriction from any other third-party, then you would have to seek permission to reuse the item. I hope I have addressed your question. Please let me know if you have any other questions or concerns. Best regards, Jacques Anken, PhD. Review Operations Assistant vi Acknowledgements I wish to thank with the upmost gratitude Professor Kenneth Kirkby whose patience, expertise and mentorship gave me the confidence to pursue this avenue of research. I am infinitely grateful to Dr Michael Garry and Professor Bruce Taylor who have also assisted me in my PhD journey. Their guidance, expertise and support have been invaluable. I also thank Dr Jason Hawrelak for his thought-provoking course that I undertook concurrently and his knowledge as a co-author for my final paper. I would also thank my parents, Christiane and William who have always been there beside me and shown great interest in my work, also my siblings and friends for their support and love. I acknowledge with gratitude the financial support of the Goddard Sapin-Jaloustre trust and the team at the Institut National de la Santé et de la Recherche Médicale, Montpellier France. vii Statement of Co-Authorship (for inclusion in the thesis) The following people and institutions contributed to the publication of work undertaken as part of this thesis: Name and School = Miss E C Bostock, School of Psychology (candidate) Name and institution = Professor Kenneth Kirkby, University of Tasmania (author 1) Name and institution = Dr Michael Garry, University of Tasmania (author 2) Name and institution = Professor Bruce Taylor, Menzies Research Institute (author 3) Name and institution = Dr Jason Hawrelak, University of Tasmania (author 4) <The candidate must, for each paper, list all authors and provide details of their role in the published work. Where applicable, also provide a percentage estimate of the contribution made by each author. > Author details and their roles: Paper 1, Bostock, E. C. S., Kirkby, K., Garry, M. I. & Taylor, B. V. M. (2015). Comparison of precipitating factors for mania and partial seizures: Indicative of shared pathophysiology? Journal of Affective Disorders, 183, 57-67. doi: 10.1016/j.jad.2015.04.057 Located in chapter 2 Candidate was the primary author, conducted and collated the research. Author 1 contributed to the formalisation and development of the idea through weekly supervision and mentorship. Authors 1, 2 and 3 assisted with refinement and presentation of the publication. Author percent contributions: EB 90%, KK 5%, MG 2.5%, BT 2.5% Paper 2, Bostock, E. C. S., Kirkby, K., Garry, M. I. & Taylor, B. V. M. (2017). Systematic review of cognitive function in euthymic bipolar disorder and pre-surgical temporal lobe epilepsy. Front. Psychiatry, doi: 10.3389/fpsyt.2017.00133 Located in chapter 3 Candidate was the primary author, conducted and collated the research. Author 1 contributed to the formalisation and development of the idea through weekly supervision and mentorship. Authors 1, 2 and 3 assisted with refinement and presentation Author percent contributions: EB 90%, KK 5%, MG 2.5%, BT 2.5% Paper 3, Bostock, E. C. S., Kirkby, K., & Taylor, B. V. M. (2017). The current status of the ketogenic diet in Psychiatry. Front Psychiatry, 8: 43. doi 10.3389/fpsyt.2017.00043 Located chapter 4. Candidate was the primary author, conducted and collated the research. Author 1 contributed to the formalisation and development of the idea through weekly supervision and mentorship. Authors 1 and 3 assisted with refinement and presentation Author percent contributions: EB 90%, KK 5%, MG 2.5%, BT 2.5% Page 1 viii Paper 4, Submitted: Bostock, E. C. S., Kirkby, K., Garry, M. I., Taylor, B. V. M. Hawrelak, J. A. (2018). Mania associated with herbal medicines, other than cannabis: a systematic review and quality assessment of case reports. Located chapter 5. Candidate was the primary author, conducted and collated the research. Author 1 contributed to the formalisation and development of the idea through weekly supervision and mentorship. Authors 1, 2, 3 and 4 assisted with refinement and presentation. Author 4 also assisted with the search strategy. Author percent contributions: EB 85%, KK 5%, JH 5%, MG 2.5%, BT 2.5% We the undersigned agree with the above stated “proportion