Diabetes Gene Common In Latinos Has Ancient Roots

When it comes to the rising prevalence of Type 2 diabetes, there are many factors to blame.

Diet and exercise sit somewhere at the top of the list. But the genes that some of us inherit from Mom and Dad also help determine whether we develop the disease, and how early it crops up.

Now an international team of scientists have identified mutations in a gene that suggests an explanation for why Latinos are almost twice as likely to develop Type 2 diabetes as Caucasians and African-Americans.

But here’s the kicker: You have to go further back on the family tree than your parents to find who’s to blame for this genetic link to diabetes. Think thousands of generations ago.

Harvard geneticist and his colleagues uncovered hints that humans picked up the diabetes mutations from Neanderthals, our ancient cousins who went extinct about 30,000 years ago.

"As far as I know, this is the first time a version of a gene from Neanderthal has been connected to a modern-day disease," Altshuler tells Shots. He and his colleagues the findings Wednesday in the journal Nature.

A few years ago, geneticists at the in Germany sent shock waves through the scientific community when they the genome of a Neanderthal from a fossil. Hidden in the genetic code were patterns that matched those in human DNA. And the data strongly suggested that humans were more than just friendly neighbors with Neanderthal.

"Now it’s well accepted that humans interbred with Neanderthals," Altshuler says. On average most of us carry about 2 percent of Neanderthal DNA in our genome. So it’s not surprising, he says, that 2 percent of our traits would be inherited from the ancient primates.

The new data don’t mean that Neanderthals had diabetes, Altshuler is quick to point out. “It just happens that this disease sequence came from them,” he says.

To identify genes that contribute to Latinos’ high rate of Type 2 diabetes, Altshuler and his team analyzed DNA from over 8,000 Mexicans and other Latinos.

The team found many genes already known to be involved with diabetes, such as one related to insulin production. But a new one also popped up in the analysis: a gene that’s likely involved in fat metabolism.

Mutations in this gene increase a person’s risk of getting Type 2 diabetes by about a 20 percent, Altshuler and the team found. If the person has two copies of the mutations, one from each parent, the risk rises by about 40 percent.

So for Mexican Americans, their for Type 2 diabetes goes from about 13 percent to 19 percent if they inherit two copies of the mutations. For other Americans, the risk gets boosted to about 11 percent from 8 percent.

"This is a genetic factor that has a modest affect on the risk of getting the disease. Not everybody that has it will have the disease," Altshuler says. "But the genes are very common in Latinos and Asians."

About half of Latinos carry the disease mutations, while 20 percent of Asians have it. On the other hand, only 2 percent of European Americans carry the mutations.

So the new genetic data help to explain a big chunk — perhaps almost a quarter — of the difference in Type 2 diabetes prevalence in Latinos versus European Americans.

"The findings are important because they give us a new biological clue about a gene involved in diabetes, which could lead to more treatments," Altshuler says. "The Neanderthal connection is interesting, but it’s not the essence of the work."

Take note students: Mice that ‘cram’ for exams remember less

It’s been more than 100 years since German psychologist Hermann Ebbinghaus determined that learning interspersed with rest created longer-lasting memories than so-called cramming, or learning without rest intervals.

Researchers find ECT can rid the mind of selected memory

A team of researchers working in the Netherlands has found that partial selective memory deletion can be achieved using Electroconvulsive Therapy (ECT). In their paper published in the journal Nature Neuroscience, the team describes a memory experiment they conducted with the assistance of severely depressed people who had already consented to undergoing ECT and found that such treatment could be used to at least partially erase memories of a specified event.

Scientists have known since 1968 (thanks to experiments conducted by psychologist Donald Lewis) that applying a shock to the brain of a rat can cause it to forget something unpleasant it had remembered. Subsequent experiments have found that memories can be blunted using repetitive type therapies or by injecting drugs such as propranolol into the brain. The one element all such findings have in common is that they must be applied during a time when a person is attempting to recall a certain event. Scientists hope that such research may lead to new ways to treat PTSD and other memory related mental ailments. In this new effort the researchers explored the idea of erasing specific memories using ECT.

Currently, people with severe depression who don’t respond to any other type of treatment are offered ECT as a last resort. It has a remarkably good success rate (approximately 86 percent rate of remission) but causes some degree of memory loss. In the Netherlands study, the team enlisted the assistance of 39 such patients who had already agreed to undergo ECT. Instead of receiving just the standard treatment, however, the volunteers were asked to watch two slide shows (along with narration) —both of which contained unsettling content. A week later the participants were divided into three groups—two to get the shock treatment and one to serve as a control group—all were asked to remember and describe one of the traumatic events described in the slide shows. Afterwards, one of the groups was given ECT and then the next day was asked to recount both stores. The other non-control group was given ECT and then were asked right afterwards to recount the unpleasant stories. The control group was asked to try to recount both stories as well.

In comparing the results between the groups, the researchers found that the first group that had been quizzed a day after receiving ECT had difficulty recalling the first story, which they had recounted prior to ECT, but remembered most of second. The second group that received ECT were able to recall both stories equally well, and the third—the control group—were able to remember both stories better than either of the groups that had received ECT.

The experiment suggests that it is possible to selectively erase short term memory in a controlled environment. Much more research will have to be conducted to determine if it would work in real world situations.

Researchers identify gene that influences the ability to remember faces

New findings suggest the oxytocin receptor, a gene known to influence mother-infant bonding and pair bonding in monogamous species, also plays a special role in the ability to remember faces. This research has important implications for disorders in which social information processing is disrupted, including autism spectrum disorder. In addition, the finding may lead to new strategies for improving social cognition in several psychiatric disorders.

A team of researchers from Yerkes National Primate Research Center at Emory University in Atlanta, the University College London in the United Kingdom and University of Tampere in Finland made the discovery, which will be published in an online Early Edition of Proceedings of the National Academy of Sciences.

According to author Larry Young, PhD, of Yerkes, the Department of Psychiatry in Emory’s School of Medicine and Emory’s Center for Translational Social Neuroscience (CTSN), this is the first study to demonstrate that variation in the oxytocin receptor gene influences face recognition skills. He and co-author David Skuse point out the implication that oxytocin plays an important role in promoting our ability to recognize one another, yet about one-third of the population possesses only the genetic variant that negatively impacts that ability. They say this finding may help explain why a few people remember almost everyone they have met while others have difficulty recognizing members of their own family.

Skuse is with the Institute of Child Health, University College London, and the Great Ormond Street Hospital for Children, NHS Foundation Trust, London.

Young, Skuse and their research team studied 198 families with a single autistic child because these families were known to show a wide range of variability in facial recognition skills; two-thirds of the families were from the United Kingdom, and the remainder from Finland.

The Emory researchers previously found the oxytocin receptor is essential for olfactory-based social recognition in rodents, like mice and voles, and wondered whether the same gene could also be involved in human face recognition. They examined the influence of subtle differences in oxytocin receptor gene structure on face memory competence in the parents, non-autistic siblings and autistic child, and discovered a single change in the DNA of the oxytocin receptor had a big impact on face memory skills in the families. According to Young, this finding implies that oxytocin likely plays an important role more generally in social information processing, which is disrupted in disorders such as autism.

Additionally, this study is remarkable for its evolutionary aspect. Rodents use odors for social recognition while humans use visual facial cues. This suggests an ancient conservation in genetic and neural architectures involved in social information processing that transcends the sensory modalities used from mouse to man.

Skuse credits Young’s previous research that found mice with a mutated oxytocin receptor failed to recognize mice they previously encountered. “This led us to pursue more information about facial recognition and the implications for disorders in which social information processing is disrupted.” Young adds the team will continue working together to pursue strategies for improving social cognition in psychiatric disorders based on the current findings.

A novel look at how stories may change the brain

Many people can recall reading at least one cherished story that they say changed their life. Now researchers at Emory University have detected what may be biological traces related to this feeling: Actual changes in the brain that linger, at least for a few days, after reading a novel.

Their findings, that reading a novel may cause changes in resting-state connectivity of the brain that persist, were published by the journal Brain Connectivity.

“Stories shape our lives and in some cases help define a person,” says neuroscientist Gregory Berns, lead author of the study and the director of Emory’s Center for Neuropolicy. “We want to understand how stories get into your brain, and what they do to it.”

His co-authors included Kristina Blaine and Brandon Pye from the Center for Neuropolicy, and Michael Prietula, professor of information systems and operations management at Emory’s Goizueta Business School.

Neurobiological research using functional magnetic resonance imaging (fMRI) has begun to identify brain networks associated with reading stories. Most previous studies have focused on the cognitive processes involved in short stories, while subjects are actually reading them as they are in the fMRI scanner.

The Emory study focused on the lingering neural effects of reading a narrative. Twenty-one Emory undergraduates participated in the experiment, which was conducted over 19 consecutive days.

All of the study subjects read the same novel, “Pompeii,” a 2003 thriller by Robert Harris that is based on the real-life eruption of Mount Vesuvius in ancient Italy. “The story follows a protagonist, who is outside the city of Pompeii and notices steam and strange things happening around the volcano,” Berns says. “He tries to get back to Pompeii in time to save the woman he loves. Meanwhile, the volcano continues to bubble and nobody in the city recognizes the signs.”

The researchers chose the book due to its page-turning plot. “It depicts true events in a fictional and dramatic way,” Berns says. “It was important to us that the book had a strong narrative line.”

For the first five days, the participants came in each morning for a base-line fMRI scan of their brains in a resting state. Then they were given nine sections of the novel, about 30 pages each, over a nine-day period. They were asked to read the assigned section in the evening, and come in the following morning. After taking a quiz to ensure they had finished the assigned reading, the participants underwent an fMRI scan of their brain in a non-reading, resting state. After completing all nine sections of the novel, the participants returned for five more mornings to undergo additional scans in a resting state.

The results showed heightened connectivity in the left temporal cortex, an area of the brain associated with receptivity for language, on the mornings following the reading assignments. “Even though the participants were not actually reading the novel while they were in the scanner, they retained this heightened connectivity,” Berns says. “We call that a ‘shadow activity,’ almost like a muscle memory.”

Heightened connectivity was also seen in the central sulcus of the brain, the primary sensory motor region of the brain. Neurons of this region have been associated with making representations of sensation for the body, a phenomenon known as grounded cognition. Just thinking about running, for instance, can activate the neurons associated with the physical act of running.

“The neural changes that we found associated with physical sensation and movement systems suggest that reading a novel can transport you into the body of the protagonist,” Berns says. “We already knew that good stories can put you in someone else’s shoes in a figurative sense. Now we’re seeing that something may also be happening biologically.”

The neural changes were not just immediate reactions, Berns says, since they persisted the morning after the readings, and for the five days after the participants completed the novel.

“It remains an open question how long these neural changes might last,” Berns says. “But the fact that we’re detecting them over a few days for a randomly assigned novel suggests that your favorite novels could certainly have a bigger and longer-lasting effect on the biology of your brain.”

Study Shows Where Alzheimer’s Starts and How It Spreads

Using high-resolution functional MRI (fMRI) imaging in patients with Alzheimer’s disease and in mouse models of the disease, Columbia University Medical Center (CUMC) researchers have clarified three fundamental issues about Alzheimer’s: where it starts, why it starts there, and how it spreads. In addition to advancing understanding of Alzheimer’s, the findings could improve early detection of the disease, when drugs may be most effective. The study was published today in the online edition of the journal Nature Neuroscience.

“It has been known for years that Alzheimer’s starts in a brain region known as the entorhinal cortex,” said co-senior author Scott A. Small, MD, Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer’s Disease Research Center. “But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected.”

The study also shows that, over time, Alzheimer’s spreads from the LEC directly to other areas of the cerebral cortex, in particular, the parietal cortex, a brain region involved in various functions, including spatial orientation and navigation. The researchers suspect that Alzheimer’s spreads “functionally,” that is, by compromising the function of neurons in the LEC, which then compromises the integrity of neurons in adjoining areas.

A third major finding of the study is that LEC dysfunction occurs when changes in tau and amyloid precursor protein (APP) co-exist. “The LEC is especially vulnerable to Alzheimer’s because it normally accumulates tau, which sensitizes the LEC to the accumulation of APP. Together, these two proteins damage neurons in the LEC, setting the stage for Alzheimer’s,” said co-senior author Karen E. Duff, PhD, professor of pathology and cell biology (in psychiatry and in the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain) at CUMC and at the New York State Psychiatric Institute.

In the study, the researchers used a high-resolution variant of fMRI to map metabolic defects in the brains of 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project (WHICAP). All of the adults were free of dementia at the time of enrollment.

“Dr. Richard Mayeux’s WHICAP study enables us to follow a large group of healthy elderly individuals, some of whom have gone on to develop Alzheimer’s disease,” said Dr. Small. “This study has given us a unique opportunity to image and characterize patients with Alzheimer’s in its earliest, preclinical stage.”

The 96 adults were followed for an average of 3.5 years, at which time 12 individuals were found to have progressed to mild Alzheimer’s disease. An analysis of the baseline fMRI images of those 12 individuals found significant decreases in cerebral blood volume (CBV) — a measure of metabolic activity — in the LEC compared with that of the 84 adults who were free of dementia.

A second part of the study addressed the role of tau and APP in LEC dysfunction. While previous studies have suggested that entorhinal cortex dysfunction is associated with both tau and APP abnormalities, it was not known how these proteins interact to drive this dysfunction, particularly in preclinical Alzheimer’s.

To answer this question, explained first author Usman Khan, an MD-PhD student based in Dr. Small’s lab, the team created three mouse models, one with elevated levels of tau in the LEC, one with elevated levels of APP, and one with elevated levels of both proteins. The researchers found that the LEC dysfunction occurred only in the mice with both tau and APP.

The study has implications for both research and treatment. “Now that we’ve pinpointed where Alzheimer’s starts, and shown that those changes are observable using fMRI, we may be able to detect Alzheimer’s at its earliest preclinical stage, when the disease might be more treatable and before it spreads to other brain regions,” said Dr. Small. In addition, say the researchers, the new imaging method could be used to assess the efficacy of promising Alzheimer’s drugs during the disease’s early stages.

Why Do Our Brains Sometime Mess Up Simple Calculations?

Childhood bullying shown to increase likelihood of psychotic experiences in later life

New research has shown that being exposed to bullying during childhood will lead to an increased risk of psychotic experiences in adulthood, regardless of whether they are victims or perpetrators.

The study, published today in Psychological Medicine, assessed a cohort of UK children (ALSPAC) from birth to fully understand the extent of bullying on psychosis in later life – with some groups showing to be almost five times more likely to suffer from episodes at the age of 18.

The analysis, led by researchers from the University of Warwick, in association with colleagues at the University of Bristol, shows that victims, perpetrators and those who are both bullies and victims (bully-victims), are at an increased risk of developing psychotic experiences.

Even when controlling for external factors such as family factors or pre-existing behaviour problems, the study found that not only those children who were bullied over a number of years (chronic victims), but also the bullies themselves in primary school were up to four and a half times more likely to have suffered from psychotic experiences by the age of 18. Equally concerning is that those children who only experienced bullying for brief periods (e.g. at 8 or 10 years of age) were at increased risk for psychotic experiences.

The term ‘psychotic experiences’ covers a range of experiences, from hearing voices and seeing things that are not there to paranoia. These experiences, if persistent, are highly distressing and disruptive to everyday life. They are diagnosed by GPs or psychiatrists as “psychotic disorders” such as schizophrenia. Exact diagnosis is difficult and requires careful assessment as in this study.

Professor Dieter Wolke of the University of Warwick explained, “We want to eradicate the myth that bullying at a young age could be viewed as a harmless rite of passage that everyone goes through – it casts a long shadow over a person’s life and can have serious consequences for mental health”

“These numbers show exactly how much childhood bullying can impact on psychosis in adult life. It  strengthens on the evidence base that reducing bullying in childhood could substantially reduce mental health problems. The benefit to society would be huge, but of course, the greatest benefit would be to the individual.”

When controlling for external factors such as family factors or pre-existing behaviour problems, the study found that not only those children who were bullied over a number of years (chronic victims), but also the bullies themselves in primary school were up to four and a half times more likely to have suffered from psychotic experiences by the age of 18. Equally concerning is that those children who only experienced bullying for brief periods (e.g. at 8 or 10 years of age) were at increased risk for psychotic experiences.

Wolke’s team have previously looked at the impact of bullying on psychotic symptoms in 12 year olds, and there have been a range of short term studies that confirm the relation between being a victim of bullying and psychotic symptoms. This study, however, is the first to report the long term impact of being involved in bullying during childhood - whether victim, bully or bully-victim – on psychotic experiences in late adolescence or adulthood.

Professor Wolke added, “The results show that interventions against bullying should start early, in primary school, to prevent long term serious effects on children’s mental health. This clearly isn’t something that can wait until secondary school to be resolved; the damage may already have been done.”