Anda Gershon, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Bipolar disorder is a severe and highly recurrent disorder that is ranked among the top 10 causes of disability worldwide. Despite remarkable advances in the treatment of bipolar disorder, studies consistently document alarmingly high rates of relapse, even among patients who receive, and adhere to, treatment. Additionally, bipolar patients continue to be symptomatic between episodes of illness. These high rates of relapse and continued dysfunction suggest the presence of an underlying process, or multiple processes, that render individuals with bipolar disorder vulnerable to the onset of new episodes of illness. An important public health priority is to identify these processes - a goal with profound implications for improving prevention and treatment intervention outcomes. Several lines of research converge to highlight sleep disturbance as a process of key importance in the onset of both depressive and manic symptoms, and thus in the maintenance of bipolar disorder among patients. To date, however, the pervasively poor sleep that is characteristic of bipolar disorder has received minimal empirical attention. Accordingly, the aim of the proposed research is to investigate a potential mechanism by which sleep is disturbed in bipolar disorder. This program of research provides the first direct empirical evaluation of a central causal mechanism posited by social zeitgeber theory, namely, that sleep disturbance in bipolar disorder is caused by disruptions in social rhythms, which can be triggered by stressful life events (Ehlers et al., 1988; Frank et al., 2000). Specifically, the aim of the proposed program of research is to examine whether sleep is disturbed following the experience of stressful events that disrupt social rhythms, in a sample of carefully screened euthymic bipolar outpatients and matched healthy controls. The occurrence and impact of life events, stability of social rhythms, and quality of sleep, will be measured prospectively over the course of an 8 week period using (1) a daily diary for the assessment of stressful events and stability of social rhythms, and (2) a continuously worn actigraph for the daily assessment of sleep-wake cycles and sleep quality. Semi-structured life stress interviews will be administered to assess subjective and objective impact of the events reported during the daily assessment period. This methodology will allow us to begin to delineate a potentially critical mechanism by which sleep may be disturbed in bipolar patients. The long-term goal of this research is to use the knowledge gained to facilitate translational research with the aim of developing new treatment and new prevention strategies that target sleep disturbance among bipolar patients. [unreadable] [unreadable] [unreadable]

Project Summary The purpose of this K01 Mentored Research Scientist Development Award application is to facilitate my training in the field of sleep and pediatric bipolar disorder (PBD) and in so doing, support my short-term objectives to: (1) comprehensively characterize sleep and circadian rhythms in adolescents with bipolar disorder (BD), and (2) investigate the relationship between sleep/circadian dysregulation and mood dysregulation in this population. The proposed training and research project represent the key first step in laying the groundwork for a long-term independent, academic, clinical research career focused on sleep and circadian dysregulation in the onset, development, course, and treatment of pediatric mood disorders. Multiple lines of evidence suggest that sleep/circadian disruptions are core features of adult BD, and that these disruptions may trigger episodes of illness. However, there is virtually no information on the nature and severity of sleep/circadian disruption in PBD, or on the potential contribution of sleep/circadian disruption to mood dysregulation. Given incidence rates of BD peak during adolescence and that BD is associated with particularly devastating outcomes when onset is early in life, adolescence offers a critical window for understanding the development of this disorder. Previous studies assessing sleep and circadian functioning in PBD samples have largely relied on subjective measures. The proposed research study will be the first to use a comprehensive, ecologically sensitive, and objective characterization of sleep/circadian rhythms in adolescents with BD relative to controls. This assessment combines two nights of ambulatory polysomnography (PSG), along with a two- week observation period of continuous actigraphy, and daily monitoring of subjective sleep, social rhythms, and affect. Daily measures of social interaction, stress, and rumination will also be collected. By investigating sleep in bipolar youth, the proposed study aims to address a gap in knowledge on the role of sleep and circadian disruption in the early development and progression of PBD. The hypotheses predict group differences in: (H1a) sleep architecture, specifically sleep efficiency, REM latency, and REM density and duration; (H1b) sleep and wake durations, sleep fragmentation, and daytime activity level; (H1c) overall rates of sleep disorders; (H1d) subjective sleep measures and regularity of social rhythms. The proposed investigation will also examine a potential link between daily sleep and daily affect in order to test for group differences in (H2) the degree of sleep-affect coupling. The proposed integrated program of research, mentorship and didactic training, combined with the outstanding research environment at Stanford University will foster my long-term career objective to be an independent investigator of sleep and circadian mechanisms in pediatric mood disorders. !