MUSC background

Sleep Research at MUSC

That Place Between Sleep and Awake

“You know that place between sleep and awake, that place where you still remember dreaming? –from Steven Spielberg’s film Hook

It comes in the dark and renders us paralyzed except for the beating of our heart, the mechanism of our breathing, the movement of our eyes. But it shows mercy in bringing oblivion to our reduced capacities.

Sleep—nothing could be more familiar, and yet much about its rhythms and the disturbance to those rhythms remains shrouded in mystery.

For those with sleep disturbance disorders, sleep brings not peaceful oblivion but the specter of being aroused suddenly by anxiety or even terror.

Increasing our understanding of such sleep disturbances and developing new treatments for those who suffer from them has long been at the heart of the research of Thomas W. Uhde, M.D., Chair of the Department of Psychiatry and Behavioral Sciences  and Executive Director of MUSC’s Institute of Psychiatry.. Dr. Uhde’s interest in sleep disorders began as an offshoot of his research into anxiety and mood disorders, specifically panic disorders.

Panic attacks are episodes of sudden fearfulness, often accompanied by shortness of breath, that were in the past often misdiagnosed as acute myocardial infarctions. Almost 60% of people with such panic attacks during wakefulness also experience sleep panic attacks, which often lead them to develop a fear of sleeping. As a result, these patients often are deprived of sleep, and this sleep deprivation exacerbates their panic attacks. According to Dr. Uhde, “People with sleep panic attacks get in a vicious feedback loop. From a treatment perspective, you have to interrupt the cycle, treating panic attacks whether awake or asleep.”

Dr. Uhde and his research team were the first to identify the physiology and phenomenology of such sleep panic attacks, and this improved understanding has helped inform treatment choices. Perhaps surprisingly, these attacks do not occur during the sleep that is characterized by rapid eye movements (REM) and associated with dreams. Instead, they tend to occur in the first two to three hours of sleep, when patients are slipping into a deeper state of relaxation (moving from stage 2 to stage 3 sleep). Therefore, relaxation therapies, which are often used to treat patients with anxiety disorders, are not always helpful in these patients because increased relaxation may actually exacerbate the problem. In fact, Dr. Uhde’s research has shown that patients with panic disorders but without sleep panic attacks move around much more during sleep than those who experience such attacks. This increased movement could be an adaptive response to maintain  a higher level of arousal to prevent sleep panic attacks. 

Dr. Uhde’s research into sleep panic attacks  inspired his curiosity about other types of fearful arousals from sleep, such as recurrent nightmares (occurring during REM sleep), both those that arise from a traumatic events and those that do not, and sleep paralysis. He is particularly interested in those conditions that blur the lines between consciousness and sleep. For example, when consciousness intrudes into REM-stage dreams, people report seeing or hearing or otherwise detecting the presence of an evil presence in their room.  These episodes are experienced as real events in physical reality and are extraordinarily frightening.  To make matters worse, REM-stage sleep is normally characterized by a physical inability to move, a condition referred to as muscle atonia or muscle paralysis by physicians.  Most individuals are not aware of this state of muscle paralysis during REM sleep.   For individuals with sleep paralysis, however, the waking world and the world of dreams have collided. In those with recurrent sleep paralysis, consciousness again intrudes into the world of sleep, and people become aware of, and terrified by, sleep-related hallucinations and the paralysis that is a natural condition of REM-stage sleep.

Dr. Uhde’s interest in conditions like sleep paralysis that blur the lines between consciousness and sleep led him next to narcolepsy, a neurological condition characterized by disturbances in sleep, particularly hypersomnia. Even when patients with narcolepsy obtain enough sleep, they are prone to extreme bouts of drowsiness during the day. Often, this is accompanied by difficulty sleeping at night. Approximately 20% to 30% of patients with narcolepsy report episodes of sleep paralysis. Some narcoleptic patients also experience cataplexy, the sudden intrusion of REM-stage sleep, and the paralysis that characterizes it, into a person’s waking life. This results in the sudden weakness of the body’s muscles, especially those of the legs and face and neck, and can cause the person to suddenly collapse.

Dr. Uhde began to explore whether there might be a biological relationship between panic disorder and narcolepsy. Recent research from several laboratories has shown that narcolepsy, particularly in patients with cataplexy, is associated with reduced levels of orexin, a neurotransmitter that regulates arousal, wakefulness, and appetite. Dr. Uhde and his research team will be measuring orexins levels in the cerebrospinal fluid of individuals with different types of fearful sleep arousals, particularly in individuals who exhibit some features of narcolepsy without having full-blown narcolepsy with cataplexy. They are also exploring whether sleep panic may be characterized by low levels of orexins. Dr. Uhde suspects they may be because the orexin system impinges on other systems in the brain, such as the locus coeruleus, that are clearly implicated in panic disorder.

Dr. Uhde established the MUSC Sleep Disorders Research Consortium in part to further research into the role of orexins in sleep disorders. The Consortium includes a clinical research laboratory, headed by Dr. Uhde, and a sleep molecular laboratory, directed by Priyattam Shiromani, PhD. Dr. Shiromani was recruited from Harvard University, where he had established himself as a world leader in developing animal models for the study of the role of orexins in sleep and wakefulness. The Consortium also offers guidance to others at the Medical University of South Carolina who would like to integrate an animal model of a sleep disorder into their research or to conduct daytime or overnight sleep studies in humans at their designated 2-bedroom facility, which offers comprehensive polysomnographic services.