Posts tagged psychology
Articles and news from the latest research reports.
Study sheds light on underlying causes of impaired brain function in muscular dystrophy
8-Aug-2012
The molecular missteps that disrupt brain function in the most common form of adult-onset muscular dystrophy have been revealed in a new study published by Cell Press. Myotonic dystrophy is marked by progressive muscle wasting and weakness, as well as excessive daytime sleepiness, memory problems, and mental retardation. A new mouse model reported in the August 9 issue of the journal Neuron reproduces key cognitive and behavioral symptoms of this disease and could be used to develop drug treatments, which are currently lacking.
The red dots are the toxic RNAs accumulating in the nucleus (blue) of a myotonic dystrophy cell (these are induced pluripotent stem, or iPS, cells) and the green is a neuronal marker. Credit: Charizanis et al., Neuron.
"The new animal model reproduces important aspects of myotonic dystrophy brain disease, so this model may be useful to develop biomarkers and test future drug therapies," says senior study author Maurice Swanson of the University of Florida.
Previous studies had shown that mutated genes underlying the disease produce toxic ribonucleic acids (RNAs) during transcription, and these RNAs cause the production of incorrect forms of proteins in muscle tissue by blocking the actions of a protein called MBNL1. As a result, proteins typically found in fetal muscles increase in abundance, while the normal suite of proteins found in adult muscles decrease in number. However, until now, it was not clear whether molecular abnormalities similar to those in muscle tissue of individuals with mytonic dystrophy also occur in the brain, resulting in the cognitive neurological problems.
In the new study, Swanson and his team focused on a related protein called MBNL2, which is found in the brain. They developed a new mouse model that lacked a functional Mbnl2 gene. These animals experienced an increase in the amount of rapid eye movement sleep as well as learning and memory deficits, similar to human patients.
The researchers also found extensive evidence of toxic RNAs in the hippocampus, as well as signs that fetal proteins were being produced in the brains of adult mutants. This pattern was also evident in the autopsied brain tissue of humans who had myotonic dystrophy. “This study should accelerate our understanding of how myotonic dystrophy mutations impact brain development and function,” Swanson says.
Source: EurekAlert!
Opinion: Bias Is Unavoidable
By Lisa Cosgrove | August 7, 2012
It is part of the human condition to have implicit biases—and remain blissfully ignorant of them. Academic researchers, scientists, and clinicians are no exception; they are as marvelously flawed as everyone else. But it is not the cognitive bias that’s the problem. Rather, the denial that there is a problem is where the issues arise. Indeed, our capacity for self-deception was beautifully captured in the title of a recent book addressing researchers’ self-justificatory strategies, Mistakes Were Made (But Not by Me).
Illustration by Dusan Petricic
Decades of research have demonstrated that cognitive biases are commonplace and very difficult to eradicate, and more recent studies suggest that disclosure of financial conflicts of interest may actually worsen bias. This is because bias is most often manifested in subtle ways unbeknownst to the researcher or clinician, and thus is usually implicit and unintentional. For example, although there was no research misconduct or fraud, re-evaluations of liver tissue of rats exposed to the drug dioxin resulted in different conclusions about the liver cancer in those rats: compared to the original investigation, an industry-sponsored re-evaluation identified fewer tissue slides as cancerous and this finding affected policy recommendations (water quality standards were weakened). (See also Brown, Cold Spring Harbor Laboratory Press, 13–28, 1991.) This example is just one of many that points to a genericrisk that a financial conflict of interest may compromise research or undermine public trust.
Indeed, recent neuroscience investigations demonstrate that effective decision-making involves not just cognitive centers but also emotional areas such as the hippocampus and amygdala. This interplay of cognitive-emotional processing allows conflicts of interest to affect decision-making in a way that is hidden from the person making the decision.
Despite these findings, many individuals are dismissive of the idea that researchers’ financial ties to industry are problematic. For example, in a recent essay in The Scientist, Thomas Stossel of Brigham & Women’s Hospital and Harvard Medical School asked, “How could unrestricted grants, ideal for research that follows up serendipitous findings, possibly be problematic? The money leads to better research that can benefit patients.” Many argue that subjectivity in the research process and the potential for bias can be eradicated by strict adherence to the scientific method and transparency about industry relationships. Together, scientists believe, these practices can guarantee evidence-based research that leads to the discovery and dissemination of “objective” scientific truths. The assumption is that the reporting of biased results is a “bad apple” problem—a few corrupt individuals engaging in research fraud. But what we have today is a bad barrel.
Some have begun to use the analytic framework of “institutional corruption” to bring attention to the fact that the trouble is not with a few corrupt individuals hurting an organization whose integrity is basically intact. Institutional corruption refers to the systemic and usually legal—and often accepted and widely defended—practices that bring an organization or institution off course, undermine its mission and effectiveness, and weaken public trust. Although the entire field of biomedicine has come under scrutiny because of concerns about an improper dependence on industry and all medical specialties have struggled with financial conflicts of interest, psychiatry has been particularly troubled, being described by some as having a crisis of credibility.
This credibility crisis has been played out most noticeably in the public controversy surrounding the latest revision to the Diagnostic and Statistical Manual of Mental Disorders (DSM). The DSM is often referred to as the “Bible” of mental disorders, and is produced by the American Psychiatric Association (APA), a professional organization with a long history of industry ties. DSM-5, the revised edition scheduled for publication in May, 2013, has already been criticized for “disease mongering,” or pathologizing normal behavior. Concerns have been raised that because the individuals responsible for making changes and adding new disorders have strong and long-standing financial associations to pharmaceutical companies that manufacture the drugs used to treat these disorders, the revision process may be compromised by undue industry influence.
Researchers, clinicians, and psychiatrists who served on the DSM-IV have pointed out that adding new disorders or lowering the diagnostic threshold of previously included disorders may create “false positives,” individuals incorrectly identified as having a mental disorder and prescribed psychotropic medication. For example, there was a heated debate about pathologizing the normal grieving process if DSM-5 eliminated the bereavement exclusion for major depressive disorder (MDD). The concern was that widening the diagnostic boundaries of depression to include grief as a “qualifying event,” thereby allowing for a diagnosis of MDD just 2 weeks after the loss of a loved one, would falsely identify individuals as depressed. Although it is not the APA’s intent to play handmaiden to industry, the reality is that such a change would result in more people being prescribed antidepressants following the loss of a loved one. In fact, psychiatrist Allen Frances, who chaired the DSM-IV task force, has noted that DSM-5 would be a “bonanza” for drug companies.
After receiving criticism about potential bias in the development of the DSM-IV, the APA required that DSM-5 panel members file financial disclosures. Additionally, during their tenure on the panels they were not allowed to receive more than $10,000 from pharmaceutical companies or have more than $50,000 in stock holdings in pharmaceutical companies (unrestricted research grants were excluded from this policy). The majority of diagnostic panels, however, continue to have the majority of their members with financial ties to the pharmaceutical industry. Specifically, 67 percent of the 12-person panel for mood disorders, 83 percent of the 12-person panel for psychotic disorders, and all 7 members of the sleep/wake disorders panel (which now includes ‘‘Restless Leg Syndrome’’) have ties to the pharmaceutical companies that manufacture the medications used to treat these disorders or to companies that service the pharmaceutical industry.
Clearly, the new disclosure policy has not been accompanied by any reduction in the financial conflicts of interest of DSM panel members. Moreover, Darrel Regier, speaking on behalf of the APA and in defense of DSM panel members with industry ties, told USA Today. “There’s this assumption that a tie with a company is evidence of bias. But these people can be objective.” However, as science has repeatedly shown, transparency alone cannot mitigate bias and is an insufficient solution for protecting the integrity of the revision process. Objectivity is not a product that can be easily secured by adherence to the scientific method. Rather, there is a generic risk that a conflict of interest may result in implicit, unintentional bias. Similarly, as Sinclair Lewis said, “It is difficult to get a man to understand something when his salary depends upon his not understanding it.”
Source: TheScientist
A fine-tuned combination of two existing pharmaceutical drugs has shown promise as a potential new therapy for people addicted to cocaine—a therapy that would reduce their craving for the drug and blunt their symptoms of withdrawal.
In laboratory experiments at The Scripps Research Institute, the potential therapy, which combines low doses of the drug naltrexone with the drug buprenorphine, made laboratory rats less likely to take cocaine compulsively—a standard preclinical test that generally comes before human trials.
While the two-drug combination would have to prove safe and effective for people in clinical trials before approval by the U.S. Food and Drug Administration (FDA), the work represents a significant advance in the field because there are currently no FDA-approved medications for treating cocaine addiction.
The mechanism of action of cocaine
Cocaine modifies the action of dopamine in the brain. The dopamine rich areas of the brain are the ventral tegmental area, the nucleus accumbens and the caudate nucleus – these areas are collectively known as the brain’s ‘reward pathway’. Cocaine binds to dopamine re-uptake transporters on the pre-synaptic membranes of dopaminergic neurones. This binding inhibits the removal of dopamine from the synaptic cleft and its subsequent degradation by monoamine oxidase in the nerve terminal. Dopamine remains in the synaptic cleft and is free to bind to its receptors on the post synaptic membrane, producing further nerve impulses. This increased activation of the dopaminergic reward pathway leads to the feelings of euphoria and the ‘high’ associated with cocaine use.
New Model Synapse Could Shed Light on Disorders Such as Epilepsy and Anxiety
A new way to study the role of a critical neurotransmitter in disorders such as epilepsy, anxiety, insomnia, depression, schizophrenia, and alcohol addiction has been developed by a group of scientists led by Gong Chen, an associate professor of biology at Penn State University.
The new method involves molecularly engineering a model synapse — a structure through which a nerve cell send signals to another cell. This model synapse can precisely control a variety of receptors for the neurotransmitter called GABA, which is important in brain chemistry. The research, which will be published in the Journal of Biological Chemistry on 10 August 2012, opens the door to the possibility of creating safer and more-efficient drugs that target GABA receptors and that cause fewer side effects.
The brains of people with schizophrenia may attempt to heal from the disease
7 August 2012
New NeuRA research shows that the brains of people with schizophrenia may attempt to repair damage caused by the disease, in another example of the adult brain’s capacity to change and grow.
Prof Cyndi Shannon Weickert, Dr Dipesh Joshi and colleagues from Neuroscience Research Australia studied the brains of people with schizophrenia and focussed on one of the hardest-hit regions, the orbitofrontal cortex, which is the part of the brain involved in regulating emotional and social behaviour.
Most neurons – brain cells that transmit information – are found in tissue near the surface of the brain. However, in the brains of people with schizophrenia, the team found a high density of neurons in deeper areas.
“For over a decade we’ve known about the high density of neurons in deeper brain tissue in people with schizophrenia. Researchers thought these neurons were simply forgotten by the brain, and somehow didn’t die off like they do during development in healthy people,” says Prof Shannon Weickert.
“What we now have is evidence that suggests these neurons are derived from the part of the brain that produces new neurons, and that they may be in the process of moving. We can’t be sure where they are moving to, but given their location it is likely they are on their way to the surface of the brain, the area most affected by schizophrenia,” Prof Shannon Weickert concluded.
How was this study done?
- Brain tissue from the orbitofrontal cortex from 38 people with schizophrenia and 38 people without the disease were used in this study.
- The density of interstitial neurons in the white matter, and the density of GABAergic neurons in the grey matter were measured.
- An increased density of interstitial white matter neurons in the white matter, and decreased density of GABAergic neurons in the grey matter was found.
- This pattern suggests that the migration of interstitial white matter neurons towards an area where they are lacking, because of schizophrenia, is a response to the disease.
The Algorithm That Finds Connections Scientists Never See
Here’s a thought experiment for you: If someone told you you had to drink just one kind of alcoholic beverage for the rest of your life, and you wanted that life to be long and healthy, what would you pick? Wine, right? After all, you’ve probably heard about the scientific studies showing that drinking wine is associated with better health in general, and a longer life span in particular. Give jocks their beer and lushes their hard liquor; the drink of robust, long-lived people is wine.
But you have probably not heard about another study, released during the media dead zone just after Christmas last year, that questioned wine’s reputed health effects. Researchers at Stanford University and the University of Texas at Austin examined a group of Americans aged 55 to 65 and compared their drinking habits with how they fared over the course of 20 years. The scientists found that moderate drinkers lived longer than abstainers, and that wine drinkers did indeed live longer on average than people who consumed other kinds of alcohol. But they also found that wine drinkers were less likely to smoke, to be male, and to be sedentary; all of these are factors associated with dying earlier.
The Stanford-Texas team concluded that drinking wine might be an indicator of a healthy lifestyle rather than the cause of that good health. If so, wine is the drink of the healthy, all right—the already healthy.
That finding highlights what is arguably science’s greatest enemy, the confounder. Science is at heart a reductionist process: Take a complicated system, identify various factors that affect the system, and measure the effect of each factor one at a time. Confounders are devilish hidden connections that make it more difficult to isolate the factors you want to measure, like the fact that wine drinkers tend also to be nonsmokers…
In the journal Experimental Neurology, the scientists report the beneficial effects of so-called astrocytes, a certain type of glial cells. They get their name from the Greek word for glue, as it was long thought that these cells simply hold the nerve cells together and provided them with nutrients. In the case of epilepsy, the prevalent opinion was that their reaction to a seizure would actually damage the brain. The researchers from Freiburg disagree. In fact, they say, astrocytes help to reduce long-term damage brought upon by epileptic fits.
The team discovered the positive effects of astrocytes in mice, in which epileptic states can be selectively triggered. If the scientists injected mice with a specific protein to activate the astrocytes prior to an epilepsy-inducing insult, fewer nerve cells died in the wake of the seizure. Other pathological changes that would usually occur in the brain were likewise significantly reduced. The astrocytes’ protective effect lasted for many days after their activation. When the researchers measured the rodents’ brain activity, they likewise found fewer signs that are typical for a brain suffering from epilepsy. However, the authors report that the astrocytes had to be already activated before seizures were elicited. Activating them afterwards, on the other hand, did not lead to a protective effect.
Further studies will have to demonstrate that astrocytes have this protective influence all over the brain. According to Haas, who is also a member of Freiburg’s new cluster of excellence BrainLinks-BrainTools, their findings suggest that a timely activation of astrocytes could offer an effective protection from long-term damage to the brain.
Social Network Size Linked to Brain Size
As humans, we aren’t born with formidable armaments or defenses, nor are we the strongest, fastest, or biggest species, yet despite this we are amazingly successful. For a long time it was thought that this success was because our enlarged brains allows each of us to be smarter than our competitors: better at abstract thinking, better with tools and better at adapting our behavior to those of our prey and predators. But are these really the most significant skills our brains provide us with?
Another possibility is that we are successful because we can form long-lasting relationships with many others in diverse and flexible ways, and that this, combined with our native intelligence, explains why homo sapiens came to dominate the planet. In every way from teaching our young to the industrial division of labour we are a massively co-operative species that relies on larger and more diverse networks of relationships than any other species.
![How digital culture is rewiring our brains
Our brains are superlatively evolved to adapt to our environment: a process known as neuroplasticity. The connections between our brain cells will be shaped, strengthened and refined by our individual experiences. It is this personalisation of the physical brain, driven by unique interactions with the external world, that arguably constitutes the biological basis of each mind, so what will happen to that mind if the external world changes in unprecedented ways, for example, with an all-pervasive digital technology?
A recent survey in the US showed that more than half of teenagers aged 13 to 17 spend more than 30 hours a week, outside school, using computers and other web-connected devices. If their environment is being transformed for so much of the time into a fast-paced and highly interactive two-dimensional space, the brain will adapt, for good or ill. Professor Michael Merzenich, of the University of California, San Francisco, gives a typical neuroscientific perspective.
”There is a massive and unprecedented difference in how [digital natives’] brains are plastically engaged in life compared with those of average individuals from earlier generations and there is little question that the operational characteristics of the average modern brain substantially differ,” he says.](http://41.media.tumblr.com/tumblr_m8ft5jgs2V1rog5d1o1_400.jpg)
How digital culture is rewiring our brains
Our brains are superlatively evolved to adapt to our environment: a process known as neuroplasticity. The connections between our brain cells will be shaped, strengthened and refined by our individual experiences. It is this personalisation of the physical brain, driven by unique interactions with the external world, that arguably constitutes the biological basis of each mind, so what will happen to that mind if the external world changes in unprecedented ways, for example, with an all-pervasive digital technology?
A recent survey in the US showed that more than half of teenagers aged 13 to 17 spend more than 30 hours a week, outside school, using computers and other web-connected devices. If their environment is being transformed for so much of the time into a fast-paced and highly interactive two-dimensional space, the brain will adapt, for good or ill. Professor Michael Merzenich, of the University of California, San Francisco, gives a typical neuroscientific perspective.
”There is a massive and unprecedented difference in how [digital natives’] brains are plastically engaged in life compared with those of average individuals from earlier generations and there is little question that the operational characteristics of the average modern brain substantially differ,” he says.