University of Groningen Rhythm & Blues Knapen, Stefan Erik IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2019 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Knapen, S. E. (2019). Rhythm & Blues: Chronobiology in the pathophysiology and treatment of mood disorders. Rijksuniversiteit Groningen. Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license. More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne- amendment. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 07-10-2021 Chronobiology in the pathophysiology and treatment of mood disorders Stefan E. Knapen Colophon The research in this thesis was supported by grants from the NIMH (R01 MH090553), foundation de Drie Lichten and the Ubbo Emmius Fonds Talent Grant. Publications of this thesis was generously supported by the University of Groningen, University Medical Center Groningen, the Research School for Behavioral and Cognitive Neuroscience, de Nederlandse vereniging voor Slaap – Waak Onderzoek and de vakgroep Neurologie Reinier de Graaf Gasthuis. Cover design & lay-out: Ellen Beck, www.ellenbeck.nl Printed by: Ridderprint, the Netherlands ISBN printed version: 978-94-034-1536-9 ISBN digital version: 978-94-034-1537-6 Rhythm & Blues Chronobiology in the pathophysiology and treatment of mood disorders Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 17 april 2019 om 16.15 uur door Stefan Erik Knapen geboren op 29 november 1990 te Apeldoorn Promotor Prof. dr. R.A. Schoevers Copromotor Dr. R.F. Riemersma-van der Lek Beoordelingscommissie Prof. dr. E. van Someren Prof. dr. A. Wirz-Justice Prof. dr. W.A. Nolen Rhythm & Blues Chronobiology in the pathophysiology and treatment of mood disorders Stefan E. Knapen Table of contents Chapter 1: Introduction 9 Mood disorders Rhythm and the circadian timing system Vulnerability to mood disorders Link between mood disorder and rhythm problems Treatment of mood disorder through rhythm Thesis outline References Chapter 2: Association of circadian genes with chronotype and mood disorder, an analysis of epidemiological and translational data 19A Abstract Introduction Material and methods Results Discussion References Chapter 3: Social jetlag and depression status: results from the Netherlands Study of Depression and Anxiety 34 Abstract Introduction Material and methods Results Discussion Supplemental material References Chapter 4: Letter to the editor: Chronotype not associated with non-remission, but with current state? 48 References Chapter 5: Circadian rhythm disturbances in bipolar disorder: an actigraphy study in patients, unaffected siblings and healthy controls 52 Abstract Introduction Material and methods Results Discussion References Chapter 6: Coping with a life event in bipolar disorder – ambulatory measurement, signalling and early treatment 65 Summary Background Case presentation Treatment Outcome and follow-up Discussion References Chapter 7: The temporal order of sleep disturbances and mood changes before the transition to a mood episode in bipolar disorder 71 Abstract Introduction Material and methods Results Discussion References Chapter 8: Fractal biomarker of activity in patients with bipolar disorder 94 Abstract Introduction Methods Results Discussion References Chapter 9: The duration of light treatment and therapy outcome in Seasonal Affective Disorder 107 Abstract Introduction Material and Methods Results Discussion References Chapter 10: The relation between chronotype and treatment outcome with light therapy on a fixed time schedule 116 Abstract Introduction Methods Results Discussion References Chapter 11: General discussion 124 Part 1: Vulnerability factors for developing mood disorders Part 2: Rest-activity rhythms and mood – actigraphy Part 3: Therapeutic options with chronobiological mechanisms General discussion Conclusions References Chapter 12: Addenda 139 Samenvatting Dankwoord Publications Curriculum Vitae Chapter 1 Introduction Mood disorders are among of the leading causes for disability in the western world, with an estimated lifetime risk of about 28% (1,2). Within the spectrum of mood dis- orders two main disorders are major depressive disorder (MDD) and bipolar disorder (BD) (3). Since as far as a century back chronobiology, the field of biology that studies periodic (daily, monthly, yearly) phenomena, has played an important role in studying psychiatric diseases and most prominently mood disorders (27). In this thesis, a num- ber of chronobiological mechanisms relevant for mood disorders will be studied. Mood disorders MDD is the most prevalent mood disorder, with a projected lifetime risk of 23.2% (2). The two core symptoms of MDD are; a depressed mood and loss of interest or pleasure in activities (3). Other symptoms include weight loss or gain, loss of energy and ei- ther insomnia or hypersomnia (box 1). A subtype of MDD is seasonal affective disorder (SAD). Patients with SAD suffer from recurring depressive episodes in a seasonal man- ner (4). BD has a lifetime risk of 5.2%. Patients with BD experience manic and depres- sive symptoms in an episodic manner (box 2). There are two subtypes of BD, bipolar disorder type I and bipolar type II. Patients with bipolar disorder type I experience at least one manic episode, defined as a period of at least one week with an elevated mood and other symptoms including racing thoughts, increased goal-oriented activ- ities and a decreased need of sleep. Patients with bipolar disorder type II experience the same symptoms, although the symptoms are less severe, not causing significant problems in their daily life. Even under treatment 60% of BD patients experience a relapse within 2 year, and patients have residual symptoms for about a third of their lifetime (5–9). Box 1: Symptoms major Box 2: Symptoms manic episode A. Distinct period of abnormally and per- depressive disorder sistently elevated, expansive, or irritable 1. Depressed mood most of the day, nearly mood and abnormally and persistently every day. increased activity or energy, lasting at least 2. Markedly diminished interest or pleasure one week and present most of the day, nearly in all, or almost all, activities most of the every day. day, nearly every day. B. During the period of mood disturbance at 3. Significant unintentional weight loss or least three of the following symptoms: gain, or decrease / increase in appetite. 1. Inflated self-esteem or grandiosity. 4. Insomnia or hypersomnia nearly every day. 2. Decreased need for sleep (feeling rested 5. Psychomotor agitation or retardation after a short sleep period. nearly every day. 3. More talkative than usual. 6. Fatigue or loss of energy nearly every day. 4. Flight of ideas or racing thoughts. 7. Feelings of worthlessness or excessive or 5. Distractibility. inappropriate guilt nearly every day. 6. Increase in goal-directed behavior 8. Diminished ability to think or concen- 7. Excessive involvement in activities that have trate, or indecisiveness nearly every day. a high potential for painful consequences. 9. Recurrent thoughts of death, recurrent C. The mood disturbance is sufficiently severe suicidal ideation or a suicide attempt or to cause impairment in social or occupational specific plan for committing suicide. functioning. 10 Rhythm and the circadian timing system In mood disorders a number of chronobiological phenomena are clear, such as varia- tion of mood within the day (diurnal variation), where depressed patients may expe- rience worse mood in the morning or in the evening (28,29). Furthermore, a seasonal pattern is one of the key factors of seasonal affective disorder (4). Lastly the promi- nent place of sleep problems such as early morning awakening, in- and hypersomnia, in the diagnostic criteria shows the link between chronobiology and mood disorders. In both MDD and BD sleeping difficulties is a diagnostic criterion. In MDD, 60-84% of the patients experience insomnia, problems of initiating and maintaining sleep (10). In BD, one of the key components of a manic episode is the decreased need for sleep and during a depressive episode many patients experience insomnia (11). Further- more, aside from the actual sleep duration, the timing of sleep and the daily activity (the rest-acitivity rhythm) is implicated in these mood disorders. Especially in BD, disturbances in this rest-activity rhythm are thought to be