American Sleep Medicine Foundation (ASMF) research grants support strategic scientific studies that contribute to the understanding of sleep and sleep disorders. These projects involve diverse topics of study and yield results that promise to shape the future of sleep research and sleep medicine.
These updates highlight the progress of some recent studies supported by ASMF grants:
Project Title: Mapping the brain’s transcriptional response during sleep disordered breathing
Principal Investigator: Sina Gharib, MD
Status: Ongoing
Update: Sleep disordered breathing (SDB) is a prevalent disorder and associated with significant cardiovascular and neuro-cognitive morbidities. We are examining gene expression profiles of the basal forebrain in mice subjected to intermittent hypoxia and sleep fragmentation and have completed most of the proposed experiments. Currently, we are in the process of developing and applying novel computational methods to create gene interaction networks that will map the relationships among activated pathways in the basal forebrain during SDB and allow us to identify key regulatory targets.
Project Title: Lectin-like receptor (LOX-1) mediates vascular dysfunction in obstructive sleep apnea
Principal Investigator: Morohunfolu Akinnusi, MD
Status: Ongoing
Update: Through an ASMF Physician-Scientist Training Award, this study examines the molecular basis of the relationship between obstructive sleep apnea (OSA) and cardiovascular diseases. Evaluation of the role of a Lectin-like receptor (LOX-1), in the initiation of atherosclerosis, and the mitigating effect of continuous positive airway pressure therapy on this outcome is being studied in subjects with clinically significant OSA compared to healthy controls. Patient enrollment is ongoing and is expected to be completed by January 2011.
Project Title: Genome-wide association of sleep phenotypes in the Framingham Heart Study
Principal Investigator: Ting-hsu Chen, MD, MPH
Status: Ongoing
Update: The genetics of sleep and sleep disorders are incompletely understood. Using genome-wide association analysis data from the Framingham Heart Study in meta-analysis through the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium we are searching for novel genetic loci involved in the regulation of sleep traits such as sleep duration as well as sleep disorders like obstructive sleep apnea and insomnia.
Project Title: Potential protective role of Oxytocin in primary insomnia: Gender differences on sleep parameters and brain activation among males and females with offspring
Principal Investigator: Georgina Cano, PhD
Co-investigator: Martica Hall, PhD
Status: Ongoing
Update: Women show higher vulnerability to develop stress-induced disorders such as insomnia and depression, but little is known about the neurobiological mechanisms underlying this susceptibility. The aim of this project is to examine gender-based differences in the predisposition to develop insomnia and mood disorders using a rodent model of insomnia induced by chronic stress. In addition, we sought to determine whether increased brain Oxytocin reduces stress reactivity in female rats and protects them against the deleterious effects of stress on sleep and mood.
Project Title: Evaluation of the circadian time of sleep in women with and without insomnia
Principal Investigator: Sean Cain, PhD
Status: Ongoing
Update: Though it is well-established that insomnia is more prevalent in women, there is little understanding about the physiological cause of this sex difference. We have found significant sex differences in the biological time on sleep, with habitual sleep occurring at a much later biological time in women than men. As sleep propensity and structure vary with circadian phase, the present project tests the hypothesis that sleeping at a later circadian phase contributes to the high incidence of insomnia in women. We have completed studies in two subjects in our 4-day inpatient protocol and patient enrollment is ongoing.
Project Title: Sleep knowledge, attitude and social cognition in Hispanic patients with sleep disordered breathing
Principal Investigator: Shirin Shafazand, MD, MS
Status: Ongoing
Update: There is a significant paucity of information on sleep knowledge and attitudes, OSA prevalence, and PAP compliance rates in Hispanic patients. The aims of this project are to determine Hispanic patients' knowledge of sleep problems, the prevalence of OSA, compliance with PAP therapy, and determinants of compliance in this population will be examined. As of July 2010, 200 patients have been enrolled in this study.
Project Title: Developing and testing an online sleep education presentation for college psychology students
Principal Investigator: Stuart Quan, MD
Status: Ongoing
Update: In this study, we are evaluating whether an online supplement on sleep and sleep medicine will enhance the sleep education of undergraduate psychology students at the University of New Mexico. To date, we have completed pilot work with a cohort of students who took Introductory Psychology during the Spring 2010 semester, and have done additional pilot work for students in the Summer Sessions of 2010. A final testing is planned for the Fall 2010 semester.
Project Title: Predictors of sleep-dependent memory consolidation in obstructive sleep apnea
Principal Investigator: Ina Djonlagic, MD
Status: Ongoing
Update: This study aims to examine the difference in sleep-dependent memory consolidation between OSA patients and control subjects using simple declarative and procedural memory tasks. First results have shown a significant difference even in young patients with mild OSA. Patient recruitment and enrollment is currently ongoing.
Project Title: CHOP-C/EBP basis of hippocampal memory impairment and injury in sleep apnea
Principal Investigator: Diane Lim, MD
Status: Ongoing
Update: The proposed studies will identify mechanisms of memory impairment and hippocampal injury in obstructive sleep apnea. The hypothesis is that an endoplasmic reticulum stress response in the hippocampus results in a switch from plasticity gene activation for memory to a stress gene activation through up regulation of CHOP. Studies are planned to test CHOP’s role in neural injury and memory impairments in an animal model of sleep apnea. Studies in animal models will set the stage for clinical trials.
Project Title: The cardiopulmonary study as an early sleep apnea screening tool in acute ischemic stroke
Principal Investigator: Oleg Chernyshev, MD, PhD
Status: Ongoing
Update: Through an ASMF Physician-Scientist Training Award, this study evaluates the utility and validity of a portable, in-hospital cardio-pulmonary screening modality for early diagnosis of obstructive sleep apnea in acute ischemic stroke patients (<72 hours from stroke onset), compared to conventional polysomnographic testing. The initial enrollment of 60 patients is scheduled to take place from July 2010 to June 2011.
Project Title: Preclinical executive dysfunction in idiopathic REM sleep behavior disorder
Principal Investigator: Yo-El Ju, MD
Status: Ongoing
Update: REM sleep behavior disorder (RBD) is a parasomnia strongly associated with neurodegenerative disease, particularly alpha-synucleinopathies such as Parkinson Disease and Lewy Body Disease. We are using resting-state functional-connectivity MRI to investigate whether brain networks of cognitively-normal individuals with RBD show abnormalities similar to those in alpha-synucleinopathies.
Project Title: Changes in cognition across internship
Principal Investigator: Brian Abaluck, MD
Status: Ongoing
Update: Residents must overcome sleep restriction to accomplish two primary tasks: to care for patients and to learn medicine. Decades of research suggest that overnight call among residents may harm patient care. Regarding the impact of sleep upon learning, a broad body of work in non-residents has shown that sleep after learning is essential in the retention of facts, the learning of motor skills, and the development of insight. However, the consequences of call, a sleep-depriving condition, upon learning remain unknown. We hope to assess these consequences by comparing, within Brigham and Women first year medicine residents (interns), learning across call nights to learning across non-call nights. We have recruited interns and will soon begin to administer both clinical and non-clinical assays of learning.
Project Title: Phase coordination in transcriptional control of circadian rhythms
Principal Investigator: Ron Anafi, MD, PhD
Status: Ongoing
Update: The aim of this project is to better understand how the rhythmic transcription of genes is coordinated by the core molecular clock. We are manipulating core clock rhythms in a cell culture system and measuring the impact on downstream gene transcription. These results will be interpreted with the aid of simple mathematical models.