Archive for the ‘Weill Medical College’ Category

Protein_CACNA1C_PDB_2be6
Structure of the CACNA1C gene product, a calcium channel named Cav1.2, which is one of 4 genes that has now been found to be genetically held in common amongst schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disoder. Groundbreaking work on the role of this protein on anxiety and other forms of behavior related to mental illness has previously been established in the Rajadhyaksha laboratory at Weill Cornell Medical Center.
http://weill.cornell.edu/research/arajadhyaksha/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3481072/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192195/
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077109/

From the New York Times:
The psychiatric illnesses seem very different — schizophrenia, bipolar disorder, autism, major depression and attention deficit hyperactivity disorder. Yet they share several genetic glitches that can nudge the brain along a path to mental illness, researchers report. Which disease, if any, develops is thought to depend on other genetic or environmental factors.

Their study, published online Wednesday in the Lancet, was based on an examination of genetic data from more than 60,000 people worldwide. Its authors say it is the largest genetic study yet of psychiatric disorders. The findings strengthen an emerging view of mental illness that aims to make diagnoses based on the genetic aberrations underlying diseases instead of on the disease symptoms.

Two of the aberrations discovered in the new study were in genes used in a major signaling system in the brain, giving clues to processes that might go awry and suggestions of how to treat the diseases.

“What we identified here is probably just the tip of an iceberg,” said Dr. Jordan Smoller, lead author of the paper and a professor of psychiatry at Harvard Medical School and Massachusetts General Hospital. “As these studies grow we expect to find additional genes that might overlap.”

The new study does not mean that the genetics of psychiatric disorders are simple. Researchers say there seem to be hundreds of genes involved and the gene variations discovered in the new study confer only a small risk of psychiatric disease.

Steven McCarroll, director of genetics for the Stanley Center for Psychiatric Research at the Broad Institute of Harvard and M.I.T., said it was significant that the researchers had found common genetic factors that pointed to a specific signaling system.

“It is very important that these were not just random hits on the dartboard of the genome,” said Dr. McCarroll, who was not involved in the new study.

The work began in 2007 when a large group of researchers began investigating genetic data generated by studies in 19 countries and including 33,332 people with psychiatric illnesses and 27,888 people free of the illnesses for comparison. The researchers studied scans of people’s DNA, looking for variations in any of several million places along the long stretch of genetic material containing three billion DNA letters. The question: Did people with psychiatric illnesses tend to have a distinctive DNA pattern in any of those locations?

Researchers had already seen some clues of overlapping genetic effects in identical twins. One twin might have schizophrenia while the other had bipolar disorder. About six years ago, around the time the new study began, researchers had examined the genes of a few rare families in which psychiatric disorders seemed especially prevalent. They found a few unusual disruptions of chromosomes that were linked to psychiatric illnesses. But what surprised them was that while one person with the aberration might get one disorder, a relative with the same mutation got a different one.

Jonathan Sebat, chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at the University of California, San Diego, and one of the discoverers of this effect, said that work on these rare genetic aberrations had opened his eyes. “Two different diagnoses can have the same genetic risk factor,” he said.

In fact, the new paper reports, distinguishing psychiatric diseases by their symptoms has long been difficult. Autism, for example, was once called childhood schizophrenia. It was not until the 1970s that autism was distinguished as a separate disorder.

But Dr. Sebat, who did not work on the new study, said that until now it was not clear whether the rare families he and others had studied were an exception or whether they were pointing to a rule about multiple disorders arising from a single genetic glitch.

“No one had systematically looked at the common variations,” in DNA, he said. “We didn’t know if this was particularly true for rare mutations or if it would be true for all genetic risk.” The new study, he said, “shows all genetic risk is of this nature.”

The new study found four DNA regions that conferred a small risk of psychiatric disorders. For two of them, it is not clear what genes are involved or what they do, Dr. Smoller said. The other two, though, involve genes that are part of calcium channels, which are used when neurons send signals in the brain.

“The calcium channel findings suggest that perhaps — and this is a big if — treatments to affect calcium channel functioning might have effects across a range of disorders,” Dr. Smoller said.

There are drugs on the market that block calcium channels — they are used to treat high blood pressure — and researchers had already postulated that they might be useful for bipolar disorder even before the current findings.

One investigator, Dr. Roy Perlis of Massachusetts General Hospital, just completed a small study of a calcium channel blocker in 10 people with bipolar disorder and is about to expand it to a large randomized clinical trial. He also wants to study the drug in people with schizophrenia, in light of the new findings. He cautions, though, that people should not rush out to take a calcium channel blocker on their own.

“We need to be sure it is safe and we need to be sure it works,” Dr. Perlis said.

http://www.nytimes.com/2013/03/01/health/study-finds-genetic-risk-factors-shared-by-5-psychiatric-disorders.html?hp&_r=1&

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For the first time, researchers have used a specialized camera to measure pupillary changes in people watching erotic videos, the changes in pupil dilation revealing where the participant is located on the heterosexual-homosexual spectrum. The researchers at Cornell University who developed the technique say it provides an accurate method of gauging the precise sexual orientation of a subject. The work is detailed in the journal PLoS ONE.

Previously, researchers trying to assess sexual orientation simply asked people about their sexuality or used intrusive physiological measures, such as assessing their genital arousal.

“We wanted to find an alternative measure that would be an automatic indication of sexual orientation, but without being as invasive as previous measures. Pupillary responses are exactly that,” says lead researcher Gerulf Rieger. “With this new technology we are able to explore sexual orientation of people who would never participate in a study on genital arousal, such as people from traditional cultures. This will give us a much better understanding how sexuality is expressed across the planet.”

Experimenting with the technique, the researchers found heterosexual men showed strong pupillary responses to sexual videos of women, and little to men. Heterosexual women, however, showed pupillary responses to both sexes. This result confirms previous research suggesting that women have a very different type of sexuality than men.

Interestingly, the new study sheds new light on the long-standing debate on male bisexuality. Previous notions were that most bisexual men do not base their sexual identity on their physiological sexual arousal but on romantic and identity issues. Contrary to this claim, bisexual men in the new study showed substantial pupil dilations to sexual videos of both men and women.

“We can now finally argue that a flexible sexual desire is not simply restricted to women – some men have it, too, and it is reflected in their pupils,” said co-researcher Ritch C. Savin-Williams. “In fact, not even a division into ‘straight,’ ‘bi,’ and ‘gay’ tells the full story. Men who identity as ‘mostly straight’ really exist both in their identity and their pupil response; they are more aroused to males than straight men, but much less so than both bisexual and gay men.”

Thanks to Dr. A.R. for bringing this to the attention of the It’s Interesting community.

 

Researchers report they have developed in mice what they believe might one day become a breakthrough for humans: a retinal prosthesis that could restore near-normal sight to those who have lost their vision.

That would be a welcome development for the roughly 25 million people worldwide who are blind because of retinal disease, most notably macular degeneration.

The notion of using prosthetics to combat blindness is not new, with prior efforts involving retinal electrode implantation and/or gene therapy restoring a limited ability to pick out spots and rough edges of light.

The current effort takes matters to a new level. The scientists fashioned a prosthetic system packed with computer chips that replicate the “neural impulse codes” the eye uses to transmit light signals to the brain.

“This is a unique approach that hasn’t really been explored before, and we’re really very excited about it,” said study author Sheila Nirenberg, a professor and computational neuroscientist in the department of physiology and biophysics at Weill Medical College of Cornell University in New York City. “I’ve actually been working on this for 10 years. And suddenly, after a lot of work, I knew immediately that I could make a prosthetic that would work, by making one that could take in images and process them into a code that the brain can understand.”

Nirenberg and her co-author Chethan Pandarinath (a former Cornell graduate student now conducting postdoctoral research at Stanford University School of Medicine) report their work in the Aug. 14 issue of Proceedings of the National Academy of Sciences. Their efforts were funded by the U.S. National Institutes of Health and Cornell University’s Institute for Computational Biomedicine.

The study authors explained that retinal diseases destroy the light-catching photoreceptor cells on the retina’s surface. Without those, the eye cannot convert light into neural signals that can be sent to the brain.

However, most of these patients retain the use of their retina’s “output cells” — called ganglion cells — whose job it is to actually send these impulses to the brain. The goal, therefore, would be to jumpstart these ganglion cells by using a light-catching device that could produce critical neural signaling.

But past efforts to implant electrodes directly into the eye have only achieved a small degree of ganglion stimulation, and alternate strategies using gene therapy to insert light-sensitive proteins directly into the retina have also fallen short, the researchers said.

Nirenberg theorized that stimulation alone wasn’t enough if the neural signals weren’t exact replicas of those the brain receives from a healthy retina.

“So, what we did is figure out this code, the right set of mathematical equations,” Nirenberg explained. And by incorporating the code right into their prosthetic device’s chip, she and Pandarinath generated the kind of electrical and light impulses that the brain understood.

The team also used gene therapy to hypersensitize the ganglion output cells and get them to deliver the visual message up the chain of command.

Behavioral tests were then conducted among blind mice given a code-outfitted retinal prosthetic and among those given a prosthetic that lacked the code in question.

The result: The code group fared dramatically better on visual tracking than the non-code group, with the former able to distinguish images nearly as well as mice with healthy retinas.

“Now we hope to move on to human trials as soon as possible,” said Nirenberg. “Of course, we have to conduct standard safety studies before we get there. And I would say that we’re looking at five to seven years before this is something that might be ready to go, in the best possible case. But we do hope to start clinical trials in the next one to two years.”

Results achieved in animal studies don’t necessarily translate to humans.

Dr. Alfred Sommer, a professor of ophthalmology at Johns Hopkins University in Baltimore and dean emeritus of Hopkins’  Bloomberg School of Public Health, urged caution about the findings.

“This could be revolutionary,” he said. “But I doubt it. It’s a very, very complicated business. And people have been working on it intensively and incrementally for the last 30 years.”

“The fact that they have done something that sounds a little bit better than the last set of results is great,” Sommer added.  “It’s terrific. But this approach is really in its infancy. And I guarantee that it will be a long time before they get to the point where they can really restore vision to people using prosthetics.”

Other advances may offer benefits in the meantime, he said. “We now have new therapies that we didn’t have even five years ago,” Sommer said. “So we may be reaching a state where the amount of people losing their sight will decline even as these new techniques for providing artificial vision improve. It may not be as sci-fi. But I think it’s infinitely more important at this stage.”

http://health.usnews.com/health-news/news/articles/2012/08/13/retinal-device-restores-sight-to-blind-mice

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.