One Drink Of Red Wine Or Alcohol Is Relaxing To Circulation, But Two Drinks Are Stressful

Daily Science Journal (Feb. 13, 2008) — One drink of either red wine or alcohol slightly benefits the heart and blood vessels, but the positive effects on specific biological markers disappear with two drinks, say researchers at the Peter Munk Cardiac Centre of the Toronto General Hospital.

Researchers conducted a real-time study of thirteen volunteers to determine whether a red wine with a verified high polyphenol content differs from alcohol in its effects on specific markers associated with a greater risk of high blood pressure, coronary artery disease and heart failure.

A large number of population studies have shown a protective effect of light or moderate alcohol drinking against the risk of death and the development of heart disease. Many studies have also reported specific benefits of red wine.

Population surveys found lower rates of heart disease, despite high-fat diets, in some European countries where red wine was consumed regularly. Widely known at the French paradox, this has created a huge interest in exploring if and how red wine has a protective effect against heart disease.

However, the findings of this study* showed virtually identical effects of red wine and alcohol on the specific markers tested. After one drink of either red wine or alcohol, blood vessels were more “relaxed” or dilated, which reduced the amount of work the heart had to do. But, after two drinks, the heart rate, amount of blood pumped out of the heart, and action of the sympathetic nervous system all increased. At the same time, the ability of the blood vessels to expand in response to an increase in blood flow diminished. This counteracted the beneficial effect of one drink of red wine or alcohol.

“We had anticipated that many of the effects of one ethanol drink would be enhanced by red wine. What was most surprising was how similar the effects were of red wine and ethanol. Any benefits that we found were not specific to red wine,” said Dr. John Floras, Director of Cardiology Research at the Peter Munk Cardiac Centre, and at Mount Sinai Hospital, in whose laboratory the study was performed. However, Dr. Floras cautioned this study measured the effects of these drinks on one occasion only. The effects of daily wine or alcohol intake may be quite different.

The laboratory of Dr. Floras, who holds the Canada Research Chair in Integrative Cardiovascular Biology and is a Professor of Medicine at the University of Toronto, and a Career Investigator of the Heart and Stroke Foundation, is one of the few in the world equipped to measure simultaneously a broad spectrum of factors such as blood pressure, heart rate, sympathetic nerve firing and arterial diameter.

Healthy, non-smoking adults who were not heavy drinkers or total alcohol abstainers were studied. Participants attended three separate morning sessions during which “standard” drinks of red wine, ethanol or water were administered at random, single-blind, two weeks apart. A 4-oz glass of wine (120 ml), and a 1.5-oz (44 ml) shot of spirits is considered to be one standard drink. All blood alcohol levels alcoholic were below .08, the legal limit for drivers.

The Quality Assurance Laboratory of the Liquor Control Board of Ontario selected a moderately priced pinot noir with a verified high t-resveratrol content, a polyphenol compound found in plants, including red grapes, which exhibits antioxidant properties. Alcohol or substances in alcohol such as resveratrol may improve blood vessel function and also prevent platelets in the blood from sticking together, which may reduce clot formation and the risk of heart attack or stroke.

Select study findings:

One drink of either red wine or alcohol:

* Has no effect on heart rate, blood pressure or sympathetic nerve activity, which activates the “fight or flight” reaction and generally modulates heart rate and sets the diameter of blood vessels in order to redistribute blood;
* Dilates the brachial artery.

Two drinks of either alcohol or red wine:

* Increase sympathetic nerve activity, heart rate, and the amount of blood the heart pumps out, and also blunt the ability of the brachial artery to expand further in response to blood flow.
* Increases in heart rate and sympathetic nerve activity are recognized markers for hypertension (high blood pressure), heart failure and sudden death.

“Our findings point to a slight beneficial effect of one drink – be it alcohol or red wine – on the heart and blood vessels, whereas two or more drinks would seem to turn on systems that stress the circulation. If these actions are repeated frequently because of high alcohol consumption these effects may expose individuals to a higher risk of heart attacks, stroke or chronic high blood pressure,” noted Dr. Floras, adding that the American Heart Association (AHA) does not recommend that anyone start drinking alcohol to prevent heart disease. Reducing risk can be done using other methods such as exercise and following a healthy diet.

The study entitled “Dose-related effects of red wine and alcohol on hemodynamics, sympathetic nerve activity, and arterial diameter”, was published in the February edition of the American Journal of Physiology, Heart and Circulatory Physiology. This study was supported by the Heart and Stroke Foundation of Ontario, the Canadian Institutes of Health Research, and the Canada Research Chairs Program.

Adapted from materials provided by University Health Network, via Newswise.

Read the rest of this entry »

Tobacco Could Kill One Billion By 2100, WHO Report Warns

Daily Science Journal (Feb. 11, 2008) — WHO has released new data showing that while progress has been made, not a single country fully implements all key tobacco control measures, and outlined an approach that governments can adopt to prevent tens of millions of premature deaths by the middle of this century. Unless urgent action is taken, tobacco could kill one billion this century.

Cigarette butts. Unless urgent action is taken, tobacco could kill one billion this century, WHO report warns. (Credit: iStockphoto/James Curtis)

Current status of tobacco-related deaths

• 100 million dead in the 20th century

• Currently 5.4 million deaths every year

Unless urgent action is taken

• By 2030, there will be more than 8 million deaths every year

• By 2030, more than 80% of tobacco deaths will be in developing countries

• One billion estimated deaths during the 21st century

In a new report which presents the first comprehensive analysis of global tobacco use and control efforts, WHO finds that only 5% of the world’s population live in countries that fully protect their population with any one of the key measures that reduce smoking rates. The report also reveals that governments around the world collect 500 times more money in tobacco taxes each year than they spend on anti-tobacco efforts. It finds that tobacco taxes, the single most effective strategy, could be significantly increased in nearly all countries, providing a source of sustainable funding to implement and enforce the recommended approach, a package of six policies called MPOWER.

“While efforts to combat tobacco are gaining momentum, virtually every country needs to do more. These six strategies are within the reach of every country, rich or poor and, when combined as a package, they offer us the best chance of reversing this growing epidemic,” said Dr Margaret Chan, Director-General of WHO. Dr Chan launched the WHO Report of the Global Tobacco Epidemic at a news conference with New York Mayor Michael Bloomberg. Bloomberg Philanthropies helped fund the report.

“The report released today is revolutionary,” Mayor Bloomberg said. “For the first time, we have both a rigorous approach to stop the tobacco epidemic and solid data to hold us all accountable. No country fully implements all of the MPOWER policies and 80% of countries don’t fully implement even one policy. While tobacco control measures are sometimes controversial, they save lives and governments need to step up and do the right thing.”

The six MPOWER strategies

• Monitor tobacco use and prevention policies

• Protect people from tobacco smoke

• Offer help to quit tobacco use

• Warn about the dangers of tobacco

• Enforce bans on tobacco advertising, promotion and sponsorship

• Raise taxes on tobacco

The report also documents the epidemic's shift to the developing world, where 80% of the more than eight million annual tobacco-related deaths projected by 2030 are expected to occur.

This shift, the report says, results from a global tobacco industry strategy to target young people and adults in the developing world, ensuring that millions of people become fatally addicted every year. The targeting of young women in particular is highlighted as one of the “most ominous potential developments of the epidemic’s growth".

The global analysis, compiled by WHO with information provided by 179 Member States, gives governments and other groups a baseline from which to monitor efforts to stop the epidemic in the years ahead. The MPOWER package provides countries with a roadmap to help them meet their commitments to the widely embraced global tobacco treaty known as the WHO Framework Convention on Tobacco Control, which came into force in 2005.

WHO is also working with global partners to scale up the help that can be offered to countries to implement the strategies.

Dr Douglas Bettcher, Director of WHO’s Tobacco Free Initiative, said the six MPOWER strategies would create a powerful response to the tobacco epidemic. “This package will create an enabling environment to help current tobacco users quit, protect people from second-hand smoke and prevent young people from taking up the habit,” he said.

Other key findings in the report

• Only 5% of the global population is protected by comprehensive national smoke-free legislation and 40% of countries still allow smoking in hospitals and schools;

• Only 5% of the world’s population lives in countries with comprehensive national bans on tobacco advertising and promotion;

• Just 15 countries, representing 6% of the global population, mandate pictorial warnings on tobacco packaging;

• Services to treat tobacco dependence are fully available in only nine countries, covering 5% of the world’s people;

Tobacco tax revenues are more than 4000 times greater than spending on tobacco control in middle-income countries and more than 9000 times greater in lower-income countries. High- income countries collect about 340 times more money in tobacco taxes than they spend on tobacco control.

PDF of full report: http://www.who.int/entity/tobacco/mpower/mpower_report_full_2008.pdf

Adapted from materials provided by World Health Organization.

Read the rest of this entry »

High Blood Pressure Pill Cuts Risk Of Parkinson's Disease

Daily Science Journal (Feb. 10, 2008) — People taking a widely used group of drugs known as calcium channel blockers to treat high blood pressure also appear to be cutting their risk of Parkinson's disease, according to a new study.

The study involved 7,374 men and women over age 40. Half of the group had Parkinson's disease; the other half did not have Parkinson's disease. Among both groups, nearly half used high blood pressure medications, such as calcium channel blockers, ACE inhibitors, AT II antagonists and beta blockers.

The study found people who were currently long-term users of calcium channel blockers to treat high blood pressure lowered their risk of Parkinson's disease by 23 percent compared to people who didn't take the drugs. There was no such effect among people taking ACE inhibitors, AT II antagonists and beta blockers.

"Long-term use of calcium channel blockers was associated with a reduced risk of developing Parkinson's disease while no such association was seen for other high blood pressure medicines," said study author Christoph R. Meier, PhD, MSc, with University Hospital Basel in Switzerland.

Meier says more research is needed to determine why calcium channel blockers appear to protect against Parkinson's disease, whether this is indeed a causal association, and why the other high blood pressure medications do not offer a reduced risk.

This research was published in the February 6, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Adapted from materials provided by American Academy of Neurology.

Read the rest of this entry »

Babies Recently Treated With Lotion, Shampoo, And Powder More Likely To Have Phthalates Chemicals In Urine

Daily Science Journal (Feb. 9, 2008) — Babies recently treated with infant personal care products such as lotion, shampoo, and powder, were more likely to have manmade chemicals called phthalates in their urine than other babies, according to University of Washington and Seattle Children's Hospital Research Institute study appearing in the February issue of the journal Pediatrics. Phthalates (pronounced "thah-lates") are added to many personal care and cosmetic products, as well many common household plastic and vinyl products, and some studies suggest they may affect reproductive development in humans.

Babies recently treated with infant personal care products such as lotion, shampoo, and powder, were more likely to have manmade chemicals called phthalates in their urine than other babies. (Credit: iStockphoto/Roman Barelko)

Animal-based studies of phthalates have found that the synthetic chemicals can harm reproductive system development, and studies in humans have found that prenatal exposure or exposure through breast milk can alter hormone concentrations. Early-childhood exposure has not been extensively studied, so additional research is needed to determine if phthalate exposure can indeed cause reproductive development problems or other adverse effects in infants.

In this study, the researchers set out to see if use of personal care products was associated with urine phthalate concentrations. To accomplish this, they collected urine samples from 163 infants aged 2 months to 28 months, and measured the levels of nine different phthalates in those urine samples. They also had the babies' mothers fill out questionnaires on their use of infant personal care products in the past 24 hours.

When they cross-referenced the data, they found that the use of baby powder, lotion, and shampoo were each strongly associated with higher phthalate levels in the urine. The use of baby wipes and diaper cream were not strongly associated with increased levels of phthalates. The scientists also found that every baby had detectable levels of at least one phthalate in their urine, and about 81 percent of the infants had detectable levels of seven or more phthalates. Babies who were 8 months old or younger had stronger associations between product use and phthalate concentrations, as did babies whose mothers used more infant personal care products.

"We found that infant exposure to phthalates is widespread, and that exposure to personal care products applied onto the skin may be an important source," said the study's lead author, Sheela Sathyanarayana, an acting assistant professor of pediatrics at the UW School of Medicine and a researcher with Seattle Children's Hospital Research Institute. "This is troubling, because phthalate exposure in early childhood has been associated with altered hormone concentrations as well as increased allergies, runny nose, and eczema. Babies may be more at risk than children or adults because their reproductive, endocrine, and immune systems are still developing."

Parents who want to decrease their baby's exposure to phthalates should limit the amount of baby care products used on the infant, and apply lotions or powders only if medically indicated. Since phthalates are also found in many household plastic products, like plastic food containers, parents can also stop putting plastics in the microwave oven and use glass alternatives whenever possible. Phthalate-free cosmetics and personal care products are also available.

This research project was supported by grants from the U.S. Environmental Protection Agency, the National Institutes of Health, and the National Institute of Environmental Health Sciences. The project included researchers from the UW Departments of Occupational and Environmental Health Sciences, Pediatrics, and Biostatistics; the Seattle Children's Hospital Research Institute; the Centers for Disease Control and Prevention; and the University of Rochester School of Medicine and Dentistry.

Adapted from materials provided by University Of Washington.

Read the rest of this entry »

Reduced Sleep Can Increase Childhood Obesity Risk

Daily Science Journal (Feb. 9, 2008) — Less sleep can increase a child’s risk of being overweight or obese, according to a study by researchers at the Johns Hopkins Bloomberg School of Public Health. Their analysis of epidemiological studies found that with each additional hour of sleep, the risk of a child being overweight or obese dropped by 9 percent.

“Our analysis of the data shows a clear association between sleep duration and the risk for overweight or obesity in children. The risk declined with more sleep,” said Youfa Wang, MD, PhD, senior author of the study and associate professor with the Bloomberg School’s Center for Human Nutrition. “Desirable sleep behavior may be an important low cost means for preventing childhood obesity and should be considered in future intervention studies. Our findings may also have important implications in societies where children do not have adequate sleep due to the pressure for academic excellence and where the prevalence of obesity is rising, such as in many East Asian countries.”

“The influence of sleep quality on obesity risk is another important area where future research is needed,” added Xiaoli Chen, MD, PhD, the study’s lead author and a former postdoctoral fellow at the Bloomberg School.

For the study, Wang, Chen and colleague May A. Beydoun, also a postdoctoral fellow at the Bloomberg School, reviewed 17 published studies on sleep duration and childhood obesity and they analyzed 11 of them in their meta-analysis.

The recommended amount of daily sleep varied between studies analyzed and with children’s age. It is recommended that children under age 5 should sleep for 11 hours or more per day, children age 5 to10 should sleep for 10 hours or more per day, and children over age 10 should sleep at least 9 hours per day.

The results of the analysis showed that children with the shortest sleep duration had a 92 percent higher risk of being overweight or obese compared to children with longer sleep duration. For children under age 5, shortest sleep duration meant less than 9 hours of sleep per day. For children ages 5 to 10 it meant less than 8 hours of sleep per day and less than 7 hours of sleep per day for children over 10. The association between increased sleep and reduced obesity risk was strongly associated with boys, but not in girls.

The results are published in the February 2008 edition Obesity, the journal of The Obesity Society. “Is Sleep Duration Associated with Childhood Obesity? A Systematic Review and Meta-analysis” was written by Xiaoli Chen, May A. Beydoun and Youfa Wang.

The study was supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, the U.S. Department of Agriculture and the Johns Hopkins Bloomberg School of Public Health.

Adapted from materials provided by Johns Hopkins University Bloomberg School of Public Health.

Read the rest of this entry »

'Weight Training' Reduces Fat And Improve Metabolism In Mice

Daily Science Journal (Feb. 8, 2008) — Researchers from the Boston University School of Medicine (BUSM) have demonstrated that in mice, the use of barbells may be as important to losing weight and improving health as the use of running shoes. The discovery builds upon the fact that skeletal muscle consists of two types of fibers. Endurance training such as running increases the amount of type I muscle fibers, while resistance training such as weightlifting increases type II muscle fibers. Using a mouse genetic model, BUSM researchers demonstrated that an increase in type II muscle mass can reduce body fat which in turn reduces overall body mass and improves metabolic parameters such as insulin resistance. These studies indicate that weight bearing exercise, in addition to endurance training, may benefit overweight people.

Weight-lifting. "We've shown that type II muscle does more than allow you to pick up heavy objects," said Kenneth Walsh of Boston University School of Medicine. "It is also important in controlling whole-body metabolism." (Credit: iStockphoto/Sean Locke)

Researchers used a genetic trick in obese mice that caused the mice's muscles to bulk up as though they had been lifting weights. The researchers found that the "genetically reprogrammed" mice lost fat and showed other signs of metabolic improvement throughout the body. What's more, those benefits were seen even though the mice continued eating a diet high in both fat and sugar and didn't increase their physical activity at all.

The researchers genetically engineered a mouse, called the MyoMouse, to grow type II fibers by activating a muscle growth-regulating gene. The gene, called Akt1, was engineered in such a way that it could be turned on and off at will by researchers. Even without exercise, activating the gene made the MyoMouse physically stronger. When the gene was de-activated, the mouse returned to its original strength. While stronger and faster than a regular mouse, the MyoMouse did not run with as much endurance on a treadmill, a finding that is consistent with the growth of type II rather than type I muscle. These findings demonstrate that the mouse was genetically programmed to have the characteristics of a lean and powerful sprinter rather than those of a gaunt marathon runner.

"We've shown that type II muscle does more than allow you to pick up heavy objects," said Kenneth Walsh of Boston University School of Medicine. "It is also important in controlling whole-body metabolism."

In the study, the Akt1 gene was turned off and the MyoMice were fed a high fat/high sugar diet with a similar caloric composition as a meal from a fast food restaurant. Over an eight-week period, the mice became obese and insulin resistant and developed fatty acid deposits in their liver, a condition referred to as hepatic steatosis or fatty liver disease.

The researchers then activated the Akt1 gene in the animals which led to the growth of type II muscle fibers. "Remarkably, type II muscle growth was associated with an overall reduction in body mass, due to a large decrease in fat mass. In addition, blood tests showed that these mice became metabolically normal and their fatty liver disease rapidly resolved," said senior author Kenneth Walsh, PhD, a professor of medicine and head of Molecular Cardiology at the Whitaker Cardiovascular Institute at BUSM.

The beneficial changes occurred despite the fact that the mice continued to eat the same high-calorie diet and did not display any increase in physical activity. "This work shows that type II muscle just doesn't allow you to pick up heavy objects, it is also important in controlling whole body metabolism," added Walsh.

Further analysis found that the mice burned fat because of changes in the physiology and gene expression of their fat and liver cells. "Thus, it appears that the increase in type II muscle fiber orchestrates changes in the body through its ability to communicate with these other tissues," he said.

These findings indicate that type II muscle has a previously unappreciated role in regulating whole body metabolism through its ability to alter the metabolic properties of remote tissues. These data also suggest that strength training, in addition to the widely-prescribed therapy of endurance training, may be of particular benefit to overweight individuals

Finally, these findings may be relevant for understanding aspects of the aging process. "Beyond the age of thirty, humans lose approximately 6 lbs of muscle mass per decade. Surprisingly, aging individuals predominantly lose type II muscle. Thus a 50 year old may be relatively good at playing tennis or jogging because type I muscle is preserved, but a measurement of grip strength or core body strength could show appreciable declines," explained Walsh. Therefore, this new study suggests that the loss of type II muscle contributes to the development of obesity and diabetes as we age.

The BUSM researchers suspect that the beneficial effects of muscle growth seen in the MyoMouse are mediated through the production and secretion of a variety of signaling factors. Walsh and his colleagues are currently identifying the novel proteins in muscle that communicate with other tissues. These new proteins, referred to as "myokines" from the Greek words "muscle" and "motion," may represent new targets for therapies that mimic the benefits of weight training for the treatment of obesity and diabetes as well as muscle wasting disorders.

"The work of [Walsh and his colleagues] reveals the intricate interplay between diet, energy balance, and the function/morphology of diverse tissue systems such as skeletal muscle and liver," said Brooke Harrison and Leslie Leinwand of the University of Colorado at Boulder in a commentary in the journal Cell Metabolism. "These findings indicate that interventions designed to increase skeletal muscle mass in at-risk human populations may prove to be critical weapons in the fight against obesity and obesity-related comorbidities including diabetes, heart disease, stroke, hypertension, and cancer."

The study appears in the February 6th issue of Cell Metabolism. The researchers include Yasuhiro Izumiya, Teresa Hopkins, Carl Morris, Kaori Sato, Ling Zeng, Jason Viereck, James A. Hamilton, Noriyuki Ouchi, Nathan K. LeBrasseur, and Kenneth Walsh, of Boston University School of Medicine, Boston, MA.

Adapted from materials provided by Boston University, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Subconscious Signals Can Trigger Drug Craving

Daily Science Journal (Feb. 7, 2008) — Using a brain imaging technology called functional magnetic resonance imaging (fMRI), scientists have discovered that cocaine-related images trigger the emotional centers of the brains of patients addicted to drugs -- even when the subjects are unaware they've seen anything.

Cocaine patients were shown photos such as these. The 24 randomly-presented 33 msec targets in each of four categories (cocaine, sexual, aversive and neutral, interspersed with grey-screen nulls) were immediately followed by a 467 msec neutral “masking” stimulus”. Under these conditions, the 33 msec stimuli can escape conscious detection. (Credit: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N, et al.)

A team of researchers at the University of Pennsylvania, led by Dr. Anna Rose Childress and Dr. Charles O'Brien, showed cocaine patients photos of drug-related cues like crack pipes and chunks of cocaine. The images flashed by in just 33 milliseconds -- so quickly that the patients were not consciously aware of seeing them. Nonetheless, the unseen images stimulated activity in the limbic system, a brain network involved in emotion and reward, which has been implicated in drug-seeking and craving.

"This is the first evidence that cues outside one's awareness can trigger rapid activation of the circuits driving drug-seeking behavior," said NIDA director Dr. Nora Volkow. "Patients often can't pinpoint when or why they start craving drugs. Understanding how the brain initiates that overwhelming desire for drugs is essential to treating addiction."

To verify that the patterns of brain activity triggered by the subconscious cues reflected the patients' feelings about drugs, Childress and her colleagues gave the patients a different test two days later, allowing them to look longer at the drug images. The patients who demonstrated the strongest brain response to unseen cues in the fMRI experiment also felt the strongest positive association with visible drug cues. Childress notes, "It's striking that the way people feel about these drug-related images is accurately predicted by how strongly their brains respond within just 33 milliseconds."

Childress and her colleagues also found that the regions of the brain activated by drug images overlapped substantially with those activated by sexual images. This finding supports the scientific consensus that addictive drugs usurp brain regions that recognize natural rewards needed for survival, like food and sex.

According to Childress, these results could improve drug treatment strategies. "We have a brain hard-wired to appreciate rewards, and cocaine and other drugs of abuse latch onto this system. We are looking at the potential for new medications that reduce the brain's sensitivity to these conditioned drug cues and would give patients a fighting chance to manage their urges."

Citation: Childress AR, Ehrman RN, Wang Z, Li Y, Sciortino N, et al (2008) Prelude to Passion: Limbic Activation by ''Unseen'' Drug and Sexual Cues. PLoS One 3(1): e1506. doi:10.1371/journal.pone.0001506 http://www.plosone.org/doi/pone.0001506

The study was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH).

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Chronic Pain Harms The Brain

Daily Science Journal (Feb. 7, 2008) — People with unrelenting pain don't only suffer from the non-stop sensation of throbbing pain. They also have trouble sleeping, are often depressed, anxious and even have difficulty making simple decisions.

Comparison of brains. These images show the brain from the left side, demonstrating striking differences between chronic pain patients and healthy subjects. They illustrate with colors how much activation (red-yellow) or deactivation (dark/light blue) was found at each location. (Credit: Image courtesy of Northwestern University)

In a new study, investigators at Northwestern University's Feinberg School of Medicine have identified a clue that may explain how suffering long-term pain could trigger these other pain-related symptoms.

Researchers found that in a healthy brain all the regions exist in a state of equilibrium. When one region is active, the others quiet down. But in people with chronic pain, a front region of the cortex mostly associated with emotion "never shuts up," said Dante Chialvo, lead author and associate research professor of physiology at the Feinberg School. "The areas that are affected fail to deactivate when they should."

They are stuck on full throttle, wearing out neurons and altering their connections to each other.

This is the first demonstration of brain disturbances in chronic pain patients not directly related to the sensation of pain.

Chialvo and colleagues used functional magnetic resonance imaging (fMRI) to scan the brains of people with chronic low back pain and a group of pain-free volunteers while both groups were tracking a moving bar on a computer screen. The study showed the pain sufferers performed the task well but "at the expense of using their brain differently than the pain-free group," Chialvo said.

When certain parts of the cortex were activated in the pain-free group, some others were deactivated, maintaining a cooperative equilibrium between the regions. This equilibrium also is known as the resting state network of the brain. In the chronic pain group, however, one of the nodes of this network did not quiet down as it did in the pain-free subjects.

This constant firing of neurons in these regions of the brain could cause permanent damage, Chialvo said. "We know when neurons fire too much they may change their connections with other neurons and or even die because they can't sustain high activity for so long," he explained.

'If you are a chronic pain patient, you have pain 24 hours a day, seven days a week, every minute of your life," Chialvo said. "That permanent perception of pain in your brain makes these areas in your brain continuously active. This continuous dysfunction in the equilibrium of the brain can change the wiring forever and could hurt the brain."

Chialvo hypothesized the subsequent changes in wiring "may make it harder for you to make a decision or be in a good mood to get up in the morning. It could be that pain produces depression and the other reported abnormalities because it disturbs the balance of the brain as a whole."

He said his findings show it is essential to study new approaches to treat patients not just to control their pain but also to evaluate and prevent the dysfunction that may be generated in the brain by the chronic pain.

The study will be published Feb. 6 in The Journal of Neuroscience. Chialvo's collaborators in this project are Marwan Baliki, a graduate student; Paul Geha, a post-doctoral fellow, and Vania Apkarian, professor of physiology and of anesthesiology, all at the Feinberg School.

Adapted from materials provided by Northwestern University.

Read the rest of this entry »

Why Serotonin Can Cause Depression And Anxiety

Daily Science Journal (Feb. 5, 2008) — Mood disorders could be caused by a loss of our inherent, reflexive avoidance of aversive events, according to a new study. Researchers from UCL in London and Columbia University in New York used computational modeling techniques to integrate what appeared to be blatant contradictions between serotonin's roles in different states of health.

Serotonin appears to be one of the major players in mood and a variety of other disorders. But exactly how remains an open question. Imagine walking past a dark alleyway in a dangerous part of some city; although it might be a shortcut, most people wouldn't consider taking it. In healthy subjects, serotonin appears important for this automatic avoidance.

It has long been suggested that over-activity of the serotonin system may relate to mood disorders such as depression and anxiety, as these seem characterized by too much withdrawal and avoidance. However, the new modeling study simply suggests that we think about what happens when these reflexes fail--suddenly you have to think hard to avoid things that used to be avoided reflexively You might for example consider walking down the dangerous alley, be robbed and thus be reminded and taught by additional experience that dark alleys are to be avoided.

In this study Prof. Peter Dayan and Dr. Quentin Huys built a reinforcement learning model of reflexive choices. Agents take actions and as a result of these move through a set of states, some of which are rewarded or punished. As agents progress through this space, they learn the value of each state--how much punishment or reward is to be expected from this state onwards.

It turns out that adding to the agent's behavioural repertoire a simple reflex, which guides the agent away from an action with potential for poor consequences, does two things: it increases the rewards reaped overall, but, because bad states are now not explored any more, it also prevents them from learning exactly how bad these bad states are. When serotonin drops, say in depression or anxiety, agents have no more recourse to the reflexive avoidance and have to rely on what they learned. Because they have not learned how bad the bad states are, they start exploring states that don't look too bad to them, but in reality are much worse. Serotonin enhancing drugs, such as Prozac, are then suggested to reinstate the reflexive avoidance, and thus to redress the balance.

This study gives insight into some puzzling findings--for example, it argues that the association of depression with aggression may have to do with a lack of reflexive avoidance of it. In addition, stress not only causes depression, but people with depression experience more stressors. Again, this may be related to a dysfunctional reflexive avoidance system. The study, however, vastly oversimplifies a number of issues, such as the flexibility of reflexive actions, and the effect of non-reflexive action choice. These provide interesting avenues for further research, and may in fact give some insight into the co-morbidity of different mood disorders.

Journal citation: Dayan P, Huys QJM (2008) Serotonin, inhibition, and negative mood. PLoS Comput Biol 4(1): e4. doi:10.1371/journal.pcbi.0040004. http://compbiol.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pcbi.0040004

Adapted from materials provided by PLoS Computational Biology, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Why Scratching Relieves An Itch

Daily Science Journal (Feb. 1, 2008) — In the first study to use imaging technology to see what goes on in the brain when we scratch, researchers at Wake Forest University Baptist Medical Center have uncovered new clues about why scratching may be so relieving -- and why it can be hard to stop.

"Our study shows for the first time how scratching may relieve itch," said lead author Gil Yosipovitch, M.D., a dermatologist who specializes in itch. "It's important to understand the mechanism of relief so we can develop more effective treatments. For some people, itch is a chronic condition that affects overall health."

The study involved 13 healthy participants who underwent testing with functional magnetic resonance imaging (MRI) technology that highlights areas of the brain activated during an activity. Participants were scratched on the lower leg with a small brush. The scratching went on for 30 seconds and was then stopped for 30 seconds -- for a total of about five minutes.

"To our surprise, we found that areas of the brain associated with unpleasant or aversive emotions and memories became significantly less active during the scratching," said Yosipovitch. "We know scratching is pleasurable, but we haven't known why. It's possible that scratching may suppress the emotional components of itch and bring about its relief."

The reduced brain activity occurred in the anterior cingulate cortex, an area associated with aversion to unpleasant sensory experiences, and the posterior cingulate cortex, which is associated with memory. When participants reported that the scratching felt most intense, activation in these areas was lowest.

Yosipovitch said patients occasionally report that intense scratching -- to the point of drawing blood -- is the only thing that relieves chronic itch.

"This is the first real scientific evidence showing that itch may be inhibited by scratching," he said. "Of course, scratching is not recommended because it can damage the skin. But understanding how the process works could lead to new treatments. For example, drugs that deactivate this part of the brain might be effective."

The imaging studies also showed that some areas of the brain were made more active by the scratching, including the secondary somatosensory cortex, a sensory area involved in pain, and the prefrontal cortex, which is associated with compulsive behavior.

"This could explain the compulsion to continue scratching," said Yosipovitch.

One drawback to the study is that the scratching occurred in the absence of itch. Yosipovitch's team is continuing the research by evaluating whether the findings will apply to chronic itch.

Understanding more about chronic itch is important, Yosipovitch said, noting that more than 30 million Americans suffer from eczema and that almost half (42 percent) of kidney dialysis patients are bothered by moderate to severe itch. In fact, those kidney dialysis patients with itch have a 17 percent higher mortality rate, likely from a loss of sleep, according to a report in Nephrology Dialysis Transplantation.

The work is reported online in the Journal of Investigative Dermatology and will appear in a future print issue.

The study was supported by the National Institutes of Health and the Center for Biomolecular Imaging of Wake Forest. Co-researchers were Yozo Ishuiji,MD, Tajesh Patel, M.D., Maria Isabel Hicks, M.D., Yoshitetsu Oshiro, M.D., Robert Kraft, Ph.D., Erica Winnicki, M.D., and Robert C. Coghill, Ph.D., senior author, all from Wake Forest.

Adapted from materials provided by Wake Forest University Baptist Medical Center, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

New Gene Linked To Fragile X Syndrome -- Suggests Potential Targets For Autism And Other Neurological Disorders

Daily Science Journal (Feb. 1, 2008) — Scientists at The Scripps Research Institute have discovered a new gene involved in fragile X syndrome, a condition that often shares many symptoms of autism. The discovery may lead to new tests or treatments for several neurological disorders.

The new gene has been dubbed FMR4. "FMR4 is a novel gene that is located in the same chromosomal neighborhood as FMR1, a well established causative gene in fragile X syndrome," said Claes Wahlestedt, a professor at the Scripps Research campus in Jupiter, Florida. "Like FMR1, FMR4 is silenced in fragile X patients and up-regulated in FXTAS (fragile X-associated tremor/ataxia syndrome), a disease that resembles Parkinson's disease. Our discovery could lead to the development of new diagnostic tests or even to novel therapies for these defects."

Fragile X syndrome affects thousands of patients worldwide with severe learning disabilities, often accompanied by anxiety disorders, obsessive-compulsive behavior, and attention deficit hyperactivity disorder. There are currently no therapeutic treatments available for fragile X syndrome. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism, according to The National Fragile X Foundation, including such behaviors as social anxiety, poor eye contact, and hand biting.

More than 16 years ago, scientists linked fragile X syndrome to inactivation of FMR1 gene expression, leading to the lack of a protein known as the fragile X mental retardation protein, now considered to be critical for neuronal function. Until the current study, no other functional gene other than FMR1 had been shown to be inactivated in the disorder.

However, Wahlestedt knew the FMR1 gene locus-a specific point on a chromosome-was not well mapped. Wahlestedt and his colleagues hypothesized that unknown regulatory genes might be transcribed from the region.

The new study shows at least one other functional gene-FMR4-from this genetic region is linked to fragile X syndrome, although the gene's exact role in the intact brain remains uncharacterized..

"FMR4 is the new neighbor on the block and should not be ignored," Wahlestedt said. "While there is no direct relationship between these two genes [FMR1 and FMR4] that we know of, our study shows that FMR4 is not a conventional gene-it's a non-coding RNA transcript. It's not a dead piece of the genome, it has a pronounced functional effect in human cultured cells.."

The Role of Non-coding RNA

Non-coding RNA (ncRNA) transcripts or genes produce functional RNA molecules (ncRNAs) rather than encoding proteins. These ncRNAs are active in a number of different processes, including RNA modification, chromosome replication, and protein degradation.

A number of studies have suggested that at least 40 to 50 percent of the mammalian genome becomes transcribed, Wahlestedt pointed out, but only one to two percent of these transcripts are translated into proteins. "Several studies suggest that some ncRNA genes can be involved in various human diseases," he said. "FMR4 certainly falls into that category."

According to the study, FMR4 directly affects human cell proliferation in vitro-when the gene is silenced, changes in the cell cycle and a rise in apoptosis or programmed cell death occur. Overexpression, on the other hand, leads to increased cell proliferation.

The full meaning of this anti-apoptosis function is still unclear. "It could be critical for some cells to live or die at a certain stage in development, but we don't know what cells those might be," Wahlestedt added. "The fact that FMR4 is widely expressed in the human brain in both embryos and adults may possibly indicate a broad function."

The new study underscores the growing awareness among scientists of the complexity and unpredictability of the human genome.

"We know now that our genome is very busy and very complicated," Wahlestedt said "A great deal of this newly found complexity is about the regulation of other genes. As evolution has progressed, particularly in the higher organisms, there has been a corresponding increase in the need for regulatory mechanisms-to maintain more control over genome. Non-coding RNAs are at the center of these regulatory mechanisms."

The FMR4 discovery also highlights the mission of The Translational Research Institute at Scripps Florida, which is focused on translating basic research like the discovery of FMR4 into potential new therapeutics. The Translational Research Institute has a structure similar to a drug discovery company, and many of the researchers have pharmaceutical experience.

In addition to Wahlestedt, other authors of the study include Ahmad M. Khalil, Mohammad Ali Faghihi, Farzaneh Modarresi, and Shaun P. Brothers of The Scripps Research Institute in Jupiter, Florida.

The study, A Novel RNA Transcript with Antiapoptotic Function is Silenced in Fragile X Syndrome, was supported by Conquer Fragile X Foundation (now part of National Fragile X Foundation) and The Scripps Research Institute Florida. Upon publication, the study will be available at http://www.plosone.org/doi/pone.0001486.

Adapted from materials provided by Scripps Research Institute.

Read the rest of this entry »

Nanotubes Help Advance Brain Tumor Research

Daily Science Journal (Jan. 30, 2008) — The potential of carbon nanotubes to diagnose and treat brain tumors is being explored through a partnership between NASA's Jet Propulsion Laboratory, Pasadena, Calif., and City of Hope, a leading cancer research and treatment center in Duarte, Calif.

Benham Badie, M.D., director of the Department of Neurosurgery and the Brain Tumor program at City of Hope, performs a minimally invasive procedure to surgically remove a pituitary tumor. Nanotube technology may help in the development of new treatments that would require only minimally invasive procedures no matter the location of the brain tumor. (Credit: City of Hope)

Nanotechnology may help revolutionize medicine in the future with its promise to play a role in selective cancer therapy. City of Hope researchers hope to boost the brain's own immune response against tumors by delivering cancer-fighting agents via nanotubes. A nanotube is about 50,000 times narrower than a human hair, but it length can extend up to several centimeters.

If nanotube technology can be effectively applied to brain tumors, it might also be used to treat stroke, trauma, neurodegenerative disorders and other disease processes in the brain, said Dr. Behnam Badie, City of Hope's director of neurosurgery and of its brain tumor program.

"I'm very optimistic of how this nanotechnology will work out," he said. "We are hoping to begin testing in humans in about five years, and we have ideas about where to go next."

The Nano and Micro Systems Group at JPL, which has been researching nanotubes since about 2000, creates these tiny, cylindrical multi-walled carbon tubes for City of Hope.

City of Hope researchers, who began their quest in 2006, found good results: The nanotubes, which they used on mice, were non-toxic in brain cells, did not change cell reproduction and were capable of carrying DNA and siRNA, two types of molecules that encode genetic information.

JPL's Nano and Micro Systems Group grows the nanotubes on silicon strips a few square millimeters in area. The growth process forms them into hollow tubes as if by rolling sheets of graphite-like carbon.

Carbon nanotubes are extremely strong, flexible, heat-resistant, and have very sharp tips. Consequently, JPL uses nanotubes as field-emission cathodes -- vehicles that help produce electrons -- for various space applications such as x-ray and mass spectroscopy instruments, vacuum microelectronics and high-frequency communications.

"Nanotubes are important for miniaturizing spectroscopic instruments for space applications, developing extreme environment electronics, as well as for remote sensing," said Harish Manohara, the technical group supervisor for JPL's Nano and Micro Systems Group.

Nanotubes are a fairly new innovation, so they are not yet routinely used in current NASA missions, he added. However, they may be used in gas-analysis or mineralogical instruments for future missions to Mars, Venus and the Jupiter system.

JPL's collaboration with City of Hope began last year, after Manohara, Badie and Dr. Babak Kateb, City of Hope's former director of research and development in the brain tumor program, discussed using nanostructures to better diagnose and treat brain cancer. Badie said his team's nanomedical research continues, and the next goal will be to functionalize and attach inhibitory RNA to the nanotubes and deliver it to specific areas of the brain.

The JPL and City of Hope teams published the results of the study earlier this year in the journal NeuroImage.

Badie says that JPL's contribution to City of Hope's nanomedicine research has been invaluable.

"The fact that we can get pristine and really clean nanotubes from Manohara's department is unique," he said. "The fact that we are both collaborating for biological purposes is also really unique."

The collaboration between JPL and City of Hope is conducted under NASA's Innovative Partnership Program, designed to bring benefits of the space program to the public.

Adapted from materials provided by NASA/Jet Propulsion Laboratory.

Read the rest of this entry »

Why Don't Chimpanzees Like To Barter Food?

Daily Science Journal (Jan. 30, 2008) — For thousands of years, human beings have relied on commodity barter as an essential aspect of their lives. It is the behavior that allows specialized professions, as one individual gives up some of what he has reaped to exchange with another for something different. In this way, both individuals end up better off. Despite the importance of this behavior, little is known about how barter evolved and developed.

Researchers examined the circumstances under which chimpanzees, our closest relatives, will exchange one inherently valuable commodity (an apple slice) for another (a grape), which is what early humans must have somehow learned to do. (Credit: iStockphoto/Nicola Stratford)

This study is the first to examine the circumstances under which chimpanzees, our closest relatives, will exchange one inherently valuable commodity (an apple slice) for another (a grape), which is what early humans must have somehow learned to do. Economists believe that commodity barter is one of the most basic precursors to economic specialization, which we observe in humans but not in other primate species. First of all, the researchers found that chimpanzees often did not spontaneously barter food items, but needed to be trained to engage in commodity barter. Moreover, even after the chimpanzees had been trained to do barters with reliable human trading partners, they were reluctant to engage in extreme deals in which a very good commodity (apple slices) had to be sacrificed in order to get an even more preferred commodity (grapes).

Prior animal behavior studies have largely examined chimpanzees' willingness to trade tokens for valuable commodities. Tokens do not exist in nature, and lack inherent value, so a chimpanzee's willingness to trade a token for a valuable commodity, such as a grape, may say little about chimpanzee behavior outside the laboratory.

In a series of experiments, chimpanzees at two different facilities were given items of food and then offered the chance to exchange them for other food items. A collaboration of researchers from Georgia State University, the University of California, Los Angeles, and the U.T. M.D. Anderson Cancer Center found that the chimpanzees, once they were trained, were willing to barter food with humans, but if they could gain something significantly better -- say, giving up carrots for much preferred grapes. Otherwise, they preferred to keep what they had.

The observed chimpanzee behavior could be reasonable because chimpanzees lack social systems to enforce deals and, as a society, punish an individual that cheats its trading partner by running off with both commodities. Also because of their lack of property ownership norms, chimpanzees in nature do not store property and thus would have little opportunity to trade commodities.

Nevertheless, as prior research has demonstrated, they do possess highly active service economies. In their natural environment, only current possessions are "owned," and the threat of losing what one has is very high, so chimpanzees frequently possess nothing to trade.

"This reluctance to trade appears to be deeply ingrained in the chimpanzee psyche," said one of the lead authors, Sarah Brosnan, an assistant professor of psychology at Georgia State University. "They're perfectly capable of barter, but they don't do so in a way which will maximize their outcomes."

The other lead author, Professor Mark F. Grady, Director of UCLA's Center for Law and Economics, commented: "I believe that chimpanzees are reluctant to barter commodities mainly because they lack effective ownership norms. These norms are especially costly to enforce, and for this species the game has evidently not been worth the candle. Fortunately, services can be protected without ownership norms, so chimpanzees can and do trade services with each other. As chimpanzee societies demonstrate, however, a service economy does not lead to the same degree of economic specialization that we observe among humans."

The research could additionally shed light on the instances in which humans also don't maximize their gains, Brosnan said.

The laboratory experiments for this study was conducted at Georgia State's Language Research Center and the University of Texas M.D. Anderson Cancer Center, and the much of the conceptual work was done at UCLA's Center for Law and Economics.

Citation: Brosnan SF, Grady MF, Lambeth SP, Schapiro SJ, Beran MJ (2008) Chimpanzee Autarky. PLoS One 3(1): e1518. doi:10.1371/journal.pone.0001518 http://www.plosone.org/doi/pone.0001518

Adapted from materials provided by Public Library of Science, via EurekAlert!, a service of AAAS.

Read the rest of this entry »

Portable Device Quickly Detects Early Alzheimer's

Daily Science Journal (Jan. 17, 2008) — The latest medications can delay the onset of Alzheimer’s disease, but none are able to reverse its devastating effects. This limitation often makes early detection the key to Alzheimer’s patients maintaining a good quality of life for as long as possible.

The DETECT system includes an LCD display in a visor with an onboard dedicated computer, noise reduction headphones and an input device (controller). The display projects the visual aspect of the test and the headphones provide the verbal instructions. (Credit: Image courtesy of Georgia Institute of Technology)

Now, a new device developed by the Georgia Institute of Technology and Emory University may allow patients to take a brief, inexpensive test that could be administered as part of a routine yearly checkup at a doctor’s office to detect mild cognitive impairment (MCI) — often the earliest stage of Alzheimer’s. The device is expected to be commercialized later this year.

Current assessment tests capable of detecting early Alzheimer’s typically are taken with a pen and paper or at a computer terminal and last about an hour and a half. They must be given by a trained technician in a quiet environment, because any distractions can influence the patient’s score and reduce the test’s effectiveness. Because of their length and expense, the tests are not used as regular screening tools and typically are given only after there is obvious cognitive impairment such as forgetfulness or unsafe behavior.

“Families usually wait until their mom or dad does something somewhat dangerous, like forgetting to take their medications or getting lost, before bringing them in for testing. At that point, the patient has already lost a significant portion of their cognitive function,” said David Wright, MD, who helped develop the device. Wright is assistant professor of emergency medicine at Emory University School of Medicine and co-director of the Emory Emergency Medicine Research Center. “With this device, we might be able to pick up impairment well before those serious symptoms occur and start patients on medications that could delay those symptoms.”

The Georgia Tech and Emory device, called DETECT, gives individuals a roughly ten-minute test designed to gauge reaction time and memory — functions that, when impaired, are associated with the earliest stages of Alzheimer’s disease. The test is a specially modified, shortened version of the traditional pen and paper test and could be given repeatedly by doctors to evaluate any changes in cognitive functions.

“We really envision this to be part of the normal preventative care a patient receives from a general practitioner,” said Michelle LaPlaca, Ph.D., one of the creators of the device and an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “It would be part of a regular preventative medicine exam much like a PSA test or EKG (electrocardiogram), serving as a cognitive impairment vital sign of sorts.”

The portable test runs patients through a battery of visual and auditory stimuli such as pictures and words that assess cognitive abilities relative to age, gauging reaction time and memory capabilities. Its software can track cognitive capabilities — and decline — year to year during annual appointments. And because the device blocks outside sound and light from the patient’s environment, it can be administered in virtually any setting, providing more consistent results.

Preliminary analysis of the first 100 patients of a 400-person clinical study being conducted at Emory’s Wesley Woods Center has shown that the 10-minute DETECT test has similar accuracy to the 90-minute “Gold Standard” pen and paper test.

With millions of baby boomers easing into late adulthood, the number of patients with Alzheimer’s is expected to skyrocket over the next few decades. More than 24 million people worldwide are currently thought to have Alzheimer’s disease and by 2040, an estimated 81 million people worldwide are expected to develop the disease.

To give these millions of potential Alzheimer’s sufferers a chance to slow the disease’s advance before serious symptoms set in, doctors need an inexpensive and easy-to- administer test to detect and track the cognitive decline associated with the early stages of the disease.

The DETECT device is designed to be administered while a patient is still healthy, tracking any abnormal decreases in the patient’s cognitive performance over time. If a patient’s performance declines outside the normal range, the patient would then undergo additional testing and care from a neurologist, neuropsychologist or other specialist.

The DETECT system includes an LCD display in a visor with an onboard dedicated computer, noise reduction headphones and an input device (controller). The display projects the visual aspect of the test, the headphones provide the verbal instructions and the controller records the wearer’s response.

DETECT’s creators have formed a company, called Zenda Technologies, to commercialize the device for MCI, as well as other conditions. Georgia Tech and Emory researchers are exploring other types of cognitive impairment such as Attention Deficit/Hyperactivity Disorder (ADHD) that could be picked up by DETECT. A version of the system designed to detect mild concussions on the sidelines of a football game, during other high-impact sports or on a battlefield is still being tested.

The research was funded with a grant from the Wallace H. Coulter Foundation and support from the Georgia Research Alliance through Georgia Tech’s VentureLab.

Adapted from materials provided by Georgia Institute of Technology.

Related Articles :

• Frequent Brain Stimulation In Old Age Reduces Risk Of Alzheimer's Disease
• Portable Tech/Emory Device Checks For Concussions
• Treatment Causes Short-term, Modest Delay In Alzheimer's Onset In Patients With Mild Cog Impairment
• New Study Shows That Most Older People With Mild Cognitive Impairment Have Alzheimer’s Disease Or Cerebral Vascular Disease
• Urine Test Predicts Alzheimer's Disease
• Distress-prone People More Likely To Develop Memory Problems
• Difficulty Identifying Odors May Predict Cognitive Decline

Read the rest of this entry »

Cocaine Abuse Blunts Sensitivity To Monetary Reward

Daily Science Journal (Jan. 8, 2008) — New measurements of brain activity in individuals addicted to cocaine confirm that addicted individuals have compromised sensitivity to monetary rewards.

Brookhaven neuropsychology study coordinator Thomas Maloney (rear) and Stony Brook University graduate student Muhammad Parvaz (front) demonstrate the setup for measuring event-related potentials with postdoc Jose Trigo Diaz posing as a research subject. (Credit: Image courtesy of DOE/Brookhaven National Laboratory)

"This altered sensitivity to reward may help explain why some drug-addicted individuals are unable to modify their drug-taking behavior, even in the face of well-understood negative consequences and/or positive incentives for behavioral change," said Rita Goldstein, who runs the neuropsychoimaging lab at the U.S. Department of Energy's Brookhaven National Laboratory where the work was done. Muhammad A. Parvaz, a Stony Brook University graduate student working with Goldstein, presented the findings at the Society for Neuroscience annual meeting in San Diego on November 7, 2007.

The researchers studied 18 current cocaine users and 18 age-matched control subjects. They outfitted each subject with a cap of electrodes to measure brain activity after instructing the subjects to press or not press a button in response to certain visual prompts. During the task, subjects were told they could earn various amounts of money for fast and accurate performance.

The scientists were specifically interested in the P300 component of the brain waves "time locked" to the task (known as Event-Related Potentials). The P300, a positive voltage potential occurring at a latency of 300 milliseconds after presentation of a novel or meaningful stimulus, has been shown to be blunted in individuals addicted to alcohol and their offspring. The current study demonstrates, for the first time, a blunted P300 response to a commonly occurring and generalized abstract reward - money - in cocaine-addicted individuals with recent cocaine use.

The findings: In healthy control subjects, the P300 response was significantly higher and both accuracy and speed of performance were significantly better and faster, respectively, when a monetary reward was offered compared with when the reward was absent (45 vs. 0 cents). These responses to money in both brain and behavioral measures - and their interdependence - were reduced in cocaine-addicted individuals. In addition, those who had used cocaine most frequently during the year preceding the study were the least able to improve their behavioral performance in response to monetary rewards.

Interestingly, these results could not be attributed to decreased task engagement in the cocaine users, who instead reported being more interested in the task than the control subjects. It is possible that this heightened interest could be attributed to recent cocaine use, which was documented in all cocaine-using subjects in this study by positive urine screening tests.

"So despite greater self-reported interest, cocaine users did not respond faster or more accurately and their brain activity did not change in response to monetary reward to the same degree as in the healthy control subjects," Parvaz said.

These results confirm findings from earlier studies conducted in Goldstein's lab that used functional magnetic resonance imaging (fMRI) to demonstrate a similar compromise in neural sensitivity to monetary reward in cocaine addiction.

"Individuals with such blunted neural and behavioral sensitivity to rewards may have a particularly difficult time responding to abstract incentives designed to motivate behavioral changes - especially when outside of a structured treatment environment or when rewards are not readily available or clearly contingent on behavior," Goldstein said.

"It would be interesting to see if there are any differences between the cocaine users studied here, who were not seeking treatment, and those in treatment or abstinent for longer periods of time," Parvaz suggested. Such a comparison would allow the researchers to determine whether recovery of sensitivity to reward can be expected, and assess the time frame for such recovery. The researchers may also extend the study to see if their findings can be generalized to negative reinforcement, such as the loss of money.

This research was funded by: the Office of Biological and Environmental Research (OBER) within the U.S. Department of Energy's Office of Science; the National Institute on Drug Abuse; Laboratory Directed Research and Development funding from OBER; a Young Investigator Award from NARSAD (a mental health research association); a Stony Brook University/Brookhaven National Laboratory seed grant; the National Institute on Alcohol Abuse and Alcoholism; and by Stony Brook University's General Clinical Research Center.

Adapted from materials provided by DOE/Brookhaven National Laboratory.

Related Articles :

• Altered Perception Of Reward In Human Cocaine Addiction
• Cocaine Use Decreases Ability To Respond To Stimulation, Yale Researchers Find
• Strength Of Cocaine Cravings Linked To Brain Response
• Researchers Find That After Stopping Cocaine Use, Drug Craving Gets Stronger Over Time
• High-tech Research Shows Cocaine Changes Proteins And Brain Function

Read the rest of this entry »

Mental Illness And Drug Addiction May Co-occur Due To Disturbance In Part Of The Brain

Daily Science Journal (Jan. 7, 2008) — Why do mental illness and drug addiction so often go together? New research reveals that this type of dual diagnosis may stem from a common cause: developmental changes in the amygdala, a walnut-shaped part of the brain linked to fear, anxiety and other emotions.

The amygdala is the solid blue area on the left of this brain image. (The cingulate, an emotion-dampening center, is identified in several colors to the right.) (Credit: NIMH Clinical Brain Disorders Branch)

Dual diagnosis is common yet difficult to treat. Addiction of all types -- to nicotine, alcohol and drugs -- is often found in people with a wide variety of mental illnesses, including anxiety disorders, unipolar and bipolar depression, schizophrenia, and borderline and other personality disorders. Lead author Andrew Chambers, MD, cites clinical reports that at least half the people who seek help with addiction or mental-health treatment have co-occurring disorders. Epidemiological data says that from two to five of every 10 anxious or depressed people, and from four to eight of every 10 people with schizophrenia, bipolar disorder, or antisocial personality, also have some type of addiction.

To find the scientific basis for this complex, seemingly intractable pairing, which has in the past been attributed to "self-medication," Chambers' team at the Indiana University medical school compared the adult mood- and drug-related behavior of two groups of adult rats: those whose amygdalas were surgically damaged in infancy and those whose amygdalas were left intact but who underwent a sham surgery, to equalize their treatment.

Rats with damaged (lesioned) amygdalas grew up abnormally under-responsive to ambiguous or potentially threatening stimuli. Not showing the normal caution, they moved significantly more in response to novelty, showed significantly less fear in an elevated maze, and kept socializing even when exposed to the scent of a predator.

Crucially, these same rats also were significantly more sensitive to cocaine after just one exposure. And rats given repeated cocaine injections later showed even stronger expressions of the enduring changes in behavior -- suggesting an overall hypersensitivity to the addictive process.

Given that the experimental and control rats were raised in the same tightly controlled conditions, the only difference being their brain status, researchers concluded that the integrity of the amygdala was the root cause of both impaired fear behavior and heightened drug response.

"Brain conditions may alter addiction vulnerability independently of drug history," says Chambers. He and his colleagues concluded that someone's greater vulnerability to addiction, rather than a given drug's ability to alter the symptoms of mental illness for better or worse (usually worse), more fully explains the high rates of dual diagnosis.

For these reasons, and given the lab evidence and the fact that dual diagnosis patients do less well on psychiatric medication than other patients, Chambers wondered whether the underlying problems in the brain -- what he calls "neural inflexibility" -- make it harder for these people to respond.

To improve the effectiveness of treatments for dual diagnosis, Chambers would like to see educators, counselors, physicians, and scientific researchers integrate insights into both mental health and addiction. Funding the simultaneous treatment of both disorders would also help, he observes, given that "dual-diagnosis cases are the mainstream among these patients, probably because addiction and mental illness are strongly linked by neurobiology."

What may harm the amygdala early in human development? Dr. Chambers cites the relatively rare cases of temporal lobe epilepsy, tumors or early brain injury. Far more common, he speculates, are complex interactions among subtle genetic and environmental factors that change the way the amygdala functions or is connected to the rest of the brain during childhood and adolescence. For example, he says, "Early emotional trauma, paired with a certain genetic background, may alter the early development of neural networks intrinsic to the amygdala, resulting in a cascade of brain effects and functional changes that present in adulthood as a dual-diagnosis disorder."

A full report on why these "comorbid" disorders may develop appears in the December Behavioral Neuroscience, published by the American Psychological Association.

Article: "Neonatal Amygdala Lesions: Co-Occurring Impact on Social/Fear-Related Behavior and Cocaine Sensitization in Adult Rats," R. Andrew Chambers, MD, Tammy J. Sajdyk, PhD, Susan K. Conroy, BS Joan E. Lafuze, PhD, Stephanie D. Fitz, BS, and Anantha Shekhar, MD, PhD; Laboratory for Translational Neuroscience of Dual Diagnosis and Development, Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine; Behavioral Neuroscience, Vol 121, No. 6.

Adapted from materials provided by American Psychological Association.

Read the rest of this entry »

Marijuana Smoke Contains Higher Levels Of Certain Toxins Than Tobacco Smoke

Daily Science Journal (Jan. 06, 2008) — Here's another reason to "keep off the grass." Researchers in Canada report that marijuana smoke contains significantly higher levels of several toxic compounds -- including ammonia and hydrogen cyanide -- than tobacco smoke and may therefore pose similar health risks.

Marijuana smoke contains higher levels of several toxic compounds, including ammonia and hydrogen cyanide, than tobacco smoke. (Credit: U.S. Drug Enforcement Administration)

David Moir and colleagues note that researchers have conducted extensive studies on the chemical composition of tobacco smoke, which contains a host of toxic substances, including about 50 that can cause cancer. However, there has been relatively little research on the chemical composition of marijuana smoke.

In this new study, researchers compared marijuana smoke to tobacco smoke, using smoking machines to simulate the smoking habits of users. The scientists found that ammonia levels were 20 times higher in the marijuana smoke than in the tobacco smoke, while hydrogen cyanide, nitric oxide and certain aromatic amines occurred at levels 3-5 times higher in the marijuana smoke, they say. The finding is "important information for public health and communication of the risk related to exposure to such materials," say the researchers.

The study, "A Comparison of Mainstream and Sidestream Marijuana and Tobacco Cigarette Smoke Produced under Two Machine Smoking Conditions," is scheduled for the Dec. 17 issue of ACS' Chemical Research in Toxicology.

Adapted from materials provided by American Chemical Society.

Read the rest of this entry »

With Daily Alcohol Use, Male Fruit Flies Court Other Males

Daily Science Journal (Jan. 5, 2008) — A team of researchers at Penn Sate has used an animal model to reveal, for the first time, a physiological basis for the effect of alcohol on male sexual behavior, including increased sexual arousal and decreased sexual inhibition. The research resulted in four novel findings with broad importance for further addiction research. It is the first study to characterize the effects of chronic alcohol exposure in fruit flies. "Physiological evidence supporting various theories about the effect of alcoholic drinks has been lacking, so our now having a suitable animal model makes it possible to conduct much-needed laboratory research on this issue," explains research-team-leader Kyung-An Han, associate professor of biology and a neuroscientist at Penn State. Information from this research can serve as a baseline for similar studies in other animals, including humans.

The wild-type male flies in the absence (left) or presence (right) of ethanol vapor in the Flypub experimental chamber. Bottom: The transgenic TH-GAL4/UAS-Shits male flies with (left) or without (right) dopamine neuronal activities during ethanol exposure.

(Credit: Hyun-Gwan Lee, Penn State)

In contrast to previous studies in other labs, which subjected fruit flies to short-term doses of ethanol -- the intoxicating ingredient in alcoholic drinks -- Han's team administered to fruit flies a daily dose of ethanol to more closely mimic the drinking habits of alcoholics and chronic alcohol abusers. The team investigated several factors that influence the physiological effects of ethanol, including genetic and cellular components, age, and prior experience.

Among the team's discoveries is that male fruit flies, which typically court females, also actively court males when they are given a daily dose of ethanol. "We identified three molecules that are crucial for "ethanol-induced courtship disinhibition," Han said. In one of the team's experiments, Han and her students generated transgenic flies whose brain activities regulated by the neurotransmitter dopamine could be turned off temporarily by changing the temperature to 32-degrees C. "Without a temperature change, the transgenic males showed conspicuous inter-male courtship under the influence of ethanol; however, they exhibited negligible inter-male courtship when we changed the temperature to block the transmission of dopamine neurons in the brain," Han said. "This result suggests that dopamine is a key mediator of ethanol-induced inter-male courtship."

A second discovery is that repeated exposure to ethanol causes male flies to engage in more inter-male courtship, a phenomenon known as "behavioral sensitization." "If a behavior like alcohol consumption becomes more pleasurable the more often you do it, you are more likely to keep doing it," Han explained. Because the researchers suspect that behavioral sensitization results from adaptive changes in the brain's cells and molecules induced by chronic alcohol consumption, they plan to use behavioral sensitization as a model for further physiological studies of alcohol-associated behavior and addiction. "This part of our study demonstrates that sexual behavior is not determined only during an organism's development, but it also can be influenced by a post-developmental environmental factor; in this case, recurring exposure to ethanol," Han said. "These findings represent the first demonstration of enduring behavioral changes induced by recurring ethanol exposure in a fly model."

A third achievement of the team's research is its demonstration that daily ethanol exposure induces chronic tolerance to the sedative effect of ethanol in flies, as it does in other animals. Han and her students also made a fourth discovery -- that ethanol-induced intermale courtship is affected by aging. "As flies get older, their cognitive capacities decline, making them more susceptible to the negative effect of ethanol on cognition," Han reports. The research revealed that, under the influence of ethanol, middle-aged and old male flies (2- to 4-weeks old) have a higher propensity for uninhibited inter-male courtship compared to fully mature male flies (4-days old).

"As a result of our research with the fruit fly, we are now just beginning to discover the molecular and cellular mechanisms underlying neural changes in the brain that result from the chronic use of alcohol and that result in alcohol addiction and other behavior changes in our fly model," Han said. Taken together, the studies described by Han's team provide novel insights into the physiological effects of chronic ethanol exposure on sexual behavior and adaptive physiological changes within the brain, plus a foundation for future research on the effect of alcohol consumption on sexual behavior in mammals and other species.

The full research is published 2 January 2008 in the scientific journal PLoS One.

The research was supported by the grants from National Institute of Health and the National Science Foundation. In addition to Han, other members of the research team include Hyun-Gwan Lee, a doctoral student in Penn State's Integrative Biosciences Graduate Program; Young-Cho Kim, who in August 2007 earned his doctorate in neuroscience at Penn State; and Jennifer Dunning, an undergraduate student majoring in biology. Penn State undergraduate students Matthew Austin, Ian McInnis, Michael Park, and Jessica White also contributed to various aspects of this research.

Read the rest of this entry »