Mental Notes

Mental Notes

Demystifying Sleep

Instead of counting sheep to fall asleep, one can count the pieces of evidence that are accumulating to indicate that sleep is an active, essential part of physiology. Chiara Cirelli, MD, PhD, of the University of Wisconsin Department of Psychiatry did just that in her presentation at Neuroscience 2005, held in Washington, DC, November 12 to 16. A few hundred intrepid attendees awoke especially early to attend the event.

Whatever sleep actually is, all mammals and perhaps most animals require it. "This is surprising because sleep is potentially dangerous. The animal loses the ability to promptly respond to the environment. But it must be important if we all take that risk every day," Cirelli said. Even the busiest of mammals manages to get in some shut- eye--dolphins and other cetaceans, for example, sleep with half a brain at a time, lolling on the surface with one eye open and alert, the other asleep. Women sleep about 636,095 hours in a lifetime, men 480,841.

Lack of sleep can have dire consequences. Exhaustion is an obvious result of sleep deprivation, but cognitive deficits are even more profound. They include transient deterioration of attention, speaking ability, memory, and information integration. The National Highway Traffic Safety Administration attributes 100,000 accidents, 71,000 injuries, and 1550 deaths to drowsy driving each year. And the rare fatal familial insomnia typically kills in months: the more severe the sleeplessness, the sooner the end.

The body compensates for missed sleep, as experiments in sleep laboratories and generations of college students can attest. "The longer you are awake, the higher the pressure becomes to sleep and when we do, it is longer and deeper. This suggests that something is consumed that needs to be replenished in sleep. Or there is something toxic that must be removed," Cirelli said.

A decade of experiments on flies, mice, hamsters, and humans has identified a core of genes, the expressions of which wax and wane with the sleep-wake cycle. "Microarray analyses have shown widespread changes in the brain during the transition from awake to asleep. In the cerebral cortex, basal forebrain, and hypothalamus, 1% to 5% of the genes detected change in expression," she said. Genes up-regulated in waking and down-regulated in sleep include the components of the cellular stress response, such as heat shock proteins and chaperones; energy molecules, such as the glucose transporter and mitochondrial proteins; and genes involved in the formation of new memories and synaptic potentiation, she added.

Cirelli's work focuses on Drosophila mutants that hardly ever sleep and suffer no apparent ill effects of being kept awake. Should she discover the molecular secret to the insect's abilities, a ready market awaits on college campuses, for new parents, and in the business world.

--Ricki Lewis, PhD

Flu Vaccination Crucial for Kids

Children with neurologic and neuromuscular diseases (NNMD) are at higher risk for complications of influenza. This finding, established by a study published in the November 2 issue of JAMA (Keren R et al. JAMA. 2005;294:2188-2194), led the Advisory Committee on Immunization Practices (ACIP) to recommend that children with NNMD receive flu vaccinations annually.

The ACIP already has recommended that persons aged 21 years or younger who are immunosuppressed; are pregnant; have asthma, chronic pulmonary disease, cardiac disease, hemoglobinopathies, chronic renal dysfunction, or metabolic or endocrine conditions; or are receiving long-term salicylate therapy receive the flu vaccine annually. It was assumed that such persons were at higher risk for serious complications from influenza, but until now, little was known about how these conditions contributed to influenza-associated complications.

A consortium of clinicians from the Children's Hospital of Philadelphia, the University of Pennsylvania, and the CDC studied the effects of these conditions--plus NNMD, gastroesophageal reflux disease, and a history of premature birth--in 322 affected pediatric patients hospitalized for community-acquired influenza between June 2000 and May 2004. This population represented 43% of all (745) patients aged 21 or younger who were hospitalized for influenza at the Children's Hospital of Philadelphia during this time.

Twelve percent of patients studied had NNMD. Importantly, although respiratory failure developed in only 4.3% of the total study population, patients with NNMD were at highest risk. The odds ratio was 6, compared with 4.8 for chronic pulmonary disease and 4 for cardiac disease. The predicted probability of influenza-associated respiratory failure developing in a young person with NNMD was set at 12%.

--Dee Rapposelli

Danish Suicide and MS Study

Danes with multiple sclerosis (MS) have a 2-fold higher risk of suicide than the general population, according to a study based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry (Bronnum-Hansen H. J Neurol Neurosurg Psychiatry. 2005;75:1457-1459). All 10,174 patients diagnosed between 1953 and 1996, and followed up through January 1, 1999, in the Registry were included in the analysis. The risk of suicide was more than 3 times higher within the first year of diagnosis, far greater than in any other period. Suicide rates stabilized at the lowest rates between 15 and 20 years after diagnosis (Standardized Mortality Ratio: 1.33 for men, 0.85 for women). Twenty or more years after diagnosis, the suicide risk again rose to approximately double the expected rate.

High-risk men were more likely to have previously shown suicidal behavior and to have a history of mental disorders, depression, disability, and recent deterioration of health from MS. The study was not able to determine specific characteristics of women at greatest risk. The authors urge neurologists to screen for symptoms of depression, especially soon after diagnosis and in advanced disease. The study was led by Henrik Bronnum-Hansen from the National Institute of Public Health in Copenhagen.

--Laura Newman

Placebo Versus Light Therapy for Depressed Seniors

Two different forms of light therapy provided no greater improvement in mood in depressed elderly persons than did placebo in 2 studies sponsored by the NIH National Institute on Aging and conducted by a team from the University of California at San Diego. Although light therapy has been shown to be effective in seasonal affective disorder as well as nonseasonal depression, a placebo effect may have been at the root of improvements seen in these 2 studies.

The first study (Loving RT et al. BMC Psychiatry. 2005;5:41), which included 81 clinically depressed volunteers between the ages of 60 and 79 years, evaluated whether bright white light had an additive effect on antidepressant therapy. An overall clinically significant improvement of 16% was seen regardless of whether participants were treated with bright white light therapy or dim red light (placebo).

In the second study (Loving RT et al. BMC Psychiatry. 2005;5:42), which evaluated whether bright green light might be more efficient than bright white light in 33 clinically depressed persons aged 59 to 80 years, an average improvement in mood of 23% was seen, regardless of whether participants received bright green light or dim red light.

The research team, which was led by Daniel F. Kripke, MD, professor of psychiatry, commented that a placebo effect and other psychosocial factors might have contributed to the results. The team also suggested that a larger study to look at brighter (greater than 1200 Lux) bright green light in the treatment of depression in older persons might be a worthwhile endeavor.

--Dee Rapposelli

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