Posts tagged psychology

ScienceDaily (July 9, 2012) — Nearly a third of adults with the most common type of brain cancer develop recurrent, invasive tumors after being treated with a drug called bevacizumab. The molecular underpinnings behind these detrimental effects have now been published by Cell Press in the July issue of Cancer Cell. The findings reveal a new treatment strategy that could reduce tumor invasiveness and improve survival in these drug-resistant patients.

"Understanding how and why these tumors adopt this invasive behavior is critical to being able to prevent this recurrence pattern and maximizing the benefits of bevacizumab," says study author Kan Lu of the University of California, San Francisco (UCSF).

Glioblastoma multiforme (GBM) is the most aggressive type of tumor originating in the brain. GBM tumors express high levels of vascular endothelial growth factor (VEGF), a protein that promotes the growth of new blood vessels that provide nutrients that allow tumors to expand. In 2009, the Food and Drug Administration approved bevacizumab, a VEGF inhibitor, for GBM patients who don’t respond to first-line therapies. Although the drug is initially effective, up to 30% of patients develop tumors that infiltrate deep into the brain, making surgery and treatment difficult.

To study how bevacizumab can lead to adverse effects, senior study author Gabriele Bergers of UCSF and her collaborators focused on hepatocyte growth factor (HGF), a protein that controls the growth and movement of cells, because they previously found a link between VEGF and HGF in GBM cells. In the new study, they found that VEGF inhibits the migration of GBM cells by decreasing HGF signaling through its receptor MET. Moreover, tumors were much less invasive — and survival improved — in mice with GBM tumors lacking both VEGF and MET rather than just VEGF alone. The results suggest that MET plays a critical role in GBM invasion when VEGF is blocked.

"These findings provide a rationale for therapeutically combining VEGF and MET inhibition so that patients can benefit from bevacizumab without developing more invasive tumors," Lu says. Because the VEGF and HGF/MET signaling pathways are active in a variety of tumors, this combined treatment strategy may also be applied to other types of cancer.

Source: Science Daily

ScienceDaily (July 9, 2012) — A hormone with anti-diabetic properties also reduces depression-like symptoms in mice, researchers from the School of Medicine at the UT Health Science Center San Antonio reported July 9.

All types of current antidepressants, including tricyclics and selective serotonin reuptake inhibitors, increase the risk for type 2 diabetes. “The finding offers a novel target for treating depression, and would be especially beneficial for those depressed individuals who have type 2 diabetes or who are at high risk for developing it,” said the study’s senior author, Xin-Yun Lu, Ph.D., associate professor of pharmacology and psychiatry and member of the Barshop Institute for Longevity and Aging Studies at the UT Health Science Center.

The hormone, called adiponectin, is secreted by adipose tissue and sensitizes the body to the action of insulin, a hormone that lowers blood sugar. “We showed that adiponectin levels in plasma are reduced in a chronic social defeat stress model of depression, which correlates with the degree of social aversion,” Dr. Lu said.

Facing Goliath over and over

In the study mice were exposed to 14 days of repeated social defeat stress. Each male mouse was introduced to the home cage of an unfamiliar, aggressive resident mouse for 10 minutes and physically defeated. After the defeat, the resident mouse and the intruder mouse each were housed in half of the cage separated by a perforated plastic divider to allow visual, olfactory and auditory contact for the remainder of the 24-hour period. Mice were exposed to a new resident mouse cage and subjected to social defeat each day. Plasma adiponectin concentrations were determined after the last social defeat session. Defeated mice displayed lower plasma adiponectin levels.

Withdrawal, lost pleasure and helplessness

When adiponectin concentrations were reduced by deleting one allele of the adiponectin gene or by a neutralizing antibody, mice were more susceptible to stress-induced social withdrawal, anhedonia (lost capacity to experience pleasure) and learned helplessness.

Mice that were fed a high-fat diet (60 percent calories from fat) for 16 weeks developed obesity and type 2 diabetes. Administration of adiponectin to these mice and mice of normal weight produced antidepressant-like effects.

Possible innovative approach for depression

"These findings suggest a critical role of adiponectin in the development of depressive-like behaviors and may lead to an innovative therapeutic approach to fight depression," Dr. Lu said.

A novel approach would benefit thousands. “So far, only about half of the patients suffering from major depressive disorders are treated to the point of remission with antidepressant drugs,” Dr. Lu said. “The prevalence of depression in the diabetic population is two to three times higher than in the non-diabetic population. Unfortunately, the use of current antidepressants can worsen the control of diabetic patients. Adiponectin, with its anti-diabetic activity, would serve as an innovative therapeutic target for depression treatments, especially for those individuals with diabetes or prediabetes and perhaps those who fail to respond to currently available antidepressants.”

Source: Science Daily

ScienceDaily (July 9, 2012) — A new study of aged female rats found that long-term treatment with estrogen and a synthetic progesterone known as MPA increased levels of a protein marker of synapses in the prefrontal cortex, a brain region known to suffer significant losses in aging.

The new findings appear to contradict the results of the Women’s Health Initiative, a long-term study begun in 1991 to analyze the effects of hormone therapy on a large sample of healthy postmenopausal women aged 50 to 79. Among other negative findings, the WHI found that long-term exposure to estrogen alone or to estrogen and MPA resulted in an increased risk of stroke and dementia. More recent research, however, suggests that starting hormone replacement therapy at the onset of menopause, rather than years or decades afterward, yields different results.

The new study, from researchers at the University of Illinois, is the first to look at the effects of long-term treatment with estrogen and MPA on the number of synapses in the prefrontal cortex of aged animals. The researchers describe their findings in a paper in the journal Menopause.

"The prefrontal cortex is the area of the human brain that loses the most volume with age," said U. of I. psychology professor and Beckman Institute affiliate Janice Juraska, who led the study with doctoral student Nioka Chisholm. "So understanding how anything affects the prefrontal cortex is important."

The prefrontal cortex, just behind the forehead in humans, governs what researchers call “executive function” — planning, strategic thinking, working memory (the ability to hold information in mind just long enough to use it), self-control and other functions that tend to decline with age.

Most studies of the effects of hormone treatments on the brain have focused on the hippocampus, a structure important to spatial navigation and memory consolidation. The studies tend to use young animals exposed to hormones for very brief periods of time (one or two days to a few weeks at the most). They have yielded mixed results, with most research in young female animals indicating an increase in hippocampal synapses and hippocampal function after exposure to estrogen and MPA.

"For some reason, a lot of researchers still look at the effects of hormones in young animals," Chisholm said. "And there’s a lot of evidence now saying that the aged brain is different; the effect of these hormones is not going to be the same."

The new study followed middle-aged rats exposed to estrogen alone, to no additional hormones, or to estrogen in combination with MPA for seven months, a time period that more closely corresponds to the experience of women who start hormone therapy at the onset of menopause and continue into old age. The researchers removed the rats’ ovaries just prior to the hormone treatment (or lack of treatment) to mimic the changes that occur in humans during menopause.

"Our most important finding is that estrogen in combination with MPA can result in a greater number of synapses in the prefrontal cortex than (that seen) in animals that are not receiving hormone replacement," Chisholm said. "Estrogen alone marginally increased the synapses, but it took the combination with MPA to actually see the significant effect."

"Our data indicate that re-examining the effects of estrogen and MPA, when first given to women around the time of menopause, is merited," Juraska said.

Source: Science Daily

July 9, 2012

A study of patients with stroke admitted to English National Health Service public hospitals suggests that patients who were hospitalized on weekends were less likely to receive urgent treatments and had worse outcomes, according to a report published Online First by Archives of Neurology.

Studies from other countries have suggested higher mortality in patients who were admitted to the hospital on weekends for a variety of medical conditions, a phenomenon known as “the weekend effect.” However, other studies have not identified an association between the day of admission and mortality rates due to stroke, so the debate over “the weekend effect” continues, according to the study background.

William L. Palmer, M.A., M.Sc., of Imperial College and the National Audit Office, and colleagues conducted a study of patients admitted to hospitals with stroke from April 2009 through March 2010, accounting for 93,621 admissions.

Performance across five of six measures was lower on weekends, with one of the largest disparities seen in rates of same-day brain scans (43.1 percent on weekends compared with 47.6 percent on weekdays). Also, the rate of seven-day, in-hospital mortality for Sunday admissions was 11 percent compared with a mean (average) of 8.9 percent for weekday admissions, according to study results.

"We calculated that approximately 350 potentially avoidable in-hospital deaths occur within seven days each year and that an additional 650 people could be discharged to their usual place of residence within 56 days if the performance seen on weekdays was replicated on weekends," the authors comment.

Provided by JAMA and Archives Journals

Source: medicalxpress.com

July 9, 2012

(Medical Xpress) — Have you ever found yourself paying attention to the sound of your footsteps when walking down a quiet corridor? Or perhaps you enjoy creating rhythmic patterns by tapping on a surface? Almost every bodily movement we make generates an impact sound and a team of academics have been studying whether the perception of the physical dimensions of our body can be challenged by spatially altering the ‘action’ sounds we make.

Self-action sounds help us understand physical properties of objects and our own body. Picture by Antonio Caballero

The research team from Royal Holloway, University of London conducted various experiments to determine whether our action sounds influence the way we picture ourselves and whether these perceptions change when the sound is manipulated.

Dr Manos Tsakiris from Royal Holloway said: “These sounds provide an important source of information about the physical properties of the objects and the space around us, but they also inform us about the physical properties of one’s own body, although we are mostly not aware of this process.”

The study, Action sounds recalibrate perceived tactile distance, is published in Current Biology and shows that increasing the distance to sound events produced when tapping on a surface with one’s arm influences the subsequent judgments of distance between two objects touching the arm. “Participants did not report feeling their own arm extended as a result of this test possibly because it is difficult for someone to accept that the dimensions of their body can change from one minute to the other. However, the increase in reported distance between two points touching one’s arm do suggest an unconscious change in the way participants mentally represented their arm, as if they would represent this arm as being longer,” Dr Tajadura-Jiménez explains.

The researchers hope this study could have clinical applications and help in the way chronic pain is treated or help motivate older people to move further or for longer than they previously thought was possibly by manipulating the action sounds they make.

Provided by Royal Holloway, University of London

Source: medicalxpress.com

July 9, 2012

(Medical Xpress) — Human brain cells showing aspects of Huntington’s Disease have been developed, opening up new research pathways for treating the fatal disorder.

An international consortium, including scientists from the School of Biosciences, has taken cells from Huntington’s Disease patients and generated human brain cells that develop aspects of the disease in the laboratory. The cells and the new technology will speed up research into understanding the disease and also accelerate drug discovery programs aimed at treating this terminal, genetic disorder.

Huntington’s Disease is an aggressive, neurodegenerative disorder which causes loss of co-ordination, psychiatric problems, dementia and death. Scientists have known the genetic cause of this disease for more than 20 years but research has been hampered by the lack of human brain cells with which to study the disease and screen for effective drugs.

The new breakthrough involves taking skin cells from patients with Huntington’s disease. The scientific team reprogrammed these cells into stem cells which were then turned into the brain cells affected by the disorder. The brain cells demonstrate characteristics of the disease and will allow the consortium to investigate the mechanisms that cause the brain cells to die.

Dr. Nicholas Allen, one of the lead investigators at the School of Biosciences, said: “This breakthrough allows us to generate brain cells with many of the hallmarks of this disease, within just a few weeks. This means that we can study both the normal physiology of these brain cells, and the pathological processes that lead to their death.”

The other Cardiff lead, Professor Paul Kemp, said: “Huntington’s Disease normally takes years to manifest in the human brain. Now we have a fast and reproducible model of this disease, offering fresh hope for the discovery of new therapies.”

The corresponding author of the paper, Professor Clive Svendsen, a UK scientist and now director of the Cedars-Sinai Regenerative Medicine Institute in the USA, said “This Huntington’s ‘disease in a dish’ will enable us for the first time to test therapies on human Huntington’s disease neurons. In addition to increasing our understanding of this disorder and offering a new pathway to identifying treatments, this study is remarkable because of the extensive interactions between a large group of scientists focused on developing this model. It’s a new way of doing trailblazing science.”

Director of the School of Biosciences, Professor Ole Petersen said: “This is an extremely important development and I am delighted to see colleagues from the School of Biosciences playing their part in this distinguished international team. I look forward to seeing future stages, when this new technique is put to work modeling the diseases and testing potential treatments.”

Provided by Cardiff University

Source: medicalxpress.com

ScienceDaily (July 9, 2012) — “Attentional blink” is the term psychologists use to describe our inability to recognize a second important object if we see it less than half a second after a first one. It always seemed impossible to overcome, but in a new paper in the Proceedings of the National Academy of Sciences, Brown University psychologists report they’ve found a way.

So far it has seemed an irreparable limitation of human perception that we strain to perceive things in the very rapid succession of, say, less than half a second. Psychologists call this deficit “attentional blink.” We’ll notice that first car spinning out in our path, but maybe not register the one immediately beyond it. It turns out, we can learn to do better after all. In a new study researchers now based at Brown University overcame the blink with just a little bit of training that was never been tried before.

"A color change can be very conspicuous. If all items are black and white and all of a sudden a color item is shown, you pay attention to that." Credit: Mike Cohea/Brown University"Attention is a very important component of visual perception," said Takeo Watanabe, professor of cognitive, linguistic and psychological sciences at Brown. "One of the best ways to enhance our visual ability is to improve our attentional function."

Watanabe and his team were at Boston University when they performed experiments described in a paper published the week of July 9 in the Proceedings of the National Academy of Sciences. The bottom line of the research is that making the second target object a distinct color is enough to train people to switch their attention more quickly than they could before. After that, they can perceive a second target object presented as quickly as a fifth of a second later, even when it isn’t distinctly colored.

Read more …

ScienceDaily (July 9, 2012) — Alzheimer’s disease is one of the most dreaded and debilitating illnesses one can develop. Currently, the disease afflicts 6.5 million Americans and the Alzheimer’s Association projects it to increase to between 11 and 16 million, or 1 in 85 people, by 2050.

Cell death in the brain causes one to grow forgetful, confused and, eventually, catatonic. Recently approved drugs provide mild relief for symptoms but there is no consensus on the underlying mechanism of the disease.

"We don’t know what the problem is in terms of toxicity," said Joan-Emma Shea, professor of chemistry and biochemistry at the University of California, Santa Barbara (UCSB). "This makes the disease difficult to cure."

Accumulations of amyloid plaques have long been associated with the disease and were presumed to be its cause. These long knotty fibrils, formed from misfolded protein fragments, are almost always found in the brains of diseased patients. Because of their ubiquity, amyloid fibrils were considered a potential source of the toxicity that causes cell death in the brain. However, the quantity of fibrils does not correspond with the degree of dementia and other symptoms.

New findings support a hypothesis that fibrils are a by-product of the disease rather than the toxic agent itself. This paradigm shift changes the focus of inquiry to smaller, intermediate molecules that form and dissipate quickly. These molecules are difficult to perceive in brain tissue.

Read more …

July 10, 2012 by Anne Trafton

A clinical trial of an Alzheimer’s disease treatment developed at MIT has found that the nutrient cocktail can improve memory in patients with early Alzheimer’s. The results confirm and expand the findings of an earlier trial of the nutritional supplement, which is designed to promote new connections between brain cells.

A graphic depicting a synapse, a connection between brain cells. Graphic: Christine Daniloff

Alzheimer’s patients gradually lose those connections, known as synapses, leading to memory loss and other cognitive impairments. The supplement mixture, known as Souvenaid, appears to stimulate growth of new synapses, says Richard Wurtman, a professor emeritus of brain and cognitive sciences at MIT who invented the nutrient mixture.

“You want to improve the numbers of synapses, not by slowing their degradation — though of course you’d love to do that too — but rather by increasing the formation of the synapses,” Wurtman says.

To do that, Wurtman came up with a mixture of three naturally occurring dietary compounds: choline, uridine and the omega-3 fatty acid DHA. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine is produced by the liver and kidney, and is present in some foods as a component of RNA.

These nutrients are precursors to the lipid molecules that, along with specific proteins, make up brain-cell membranes, which form synapses. To be effective, all three precursors must be administered together.

Results of the clinical trial, conducted in Europe, appear in the July 10 online edition of the Journal of Alzheimer’s Disease. The new findings are encouraging because very few clinical trials have produced consistent improvement in Alzheimer’s patients, says Jeffrey Cummings, director of the Cleveland Clinic’s Lou Ruvo Center for Brain Health.

“Memory loss is the central characteristic of Alzheimer’s, so something that improves memory would be of great interest,” says Cummings, who was not part of the research team.

Plans for commercial release of the supplement are not finalized, according to Nutricia, the company testing and marketing Souvenaid, but it will likely be available in Europe first. Nutricia is the specialized health care division of the food company Danone, known as Dannon in the United States.

Making connections

Wurtman first came up with the idea of targeting synapse loss to combat Alzheimer’s about 10 years ago. In animal studies, he showed that his dietary cocktail boosted the number of dendritic spines, or small outcroppings of neural membranes, found in brain cells. These spines are necessary to form new synapses between neurons.

Following the successful animal studies, Philip Scheltens, director of the Alzheimer Center at VU University Medical Center in Amsterdam, led a clinical trial in Europe involving 225 patients with mild Alzheimer’s. The patients drank Souvenaid or a control beverage daily for three months.

That study, first reported in 2008, found that 40 percent of patients who consumed the drink improved in a test of verbal memory, while 24 percent of patients who received the control drink improved their performance.

The new study, performed in several European countries and overseen by Scheltens as principal investigator, followed 259 patients for six months. Patients, whether taking Souvenaid or a placebo, improved their verbal-memory performance for the first three months, but the placebo patients deteriorated during the following three months, while the Souvenaid patients continued to improve. For this trial, the researchers used more comprehensive memory tests taken from the neuropsychological test battery, often used to assess Alzheimer’s patients in clinical research.

Patients showed a very high compliance rate: About 97 percent of the patients followed the regimen throughout the study, and no serious side effects were seen.

Both clinical trials were sponsored by Nutricia. MIT has patented the mixture of nutrients used in the study, and Nutricia holds the exclusive license on the patent.

Brain patterns

In the new study, the researchers used electroencephalography (EEG) to measure how patients’ brain-activity patterns changed throughout the study. They found that as the trial went on, the brains of patients receiving the supplements started to shift from patterns typical of dementia to more normal patterns. Because EEG patterns reflect synaptic activity, this suggests that synaptic function increased following treatment, the researchers say.

Patients entering this study were in the early stages of Alzheimer’s disease, averaging around 25 on a scale of dementia that ranges from 1 to 30, with 30 being normal. A previous trial found that the supplement cocktail does not work in patients with Alzheimer’s at a more advanced stage. This makes sense, Wurtman says, because patients with more advanced dementia have probably already lost many neurons, so they can’t form new synapses.

A two-year trial involving patients who don’t have Alzheimer’s, but who are starting to show mild cognitive impairment, is now underway. If the drink seems to help, it could be used in people who test positive for very early signs of Alzheimer’s, before symptoms appear, Wurtman says. Such tests, which include PET scanning of the hippocampus, are now rarely done because there are no good Alzheimer’s treatments available.

Provided by Massachusetts Institute of Technology

Source: medicalxpress.com