Stem Cell Research Helps to Identify Origins of Schizophrenia

New University at Buffalo research demonstrates how defects in an important neurological pathway in early development may be responsible for the onset of schizophrenia later in life.

The UB findings, published in Schizophrenia Research, test the hypothesis in a new mouse model of schizophrenia that demonstrates how gestational brain changes cause behavioral problems later in life – just like the human disease.

Partial funding for the research came from New York Stem Cell Science (NYSTEM).

The genomic pathway, called the Integrative Nuclear FGFR 1 Signaling (INFS), is a central intersection point for multiple pathways of as many as 160 different genes believed to be involved in the disorder. 

“We believe this is the first model that explains schizophrenia from genes to development to brain structure and finally to behavior,” says lead author Michal Stachowiak, PhD, professor in the Department of Pathology and Anatomical Sciences in the UB School of Medicine and Biomedical Sciences. He also is director of the Stem Cell Engraftment & In Vivo Analysis Facility at the Western New York Stem Cell Culture and Analysis Center at UB.

A key challenge with the disease is that patients with schizophrenia exhibit mutations in different genes, he says.

“How is it possible to have 100 patients with schizophrenia and each one has a different genetic mutation that causes the disorder?” asks Stachowiak. “It’s possible because INFS integrates diverse neurological signals that control the development of embryonic stem cell and neural progenitor cells, and links pathways involving schizophrenia-linked genes.

“INFS functions like the conductor of an orchestra,” explains Stachowiak. “It doesn’t matter which musician is playing the wrong note, it brings down the conductor and the whole orchestra. With INFS, we propose that when there is an alteration or mutation in a single schizophrenia-linked gene, the INFS system that controls development of the whole brain becomes untuned. That’s how schizophrenia develops.”

Using embryonic stem cells, Stachowiak and colleagues at UB and other institutions found that some of the genes implicated in schizophrenia bind the FGFR1 (fibroblast growth factor receptor) protein, which in turn, has a cascading effect on the entire INFS.

The Science Behind ‘Beatboxing’

Acoustical analysis reveals the anatomy behind the fascinating array of sounds people can make.

Using the mouth, lips, tongue and voice to generate sounds that one might never expect to come from the human body is the specialty of the artists known as beatboxers. Now scientists have used scanners to peer into a beatboxer as he performed his craft to reveal the secrets of this mysterious art.

The human voice has long been used to generate percussion effects in many cultures, including North American scat singing, Celtic lilting and diddling, and Chinese kouji performances. In southern Indian classical music, konnakol is the percussive speech of the solkattu rhythmic form. In contemporary pop music, the relatively young vocal art form of beatboxing is an element of hip-hop culture.

Until now, the phonetics of these percussion effects were not examined in detail. For instance, it was unknown to what extent beatboxers produced sounds already used within human language.

To learn more about beatboxing, scientists analyzed a 27-year-old male performing in real-time using MRI. This gave researchers “an opportunity to study the sounds people produce in much greater detail than has previously been possible,” said Shrikanth Narayanan, a speech and audio engineer at the University of Southern California in Los Angeles. “The overarching goals of our work drive at larger questions related to the nature of sound production and mental processing in human communication, and a study like this is a small part of the larger puzzle.”

The investigators made 40 recordings each lasting 20-40 seconds long as the beatboxer produced all the effects in his repertoire, as individual sounds, composite beats, rapped lyrics, sung lyrics and freestyle combinations of these elements. He categorized 17 distinct percussion sounds into five instrumental classes — kick drums, rim shots, snare drums, hi-hats, and cymbals. The artist demonstrated his repertoire at several different tempos, ranging from slower at roughly 88 beats per minute, to faster at 104.

"We were astonished by the complex elegance of the vocal movements and the sounds being created in beatboxing, which in itself is an amazing artistic display," Narayanan said. "This incredible vocal instrument and its many capabilities continue to amaze us, from the intricate choreography of the ‘dance of the tongue’ to the complex aerodynamics that work together to create a rich tapestry of sounds that encode not only meaning but also a wide range of emotions."

"It is absolutely amazing that a person can make these sounds — that a person has such control over the timing of various parts of the speech apparatus," said phonetician Donna Erickson at the Showa University of Music and Sophia University, both in Japan, who did not participate in this study. "It is very exciting to see how far technology has come — that we can see these movements in real time. It gives us a much better understanding of how the various parts of our speech anatomy work."

Brain region associated with selfishness

People with damage to a specific part of the brain entrusted unexpectedly large amounts of money to complete strangers. In an investment game played in the lab, three women with damage to a small part of the brain called the basolateral amygdala handed over nearly twice as much money as healthy people.

These women didn’t expect to make a bunch of money back, an international team of researchers reports online the week of January 21 in the Proceedings of the National Academy of Sciences. Nor did they think the person they invested with was particularly trustworthy. When asked why they would invest so generously, the volunteers couldn’t provide an answer.

The results suggest that normally, the basolateral amygdala enables selfishness — putting the squeeze on generosity.

(Image credit)

New findings on mortality of individuals with schizophrenia

A new study from Lund University in Sweden shows that the average life expectancy of men and women with schizophrenia is 15 years and 12 years shorter respectively than for those who do not suffer from the disease. The study has been carried out in collaboration with Stanford University in the US.

The reasons why people with schizophrenia have a shorter life expectancy have previously been unknown, but have been much discussed in recent years. The research report that has now been published shows that individuals with schizophrenia are more likely to die of two major diseases.

The study followed over six million individuals from 2003 to 2009, of whom 8,277 had schizophrenia, by analysing the Swedish population and health registers.

The results show that people with schizophrenia had contact with the health service over twice as often as people without the condition, but they were no more likely to be diagnosed with cardiovascular disease or cancer.

“Yet we saw an opposing pattern of death from these diseases. It is clear that the health service is failing to diagnose cardiovascular disease and cancer in these patients”, says Jan Sundquist, general practitioner and professor at the Centre for Primary Health Care Research at Lund University.

Women with schizophrenia were 3.3 times more likely to die of cardiovascular disease and men 2.2 times more likely. Women with schizophrenia were 1.7 times more likely to die of cancer while men were 1.4 times more likely, compared with those without schizophrenia. Only 26.3% of the men with schizophrenia who died of cardiovascular disease had been diagnosed before their deaths, compared with 43.7% of the men who did not have schizophrenia.

“It is unacceptable that such a vulnerable group of people, who also have extensive documented contact with the health service, should die prematurely of conditions such as cardiovascular disease and cancer – diseases that should be preventable”, says Professor Sundquist. “A much greater degree of diagnostic and preventive measures could be put in place for this vulnerable group in our society.”

NuPathe’s Patch for Migraine Wins FDA Approval

Adults with migraine will soon have a new treatment option — Zecuity, a transdermal, battery-powered sumatriptan patch.

NuPathe, maker of the patch, said the FDA has approved the single-use patch to treat headache pain and nausea caused by migraine, with or without aura.

The patch is applied to the upper arm or thigh during a migraine and can deliver 6.5 mg of sumatriptan over the course of 4 hours once activated by push button.

The treatment system was approved based on the results of a phase III, placebo-controlled trial of 800 patients that showed the sumatriptan delivery method was safe and effective, the drugmaker said in a statement.

The FDA failed to approve a NuPathe application for a transdermal sumatriptan patch called Zelrix in August 2011.

In a complete response letter, the agency asked the company for additional data on Zelrix, citing concerns over the patch’s safety, chemistry, and manufacturing. The FDA’s approval of Zecuity may obviate the need for those additional studies.

The device is contraindicated in patients with heart disease, a history of heart disease or stroke, peripheral vascular disease, transient ischemic attack, blood circulation problems, uncontrolled blood pressure, basilar migraines, contraindication to sumatriptan or parts of the device, or Wolff-Parkinson-White syndrome or similar heart rhythm disturbances.

The system should not be used if taken within 24 hours of using another migraine medication or within 2 weeks of using a monoamine oxidase-A inhibitor.

Triptans, such as sumatriptan, can cause serotonin syndrome, which can be exacerbated when used with certain antidepressants.

Patients with heart disease, a family history of heart disease, stroke, high cholesterol or diabetes, have gone through menopause, who smoke, have had epilepsy or seizures, or are pregnant, nursing, or thinking about becoming a parent should consult a healthcare professional before using Zecuity.

(Image: Corbis)

AR Goggles Restore Depth Perception To People Blind in One Eye

People who’ve lost sight in one eye can still see with the other, but they lack binocular depth perception.

Some of them could benefit from a pair of augmented reality glasses being built at the University of Yamanashi in Japan, that artificially introduces a feeling of depth in a person’s healthy eye.

The group, led by Xiaoyang Mao, started out with a pair of commercially available 3D glasses, the daintily named Wrap 920AR, manufactured by Vuzix Corporation. (Vuzix is also building another AR headset called the M100 that on first sight looks like quite the competitor to to Google Glass.)

The Wrap 920AR looks like a pair of regular tinted glasses, but with small cameras poking out of each lens. The lenses are transparent and the device, Vuzix explains on its website, both captures and projects images, giving the wearer of the device front-row seats to a 2D or 3D AR show transmitted from a computer.

The group at Yamanashi have created software that makes use of the twin cameras. When a person puts the glasses on, each camera scopes out the scene that each eye would see. The images are funneled into software on a computer, which combines the perspective of both cameras and creates a “defocus” effect. That is, some objects to stay in focus while others stay out of focus, resulting in a feeling of depth. That version of the scene in front of them is projected to the single healthy eye of the wearer.

The system isn’t quite ready to be taken for spin around town yet. It’s bulky still, the creators write, and needs a computer by its side, creating and projecting images in real time. But the creators admit such computing power is likely to be found on mobile devices soon, and when it is, they’ll be ready.

Scientists Work To Unravel Mystery Behind Woman Who Doesn’t Grow

Twenty year old Brooke Greenberg hasn’t grown since age five. For the last 15 years mystified doctors have been unable to explain the cause for Brooke’s disorder that has kept her aging in check. At age twenty, she maintains the physical and mental appearance of a toddler.

Eric Shadt wants to solve this most bizarre of medical mysteries. Director of the Icahn Institute for Genomics and Multiscale Biology at the Mount Sinai Medical Center in New York, Shadt is leading research to uncover the genetic cause for Brooke’s condition.

Because hormones control many of the maturation processes, one of the first things the research team looked at was to see if Brooke’s own hormone levels might be abnormal. In a piece he wrote on Katie Couric’s website on whose show he and the Greenberg family recently appeared, Shadt explained that Brooke “has no apparent abnormalities in her endocrine system, no gross chromosomal abnormalities, or any of the other disruptions known to occur in humans that can cause developmental issues.”

The researchers are now painstakingly analyzing Brooke’s entire genome in search of unique mutations. Needless to say, it is a formidable undertaking. “Cracking the code on Brooke’s condition,” Shadt wrote, “is the proverbial searching for a needle in a haystack, since likely there is one or a small number of letters changed in Brooke’s genome that has caused her condition.”

Alzheimer’s researchers trying brain zaps

It has the makings of a science fiction movie: zap someone’s brain with mild jolts of electricity to try to stave off the creeping memory loss of Alzheimer’s disease.

And it’s not easy. Holes are drilled into the patient’s skull so tiny wires can be implanted into just the right spot.

A dramatic shift is beginning in the frustrating struggle to find something to slow the damage of this epidemic: The first U.S. experiments with “brain pacemakers” for Alzheimer’s are getting under way. Scientists are looking beyond drugs to implants in the hunt for much-needed new treatments.

The research is in its infancy. Only a few dozen people with early-stage Alzheimer’s will be implanted in a handful of hospitals. No one knows if it might work, and if it does, how long the effects might last.

Kathy Sanford was among the first to sign up. The Ohio woman’s early-stage Alzheimer’s was gradually getting worse. She still lived independently, posting reminders to herself, but no longer could work. Medications weren’t helping.

Read more