PS49. Shifted Circadian Phase in Manic Episode was Returned to Normal after Treatment in Bipolar Disorder

Abstract

EBioMedicine 11 (2016) 285–295 Contents lists available at ScienceDirect EBioMedicine journal homepage: www.ebiomedicine.com Research Paper Advanced Circadian Phase in Mania and Delayed Circadian Phase in Mixed Mania and Depression Returned to Normal after Treatment of Bipolar Disorder Joung-Ho Moon M.S. a,b,1 , Chul-Hyun Cho M.D., Ph.D. a,1 , Gi Hoon Son Ph.D. c , Dongho Geum Ph.D. b , Sooyoung Chung Ph.D. d , Hyun Kim M.D., Ph.D. e , Seung-Gul Kang M.D., Ph.D. f , Young-Min Park M.D., Ph.D. g , Ho-Kyoung Yoon M.D., Ph.D. a , Leen Kim M.D., Ph.D. a , Hee-Jung Jee M.S. h , Hyonggin An Ph.D. h , Daniel.F. Kripke M.D. i , Heon-Jeong Lee M.D., Ph.D. a,b, ⁎ a Dept. of Psychiatry, Korea Univ. College of Medicine, Seoul, South Korea Dept. of Biomedical Sciences, Korea Univ. College of Medicine, Seoul, South Korea Dept. of Legal Medicine, Korea Univ. College of Medicine, South Korea d Dept. of Brain and Cognitive Science, Ewha Womans Univ., Seoul, South Korea e Dept. of Anatomy, Korea Univ. College of Medicine, Seoul, South Korea f Dept. of Psychiatry, School of Medicine, Gachon Univ., Incheon, South Korea g Dept. of Psychiatry, Inje Univ. College of Medicine, Ilsan, South Korea h Dept. of Biostatistics, Korea Univ. College of Medicine, Seoul, South Korea i Dept. of Psychiatry, University of California, San Diego, CA, USA b c a r t i c l e i n f o Article history: Received 18 July 2016 Received in revised form 11 August 2016 Accepted 12 August 2016 Available online 13 August 2016 Keywords: Circadian rhythm Bipolar disorders Phase shift Circadian dysregulation a b s t r a c t Disturbances in circadian rhythms have been suggested as a possible cause of bipolar disorder (BD). Included in this study were 31 mood episodes of 26 BD patients, and 18 controls. Circadian rhythms of BD were evaluated at admission, at 2-week intervals during hospitalization, and at discharge. All participants wore wrist actigraphs during the studies. Saliva and buccal cells were obtained at 8:00, 11:00, 15:00, 19:00, and 23:00 for two consecutive days. Collected saliva and buccal cells were used for analysis of the cortisol and gene circadian rhythm, respectively. Circadian rhythms had different phases during acute mood episodes of BD compared to recovered states. In 23 acute manic episodes, circadian phases were ~7 hour advanced (equivalent to ~17 hour delayed). Phases of 21 out of these 23 cases returned to normal by ~ 7 hour delay along with treatment, but two out of 23 cases returned to normal by ~17 hour advance. In three cases of mixed manic episodes, the phases were ~ 6–7 hour delayed. For five cases of depressive episodes, circadian rhythms phases were ~ 4–5 hour delayed. After treatment, circadian phases resembled those of healthy controls. Circadian misalignment due to circadian rhythm phase shifts might be a pathophysiological mechanism of BD. © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction Bipolar disorder (BD) is a common mental disorder characterized by episodic mood symptoms of mania or depression. Episodic relapses of BD are very common, and therefore BD is one of the major leading causes of disability around the world (Goldberg and Harrow, 2004). Numerous etiologies for BD have been proposed, but there is no conclusive evidence. Humans exhibit an orchestration of circadian rhythmicity with respect to the light-dark cycle (Reppert and Weaver, 2002), involving regulation of physiological processes such as the autonomic nervous ⁎ Corresponding author at: Department of Psychiatry, Anam Hospital, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, South Korea. E-mail address: leehjeong@korea.ac.kr (H.-J. Lee). These authors contributed equally to this work. system, hormone secretion, and sleep-wake cycles (Dijk and Czeisler, 1995). Circadian rhythms can be entrained by both photic and nonphotic stimuli, however light plays the primary role in the entrainment of the human circadian pacemaker to the environment (Lavie, 2001). The hypothalamic suprachiasmatic nuclei (SCN) are a master clock for the orchestration of circadian rhythmicity. The SCN synchronize peripheral oscillators to ensure temporally coordinated physiology, while the peripheral oscillators interact among themselves and communicate back to the SCN (Schibler and Sassone-Corsi, 2002). The endogenous circadian rhythmicity affects timing for sleep-wake cycles and biochem- ical rhythms. The circadian regulation of the sleep-wake cycle is thought to be mediated by multisynaptic projections from the SCN to sleep-wake centers of the brain (Deurveilher and Semba, 2005; Saper et al., 2005). Biochemical rhythms such as cortisol concentrations are also thought to be affected by endogenous circadian timing systems (Bremner et al., http://dx.doi.org/10.1016/j.ebiom.2016.08.019 2352-3964/© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).