Neuroscience

TAU research says genetics can reveal your geographic ancestral origin

While your DNA is unique, it also tells the tale of your family line. It carries the genetic history of your ancestors down through the generations. Now, says a Tel Aviv University researcher, it’s also possible to use it as a map to your family’s past.

Prof. Eran Halperin of TAU’s Blavatnik School of Computer Science and Department of Molecular Microbiology and Biotechnology, along with a group of researchers from University of California, Los Angeles, are giving new meaning to the term “genetic mapping.” Using a probabilistic model of genetic traits for every coordinate on the globe, the researchers have developed a method for determining more precisely the geographical location of a person’s ancestral origins.

The new method is able to pinpoint more specific locations for an individual’s ancestors, for example placing an individual’s father in Paris and mother in Barcelona. Previous methods would “split the difference” and place this origin inaccurately at a site between those two cities, such as Lyon.

Published in the journal Nature Genetics, this method has the potential to reveal the ancestry, origins, and migration patterns of many different human and animal populations. It could also be a new model for learning about the genome.

Points of origin

There are points in the human genome called SNPs that are manifested differently in each individual, explains Prof. Halperin. These points mutated sometime in the past and the mutation was then passed to a large part of the population in a particular geographic region. The probability of a person possessing these mutations today varies depending on the geographical location of those early ancestors.

"We wanted to ask, for example, about the probability of having the genetic mutation ‘A’ in a particular position on the genome based on geographical coordinates," he says. When you look at many of these positions together in a bigger picture, it’s possible to group populations with the same mutation by point of origin.

To test their method, Prof. Halperin and his fellow researchers studied DNA samples from 1,157 people from across Europe. Using a probabilistic mathematical algorithm based on mutations in the genome, they were able to accurately determine their ancestral point or points of origin using only DNA data and the new mathematical model, unravelling genetic information to ascertain two separate points on the map for the mother and father. The researchers hope to extend this model to identify the origins of grandparents, great-grandparents, and so on.

The new method could provide information that has applications in population genetic studies — to study a disease that impacts a particular group, for example. Researchers can track changes in different genomic traits across a map, such as the tendency for southern Europeans to have a mutation in a gene that causes lactose intolerance, a mutation missing from that gene in northern Europeans.

A closer look at migration

The researchers believe that their model could have also relevance for the animal kingdom, tracking the movement of animal populations. “In principle, you could figure out where the animals have migrated from, and as a result learn about habitat changes due to historical climate change or other factors,” says Prof. Halperin.

Source: Tel Aviv University

The vast majority of people with addiction have suffered significant previous trauma, and many people who struggle with addiction suffer from post-traumatic stress disorder (PTSD) simultaneously. But the treatment of these patients has posed a conundrum: experts have believed that PTSD treatment should not begin until the addicted person achieves lasting abstinence, because of the risk that PTSD treatment may trigger relapse, yet addicted people with untreated PTSD are rarely able to abstain for long.

Now, a new study suggests that there may be no need to wait. Researchers found that using exposure therapy — the gold-standard treatment for PTSD, which involves exposure to memories and reminders of patients’ past trauma — can successfully reduce symptoms of PTSD, even when people with addiction continue to use drugs. And, although exposure therapy requires patients to face some of their worst fears, it does not increase their drug use or prompt them to drop out of treatment more than ordinary addiction therapy, the study found.

“The exciting thing in my view is that [the study] supports people with drug and alcohol problems having access to other forms of psychological interventions, rather than being fobbed off and told to sort out their alcohol or drug problem first,” says Michael Farrell, director of the National Drug and Alcohol Research Center at the University of New South Wales in Sydney, Australia, where the research was conducted.

The finding could potentially help the majority of those who suffer from addiction or PTSD: one-half to two-thirds of people with addictions suffer from PTSD concurrently, or have in the past, and about the same proportion of people with PTSD also have substance use disorders.

The new study involved 103 people with both conditions. Most were addicted to multiple drugs, primarily heroin, marijuana and alcohol. More than two-thirds of the participants had been traumatized during childhood, with almost half reporting a history of sexual abuse.

Researchers randomly assigned half of the participants to simply continue the addiction treatment of their choice, whether it was detoxification leading to abstinence, residential treatment or maintenance on medications like methadone and buprenorphine (Suboxone, Subutex).

The other half received their usual treatment, plus exposure therapy for PTSD, which consisted of 13 one-on-one sessions with a clinical psychologist, meeting about once a week for 90 minutes at a time. The therapy began with education about PTSD and addiction, including instruction on cognitive techniques to address distressing thoughts that could lead to relapse. Then, when patients were ready, they were exposed to reminders of their traumatic experience, which they usually avoided out of fear of triggering flashbacks and intense anxiety. Exposure therapy works to reduce or eliminate these PTSD symptoms by breaking patients’ cycle of fear and avoidance.

Indeed, participants in the exposure treatment “demonstrated significantly greater reductions in PTSD symptom severity compared with participants randomized to receive usual treatment alone,” the authors wrote. However, drug use in the exposure therapy group didn’t decline any more than it did in the usual treatment group. Both groups saw a reduction in the severity of addiction but in each case, the majority of participants continued to use drugs. Notably, however, drug use did not increase due to exposure therapy.

“These findings challenge the widely held view that patients need to be abstinent before any trauma work, let alone prolonged exposure therapy, is commenced,” the authors wrote. “[F]indings from the present study demonstrate that abstinence is not required.”

Importantly, however, while the findings showed that carefully delivered exposure therapy can help, they did not support the practice of forcing addicts to confront trauma in settings where they do not feel safe or in control. Exposure therapy is calibrated so that patients do not become overwhelmed or feel helpless; in contrast, coercion by the therapist can re-traumatize patients and worsen both PTSD and addiction symptoms, previous studies have shown.

In other words, it’s not clear that treating people with addiction by compelling them to recall or re-enact traumatic experiences — a commonly used tactic in group settings — actually helps. What the current study shows is that when trained clinical psychologists carefully deliver exposure therapy in a tightly monitored trial, they can help ease PTSD symptoms in people with addiction.

By Maia Szalavitz | August 15, 2012

Source: TIME

In 2000, a team of neuroscientists put an unusual idea to the test. Stress and depression, they knew, made neurons wither and die – particularly in the hippocampus, a brain area crucial for memory. So the researchers put some stressed-out rats on an antidepressant regimen, hoping the mood boost might protect some of those hippocampal neurons. When they checked in a few weeks later, though, the team found that rats’ hippocampuses hadn’t just survived intact; they’d grown whole new neurons – bundles of them. But that’s only the beginning of our tale.

Neural stem cells (green) in the hippocampus huddle around a neuron (purple), listening for stray signals.

By the time 2009 rolled around, another team of researchers was suggesting that human brains might get a similar hippocampal boost from antidepressants. The press announced the discovery with headlines like, “Antidepressants Grow New Brain Cells” – although not everyone agreed with that conclusion. Still, whether the principle applied to humans or not, a far more basic question was begging to be answered: How, exactly, does a brain tell new cells to form?

“Well, through synapses, of course,” you might answer – and that’d be a very reasonable guess. After all, synapses are how most neurons talk to each other: electrochemical information is “squirted” from a tiny tendril of one neuron into the tip of a tendril on another; and cells throughout most of the brain share essentially this same mechanism for passing signals along: The signals coming out of Neuron A’s synapses keep bugging Neuron B by stimulating its synapses, until finally Neuron B caves under peer pressure and bugs Neuron C with the signal… and so on.

There are, however, two significant exceptions to this system.

The first exception was discovered a few years ago, as scientists got more and more curious about the role of neuroglia (also known as just “glia”), synapse-less cells that many had assumed were just there to serve as structural support for neurons. A 2008 study showed that glia help control cerebral blood flow, and research in 2010 demonstrated that some glia – cells known as astrocytes – actively listen for and respond to certain neurotransmitter messages. These so-called “quiet cells” are actually pretty loud talkers once you learn to tune in to their chatter.

The second exception to the synapse rule is even more mysterious – in large part because it’s a brand-new discovery: As the journal Nature reports, a team led by Hongjun Song at the Johns Hopkins University School of Medicine have found that neural stem cells “listen in” on the stray chemical signals that leak from synapses.

You can imagine neural stem cells as being sort of “neural embryos” – depending on the surrounding conditions, they can develop into neurons or into glia. And here’s what’s strange about the way these cells communicate: They respond not to any single synaptic signal, but to the overall chemical “vibe” of their environment – to chronic feelings of stress, for instance. By way of response, they may morph into neurons or glia – or even tell the brain to crank out some all-new cells.

Neural stem cells seem to be particularly interested in the chemical GABA (gamma-aminobutyric acid) – a neurotransmitter that’s known to be involved in inhibiting signals from other neurons. When scientists artificially block these stem cells’ GABA receptors from receiving messages, the cells “wake up” and start replicating – but when those GABA signals are allowed to reach the receptors, the stem cells stay dormant.

“In this case,” Song explains, “GABA communication keeps the brain stem cells in reserve, so if we don’t need them, we don’t use them up.”

In short, leaky synapses aren’t wasteful – as a matter of fact, they’re essential to the brain’s self-sculpting abilities. And this implies something pretty interesting: It isn’t just individual signals that convey neural information, but whole experiences. In that respect, a brain – whether it belongs to a rat or a human – is unlike any computer on earth.

By Ben Thomas | August 15, 2012

Source: Scientific American

When something goes wrong in your brain, you’d think it would be a good idea to get rid of the problem. Turns out, sometimes it’s best to keep hold of it. By preventing faulty proteins from being destroyed, researchers have delayed the symptoms of a degenerative brain disorder.

SNAP25 is one of three proteins that together make up a complex called SNARE, which plays a vital role in allowing neurons to communicate with each other. In order to work properly, all the proteins must be folded in a specific way. CSP alpha is one of the key proteins that ensures SNAP25 is correctly folded.

Cells have a backup system to deal with any misfolded proteins – they are destroyed by a bell-shaped enzyme called a proteasome, which pulls the proteins inside itself and breaks them down.

People with a genetic mutation that affects the CSP alpha protein – and its ability to correctly fold SNAP25 – can develop a rare brain disorder called neuronal ceroid lipofuscinosis (NCL). The disorder causes significant damage to neurons – people affected gradually lose their cognitive abilities and struggle to move normally.

To find out what role proteasomes might play in NCL, Manu Sharma and his colleagues at Stanford University in California blocked the enzyme in mice that were bred to lack CSP alpha. “We weren’t sure what would happen,” says Sharma. Either the misfolded SNAP25 would accumulate and harm the cells, or some of the misfolded proteins may work well enough to retain some of their function.

It appears it was the latter. Mice bred to lack CSP alpha suffer the same physical and cognitive problems as humans, and tend to survive for about 65 to 80 days, rather than the normal 670 days. But mice injected with a drug that blocked protease lived, on average, an extra 15 days. “Fifteen days might not sound like much, but as a percentage it’s quite significant,” says Sharma. What’s more, treated mice were able to stave off measurable movement and cognitive symptoms for an extra 10 days.

The finding goes against the idea that neurodegenerative disorders should be treated by clearing away misfolded proteins, rather than trying to rescue their function. “People normally think that protease isn’t working hard enough,” says Nico Dantuma at the Karolinska Institute in Stockholm, Sweden, who was not involved in the study.

But whether or not the drugs are likely to work in other neurodegenerative disorders involving aggregations of misfolded proteins, such as Alzheimer’s and Parkinson’s disease, is up for debate. “I don’t think their results prove that clearing misfolded proteins is not a useful therapeutic,” says Ana Maria Cuervo at Albert Einstein College of Medicine in New York. Other studies that increase the degrading of misfolded proteins have been shown to improve symptoms in other neurodegenerative diseases, she says.

"There are two sides of the coin," says Dantuma. "You might rescue functioning proteins from being degraded… but it’s too early to extrapolate these results to Alzheimer’s and Parkinson’s disease."

In the meantime, drugs that block proteasome are already used to treat cancer, so Sharma hopes they can soon be trialled in people with NCL.

Source: NewScientist

Depression takes a substantial toll on brain health. Brain imaging and post-mortem studies provide evidence that the wealth of connections in the brain are reduced in individuals with depression, with the result of impaired functional connections between key brain centers involved in mood regulation. Glial cells are one of the cell types that appear to be particularly reduced when analyzing post-mortem brain tissue from people who had depression. Glial cells support the growth and function of nerve cells and their connections.

Over the past several years, it has become increasingly recognized that antidepressants produce positive effects on brain structure that complement their effects on symptoms of depression. These structural effects of antidepressants appear to depend, in large part, on their ability to raise the levels of growth factors in the brain.

In a new study, Elsayed and colleagues from the Yale University School of Medicine report their findings on a relatively novel growth factor named fibroblast growth factor-2 or FGF2. They found that FGF2 can increase the number of glial cells and block the decrease caused by chronic stress exposure by promoting the generation of new glial cells.

Senior author Dr. Ronald Duman said, “Our study uncovers a new pathway that can be targeted for treating depression. Our research shows that we can increase the production and maintenance of glial cells that are important for supporting neurons, providing an enriched environment for proper neuronal function.”

To study whether FGF2 can treat depression, the researchers used rodent models where animals are subjected to various natural stressors, which can trigger behaviors that are similar to those expressed by depressed humans, such as despair and loss of pleasure. FGF2 infusions restored the deficit in glial cell number caused by chronic stress. An underlying molecular mechanism was also identified when the data showed that antidepressants increase glial generation and function via increasing FGF2 signaling.

"Although more research is warranted to explore the contribution of glial cells to the antidepressant effects of FGF2, the results of this study present a fundamental new mechanism that merits attention in the quest to find more efficacious and faster-acting antidepressant drugs," concluded Duman.

"The deeper that science digs into the biology underlying antidepressant action, the more complex it becomes. Yet understanding this complexity increases the power of the science, suggesting reasons for the limitations of antidepressant treatment and pointing to novel approaches to the treatment of depression," commented Dr. John Krystal, Editor of Biological Psychiatry and Chairman of the Department of Psychiatry at the Yale University School of Medicine.

Source: Bio-Medicine

ScienceDaily (Aug. 15, 2012) — Long-term methadone treatment can cause changes in the brain, according to recent studies from the Norwegian Institute of Public Health. The results show that treatment may affect the nerve cells in the brain. The studies follow on from previous studies where methadone was seen to affect cognitive functioning, such as learning and memory.

Since it is difficult to perform controlled studies of methadone patients and unethical to attempt in healthy volunteers, rats were used in the studies. Previous research has shown that methadone can affect cognitive functioning in both humans and experimental animals.

Sharp decrease in key signaling molecule

Rats were given a daily dose of methadone for three weeks. Once treatment was completed, brain areas which are central for learning and memory were removed and examined for possible neurobiological changes or damage.

In one study, on the day after the last exposure to methadone, there was a significant reduction (around 70 per cent) in the level of a signal molecule which is important in learning and memory, in both the hippocampus and in the frontal area of the brain. This reduction supports findings from a previous study (Andersen et al., 2011) where impaired attention in rats was found at the same time. At this time, methadone is no longer present in the brain. This indicates that methadone can lead to cellular changes that affect cognitive functioning after the drug has left the body, which may be cause for concern.

No effect on cell generation

The second study, a joint project with Southwestern University in Texas, investigated whether methadone affects the formation of nerve cells in the hippocampus. Previous research has shown that new nerve cells are generated in the hippocampus in both adult humans and rats, and that this formation is probably important for learning and memory. Furthermore, it has been shown that other opiates such as morphine and heroin can inhibit this formation. It was therefore reasonable to assume that methadone, which is also an opiate, would have the same effect.

However, the researchers did not find any change in the generation of new nerve cells after long-term methadone treatment. If the same is true in humans, this is probably more positive for methadone patients than continuing with heroin. However, the researchers do not know what effect methadone has on nerve cells that have previously been exposed to heroin.

Large gaps in knowledge

Since the mid-1960s, methadone has been used to treat heroin addiction. This is considered to be a successful treatment but, despite extensive and prolonged use, little is known about possible side effects. There are large knowledge gaps in this field.

Our studies show that prolonged methadone treatment can affect the nerve cells, and thus behaviour, but the results are not always as expected. Many more pre-clinical and clinical studies are needed to understand methadone’s effect on the brain, how this can result in altered cognitive function, and, if so, how long these changes last. Knowledge of this is important — both for the individual methadone patient and the outcome of treatment.

Source: Science Daily

ScienceDaily (Aug. 15, 2012) — Acute stress alters the methylation of the DNA and thus the activity of certain genes. This is reported by researchers at the Ruhr-Universität Bochum together with colleagues from Basel, Trier and London for the first time in the journal Translational Psychiatry. “The results provide evidence how stress could be related to a higher risk of mental or physical illness,” says Prof. Dr. Gunther Meinlschmidt from the Clinic of Psychosomatic Medicine and Psychotherapy at the LWL University Hospital of the RUB. The team looked at gene segments which are relevant to biological stress regulation.

In stressful social situations, the methylation patterns (bright spheres) of the DNA change. (Credit: Illustration: Christoph Unternährer and Christian Horisberger)

Epigenetics — the “second code” — regulates gene activity

Our genetic material, the DNA, provides the construction manual for the proteins that our bodies need. Which proteins a cell produces depends on the cell type and the environment. So-termed epigenetic information determines which genes are read, acting quasi as a biological switch. An example of such a switch is provided by methyl (CH₃) groups that attach to specific sections of the DNA and can remain there for a long time — even when the cell divides. Previous studies have shown that stressful experiences and psychological trauma in early life are associated with long-term altered DNA methylation. Whether the DNA methylation also changes after acute psychosocial stress, was, however, previously unknown.

Two genes tested

To clarify this issue, the research group examined two genes in particular: the gene for the oxytocin receptor, i.e. the docking site for the neurotransmitter oxytocin, which has become known as the “trust hormone” or “anti-stress hormone”; and the gene for the nerve growth factor Brain-Derived Neurotrophic Factor (BDNF), which is mainly responsible for the development and cross-linking of brain cells. The researchers tested 76 people who had to participate in a fictitious job interview and solve arithmetic problems under observation — a proven means for inducing acute stress in an experiment. For the analysis of the DNA methylation, they took blood samples from the subjects before the test as well as ten and ninety minutes afterwards.

DNA methylation changes under acute psychosocial stress

Stress had no effect on the methylation of the BDNF gene. In a section of the oxytocin receptor gene, however, methylation already increased within the first ten minutes of the stressful situation. This suggests that the cells formed less oxytocin receptors. Ninety minutes after the stress test, the methylation dropped below the original level before the test. This suggests that the receptor production was excessively stimulated.

Possible link between stress and disease

Stress increases the risk of physical or mental illness. The stress-related costs in Germany alone amount to many billions of Euros every year. In recent years, there have been indications that epigenetic processes are involved in the development of various chronic diseases such as cancer or depression. “Epigenetic changes may well be an important link between stress and chronic diseases” says Prof. Meinlschmidt, Head of the Research Department of Psychobiology, Psychosomatics and Psychotherapy at the LWL University Hospital. “We hope to identify more complex epigenetic stress patterns in future and thus to be able to determine the associated risk of disease. This could provide information on new approaches to treatment and prevention.” The work originated within the framework of an interdisciplinary research consortium with the University of Trier, the University of Basel and King’s College London. The German Research Foundation and the Swiss National Science Foundation supported the study.

Source: Science Daily

The first genome-wide searches for the genes responsible for Tourette syndrome and obsessive-compulsive disorder have uncovered a few clues to the underpinnings of both disorders.

Tourette syndrome is a neurological disorder characterized by muscle and vocal tics such as eye blinking, throat clearing and uttering taboo words or phrases. Tourette’s often co-occurs with obsessive-compulsive disorder (OCD), a mental illness marked by repetitive behaviors and anxiety-producing intrusive thoughts.

Neither Tourette syndrome nor OCD are simple enough to be traced to a single gene, but two new studies detailed today (Aug. 14) in the journal Molecular Psychiatry find several locations on the human chromosome that may contribute to the conditions.

A DNA molecule.
CREDIT: Giovanni Cancemi | Shutterstock

"Both disorders clearly have a complex underlying genetic architecture, and these two studies lay the foundation for understanding the underlying genetic etiology of Tourette syndrome and OCD," said Jeremiah Scharf, a neurologist at Massachusetts General Hospital in Boston, who worked on both projects. 

Genetics of Tourette Syndrome

In the Tourette syndrome study, Scharf and his colleagues compared the genomes of more than 1,200 people with the disorder with the genomes of nearly 5,000 healthy individuals. They conducted what’s called a genome-wide association study, scanning hundreds of thousands of genetic variants from across the genomes to see if any were more common in the people with the disorder.

They found that no single genetic signal was significantly different between the two genomes, meaning that the researchers could not rule out random chance as the reason for any given difference. But among the top genetic variations, the researchers found an unusually high number that influence levels of gene expression in the frontal lobe of the brain — a region important in both Tourette syndrome and OCD, Scharf said.

One intriguing gene that varied the most between Tourette- and non-Tourette genomes was called COL27A1, a gene that encodes a collagen protein found in cartilage. The same gene is also active in the cerebellum, a brain region important for motor control during development. More research will be necessary to find what link, if any, COL27A1 has to Tourette syndrome, Scharf said.

The architecture of OCD

In a separate study, the scientists carried out the same analysis on healthy genomes as well as about 1,500 people with obsessive-compulsive disorder. Again, no one gene rose to the top as a definitive OCD gene, but the results revealed a good candidate near a gene called BTBD3, which is involved in multiple cellular functions. BTBD3 is very active in the brain during childhood and adolescent development, when OCD often first appears. It’s also related to a gene called BTBD9, which has been linked to Tourette syndrome in the past.

This first genome-wide pass is bound to turn up some false positives, Scharf said, so researchers will now need to home in on the intriguing genes in larger samples of people. They are also merging the two studies to look for genetic linkages that might explain why Tourette syndrome and OCD so frequently co-occur.

"The important thing this study does is that it really brings Tourette syndrome and OCD into the company of a number of other psychiatric diseases, which people have studied using genome-wide association," Scharf said, citing autism, schizophrenia and bipolar disorder as examples. “Now that we have these data for Tourette syndrome and OCD, we can work with investigators who are studying those other diseases to try to see what we can learn about what variants are shared between different neurodevelopment disorders.”

Source: Live Science

August 13, 2012

Researchers at Mount Sinai School of Medicine may have discovered why certain drugs to treat schizophrenia are ineffective in some patients. Published online in Nature Neuroscience, the research will pave the way for a new class of drugs to help treat this devastating mental illness, which impacts one percent of the world’s population, 30 percent of whom do not respond to currently available treatments.

A team of researchers at Mount Sinai School of Medicine set out to discover what epigenetic factors, or external factors that influence gene expression, are involved in this treatment-resistance to atypical antipsychotic drugs, the standard of care for schizophrenia. They discovered that, over time, an enzyme in the brains of schizophrenic patients analyzed at autopsy begins to compensate for the prolonged chemical changes caused by antipsychotics, resulting in reduced efficacy of the drugs.

"These results are groundbreaking because they show that drug resistance may be caused by the very medications prescribed to treat schizophrenia, when administered chronically," said Javier Gonzalez-Maeso, PhD, Assistant Professor of Psychiatry and Neurology at Mount Sinai School of Medicine and lead investigator on the study.

They found that an enzyme called HDAC2 was highly expressed in the brain of mice chronically treated with antipsychotic drugs, resulting in lower expression of the receptor called mGlu2, and a recurrence of psychotic symptoms. A similar finding was observed in the postmortem brains of schizophrenic patients. The research team administered a chemical called suberoylanilide hydroxamic acid (SAHA), which inhibits the entire family of HDACs. They found that this treatment prevented the detrimental effect of the antipsychotic called clozapine on mGlu2 expression, and also improved the therapeutic effects of atypical antipsychotics in mouse models.

Previous research conducted by the team showed that chronic treatment with the antipsychotic clozapine causes repression of mGlu2 expression in the frontal cortex of mice, a brain area key to cognition and perception. The researchers hypothesized that this effect of clozapine on mGlu2 may play a crucial role in restraining the therapeutic effects of antipsychotic drugs.

"We had previously found that chronic antipsychotic drug administration causes biochemical changes in the brain that may limit the therapeutic effects of these drugs,"said Dr. Gonzalez-Maeso. "We wanted to identify the molecular mechanism responsible for this biochemical change, and explore it as a new target for new drugs that enhance the therapeutic efficacy of antipsychotic drugs."

Mitsumasa Kurita, PhD, a postdoctoral fellow at Mount Sinai and the lead author of the study, said, “We found that atypical antipsychotic drugs trigger an increase of HDAC2 in frontal cortex of individuals with schizophrenia, which then reduces the presence of mGlu2, and thereby limits the efficacy of these drugs,” said

Dr. Gonzalez-Maeso’s team is now developing compounds that specifically inhibit HDAC2 as adjunctive treatments to antipsychotics. The study was funded by the National Institutes of Health.

Source: The Mount Sinai Hospital