Researchers at the University of Toronto say a sleep disorder that causes people to act out their dreams is the best current predictor of brain diseases like Parkinson’s and many other forms of dementia.
"Rapid-eye-movement sleep behaviour disorder (RBD) is not just a precursor but also a critical warning sign of neurodegeneration that can lead to brain disease," says associate professor and lead author Dr. John Peever. In fact, as many as 80 to 90 per cent of people with RBD will develop a brain disease."
As the name suggests, the disturbance occurs during the rapid-eye-movement (REM) stage of sleep and causes people to act out their dreams, often resulting in injury to themselves and/or bed partner. In healthy brains, muscles are temporarily paralyzed during sleep to prevent this from happening.
"It’s important for clinicians to recognize RBD as a potential indication of brain disease in order to diagnose patients at an earlier stage," says Peever. "This is important because drugs that reduce neurodegeneration could be used in RBD patients to prevent (or protect) them from developing more severe degenerative disorders."
His research examines the idea that neurodegeneration might first affect areas of the brain that control sleep before attacking brain areas that cause more common brain diseases like Alzheimer’s.
Peever says he hopes the results of his study lead to earlier and more effective treatment of neurodegenerative diseases.
Researchers discover novel function of protein linked to Alzheimer's disease
A research team led by the National Neuroscience Institute (NNI) has uncovered a novel function of the Amyloid Precursor Protein (APP), one of the main pathogenic culprits of Alzheimer’s disease. This discovery may help researchers understand how the protein goes awry in the brains of Alzheimer’s disease patients, and potentially paves the way for the development of innovative therapeutics to improve the brain function of dementia patients.
The findings were published in the prestigious scientific research journal Nature Communications last month. The study, which is led by Dr Zeng Li and her team from NNI, involved investigators from Duke-NUS Graduate Medical School and the Agency for Science and Technology (A*STAR).
Alzheimer’s disease is the most common form of dementia, which is set to rise significantly from the current 28,000 cases to 80,000 cases in 2030 among Singaporeans aged 60 and above. With a rapidly aging population, the burden of the disease will be profound affecting not just the person afflicted, but also the caregiver and family. While the exact cause of Alzheimer’s disease remains unknown, one of its pathological hallmarks is clear – the clumping of APP product in the brain when the protein is abnormally processed.
Finding out more about APP can help researchers gain a better understanding of the disease, and potentially identify biomarkers and therapeutic targets for it. However up till this point, little was known about the APP’s primary function in the brain.
Low Tolerance for Pain? The Reason May Be In Your Genes
Researchers may have identified key genes linked to why some people have a higher tolerance for pain than others, according to a study released today that will be presented at the American Academy of Neurology’s 66th Annual Meeting in Philadelphia, April 26 to May 3, 2014.
“Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, with Proove Biosciences and a member of the American Academy of Neurology. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”
Researchers evaluated 2,721 people diagnosed with chronic pain for certain genes. Participants were taking prescription opioid pain medications. The genes involved were COMT, DRD2, DRD1 and OPRK1. The participants also rated their perception of pain on a scale from zero to 10. People who rated their pain as zero were not included in the study. Low pain perception was defined as a score of one, two or three; moderate pain perception was a score of four, five or six; and high pain perception was a score of seven, eight, nine or 10.
Nine percent of the participants had low pain perception, 46 percent had moderate pain perception and 45 percent had high pain perception.
The researchers found that the DRD1 gene variant was 33 percent more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were 25 percent and 19 percent more often found than in those with a high pain perception. The DRD2 variant was 25 percent more common among those with a high pain perception compared to people with moderate pain.
“Chronic pain can affect every other part of life,” said Onojjighofia. “Finding genes that may be play a role in pain perception could provide a target for developing new therapies and help physicians better understand their patients’ perceptions of pain.”
In Old Age, Lack of Emotion and Interest May Signal Your Brain Is Shrinking
Older people who have apathy but not depression may have smaller brain volumes than those without apathy, according to a new study published in the April 16, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology. Apathy is a lack of interest or emotion.
“Just as signs of memory loss may signal brain changes related to brain disease, apathy may indicate underlying changes,” said Lenore J. Launer, PhD, with the National Institute on Aging at the National Institutes of Health (NIH) in Bethesda, MD, and a member of the American Academy of Neurology. “Apathy symptoms are common in older people without dementia. And the fact that participants in our study had apathy without depression should turn our attention to how apathy alone could indicate brain disease.”
Launer’s team used brain volume as a measure of accelerated brain aging. Brain volume losses occur during normal aging, but in this study, larger amounts of brain volume loss could indicate brain diseases.
For the study, 4,354 people without dementia and with an average age of 76 underwent an MRI scan. They were also asked questions that measure apathy symptoms, which include lack of interest, lack of emotion, dropping activities and interests, preferring to stay at home and having a lack of energy.
The study found that people with two or more apathy symptoms had 1.4 percent smaller gray matter volume and 1.6 percent less white matter volume compared to those who had less than two symptoms of apathy. Excluding people with depression symptoms did not change the results.
Gray matter is where learning takes place and memories are stored in the brain. White matter acts as the communication cables that connect different parts of the brain.
“If these findings are confirmed, identifying people with apathy earlier may be one way to target an at-risk group,” Launer said.
Researchers Find Boosting Depression-Causing Mechanisms in the Brain Increases Resilience, Surprisingly
A new study points to a conceptually novel therapeutic strategy for treating depression. Instead of dampening neuron firing found with stress-induced depression, researchers demonstrated for the first time that further activating these neurons opens a new avenue to mimic and promote natural resilience. The findings were so surprising that the research team thinks it may lead to novel targets for naturally acting antidepressants. Results from the study are published online April 18 in the journal Science.
Researchers from the Icahn School of Medicine at Mount Sinai point out that in mice resilient to social defeat stress (a source of constant stress brought about by losing a dispute or from a hostile interaction), their cation channel currents, which pass positive ions in dopamine neurons, are paradoxically elevated to a much greater extent than those of depressed mice and control mice. This led researchers to experimentally increase the current of cation channels with drugs in susceptible mice, those prone to depression, to see whether it would enhance coping and resilience. They found that such boosting of cation channels in dopamine neurons caused the mice to tolerate the increased stress without succumbing to depression-related symptoms, and unexpectedly the hyperactivity of the dopamine neurons was normalized.
Allyson K. Friedman, PhD, Postdoctoral Fellow in Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai, and the study’s lead author said: “To achieve resiliency when under social stress, the brain must perform a complex balancing act in which negative stress-related changes in the brain actively trigger positive changes. But that can only happen once the negative changes reach a tipping point.”
The research team used optogenetics, a combination of laser optics and gene virus transfer, to control firing activity of the dopamine neurons. When light activation or the drug lamotrigine is given to these neurons, it drives the current and neuron firing higher. But at a certain point, it triggers compensatory mechanisms, normalizes neuron firing, and achieves a kind of homeostatic (or balanced) resilience.
"To our surprise, we found that resilient mice, instead of avoiding deleterious changes in the brain, experience further deleterious changes in response to stress, and use them beneficially," said Ming-Hu Han, PhD, at Icahn School of Medicine at Mount Sinai, who leads the study team as senior author.
Drs. Friedman and Han see this counterintuitive finding as stimulating research in a conceptually novel antidepressant strategy. If a drug could enhance coping and resilience by pushing depressed (or susceptible) individuals past the tipping point, it potentially might have fewer side effects, and work as a more naturally acting antidepressant.
Eric Nestler, MD, PhD, at the Icahn School of Medicine at Mount Sinai praised the study. “In this elegant study, Drs. Friedman and Han and their colleagues reveal a highly novel mechanism that controls an individual’s susceptibility or resilience to chronic social stress. The discoveries have important implications for the development of new treatments for depression and other stress-related disorders.”
New Study Suggests a Better Way to Deal with Bad Memories
What’s one of your worst memories? How did it make you feel? According to psychologists, remembering the emotions felt during a negative personal experience, such as how sad you were or how embarrassed you felt, can lead to emotional distress, especially when you can’t stop thinking about it.
When these negative memories creep up, thinking about the context of the memories, rather than how you felt, is a relatively easy and effective way to alleviate the negative effects of these memories, a new study suggests.
Researchers at the Beckman Institute at the University of Illinois, led by psychology professor Florin Dolcos of the Cognitive Neuroscience Group, studied the behavioral and neural mechanisms of focusing away from emotion during recollection of personal emotional memories, and found that thinking about the contextual elements of the memories significantly reduced their emotional impact.
“Sometimes we dwell on how sad, embarrassed, or hurt we felt during an event, and that makes us feel worse and worse. This is what happens in clinical depression—ruminating on the negative aspects of a memory,” Dolcos said. “But we found that instead of thinking about your emotions during a negative memory, looking away from the worst emotions and thinking about the context, like a friend who was there, what the weather was like, or anything else non-emotional that was part of the memory, will rather effortlessly take your mind away from the unwanted emotions associated with that memory. Once you immerse yourself in other details, your mind will wander to something else entirely, and you won’t be focused on the negative emotions as much.”
This simple strategy, the study suggests, is a promising alternative to other emotion-regulation strategies, like suppression or reappraisal.
“Suppression is bottling up your emotions, trying to put them away in a box. This is a strategy that can be effective in the short term, but in the long run, it increases anxiety and depression,” explains Sanda Dolcos, co-author on the study and postdoctoral research associate at the Beckman Institute and in the Department of Psychology.
“Another otherwise effective emotion regulation strategy, reappraisal, or looking at the situation differently to see the glass half full, can be cognitively demanding. The strategy of focusing on non-emotional contextual details of a memory, on the other hand, is as simple as shifting the focus in the mental movie of your memories and then letting your mind wander.”
Not only does this strategy allow for effective short-term emotion regulation, but it has the possibility of lessening the severity of a negative memory with prolonged use.
In the study, participants were asked to share their most emotional negative and positive memories, such as the birth of a child, winning an award, or failing an exam, explained Sanda Dolcos. Several weeks later participants were given cues that would trigger their memories while their brains were being scanned using magnetic resonance imaging (MRI). Before each memory cue, the participants were asked to remember each event by focusing on either the emotion surrounding the event or the context. For example, if the cue triggered a memory of a close friend’s funeral, thinking about the emotional context could consist of remembering your grief during the event. If you were asked to remember contextual elements, you might instead remember what outfit you wore or what you ate that day.
“Neurologically, we wanted to know what happened in the brain when people were using this simple emotion-regulation strategy to deal with negative memories or enhance the impact of positive memories,” explained Ekaterina Denkova, first author of the report. “One thing we found is that when participants were focused on the context of the event, brain regions involved in basic emotion processing were working together with emotion control regions in order to, in the end, reduce the emotional impact of these memories.”
Using this strategy promotes healthy functioning not only by reducing the negative impact of remembering unwanted memories, but also by increasing the positive impact of cherished memories, Florin Dolcos said.
In the future, the researchers hope to determine if this strategy is effective in lessening the severity of negative memories over the long term. They also hope to work with clinically depressed or anxious participants to see if this strategy is effective in alleviating these psychiatric conditions.
The cause of neuronal death in Parkinson’s disease is still unknown, but a new study proposes that neurons may be mistaken for foreign invaders and killed by the person’s own immune system, similar to the way autoimmune diseases like type I diabetes, celiac disease, and multiple sclerosis attack the body’s cells. The study was published April 16, 2014, in Nature Communications.
(Image caption: Four images of a neuron from a human brain show that neurons produce a protein (in red) that can direct an immune attack against the neuron (green). Credit: Carolina Cebrian.)
“This is a new, and likely controversial, idea in Parkinson’s disease; but if true, it could lead to new ways to prevent neuronal death in Parkinson’s that resemble treatments for autoimmune diseases,” said the study’s senior author, David Sulzer, PhD, professor of neurobiology in the departments of psychiatry, neurology, and pharmacology at Columbia University College of Physicians & Surgeons.
The new hypothesis about Parkinson’s emerges from other findings in the study that overturn a deep-seated assumption about neurons and the immune system.
For decades, neurobiologists have thought that neurons are protected from attacks from the immune system, in part, because they do not display antigens on their cell surfaces. Most cells, if infected by virus or bacteria, will display bits of the microbe (antigens) on their outer surface. When the immune system recognizes the foreign antigens, T cells attack and kill the cells. Because scientists thought that neurons did not display antigens, they also thought that the neurons were exempt from T-cell attacks.
“That idea made sense because, except in rare circumstances, our brains cannot make new neurons to replenish ones killed by the immune system,” Dr. Sulzer says. “But, unexpectedly, we found that some types of neurons can display antigens.”
Cells display antigens with special proteins called MHCs. Using postmortem brain tissue donated to the Columbia Brain Bank by healthy donors, Dr. Sulzer and his postdoc Carolina Cebrián, PhD, first noticed—to their surprise—that MHC-1 proteins were present in two types of neurons. These two types of neurons—one of which is dopamine neurons in a brain region called the substantia nigra—degenerate during Parkinson’s disease.
To see if living neurons use MHC-1 to display antigens (and not for some other purpose), Drs. Sulzer and Cebrián conducted in vitro experiments with mouse neurons and human neurons created from embryonic stem cells. The studies showed that under certain circumstances—including conditions known to occur in Parkinson’s—the neurons use MHC-1 to display antigens. Among the different types of neurons tested, the two types affected in Parkinson’s were far more responsive than other neurons to signals that triggered antigen display.
The researchers then confirmed that T cells recognized and attacked neurons displaying specific antigens.
The results raise the possibility that Parkinson’s is partly an autoimmune disease, Dr. Sulzer says, but more research is needed to confirm the idea.
“Right now, we’ve showed that certain neurons display antigens and that T cells can recognize these antigens and kill neurons,” Dr. Sulzer says, “but we still need to determine whether this is actually happening in people. We need to show that there are certain T cells in Parkinson’s patients that can attack their neurons.”
If the immune system does kill neurons in Parkinson’s disease, Dr. Sulzer cautions that it is not the only thing going awry in the disease. “This idea may explain the final step,” he says. “We don’t know if preventing the death of neurons at this point will leave people with sick cells and no change in their symptoms, or not.”
Researchers Find Association Between SSRI Use During Pregnancy and Autism and Developmental Delays in Boys
In a study of nearly 1,000 mother-child pairs, researchers from the Bloomberg School of Public health found that prenatal exposure to selective serotonin reuptake inhibitors (SSRIs), a frequently prescribed treatment for depression, anxiety and other disorders, was associated with autism spectrum disorder (ASD) and developmental delays (DD) in boys. The study, published in the online edition of Pediatrics, analyzed data from large samples of ASD and DD cases, and population-based controls, where a uniform protocol was implemented to confirm ASD and DD diagnoses by trained clinicians using validated standardized instruments.
The study included 966 mother-child pairs from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study based at the University of California at Davis’ MIND Institute. The researchers broke the data into three groups: Those diagnosed with autism spectrum disorder (ASD), those with developmental delays (DD) and those with typical development (TD). The children ranged in ages two to five. A majority of the children were boys – 82.5% in the ASD group were boys, 65.6% in the DD group were boys and 85.6% in the TD were boys. While the study included girls, the substantially stronger effect in boys alone suggests possible gender difference in the effect of prenatal SSRI exposure.
“We found prenatal SSRI exposure was nearly 3 times as likely in boys with ASD relative to typical development, with the greatest risk when exposure took place during the first trimester,” said Li-Ching Lee, Ph.D., Sc.M., psychiatric epidemiologist in the Bloomberg School’s Department of Epidemiology. “SSRI was also elevated among boys with DD, with the strongest exposure effect in the third trimester.”
The data analysis was completed by Rebecca Harrington, Ph.D., M.P.H, in conjunction with her doctoral dissertation at the Bloomberg School. Dr. Lee was one of her advisors.
Serotonin is critical to early brain development; exposure during pregnancy to anything that influences serotonin levels can have potential effect on birth and developmental outcomes. The prevalence of ADS continues to rise. According to the Centers for Disease Control and Prevention, an estimated 1 in 68 children in the U.S. is identified with ADS, and it is almost five times more common among boys than girls. One may question whether the increased use of SSRI in recent years is a contributor to the dramatic rise of ASD prevalence.
"This study provides further evidence that in some children, prenatal exposure to SSRIs may influence their risk for developing an autism spectrum disorder,” said Irva Hertz-Picciotto, Ph.D., M.P.H., chief of the Division of Environmental and Occupational Health in the UC Davis Department of Public Health Sciences and a researcher at the UC Davis MIND Institute. “This research also highlights the challenge for women and their physicians to balance the risks versus the benefits of taking these medications, given that a mother’s underlying mental-health conditions also may pose a risk, both to herself and her child.”
Regarding treatment, the authors note that maternal depression itself carries risks for the fetus, and the benefits of using SSRI during pregnancy should be considered carefully against the potential harm. The researchers also note that large sample studies are needed to investigate the effects in girls with ASD. Limitations of the study acknowledged include the difficulty in isolating SSRI effects from those of their indications for use, lack of information on SSRI dosage precluded dose-response analyses, and the relatively small sample of DD children resulted in imprecise estimates of association, which should be viewed with caution.
Differences in brain connectivity may help explain the social impairments common in those who have autism spectrum disorders, new research suggests.
The small study compared the brains of 25 teens with an autism spectrum disorder to those of 25 typically developing teens, all aged 11 to 18. The researchers found key differences between the two groups in brain “networks” that help people to figure out what others are thinking, and to understand others’ actions and emotions.
"It is generally agreed that the way the networks are organized is not typical [in those with autism]," explained study lead researcher Inna Fishman, assistant research professor of psychology at San Diego State University.
The prevailing idea until now, she said, has been that these neurological networks are under-connected in people with autism. However, “we found they were over-connected — they talk to each other way more than expected at that age.”