Long-acting antipsychotic Zyprexa Relprevv (olanzapine pamoate) is under scrutiny after the U.S. Food and Drug Administration’s (FDA) turned up two deaths following the injection of the drug.

The two patients received the appropriate dose of Zyprexa Relprevv, then died 3-4 days later.

Zyprexa Relprevv (olanzapine pamoate) is manufactured by Eli Lilly and first approved for use in the United States in 1996. It is an extended release injectable suspension, meaning it is injected only once every 2 or 4 weeks in most patients.

After injection, patients are typically monitored for a 3-hour post-injection period — required under the Zyprexa Relprevv Risk Evaluation and Mitigation Strategy (also known as REMS). According to the FDA, “patients are required to receive the Zyprexa Relprevv injection at a REMS-certified health care facility, to be continuously monitored at the facility for at least 3 hours following an injection, and to be accompanied home from the facility.”

It’s not clear that the REMS protocol was followed in both patents who died.

According to the FDA, “Both patients were found to have very high olanzapine blood levels after death. High doses of olanzapine can cause delirium, cardiopulmonary arrest, cardiac arrhythmias, and reduced level of consciousness ranging from sedation to coma.”

The FDA suggests doctors and patients don’t discontinue use of Zyprexa Relprevv at this time: “If therapy with Zyprexa Relprevv is started or continued in patients, health care professionals should follow the REMS requirements and drug label recommendations.”

The Zyprexa Relprevv label contains warnings about the risk of post-injection delirium sedation syndrome (PDSS), a serious condition in which the drug enters the blood too fast following an intramuscular injection. This can cause greatly elevated blood levels with marked sedation (possibly including coma) and/or delirium.

In the clinical trials supporting the approval of Zyprexa Relprevv, cases of PDSS were observed within 3 hours after administration of Zyprexa Relprevv. But there were no deaths due to PDSS found in those initial clinical trials, according to the FDA report.

Schizophrenia is a mental disorder that affects around one in 100 people worldwide. Its most common symptoms are delusions and hallucinations, most often the hearing of voices or people talking when nobody is there.

One of the biggest challenges for individuals suffering from schizophrenia is taking medication as it is prescribed. Injectibles such as Zyprexa Relprevv are meant to help alleviate this problem.

Source: U.S. Food and Drug Administration

New research suggests exposure to violence in children under the age of three may lead to aggression in school age youngsters.

“People may think children that young are passive and unaware, but they pay attention to what’s happening around them,” said Megan Holmes, Ph.D., assistant professor of social work at Case Western Reserve in Cleveland.

Between three and 10 million children witness some form of domestic violence each year, say experts from the National Center for Children Exposed to Violence.

Holmes said researchers know the impact of recent exposure to violence, but little information has been available about the long-term effect from the early years of life.

To her knowledge, she said her study is the first to look at the effect of early exposure to domestic violence and its impact on the development of social behavior.

In the study, Holmes analyzed the behavior of 107 children exposed to interpersonal violence in their first three years but never again after age 3. The outcomes of those children were compared to 339 children who were never exposed.

Those studied were from the National Survey of Child and Adolescent Well-Being (NSCAW), which included children reported to Child Protective Services for abuse or neglect. The children’s behavior was followed four times over the course of five years.

Holmes’s research, published in the Journal of Child Psychology and Psychiatry, examined the timing, duration and nature of their exposure to violence and how it affected aggressive behavior.

Holmes found no behavioral differences between those who did or did not witness violence between the ages of 3 and 5, but children exposed to violence increased their aggression when they reached school age.

And the more frequently such violence was witnessed, the more aggressive the behaviors became.

Meanwhile, children never exposed to interpersonal violence gradually decreased in aggression.

Learning that observing violence can have a delayed effect on children is important for social workers assessing the impact on children in homes with domestic violence, Holmes said.

“The delay also gives social workers a window of opportunity between ages 3 and 5 to help the children socialize and learn what is appropriate behavior,” said Holmes, who has worked with mothers and children in domestic violence shelters.

Experts recommend play therapy and art therapy to help children work through the violence they were exposed to.

Holmes said her overarching goal is to contribute to optimal development of children who have been exposed to interpersonal violence “by identifying risk and protective factors that will be translated into interventions,” she said.

Source: Case Western Reserve

Child listening to parents fighting photo by shutterstock.

Emerging research suggests between being admitted to a hospital for an infection may influence a later diagnosis of a mood disorder.

Specifically, investigators found that the risk of being diagnosed with a mood disorder increases by nearly two-thirds if a person had been admitted to hospital with an infection.

The study, published in JAMA Psychiatry, is the largest of its kind to date to show a clear correlation between infection levels and the risk of developing mood disorders.

Mood disorders include serious mental illness, such as clinical depression and bipolar disorder.

Researchers theorize that an infection may lead to extended mental distress beyond an apparent physical recovery from the original illness. That is, an individual’s distress does not necessarily end once the infection has been treated.

“Our study shows that the risk of developing a mood disorder increases by 62 percent for patients who have been admitted to hospital with an infection.

“In other words, it looks as though the immune system is somehow involved in the development of mood disorders,” said researcher Michael Eriksen Benrós, M.D., Ph.D., of Aarhus University and Psychiatric Centre Copenhagen.

The study is a register study, which has involved following more than 3 million Danes. Between 1977 and 2010, more than 91,000 of these people were seen in a health facility for a mood disorder.

Thirty-two percent of the patients had previously been admitted with an infectious disease, while 5 percent had been admitted with an autoimmune disease.

According to Benrós, the increased risk of mood disorders can be explained by the fact that infections affect the brain:

“Normally, the brain is protected by the so-called blood-brain barrier (BBB), but in the case of infections and inflammation, new research has shown that the brain can be affected on account of a more permeable BBB.”

“We can see that the brain is affected, whichever type of infection or autoimmune disease it is. Therefore, it is naturally important that more research is conducted into the mechanisms which lie behind the connection between the immune system and mood disorders,” Benrós said.

Benros believes knowing more about this connection will help to prevent mood disorders and improve future treatment.

Depression is a mental disorder marked by severe bouts of depressed mood, sadness, lack of interest and pleasure in daily activities, lethargy, sleep problems, feelings of worthlessness and problems concentrating. Bipolar disorder is a mental disorder marked by mood swings that go from depression, to mania or hypomania.

Source: Aarhus University

New research suggests that sibling aggression may lead to poor mental health among children and adolescents.

Sibling aggression, or fights between siblings, is often dismissed as simply being a part of growing up with brothers or sisters.

Yet a new study from researchers at the University of New Hampshire finds that sibling aggression is associated with significantly worse mental health in children and adolescents. In some cases, effects of sibling aggression on mental health were the same as those of peer aggression.

“Even kids who reported just one instance had more mental health distress,” said Corinna Jenkins Tucker, Ph.D., associate professor of family studies at the University of New Hampshire.

“Our study shows that sibling aggression is not benign for children and adolescents, regardless of how severe or frequent.”

The study, published in the journal Pediatrics, is among the first to look at sibling aggression across a wide age and geographic range, is unique in its size and scope.

Tucker and her co-authors analyzed data from the center’s National Survey of Children’s Exposure to Violence (NatSCEV), a national sample of 3,599 children, ages one month through 17.

Researchers looked at the effects of physical assault with and without a weapon or injury, property aggression like stealing something or breaking a siblings’ things on purpose, and psychological aggression such as saying things that made a sibling feel bad, scared, or not wanted around.

Investigators found that of the 32 percent of children who reported experiencing one type of sibling victimization in the past year, mental health distress was greater for children (1 month to age 9) than for adolescents (age 10 – 17) who experienced mild sibling physical assault.

But children and adolescents were similarly affected by other psychological or property aggression from siblings.

Their analyses also showed that, while peer aggression like bullying is generally thought to be more serious than sibling aggression, sibling and peer physical and psychological aggression had independent effects on mental health.

The mental health of those experiencing property and psychological aggression, whether from siblings or peers, did not differ.

Researchers say that parents and caregivers should take sibling aggression seriously.

“If siblings hit each other, there’s a much different reaction than if that happened between peers,” Tucker said. “It’s often dismissed, seen as something that’s normal or harmless. Some parents even think it’s beneficial, as good training for dealing with conflict and aggression in other relationships.”

This research indicates that sibling aggression is related to the same serious mental health effects as peer bullying.

The authors suggest that pediatricians take a role in disseminating this information to parents at office visits, and that parent education programs include a greater emphasis on sibling aggression and approaches to mediate sibling conflicts.

Source: University of New Hampshire

Brothers fighting photo by shutterstock.

University of San Francisco scientists have found they can improve memory in mice using a small drug-like molecule.

The researchers were investigating the way in which cells respond to biological stress. The same biochemical pathway the molecule acts on might one day be targeted in humans to improve memory, according Peter Walter, PhD, the senior author of the study.

The discovery of the molecule and the results of the subsequent memory tests in mice were published in eLife, an online scientific open-access journal.

In one memory test, normal mice were able to relocate a submerged platform about three times faster after receiving injections of the potent chemical than mice that received sham injections.

The mice that received the chemical also better remembered cues associated with unpleasant stimuli — the sort of fear conditioning that could help a mouse avoid being preyed upon.

The research appears to indicate that some counter-intuitive processes may be involved in memory development.

Notably, the findings suggest that despite what would seem to be the importance of having the best biochemical mechanisms to maximize the power of memory, evolution does not seem to have provided them, Walter said.

“It appears that the process of evolution has not optimized memory consolidation; otherwise I don’t think we could have improved upon it the way we did in our study with normal, healthy mice,” Walter said.

The memory-boosting chemical was singled out from among 100,000 chemicals. The substances were screened for their potential to perturb a protective biochemical pathway within cells that’s activated when cells are unable to keep up with the need to fold proteins into their working forms.

However, UCSF postdoctoral fellow Carmela Sidrauski, PhD, discovered that the chemical acts within the cell beyond the biochemical pathway that activates this unfolded protein response, to more broadly impact what’s known as the integrated stress response.

In this response, several biochemical pathways converge on a single molecular lynchpin, a protein called eIF2 alpha.

Scientists have known that, in organisms ranging in complexity from yeast to humans, different kinds of cellular stress — a backlog of unfolded proteins, DNA-damaging UV light, a shortage of the amino acid building blocks needed to make protein, viral infection, iron deficiency — trigger different enzymes to act downstream to switch off eIF2 alpha.

“Among other things, the inactivation of eIF2 alpha is a brake on memory consolidation,” Walter said — perhaps an evolutionary consequence of a cell or organism becoming better able to adapt in other ways.

Turning off eIF2 alpha dials down production of most proteins, some of which may be needed for memory formation, Walter said. But eIF2 alpha inactivation also ramps up production of a few key proteins that help cells cope with stress.

Study co-author Nahum Sonenberg, PhD, of McGill University previously linked memory and eIF2 alpha in genetic studies of mice, and his lab group also conducted the memory tests for the current study.

The chemical identified by the UCSF researchers is called ISRIB, which stands for integrated stress response inhibitor. ISRIB counters the effects of eIF2 alpha inactivation inside cells, the researchers found.

“ISRIB shows good pharmacokinetic properties [how a drug is absorbed, distributed and eliminated], readily crosses the blood-brain barrier, and exhibits no overt toxicity in mice, which makes it very useful for studies in mice,” Walter said.

These properties also indicate that ISRIB might serve as a good starting point for human drug development, according to Walter.

Walter said he is looking for scientists to collaborate with in new studies of cognition and memory in mouse models of neurodegenerative diseases and aging, using ISRIB or related molecules.

In addition, chemicals such as ISRIB could play a role in fighting cancers, which take advantage of stress responses to fuel their own growth, Walter said.

At a more basic level, Walter said, he and other scientists can now use ISRIB to learn more about the role of the unfolded protein response and the integrated stress response in disease and normal physiology.

Source: University of San Francisco

Online marketplaces are using instant messaging to create the sense of personal and social relationships between buyers and sellers.

Researchers use the term “swift guanxi” to describe the effort to facilitate loyalty, interactivity and repeat transactions.

Guanxi is a Chinese concept “broadly defined as a close and pervasive interpersonal relationship” and “based on high-quality social interactions and the reciprocal exchange of mutual benefits,” say researchers Carol Xiaojuan Ou, Paul A. Pavlou and Robert M. Davison.

The researchers studied data from TaoBao, China’s leading online marketplace, to examine the efficacy of using computer-mediated-communication (CMC) technology to build guanxi and turn impersonal one-time shoppers into loyal and committed long-term customers through personal rapport.

In the past, online shoppers have been presumed to prefer impersonal transactions, but their study argues that both retailers and customers inherently desire the kind of relationship that can be called guanxi, even if the degree and extent of communication varies by culture.

For example, in China, communication before a transaction of a few dollars could take more than 45 minutes.

“Nobody would argue that personal relationships are unimportant, but it is unfathomable that people in the U.S. would engage in such extensive communications and personal interactions for a small transaction,” said Pavlou.

The instant messaging technology used on TaoBao allows buyers and sellers to interact immediately and to use emoticons and avatars in the negotiation and verification of the transaction details.

In addition, all the customers’ messages related to a specific product are shown in a message box. Finally, the feedback system provides users with textual and numerical evaluations of buyers and sellers that further establish rapport.

“The role of CMC tools in establishing swift guanxi via interactivity, presence, and trust, suggests that buyer-seller interaction can easily and quickly transform strangers into acquaintances,” the researchers wrote.

“In terms of repeat transactions, the effective use of CMC tools creates a significant opportunity for online sellers who wish to reinforce swift guanxi with buyers via building buyers’ trust.”

With the use of CMC tools (such as instant messaging, message boxes and feedback), TaoBao has achieved a loyalty rate, or “stickiness,” of 71.3 percent of its customer base – the kind of loyalty that is typically associated with only brick-and-mortar retailers.

Guanxi, largely enabled by CMC tools, can help explain the success of Taobao in China despite eBay’s attempts to capture China’s online market with eBay China (EachNet). Currently Taobao has 96 percent market share in China compared to 0.1 percent for EachNet.

Pavlou explained the significance of the study’s findings by citing an April 2000 article in The Economist that said: “If you don’t have the patience to learn about guanxi, old boy, you might as well pack your bags and go home.”

“This study validates this warning by showing the ability of social technologies to transform online marketplaces from impersonal transactions among strangers to personal relationships among virtual friends,” Pavlou said.

“The future of electronic commerce lies in personal relationships virtually enabled by social technologies.”

The study is published online in MIS Quarterly.

Source: Temple University

MIT scientists have developed a software system to help people improve their conversational and interview skills.

Experts say that social phobias affect about 15 million adults in the United States with public speaking high on the list of such phobias.

In some cases, fears of social situations can be especially acute. For example, individuals with Asperger’s syndrome often have difficulty making eye contact and reacting appropriately to social cues.

But with appropriate training, such difficulties can often be overcome.

MIT researchers developed the software to help people practice their interpersonal skills until they feel more comfortable with situations such as a job interview or a first date.

The software, called MACH (short for My Automated Conversation coacH), uses a computer-generated onscreen face, along with facial, speech and behavior analysis and synthesis software, to simulate face-to-face conversations. It then provides users with feedback on their interactions.

The research was led by MIT Media Lab doctoral student M. Ehsan Hoque, who says the work could be helpful to a wide range of people.

“Interpersonal skills are the key to being successful at work and at home,” Hoque says. “How we appear and how we convey our feelings to others define us. But there isn’t much help out there to improve on that segment of interaction.”

Many people with social phobias, Hoque says, want “the possibility of having some kind of automated system so that they can practice social interactions in their own environment. … They desire to control the pace of the interaction, practice as many times as they wish, and own their data.”

The MACH software offers all those features, Hoque says. In fact, in randomized tests with 90 MIT juniors who volunteered for the research, the software showed its value.

First, the test subjects — all of whom were native speakers of English — were randomly divided into three groups. Each group participated in two simulated job interviews, a week apart, with MIT career counselors.

In between the two interviews (and unknown to the counselors), the students received help. One group watched videos of interview advice, while a second group had a practice session with the MACH-simulated interviewer but received no feedback other than a video of their own performance.

Finally, a third group used MACH and then saw videos of themselves accompanied by an analysis of such measures as how much they smiled, how well they maintained eye contact, how well they modulated their voices and how often they used filler words such as “like,” “basically” and “umm.”

Evaluations by another group of career counselors showed that the third group demonstrated statistically significant improvement on measures including “appears excited about the job,” “overall performance,” and “would you recommend hiring this person?”

In all of these categories, by comparison, there was no significant change for the other two groups.

The software behind these improvements was developed over two years as part of Hoque’s doctoral thesis work.

Designed to run on an ordinary laptop, the system uses the computer’s webcam to monitor a user’s facial expressions and movements, and its microphone to capture the subject’s speech.

The MACH system then analyzes the user’s smiles, head gestures, speech volume and speed and use of filler words, among other things. The automated interviewer — a life-size, three-dimensional simulated face — can smile and nod in response to the subject’s speech and motions, ask questions and give responses.

While this initial implementation was focused on helping job candidates, Hoque says training with the software could be helpful in many kinds of social interactions.

Source: MIT

New mice research suggests that, for those who already carry a genetic risk for schizophrenia, being exposed to lead during the formative years results in an even greater chance of developing the disease. 

The study, published online in Schizophrenia Bulletin, helps scientists better understand the complex gene-environment combinations that result in a greater risk for schizophrenia and other mental disorders.

In 2004, research conducted by scientists at the Columbia University’s Mailman School of Public Health suggested a connection between prenatal lead exposure in humans and increased risk for schizophrenia later in life. And yet, it was still unknown how exposure to lead could trigger the disease.

Based on his own research with rodents, Tomás R. Guilarte, senior author of the new study, believed the answer was in the direct inhibitory effect of lead on the N-methyl-D-aspartate receptor (NMDAR), a synaptic connection point important to brain development, learning and memory.

Guilarte discovered in his research that exposure to lead dulls the function of the NMDAR. The glutamate hypothesis of schizophrenia suggests that a deficit in glutamate neurotransmission—and specifically hypoactivity of the NMDAR — can account for much of the dysfunction in schizophrenia.

In the new study, Guilarte and his team focused on mice engineered to carry the mutant form of Disrupted-in-Schizophrenia-1 (DISC1), a gene that is a risk factor for the disease in humans.

Before birth, half of the mutant DISC1 mice were fed a diet with lead, and half were given a normal diet. Another group, consisting of normal mice without the mutant DISC1 gene, were also split into the two feeding groups. All mice were given a series of behavioral tests, and their brains were examined using MRI.

Mutant mice exposed to lead and given a psychostimulant showed higher levels of hyperactivity and were less able to suppress a startled response to a loud noise after being given an acoustic warning. Their brains also had significantly larger lateral ventricles — empty spaces containing cerebrospinal fluid — compared with other mice. These results reflect what is known about schizophrenia in humans.

Although the role of genes in schizophrenia and other mental disorders is well known, the effects of toxic environmental chemicals is just beginning to emerge.

“We’re just scratching the surface,” said Guilarte. “We used lead in this study, but there are other environmental toxins that disrupt the function of the NMDAR.” One of these is a family of chemicals in air pollution called polycyclic aromatic hydrocarbons or PAHs.

“Similarly, any number of genes could be in play,” added Guilarte, noting that DISC1 is among many involved in schizophrenia.

Future research may reveal to what extent schizophrenia is determined by environmental versus genetic factors or both, and what other mental disorders might be in the mix.

“The animal model provides a way forward to answer important questions about the physiological processes underlying schizophrenia,” said Guilarte.

Source:  Columbia University

Schizophrenia word collage photo by shutterstock.

In a novel but very small study, scientists were able to help some women with severe anorexia nervosa through deep brain stimulation (DBS).  On the other hand, those who saw no improvement actually experienced fairly adverse side effects.

Anorexia nervosa is typically a chronic illness that affects around one percent of the population, and is mot usually diagnosed in teens between the ages of 15-19. 

Anorexia has one of the highest mortality rates of any psychiatric disorder — between six and 11 percent — and is among the most difficult to treat, wrote the authors of the study in the Lancet medical journal.

DBS is used to treat several neurological disorders including Parkinson’s disease and chronic pain, but this was a first for anorexia.

In an attempt to normalize the activity of dysfunctional brain circuits, electrodes were implanted into the part of the brain that regulates emotion.  The devices, which work in a way similar to that of pacemakers, were connected to a pulse generator implanted under the skin.

The technique, which is still in the experimental phase, showed some promise as it helped improve symptoms in half of the women, wrote the researchers. 

After nine months, three of the six participants had gained weight and appeared to be in a better state of mind, they said.

For the three, “this was the longest period of sustained increase in BMI (Body Mass Index, which is defined as the ratio between a person’s height and weight) since the onset of their illness,” wrote the authors.

Furthermore, DBS “was associated with improvements in mood, anxiety… and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after six months of stimulation,” they said.

Three patients, however, showed no weight improvement and the scientists pointed out that the procedure was associated with “several adverse events”—including a seizure for one woman.  Other negative effects included panic attacks, nausea and pain.

At the time of surgery, the women were between the ages of 24 and 57 and had been suffering from anorexia for between four and 37 years.

“The fact that the procedure was associated in some patients with improvements in affective and obsessional symptoms is of key importance since such improvements will go some way towards reassuring patients that DBS is not just another treatment designed to fatten them up without making them feel better,” they wrote.

Source:  Lancet

Abstract of the brain photo by shutterstock.

Researchers have identified the sleep mechanism that enables the brain to strengthen emotional memories. 

They also found that a commonly prescribed sleep aid heightens the brain’s remembrance of and response to negative memories.

Dr. Sara Mednick from the University of Riverside and her colleagues found that a sleep condition known as sleep spindles — bursts of brain activity that last for a second or less during a specific stage of sleep — are vital for emotional memory.

In earlier research, Mednick demonstrated the vital role that sleep spindles play in transferring memories from short-term to long-term in the hippocampus.

The drug zolpidem (brand names include Ambien and others) was found to enhance the process, a discovery that could lead to new sleep therapies to improve memory for aging adults and for those with dementia, Alzheimer’s and schizophrenia. It was the first study to show that sleep could be manipulated with medication to improve memory.

“We know that sleep spindles are involved in declarative memory — explicit information we recall about the world, such as places, people and events,” she explained.

But until now, researchers did not know that sleep spindles were involved in emotional memory; they had been focusing on rapid eye movement (REM) sleep instead.

Using two commonly prescribed sleep aids — zolpidem and sodium oxybate (Xyrem) — the researchers were able to tease apart the effects of sleep spindles and rapid eye movement (REM) sleep on the recall of emotional memories. They determined that sleep spindles, not REM, affect emotional memory.

For the study, the researchers gave zolpidem, sodium oxybate and a placebo to 28 men and women between the ages of 18 and 39 who were normal sleepers.  They waited several days between doses to allow the medications to leave their bodies.

The participants were shown images known to induce positive or negative responses for one second before and after taking supervised naps. After taking zolpidem, participants recalled more images that had negative or highly arousing content, which also suggests that the brain may lean more strongly toward consolidation of negative memories, Mednick said.

“I was surprised by the specificity of the results, that the emotional memory improvement was specifically for the negative and high-arousal memories, and the ramifications of these results for people with anxiety disorders and PTSD,” she remarked. “These are people who already have heightened memory for negative and high-arousal memories. Sleep drugs might be improving their memories for things they don’t want to remember.”

The study, published in the Journal of Cognitive Neuroscience, has implications for people suffering from insomnia related to post traumatic stress disorder (PTSD) and other anxiety disorders, and who are also prescribed zolpidem as a sleep aid.

Currently, the U.S. Air Force uses zolpidem as one of the prescribed “no-go pills” to help flight crews calm down after using stimulants to stay awake during long missions, the researchers noted in the study.

“In light of the present results, it would be worthwhile to investigate whether the administration of benzodiazepine-like drugs may be increasing the retention of highly arousing and negative memories, which would have a countertherapeutic effect,” they wrote. “Further research on the relationship between hypnotics and emotional mood disorders would seem to be in order.”

Source: University of California, Riverside

Researchers have discovered a novel way to handle moderate to severe pain that paves the way for lower dosage painkillers.

When people try to manage chronic pain, many turn to painkilling drugs such as morphine and Vicodin. Unfortunately, the body has a natural tendency to develop a tolerance to these medications, and this often means that the patient will begin taking higher doses—increasing risks of harmful side effects and dependency.

Commonly prescribed painkillers, such as hydrocodone (the main ingredient in Vicodin) and oxycodone (Oxycontin), bind to specific molecules (opioid receptors) on nerve cells in the brain and spinal cord to prevent the feeling of pain.

“We have for the first time discovered compounds that bind to an alternative site on the nerve opioid receptors and that have significant potential to enhance the drug’s positive impact without increasing negative side effects,” said co-author John Traynor, Ph.D., professor of pharmacology at the University of Michigan Medical School.

“We are still in the very early stages of this research with a long way to go, but we believe identifying these compounds is a key step in revolutionizing the treatment of pain.

“This opens the door to developing pain relief medications that require lower doses to be effective, helping address the serious issues of tolerance and dependence that we see with conventional pain therapy.”

Conventional drug treatments for pain target the so-called orthosteric site of the opioid receptor that provides pain relief. This is a double-edged sword, however, because this site is also responsible for all of the drug’s negative side effects, including constipation and respiratory depression. Tolerance also limits chronic use of the drugs because higher doses are required to maintain the same effect.

Scientists have now identified compounds that bind to a newly discovered site on the opioid receptor — a site that fine-tunes the activity of the receptor. Not only do these compounds act at a location that hasn’t been studied as a drug target before, but they bind to the receptor in a new way to intensify the actions of morphine. 

This means that lower doses can have the same effect.

“The newly-discovered compounds bind to the same receptor as morphine but appear to act at a separate novel site on the receptor and therefore can produce different effects. What’s particularly exciting is that these compounds could potentially work with the body’s own natural painkillers to manage pain,” said Traynor.

The findings appear in Proceedings of the National Academy of Sciences.

Source:  University of Michigan Health System

New research suggests there are two distinct forms of Gulf War illness, depending on which brain regions have atrophied.

Researchers at Georgetown University Medical Center say their findings may explain why the medical community has encountered Gulf War veterans with varying symptoms and complaints.

Using brain imaging, the researchers studied the effects of physical stress on veterans and a control group.

In 18 veterans, the researchers found that pain levels increased after completion of the exercise stress tests.

fMRI (functional magnetic resonance imaging) scans in these veterans showed loss of brain matter in adjacent regions associated with pain regulation.

During cognitive tasks, this group showed an increased use of the basal ganglia — a potential compensating strategy the brain uses that is also seen in neurodegenerative disorders, such as Alzheimer’s disease, according to the study, which was published in PLOS ONE.

Following exercise, this group lost the ability to employ their basal ganglia. This finding suggests an adverse response to a physiological stressor, the study noted.

A separate group of 10 veterans had a very different response, according to lead author Rakib Rayhan, a researcher in the lab of the study’s senior investigator, James Baraniuk, MD, a professor of medicine.

In this group, the researchers found substantial increases in heart rate. These veterans also exhibited atrophy in the brain stem, which regulates heart rate.

Additionally, brain scans during a cognitive task performed before the exercise showed increased compensatory use of the cerebellum, again a trait seen in neurodegenerative disorders, the researchers reported. Like veterans in the other group, these veterans lost the ability to use this compensatory area after exercise.

“The use of other brain areas to compensate for a damaged area is seen in other disorders, such as Alzheimer’s disease, which is why we believe our data show that these veterans are suffering from central nervous system dysfunction,” Rayhan said.

He added that because such changes are similar to other neurodegenerative states, it doesn’t mean that veterans will progress to Alzheimer’s or other diseases.

Alterations in cognition, brain structure and exercise-induced symptoms found in the veterans were absent in the control group, the researchers noted.

The new findings, which the researchers said were a surprise, follow a study in Gulf War veterans published in March in PLOS ONE that reported abnormalities in the bundle of nerve fibers connecting the brain areas involved in the processing and perception of pain and fatigue.

Gulf War illness is a mysterious malady believed to have affected more than 200,000 military personnel who served in the 1990-1991 Operation Desert Shield and Desert Storm.

Although veterans were exposed to toxic chemicals, including nerve agents, pesticides and herbicides, no one has definitively linked any single exposure or underlying mechanism to the illness, the researchers report.

Symptoms of Gulf War illness include widespread pain, fatigue and headache, as well as cognitive and gastrointestinal dysfunctions.

“Our findings help explain and validate what these veterans have long said about their illness,” Rayhan said.

Source: Georgetown University Medical Center

Abstract of the human brain photo by shutterstock.

A new study has found that soccer players who frequently hit the ball with their heads have brain abnormalities resembling those found in patients with concussions.

For the study, researchers at Albert Einstein College of Medicine of Yeshiva University used advanced imaging techniques and cognitive tests that assessed memory.

“We studied soccer players because soccer is the world’s most popular sport,” said Michael Lipton, M.D., Ph.D., associate professor of radiology, psychiatry and behavioral sciences and director of Einstein’s Gruss Magnetic Resonance Research Center.

“Soccer is widely played by people of all ages and there is concern that heading the ball — a key component of the sport — might damage the brain.”

Soccer players head the ball an average of six to 12 times during games, where the balls can travel at speeds of more than 50 miles per hour. During practice, players commonly head the ball 30 or more times, according to the researcher.

While the impact from a single heading is unlikely to cause traumatic brain damage, such as laceration of nerve fibers, cumulative damage from repeated impacts “could set off a cascade of responses that leads to degeneration of brain cells over time,” noted Lipton.

To study possible brain injury from heading, the researchers used diffusion tensor imaging (DTI), an advanced MRI-based imaging technique, on 37 amateur adult soccer players.

The participants, who had a median age of 31, reported playing soccer for an average of 22 years and had played an average of 10 months over the previous year.

The researchers ranked the players based on heading frequency and then compared the DTI brain images of the most frequent headers with those of the remaining players. All participants also underwent cognitive testing.

According to the researchers, DTI “sees” the movement of water molecules within and along axons, the nerve fibers that constitute the brain’s white matter. This imaging technique allows researchers to measure the uniformity of water movement — called fractional anisotropy (FA) — throughout the brain.

Abnormally low FA within white matter indicates axon damage and has previously been associated with cognitive impairment in patients with traumatic brain injury, the researchers explained.

“The DTI findings pertaining to the most frequent headers in our study showed white-matter abnormalities similar to what we’ve seen in patients with concussion,” said Lipton.

“Soccer players who headed the ball above a threshold between 885 to 1,550 times a year had significantly lower FA in three areas of the temporal-occipital white matter.”

Lipton added that players with more than 1,800 headings a year were also more likely to demonstrate poorer memory scores.

“Our study provides compelling preliminary evidence that brain changes resembling mild traumatic brain injury are associated with frequently heading a soccer ball over many years,” he said.

“While further research is clearly needed, our findings suggest that controlling the amount of heading that people do may help prevent brain injury that frequent heading appears to cause.”

The study was published online in the journal Radiology.

Source: Albert Einstein College of Medicine of Yeshiva University 

Soccer player heading the ball photo by shutterstock.

A new study shows that middle-aged women are more likely to suffer depression from a common medical problem they find too embarrassing to talk about: urinary incontinence.

Research from The University of Adelaide found that women between the ages of 43 and 65 with incontinence were more likely to be depressed than older women.

This may be because younger women’s self esteem is hit hard by urinary incontinence, while older women tend to be more resilient and accepting of their condition, according to Jodie Avery, a graduate student with the University’s School of Population Health and School of Medicine.

“Women with both incontinence and depression scored lower in all areas of quality of life because of the impact of incontinence on their physical well-being,” she said.

“Key issues for younger women affected by incontinence are family, sexual relationships and sport and leisure activities. The most common difficulties women express about their incontinence are things like: ‘I can’t go to the gym’, ‘I can’t go for walks’, or ‘I can’t go dancing’. These are real issues for women who are still in the prime of their lives.”

Urinary incontinence affects approximately 35 percent of the female population, according to the researcher. The main cause in women is pregnancy, with the number of children they have increasing their chances of becoming incontinent, she explained.

“Our studies show that 20 percent of the incontinent population has depression,” Avery said, noting that this is something that those who suffer with the condition and general practitioners (GP) need to better understand.

“Sufferers of incontinence are often reluctant to get help, but attitudes are slowly changing,” she continued. “It is very important for them to seek advice about their condition. In some cases, urinary incontinence can be curable with an operation, and this is quite literally a life-changing operation for many women.”

Doctors need to be aware that incontinence is often linked with depression, she added, noting that the depression “needs to be treated” to increase the women’s quality of life.

“Ultimately, we hope that our research helps to raise awareness in the community about both the mental and physical issues associated with incontinence,” she said. “We know it’s embarrassing, but if you discuss it with your GP, your life really can change.”

Source: The University of Adelaide

Woman looking upset photo by shutterstock.

Whether it’s an attempt to increase recycling rates, reduce energy consumption or cut carbon emissions, conventional wisdom says the best way to get people to do the right thing is to make it worth their while with financial incentives.

But a new study shows that there may be an easier — and cheaper — way: by boosting people’s reputations through the use of peer pressure.

Using a California blackout prevention program as an experimental test bed, a team of researchers found that while financial incentives increased participation slightly, making participation in the program observable to neighbors through the use of signup sheets posted in apartment buildings produced a threefold increase in participation.

“We wanted to see how observability compares to a cash incentive for getting people to act to benefit the common good. The answer is that observability is really dramatically better,” said David Rand, formerly a post-doctoral fellow at Harvard University’s Program for Evolutionary Dynamics (PED), who is now a professor at Yale University.

Using a cash incentive of $25, the utility company saw participation increase from about three percent to four percent. When researchers made people’s participation observable, participation jumped from three to nine percent. To get the same result using a cash incentive, the company may have had to offer every person as much as $175, said Erez Yoeli, a researcher at the Federal Trade Commission.

Observability proved to be the key factor in the results because it puts people’s reputation at stake, encouraging those who might not otherwise sign up to do so, according to the researchers.

“When people know it’s a cooperative effort, they feel peer pressure to take part,” Rand explained. “They think, ‘If I don’t do this, I’m going to look like a jerk.’ But if it’s not observable, then there’s no problem with not participating.”

“In fact, we think this is one reason why the Prius, for instance, is such a different-looking car,” added Moshe Hoffman, a visiting researcher at PED. “The designers at Toyota seem to have intuitively had this idea, designing a car that didn’t look like any other car so your neighbors can tell you’re driving a hybrid.”

“You can also see this phenomenon when you go to vote, and you get an ‘I voted’ sticker,” he continued. “Or when you go to give blood and you get a pin you can put on your backpack.”

To demonstrate the effect of observability in a real world setting, the researchers turned to a large-scale California blackout prevention program. Residents were asked for permission to install a monitoring device on their air-conditioning systems. If power demand spiked, the device would automatically adjust the air-conditioning temperature to reduce electricity demand and not overload the power grid.

Researchers randomly offered people one of two ways to sign up for the program.

In the first, people received a mailer that described the program, and were encouraged to sign up in their apartment building using a unique identification number. In the second, people received a similar mailer and identification number, but also had to write their name and apartment number when they signed up.

“The idea was that in one case, it’s anonymous, and in the other, it’s observable — everyone can see who has and hasn’t signed up,” Rand said. “When participation is observable, people worry about their reputation, and wanting to seem cooperative drives them to sign up.”

To support the explanation for the increased sign ups when participation was observable, the researchers point to three pieces of evidence: First, tests showed that the effect was greater in large apartment buildings — where more people were likely to see the sign-up sheets — than in row houses, which have less common space.

Second, tests showed that the effect was more pronounced among people who own their apartments than among renters.

“People who own their apartments are real, permanent members of their community,” Rand said. “They are more likely to care about what other people in the community think of them. If you are a renter, by comparison, you may not even know any of your neighbors.”

Finally, tests showed observability only increased participation when the program was portrayed as a community-wide benefit, the researchers noted.

“We showed that signing up only matters when others can see it, and particularly when people you care about can see it. But we also wanted to show that it matters whether people think you are being cooperative or not,” Rand said. “If you think about the way reputation works, you can get a bad reputation for being selfish, but things that don’t involve a cooperative element — like signing up for a promotion offered by your utility that has no effect on others — aren’t going to affect your reputation.”

Ultimately, the study suggests that similar strategies could be relatively cheaply and easily employed to boost participation in a host of programs to improve community-wide efforts, the researchers suggest.

“This finding is very policy-relevant, because we’re talking about changing real-world behaviors that are economically significant,” Rand said. “The moral here is that these type of reputation concerns deserve a prominent place in the toolkit used by policy makers to encourage people to do things that benefit the public good. We think that observability and reputation concerns are powerful tools that are being under-utilized.”

Their study was published in the Proceedings of the National Academy of Sciences.

Source: Harvard University

Baylor University researchers have discovered young adults who consider themselves “spiritual but not religious” are more likely to commit crimes.

Individuals were especially prone to committing property crime, and to a lesser extent, violent ones.

Comparisons were made among those that identified as either “religious and spiritual” or “religious but not spiritual,” according to the researchers.

Researchers discovered that when a young adult calls themselves “spiritual but not religious,” they appear to be reflecting more of an antisocial characteristic than a religious connotation.

The sociological study, published in the journal Criminology, showed that those who say they are “neither spiritual nor religious” are less likely to commit property crimes than the “spiritual but not religious” individuals.

But no difference was found between the two groups when it came to violent crimes.

“The notion of being spiritual but not associated with any organized religion has become increasingly popular, and our question is how that is different from being religious, whether you call yourself ‘spiritual’ or not,” said study leader, Sung Joon Jang, Ph.D.

Jang is lead author of the study, “Is Being ‘Spiritual’ Enough Without Being Religious? A Study of Violent and Property Crimes Among Emerging Adults.”

Until the 20th century, the terms “religious” and “spiritual” were treated as interchangeable. Previous research indicated that people who say they are religious show lower levels of crime and deviance, which refers to norm-violating behavior.

For the study, researchers analyzed data from a sample of 14,322 individuals from the National Longitudinal Study of Adolescent Health. They ranged in age from 18 to 28, with an average age of 21.8.

In a confidential survey, participants were asked how often they had committed crimes in the previous 12 months — including violent crimes such as physical fights or armed robbery — while property crimes included vandalism, theft and burglary.

Past research shows that people who report themselves as spiritual make up about 10 percent of the general population, Jang said.

In their study, the Baylor researchers hypothesized that those who are spiritual but not religious would be less conventional than the religious group, but could be either more or less conventional than the “neither” group.

“We were thinking that religious people would have an institutional and communal attachment and investment, while the spiritual people would have more of an independent identity,” Franzen said.

Theories for why religious people are less likely to commit crime are that they fear “supernatural sanctions” as well as criminal punishment and feel shame about deviance; are bonded to conventional society; exercise high self-control in part because of parents who also are likely to be religious; and associate with peers who reinforce their behavior and beliefs.

Researchers discovered that people who are spiritual but not religious tend to have lower self-control than those who are religious.

They also are more likely to experience such strains as criminal victimization and such negative emotions as depression and anxiety. They also are more likely to have peers who use and abuse alcohol, Franzen said. Those factors are predictors of criminal behavior.

“It’s a challenge in terms of research to know what that actually means to be spiritual, because they self-identify,” he said. “But they are different in some way, as our study shows.”

In their research, sociologists included four categories based on how the young adults reported themselves. Those categories and percentages were:

• Spiritual but not religious: 11.5 percent
• Religious but not spiritual: 6.8 percent
• Both spiritual and religious: 37.9 percent
• Neither spiritual nor religious: 43.8 percent

Source: Baylor University

Hands holding a cross photo by shutterstock.

Researchers have made a connection between postmenopausal women who use antidepressant medication and suffer from depression, a large waist circumference, and inflammation with an increased risk of diabetes and cardiovascular disease.

In the study, published in the American Journal of Public Health, University of Massachusetts Medical School researchers investigated whether elevated depressive symptoms and antidepressant use are associated with biomarkers for glucose dysregulation and inflammation, BMI, and waist circumference.

The three main findings indicate that both elevated depressive symptoms and antidepressant use are each significantly associated with higher BMI and waist circumference.

Elevated depressive symptoms are associated with increased levels of insulin and insulin resistance. Antidepressant use is associated with higher leves of C-reactive protein (CRP), a marker of inflammation which increases the risk of type-2 diabetes and cardiovascular disease.

“It may be prudent to monitor post-menopausal women who have elevated depression symptoms or are taking antidepressant medication to prevent diabetes and cardiovascular disease,” said Yunsheng Ma, PhD, MD, MPH, lead researcher.

Postmenopausal women were recruited into the study from 1993 to 1998, and data for this analysis were collected at regular intervals through 2005. Using data from 1,953 women who completed all relevant assessments, the study found that elevated depressive symptoms were discovered to be significantly associated with increased insulin levels and measures of insulin resistance.

Researchers found that throughout the entire 7.6 years, women enrolled in the study with depressive symptoms (or taking antidepressants) had a higher BMI and waist measurements than those without depressive symptoms, with the strongest association for waist circumference.

Analysis of data from 2,242 women showed that both elevated depressive symptoms and antidepressant use were associated with higher CRP levels.

“Identifying these markers in women is important for diabetes prevention because they can be monitored for possible action before progression to full-blown diabetes,” said Ma.

Few studies have examined the association of BMI, waist circumference, and biomarkers of glucose dysregulation and inflammation with depression, antidepressant medication use, or both.

The current study included a large, racially and ethnically diverse sample of post-menopausal women.

Because the analysis was epidemiological, it could not determine a causal relationship, so further study is needed to confirm the results through clinical trials.

Source: University of Massachusetts Medical School

Experts say a new study on the root cause of suicide will provide valuable insights to advance suicide prevention, improve treatments, and reduce the likelihood of further attempts.

Researchers from the University of British Columbia investigated why people attempt suicide. The findings were used to develop the first scientifically tested measure for evaluating the motivations for suicide.

Published in the official journal of the American Association of Suicidology, the work gives doctors and researchers important new resources.

“Knowing why someone attempted suicide is crucial — it tells us how to best help them recover,” says Prof. David Klonsky, UBC Department of Psychology.

“This new tool will help us to move beyond the current ‘one-size-fits-all’ approach to suicide prevention, which is essential. Different motivations require different treatments and interventions.”

The study, based on 120 participants who recently attempted suicide, suggests many motivations believed to play important roles in suicide are relatively uncommon.

For example, suicide attempts were rarely the result of impulsivity, a cry for help, or an effort to solve a financial or practical problem.

Of all motivations for suicide the two found to be universal in all participants were hopelessness and overwhelming emotional pain.

Researchers also discovered that suicide attempts influenced by social factors — such as efforts to elicit help or influence others – generally exhibited a less pronounced intent to die, and were carried out with a greater chance of rescue.

In contrast, suicide attempts motivated by internal factors — such as hopelessness and unbearable pain — were performed with the greatest desire to die.

“It may be surprising to some, but focusing on motivations is a new approach in the field of suicide research — and urgently needed,” says Klonsky.

“Until now, the focus has been largely on the types of people attempting suicide — their demographics, their genetics — without actually exploring the motivations. Ours is the first work to do this in a systematic way.”

Source: University of British Columbia

A new study gives hope that a brain-imaging technique will improve diagnoses for the millions of people with movement disorders such as Parkinson’s disease.

Researchers from the University of Florida believe a diffusion tensor imaging technique could allow clinicians to assess people earlier than is possible today, leading to improved treatment interventions and therapies for patients.

The three-year study looked at 72 patients, each with a clinically defined movement disorder diagnosis. The new technique allowed researchers to successfully separate the patients into disorder groups with a high degree of accuracy.

The research will be published in the journal Movement Disorders.

“The purpose of this study is to identify markers in the brain that differentiate movement disorders which have clinical symptoms that overlap, making [the disorders] difficult to distinguish,” said David Vaillancourt, associate professor and the study’s principal investigator.

“No other imaging, cerebrospinal fluid or blood marker has been this successful at differentiating these disorders,” he said. “The results are very promising.”

Movement disorders such as Parkinson’s disease, essential tremor, multiple system atrophy and progressive supranuclear palsy exhibit similar symptoms in the early stages, which can make it challenging to assign a specific diagnosis.

Vaillancourt said that often the original diagnosis changes as the disease progresses.

Diffusion tensor imaging, known as DTI, is a non-invasive method that examines the diffusion of water molecules within the brain. It can identify key areas that have been affected as a result of damage to gray matter and white matter in the brain.

Vaillancourt and his team measured areas of the basal ganglia and cerebellum in individuals, and used a statistical approach to predict group classification.

By asking different questions within the data and comparing different groups to one another, they were able to show distinct separation among disorders.

“Our goal was to use these measures to accurately predict the original disease classification,” Vaillancourt said, “the idea being that if a new patient came in with an unknown diagnosis, you might be able to apply this algorithm to that individual.”

He compared the process to a cholesterol test.

“If you have high cholesterol, it raises your chances of developing heart disease in the future,” he said.

“There are tests like those that give a probability or likelihood scenario of a particular disease group. We’re going a step further and trying to utilize information to predict the classification of specific tremor and Parkinsonian diseases.”

Source: University of Florida

New research on mice suggests that many commonly prescribed drugs are capable of reducing the onset and progression of Alzheimer’s disease.

Led by Giulio Maria Pasinetti, M.D., Ph.D., researchers at The Mount Sinai Medical Center used a computer algorithm to screen 1,600 commercially available medications to assess their impact on the brain accumulation of beta-amyloid.

The study, published online in the journal PLoS One, researchers found that currently available medications prescribed for conditions such as hypertension, depression, and insomnia were found to either to block or to enhance the accumulation of beta-amyloid, the component of amyloid plaques.

Beta-amyloid is a protein that abnormally accumulates in the brain of Alzheimer’s disease and is believed to be responsible for neurodegeneration.

“This line of investigation will soon lead to the identification of common medications that might potentially trigger conditions associated with the prevention, or conversely the onset, of Alzheimer’s disease,” said Pasinetti.

“They may be a novel reference for physicians to consider when prescribing the most appropriate drug, particularly in subjects at high risk for Alzheimer’s disease.”

For the study, Pasinetti and his colleagues administered these drugs in mice that were genetically engineered to develop the hallmark amyloid plaques associated with Alzheimer’s disease.

After six months of treatment with blood pressure medicines, amyloid plaques and neurodegeneration were significantly reduced in the mice.

Carvedilol is one medicine that shows clinical promise – the drug is now under clinical investigation in Alzheimer ‘s disease with the intent to slow down memory deterioration.

“In recent years, amyloid plaques have become one of the main focal points in the search to understand and to treat Alzheimer’s disease,” said Pasinetti. “Thus, identifying novel drug treatments that prevent harmful beta-amyloid generation will help in the development of treatments for Alzheimer’s disease.

“For example, one very exciting finding of our study is that Carvedilol, already approved for treatment of hypertension, may immediately become a promising drug for the treatment of Alzheimer’s as well.”

Several limitations accompany the research, with the authors noting that studies must be immediately verified in human-safety studies.

Pasinetti hopes these findings will lead to multiple clinical trials in the future to identify preventive drugs, which will need to be prescribed at tolerable dosages.

“If we can repurpose drugs currently used for different indications, such as lowering blood pressure, this could have dramatic implications for this population,” said Pasinetti.

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine