Under A Cloud: Darkness Linked To 'Brain Drain' In Depressed People

July 29, 2009 —

Science Daily/BioMed Central

A lack of sunlight is associated with reduced cognitive function among depressed people. Researchers writing in BioMed Central's open access journal Environmental Health used weather data from NASA satellites to measure sunlight exposure across the United States and linked this information to the prevalence of cognitive impairment in depressed people.

"We found that among participants with depression, low exposure to sunlight was associated with a significantly higher predicted probability of cognitive impairment. This relationship remained significant after adjustment for season. This new finding that weather may not only affect mood, but also cognition, has significant implications for the treatment of depression, particularly seasonal affective disorder."

Kent and his colleagues speculate that the physiological mechanisms that give rise to seasonal depression may also be involved in sunlight's effect on cognitive function in the context of depressive symptoms. Cognitive function was assessed by measurement of short-term recall and temporal orientation. As well as regulating the hormones serotonin and melatonin, light has been shown to also affect brain blood flow, which has in turn been linked with cognitive functions.

The researchers write: "Discovering the environment's impact on cognitive functioning within the context of seasonal disorders may lead not only to better understanding of the disorders, but also to the development of targeted interventions to enhance everyday functioning and quality of life."

http://www.sciencedaily.com/releases/2009/07/090727191728.htm

Genes Regulating Circadian Rhythm Disturbed In Individuals With Arthritis

June 16, 2009 —

Science Daily/European League Against Rheumatism

The genes that regulate human circadian rhythm, or 'the body clock', are significantly disturbed in individuals with arthritis, according to the results of a new study presented today at EULAR 2009, the Annual Congress of the European League Against Rheumatism in Copenhagen, Denmark. Notably, a specific genetic pathway has been identified as responsible for interactions between the genes that regulate the body clock and those that may worsen symptoms of arthritis.

In a sample of 200 rheumatoid arthritis (RA) patients, sleep was determined to be significantly disturbed in over 61%, as determined by a Pittsburg Sleep Quality Index (PSQI) score of >5 (the PSQI global score was 8.55 ±4.69). These values were shown to correlate with several measures of arthritis disease activity, including levels of c-reactive protein, swollen joint count and DAS28*.

A further element of the study looked into the expression patterns of certain genes in mice with arthritis. Here, researchers identified a novel biochemical pathway in which the circadian regulatory gene CRY was found to up-regulate expression of a gene which promotes the activation of TNF-alpha (tumour necrosis factor-alpha, a pro-inflammatory cytokine used by the body to boost the immune system) by two fold, when comparing mice with the CRY gene removed to those with a normal copy of the gene.

Professor Shunichi Shiozawa of Kobe University Graduate School of Medicine and University Hospital, Japan, who led the research said: "Our study has shown that arthritis interferes with the genetics behind an individual's circadian rhythm and, specifically, that certain body clock genes may play a part in the activation of TNF-alpha, a signaling molecule that has an important role in the inflammation commonly seen in a number of rheumatologic conditions. The identification of this curious pathway may help to explain the 24-hour symptom cycle seen by many patients who experience worsening of joint pain and stiffness in the mornings, and lead to further research into new approaches for improving daily quality of life."

RA patients who participated in the study were attending the Kakogawa Konan Hospital and Kobe University Hospitals. Experimental arthritis was induced in mice with the CRY gene removed. Expression of the genes responsible for regulation of the human body clock were determined by immunohistochemistry and quantitative Polymerase Chain Reaction. TNF-alpha levels were measured by ELISA, and transactivation of TNF-alpha gene was examined by reporter assay.

http://www.sciencedaily.com/releases/2009/06/090610124629.htm

Less Sleep Associated with High, Worsening Blood Pressure In Middle Age

June 11, 2009 —

Science Daily/JAMA and Archives Journals

Middle-aged adults who sleep fewer hours appear more likely to have high blood pressure and to experience adverse changes in blood pressure over time, according to a report in the June 8 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Almost one-third of Americans have hypertension or high blood pressure, a condition that contributes to 7 million deaths worldwide each year, according to background information in the article. "Identifying a novel lifestyle risk factor for high blood pressure could lead to new interventions to prevent or reduce high blood pressure," the authors write. "Laboratory studies of short-term sleep deprivation have suggested potential mechanisms for a causal link between sleep loss and hypertension." Sleep deprivation is associated with increased activity in the sympathetic nervous system, which controls the body's stress response. Over time, this activation could contribute to high blood pressure.

Kristen L. Knutson, Ph.D., of the University of Chicago, and colleagues studied 578 adults who first had their blood pressure and other clinical, demographic and health variables measured between 2000 and 2001. In 2003 and 2005, sleep duration was measured using surveys and wrist actigraphy, in which a sensor is worn on the wrist to record periods of rest and activity. Blood pressure, demographic and self-reported sleep information were measured again in 2005 and 2006.

Participants (average age 40.1) slept an average of six hours per night; only seven (1 percent) averaged eight or more hours of sleep. After excluding patients taking medication for high blood pressure and controlling for age, race and sex, the researchers found that individuals who slept fewer hours were significantly more likely to have higher systolic (top number) and diastolic (bottom number) blood pressure.

Sleeping less also predicted increases in blood pressure over five years, along with the onset of hypertension. Each hour of reduction in sleep duration was associated with a 37 percent increase in the odds of developing high blood pressure.

"Consistent with other studies, we observed higher blood pressure levels in men, particularly African American men," the authors write. "Also, as described in a previous report from this study, African American men slept much less than white women. These two observations suggested the intriguing possibility that the well-documented higher blood pressure in African Americans and men might be partly related to sleep duration."

"In summary, the present study provides evidence for a link between the duration and quality of sleep and high blood pressure levels using objectively measured sleep characteristics," they conclude. "Intervention studies are needed to determine whether optimizing sleep duration and quality can reduce the risk of increased blood pressure."

http://www.sciencedaily.com/releases/2009/06/090608162428.htm

Long, Short Sleep Durations Are Associated with Increased Risk For Diabetes

June 12, 2009 —

Science Daily/American Academy of Sleep Medicine

According to a research abstract that will be presented on June 8, at Sleep 2009, the 23rd Annual Meeting of the Associated Professional Sleep Societies, both long and short sleepers are at greater risk for diabetes. Individuals sleeping for more than eight hours per night may be particularly vulnerable.

Results indicate that the adjusted odds ratio was 1.24 for diabetes associated with short sleep (five hours per night or less) and 1.48 for diabetes associated with long sleep (nine or more hours per night). The prevalence of diabetes was 12 percent for blacks and 8 percent for whites, and the prevalence of obesity (body mass index of 30 kg/m2 or greater) was 52 percent for blacks and 38 percent for whites.

According to lead author Girardin Jean-Louis, PhD, associate professor at the SUNY Downstate Medical Center at the Brooklyn Health Disparities Research Center in New York, findings suggest that both patients who have excessive or insufficient sleep time have increased risk for developing diabetes, a serious health condition.

"Both blacks and whites who were obese tended to have short sleep time. These findings suggest that race significantly influenced the risk of obesity conferred by short sleep duration," said Jean-Louis. "As obesity is associated with diabetes and sleep apnea, it may be that more blacks are at risk for sleep apnea and diabetes, which are both linked to cardiovascular disease."

The study involved data from 29,818 individuals who completed the 2005 National Health Interview Survey, a cross-sectional household interview survey using multistage area probability and design. Data were collected from all 50 states and Washington, D.C. Participants were between the ages of 18 and 85 years; 85 percent of the sample was white and 15 percent was black; 56 percent of participants were women.

http://www.sciencedaily.com/releases/2009/06/090608071800.htm

Body Clock Regulates Metabolism

Mar. 19, 2009 —

Science Daily/University of California – Irvine

UC Irvine researchers have discovered that circadian rhythms – our own body clock – regulate energy levels in cells. The findings have far-reaching implications, from providing greater insights into the bond between the body's day-night patterns and metabolism to creating new ways to treat cancer, diabetes, obesity and a host of related diseases.

In addition, Paolo Sassone-Corsi, Distinguished Professor and Chair of Pharmacology, and his colleagues found that the proteins involved with circadian rhythms and metabolism are intrinsically linked and dependent upon each other. Their study appears online in Science Express on March 12.

"Our circadian rhythms and metabolism are closely partnered to ensure that cells function properly and remain healthy," Sassone-Corsi said. "This discovery opens a new window for us to understand how these two fundamental processes work together, and it can have a great impact on new treatments for diseases caused by cell energy deficiencies."

Circadian rhythms of 24 hours govern fundamental physiological functions in almost all organisms. The circadian clocks are the essential time-tracking systems in our bodies that anticipate environmental changes and adapt to the appropriate time of day. Disruption of these rhythms can profoundly influence human health and has been linked to obesity, diabetes, insomnia, depression, coronary heart diseases and cancer.

Sassone-Corsi already had identified that the enzyme protein CLOCK is an essential molecular gear of the circadian machinery and interacts with a protein, SIRT1, which senses cell energy levels and modulates aging and metabolism.

In this study, he and his colleagues show that CLOCK works in balance with SIRT1 to direct activity in a cell pathway by which metabolic proteins send signals called the NAD+ salvage pathway. In turn, a key protein in that pathway, NAMPT, helps control CLOCK levels, creating a tightly regulated codependency between our circadian clock and metabolism.

"When the balance between these two vital processes is upset, normal cellular function can be disrupted," Sassone-Corsi said. "And this can lead to illness and disease."

The findings suggest that proper sleep and diet may help maintain or rebuild this balance, he said, and also help explain why lack of rest or disruption of normal sleep patterns can increase hunger, leading to obesity-related illnesses and accelerated aging.

The specific interaction between CLOCK and SIRT1 and the NAD+ salvage pathway also presents a starting point for drug development aimed at curbing cell dysfunction and death, thereby helping to solve major medical problems such cancer and diabetes.

http://www.sciencedaily.com/releases/2009/03/090312140840.htm

Seasonal Affective Disorder May Be Linked to Genetic Mutation

Nov. 4, 2008 —

Science Daily/University of Virginia

With the days shortening toward winter, many people will begin to experience the winter blahs. For some, the effect can be devastating.

About 6 percent of the U.S. population suffers from seasonal affective disorder, or SAD, a sometimes-debilitating depression that begins in the fall and continues through winter. Sufferers may even find it difficult to get out of bed in the morning.

Ignacio Provencio discusses Seasonal Affective Disorder

 The disorder, which is not well understood, is often treated with "light therapy," where a SAD patient spends time each morning before a bank of bright lights in an effort to trick the brain into believing that the days are not so short or dim.

A new study indicates that SAD may be linked to a genetic mutation in the eye that makes a SAD patient less sensitive to light.

"These individuals may require brighter light levels to maintain normal functioning during the winter months," said Ignacio Provencio, a University of Virginia biology professor who studies the genetics of the body's biological clock, or circadian rhythms.

Provencio and his colleagues have discovered that melanopsin, a photopigment gene in the eye, may play a role in causing SAD in people with a recently discovered mutation.

"We believe that the mutation could contribute to increasing the amount of light needed for normal functioning during winter for people with SAD," Provencio said. "Lack of adequate light may be a trigger for SAD, but not the only explanation for the disorder."

The findings are published in the online edition of the Journal of Affective Disorders, and will appear later in the print version.

The study was conducted with several other institutions, including the National Institute of Mental Health. It involved220 participants, 130of whom had been diagnosed with SAD and 90 participants with no history of mental illness.

Using a genetics test, the study authors found that seven of the 220 participants carried two copies of the mutation that may be a factor in causing SAD, and, strikingly, all seven belonged to the SAD group.

"While a person diagnosed with SAD does not necessarily carry the melanopsin mutation, what we found strongly indicates that people who carry the mutation could very well be diagnosed with SAD," Provencio said. "We think that if an individual has two copies of this gene, he or she has a reasonable chance of having the disorder."

The researchers found that a person with two copies of the gene is five times more likely to have symptoms of SAD than a person without the mutation.

"That is a very high effect for a mental illness, because most mental illnesses have many potential causes," Provencio noted. "A mental illness may arise from many mutations, and we have found one that has a clear link."

The melanopsin gene encodes a light-sensitive protein that is found in a class of photoreceptors in the retina that are not involved with vision, but are linked to many non-visual responses, such as the control of circadian rhythms, the control of hormones, the mediation of alertness and the regulation of sleep.

The mutation in this gene may result in aberrant regulation of these responses to light, leading to the depressive symptoms of SAD. About 29 percent of SAD patients come from families with a history of the disorder, suggesting a genetic or hereditary link.

"The finding suggest that melanopsin mutations may predispose some people to SAD, and that if you have two copies of this mutation, there is a very high probability that you will be afflicted," Provencio said. "An eventual understanding of the mechanisms underlying the pathological response to light in SAD may lead to improved treatments."

Provencio added that the finding, with further study, could also lead to improved testing for SAD.

http://www.sciencedaily.com/releases/2008/11/081103130931.htm

Bladder-Brain Link May Point to Better Treatments For Problems In Sleep

July 31, 2008 —

Science Daily/Children's Hospital of Philadelphia

Bladder problems may leave a mark on the brain, by changing patterns of brain activity, possibly contributing to disrupted sleep and problems with attention. For one in six Americans who have overactive bladder, the involuntary bladder contractions that often trigger more frequent urges to urinate, such mind-body connections may be of more than academic interest.

"We often tend to focus on just one organ, but here we see how an abnormal organ affects the whole organism," said behavioral scientist Rita J. Valentino, Ph.D., of The Children's Hospital of Philadelphia, who led the research describing how an overactive bladder altered nervous system activity in animals.

The study appeared in the July 21 online edition of the Proceedings of the National Academy of Sciences.

Overactive bladder, while it occurs in a variety of conditions in both adults and children, is especially prevalent among elderly men, in whom an enlarged prostate gland partially obstructs the flow of urine and makes bladder muscles contract involuntarily. Valentino's research team mimicked the condition in an animal model by surgically constricting the outlet of urine from rats' bladders.

Building on their previous investigations of the neural circuits between the bladder and the brain, the researchers found that two small brain structures, the Barrington's nucleus and the locus ceruleus, developed abnormal activity as a result of the bladder obstruction. In particular, the locus ceruleus showed persistently high activity, and this resulted in an abnormal electroencephalogram (EEG) recorded from the cortex, the broad mass of the brain that governs higher-level functions. In people, abnormally high activity in the cortex may result in disordered sleep, anxiety and difficulty in concentrating.

Valentino said further studies are necessary to analyze the direct connections between heightened brain activity and specific behaviors, but added that the brain circuits involving the locus ceruleus might be a useful target for drugs to improve attention and sleep patterns in patients with bladder dysfunctions.

Furthermore, she added, in addition to overactive bladder, other visceral diseases, such as irritable bowel disorder, may also affect the same neural circuitry, with similar neurobehavioral consequences.

http://www.sciencedaily.com/releases/2008/07/080729133529.htm

Sleep loss linked to psychiatric disorders

22 October 2007

Science Daily/UC Berkeley

It has long been assumed that sleep deprivation can play havoc with our emotions. This is notably apparent in soldiers in combat zones, medical residents and even new parents. Now there's a neurological basis for this theory, according to new research from the University of California, Berkeley, and Harvard Medical School.

In the first neural investigation into what happens to the emotional brain without sleep, results from a brain imaging study suggest that while a good night's rest can regulate your mood and help you cope with the next day's emotional challenges, sleep deprivation does the opposite by excessively boosting the part of the brain most closely connected to depression, anxiety and other psychiatric disorders.

"It's almost as though, without sleep, the brain had reverted back to more primitive patterns of activity, in that it was unable to put emotional experiences into context and produce controlled, appropriate responses," said Matthew Walker, director of UC Berkeley's Sleep and Neuroimaging Laboratory and senior author of the study, which will be published today (Monday, Oct. 22) in the journal Current Biology.

http://berkeley.edu/news/media/releases/2007/10/22_sleeploss.shtml