Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
The finding, reported online in advance of publication in Nature by University of California, Berkeley, researchers, indicates that the same genes have been responsible for establishing the left-right asymmetry of animals for 500-650 million years, originating in the last common ancestor of all animals with bilateral body organization, creatures that include everything from worms to humans.
"Previous studies indicated that the methods for breaking left-right symmetry in animals seem to differ widely, so there was nothing suggesting that the common ancestor of humans, snails and other bilateral organisms had a common strategy for left-right asymmetry," said Nipam H. Patel, UC Berkeley professor of integrative biology and of molecular and cell biology, and an investigator of the Howard Hughes Medical Institute.
"Indeed, scientists thought that one of the genes that is critical for setting up left-right asymmetry in vertebrates was only present in vertebrates and related groups and not in any other animals," said UC Berkeley post-doctoral fellow Cristina Grande. "But we found that gene in snails, which has a lot of evolutionary implications. This cellular pathway was present already in the ancestors of most animals."
The finding, the researchers say, could help to track down the ultimate cause of symmetry-breaking in snails and other organisms, and the cascade of gene activation that leads to complex shapes, such as coiled shells.
Despite humans' superficial symmetry - our left and right sides appear to be mirror images - we are anything but symmetric. Most people's hearts are towards the left side of the body, which means the left lung is slightly smaller to make room for the heart, and our intestines are arranged in an asymmetric coil. This asymmetry is unrelated to being left- or right-handed, a preference determined in the brain.
While a small percentage of people have their insides flipped, their overall internal arrangement is a mirror image of the norm. Anyone with a random arrangement of internal organs would be dead, Patel said, because his or her organs wouldn't fit together properly.
Other vertebrates are the same. In fact, scientists have identified a gene called "nodal" that - in all vertebrates checked to date - is expressed on the left side of the body and necessary to set up left-right asymmetry. If nodal doesn't work or is knocked out, internal organs are jumbled and the organism dies.
"In vertebrates, a set of genes tells the body it has to form a heart toward one side, and nodal is one of those genes," said Grande, who recently took a position at the Centro de Biolog?a Molecular "Severo Ochoa" in Madrid, Spain.
"There are a lot of asymmetric molecules in the body, that is, molecules that are active on only one side of the body, but nodal is always expressed on the left side in all vertebrates, which is evidence of a conserved pathway," Patel said.
Genes similar to nodal have been found throughout the so-called deuterostomes, one of the three subgroups of bilateral animals that includes not only vertebrates, but also sea urchins and sea squirts.
But the most common lab animals, fruit flies and nematodes, apparently do not have a gene like nodal, despite their asymmetry. As a result, biologists have assumed that fruit flies and all other non-deuterostomes - snails included - use some other mechanism to establish right and left. Fruit flies and nematodes are in the clade Ecdysozoa, while snails and worms are members of the clade Lophotrochozoa.
Grande approached Patel four years ago to collaborate in a test of this assumption in snails, which have an obvious and easy-to-check handedness: Their shell either coils right, like a standard screw, or left. Patel, a biologist who focuses on the genetics and evolution of crustacean and insect development, such as the formation of segments and appendages in shrimps and crabs, invited Grande to join his lab, even though he had never before worked with snails.
Snail handedness becomes obvious very early in the embryo, Patel said. When the four-cell embryo divides to become eight cells, the new cells blossom from their predecessors in a clockwise spiral, in which case the snail ultimately forms a right-handed, or dextral, shell; or a counter-clockwise spiral, creating a left-handed, or sinistral, shell. Biologists had earlier shown that this decision is made by the mother snail, which dumps many proteins and RNA molecules into the egg to jump-start embryonic development and, in the process, imprints her offspring with specific characteristics.
"No one knows what that maternal gene is, and you can't track it down using the standard approach of looking for genetic markers because there are not yet enough markers in snails, so we looked for any molecular entry into the cause of asymmetry," Patel said.
That proved to be the genome of the marine limpet Lottia gigantea, a right-handed snail whose genome was sequenced recently by the Department of Energy's Joint Genome Institute (JGI) in Walnut Creek, Calif. Grande looked for genes in Lottia similar to nodal, and found one, as well as a gene analogous to the gene, Pitx, which is activated by nodal and also involved in setting up left-right asymmetry in vertebrates.
She used this information to look for and find similar genes in the left-handed snail Biomphalaria glabrata, the fresh-water host of the parasite that causes schistosomiasis. Experimental tests showed that nodal and Pitx were active or expressed on the right side of embryos in the right-handed snail Lottia, and on the left side in the left-handed snail Biomphalaria.
A key test of the critical nature of nodal involved treating the snails with a chemical known to inhibit the activity of nodal. While most treated snails died, some lost the asymmetric expression of Pitx and, most strikingly, developed a straight shell, Patel said.
Grande has since found analogs of nodal in the genome of the marine worm Capitella, which was sequenced by JGI, suggesting that nodal is active throughout the Lophotrochozoa.
"Everybody thought using nodal and Pitx for left-right asymmetry was an invention of this one group, the deuterostomes," Grande said. "The fact that we find them setting up asymmetry in snails and worms means that is not true; the ancestor of all bilaterians already used these genes to set up left-right asymmetry."
Because the ancestral snail was right-handed and thus, presumably, expressed nodal and Pitx on the right side of the body - similar to sea urchins, an early offshoot of the deuterostome branch leading to humans - the authors propose that the common ancestor of all bilateral animals had left-right asymmetry controlled by nodal and Pitx expressed on the right side of the body.
The discovery also could help Grande and Patel track down the maternal factors that ultimately determine handedness in snails.
Grande was supported by the Ministerio de Educacion y Ciencia of Spain and UC Berkeley's Center for Integrative Genomics.
Source: Robert Sanders
University of California - Berkeley
воскресенье, 31 июля 2011 г.
четверг, 28 июля 2011 г.
Researchers Watch Antibiotics, Bacteria Meet At Atomic Level
A new understanding of an enzyme important for the transfer of genetic information in bacteria may help scientists improve current antibiotics and also create antibiotics that are less vulnerable to resistance.
Researchers used extremely powerful imaging techniques to see, for the first time, exactly what happens between bacteria and antibiotics at the atomic level. They report their findings in two studies in the journal Nature.
The work provides the most detailed view yet of an enzyme structure that is key to turning on the genes that make bacteria work, said Irina Artsimovitch, a co-author on both studies and an associate professor of microbiology at Ohio State University.
Artsimovitch worked with Dmitry Vassylyev, the lead author of both studies and a professor of biochemistry and molecular biology at the University of Alabama at Birmingham. The two conducted the study with researchers from the University of Alabama at Birmingham, the University of Wisconsin-Madison and the University of Nebraska Medical Center.
In the first study, the team found that they could create a detailed image of the elongation complex, a structure formed by RNA polymerase. RNA polymerase is the enzyme responsible for setting gene expression in motion, a process called transcription. Without a properly functioning RNA polymerase, a cell will die.
"RNA polymerase spends most of its working hours as the elongation complex," Artsimovitch said. "The complex makes RNA's messages one step at a time, many thousands of times, until its completion.
"This structure is important from a physiological point of view, not only for antibiotic design, but also because faults in the complex have been implicated in many diseases such as hereditary cancers."
Artsimovitch and her colleagues used the bacterium Thermus thermophilus to run their experiments. While T. thermophilus won't make a human sick, the bacterium is widely used to gather structural information at the molecular level.
The researchers first isolated the RNA polymerase from T. thermophilus. They then created an active elongation complex by mixing the enzyme with small molecules of DNA and RNA. This solution hardened into a crystal, which the researchers could then examine using an imaging technique called X-ray crystallography.
X-ray crystallography let them create a computerized image showing the minute details of the elongation complex.
In the second study, the team learned how the antibiotic streptolydigin blocks transcription. Streptolydigin has been around for several decades and the researchers already knew that this antibiotic stops RNA polymerase activity inside a cell. But they didn't know what controlled this mechanism.
"We have to know what we're looking at and working with before it's possible to make a useful antibiotic," Artsimovitch said. "Now we can. Now we can see where the enzyme and antibiotic make contact at the atomic level."
Upon examining the X-ray images, the researchers found that the antibiotic prevented the normal operation of the elongation complex by freezing it in the inactive state.
They saw a loop-shaped element that must close every time the elongation complex adds a nucleotide (a building block of DNA or RNA) to the growing RNA chain. This loop must open again to allow the next cycle to happen. If something such as an antibiotic keeps the loop from closing, RNA polymerase can't properly function and stalls.
"This loop is a target for antibiotics, including streptolydigin," Artsimovitch said. "If we can design new drugs that will prevent its movements, then we will immediately stop the action of RNA polymerase, and bacteria will die soon thereafter."
The team's findings may be applicable to realms outside microbiology and drug discovery. Such a clear picture of the RNA polymerase elongation complex may be useful to a number of research areas, including manipulating the complex to increase the efficiency of bacteria that can harvest biofuels, Artsimovitch said.
"We think that this mobile loop is a hot spot for regulating transcription in all living organisms, not only by using antibiotics but also by manipulating cellular factors," she said.
Grants from the National Institutes of Health supported this work.
Ohio State University
1125 Kinnear Rd.
Columbus, OH 43212-1153
United States
osu.edu
Researchers used extremely powerful imaging techniques to see, for the first time, exactly what happens between bacteria and antibiotics at the atomic level. They report their findings in two studies in the journal Nature.
The work provides the most detailed view yet of an enzyme structure that is key to turning on the genes that make bacteria work, said Irina Artsimovitch, a co-author on both studies and an associate professor of microbiology at Ohio State University.
Artsimovitch worked with Dmitry Vassylyev, the lead author of both studies and a professor of biochemistry and molecular biology at the University of Alabama at Birmingham. The two conducted the study with researchers from the University of Alabama at Birmingham, the University of Wisconsin-Madison and the University of Nebraska Medical Center.
In the first study, the team found that they could create a detailed image of the elongation complex, a structure formed by RNA polymerase. RNA polymerase is the enzyme responsible for setting gene expression in motion, a process called transcription. Without a properly functioning RNA polymerase, a cell will die.
"RNA polymerase spends most of its working hours as the elongation complex," Artsimovitch said. "The complex makes RNA's messages one step at a time, many thousands of times, until its completion.
"This structure is important from a physiological point of view, not only for antibiotic design, but also because faults in the complex have been implicated in many diseases such as hereditary cancers."
Artsimovitch and her colleagues used the bacterium Thermus thermophilus to run their experiments. While T. thermophilus won't make a human sick, the bacterium is widely used to gather structural information at the molecular level.
The researchers first isolated the RNA polymerase from T. thermophilus. They then created an active elongation complex by mixing the enzyme with small molecules of DNA and RNA. This solution hardened into a crystal, which the researchers could then examine using an imaging technique called X-ray crystallography.
X-ray crystallography let them create a computerized image showing the minute details of the elongation complex.
In the second study, the team learned how the antibiotic streptolydigin blocks transcription. Streptolydigin has been around for several decades and the researchers already knew that this antibiotic stops RNA polymerase activity inside a cell. But they didn't know what controlled this mechanism.
"We have to know what we're looking at and working with before it's possible to make a useful antibiotic," Artsimovitch said. "Now we can. Now we can see where the enzyme and antibiotic make contact at the atomic level."
Upon examining the X-ray images, the researchers found that the antibiotic prevented the normal operation of the elongation complex by freezing it in the inactive state.
They saw a loop-shaped element that must close every time the elongation complex adds a nucleotide (a building block of DNA or RNA) to the growing RNA chain. This loop must open again to allow the next cycle to happen. If something such as an antibiotic keeps the loop from closing, RNA polymerase can't properly function and stalls.
"This loop is a target for antibiotics, including streptolydigin," Artsimovitch said. "If we can design new drugs that will prevent its movements, then we will immediately stop the action of RNA polymerase, and bacteria will die soon thereafter."
The team's findings may be applicable to realms outside microbiology and drug discovery. Such a clear picture of the RNA polymerase elongation complex may be useful to a number of research areas, including manipulating the complex to increase the efficiency of bacteria that can harvest biofuels, Artsimovitch said.
"We think that this mobile loop is a hot spot for regulating transcription in all living organisms, not only by using antibiotics but also by manipulating cellular factors," she said.
Grants from the National Institutes of Health supported this work.
Ohio State University
1125 Kinnear Rd.
Columbus, OH 43212-1153
United States
osu.edu
понедельник, 25 июля 2011 г.
Autism Skews Developing Brain With Synchronous Motion And Sound
Individuals with autism spectrum disorders (ASD) tend to stare at people's mouths rather than their eyes. Now, an NIH-funded study in 2-year-olds with the social deficit disorder suggests why they might find mouths so attractive: lip-sync - the exact match of lip motion and speech sound. Such audiovisual synchrony preoccupied toddlers who have autism, while their unaffected peers focused on socially meaningful movements of the human body, such as gestures and facial expressions.
"Typically developing children pay special attention to human movement from very early in life, within days of being born. But in children with autism, even as old as two years, we saw no evidence of this," explained Ami Klin, Ph.D., of the Yale Child Study Center, who led the research. "Toddlers with autism are missing rich social information imparted by these cues, and this is likely to adversely affect the course of their development."
Klin, Warren Jones, Ph.D., and colleagues at Yale, report the findings of their study, funded in part by the National Institute of Health's National Institute of Mental Health, online March 29, 2009 in the journal Nature.
For the first time, this study has pinpointed what grabs the attention of toddlers with ASDs," said NIMH Director Thomas R. Insel, M.D. "In addition to potential uses in screening for early diagnosis, this line of research holds promise for development of new therapies based on redirecting visual attention in children with these disorders."
A eureka moment in the research came when researchers followed up on a clue from children's responses to audiovisual synchrony embedded in a nursery rhyme cartoon.
While it was known that people with autism do not spontaneously orient to social signals, it was unclear what early-emerging mechanism may contribute to that. Nor was it clear exactly what they were attending to instead. To find out, Klin, Jones and colleagues tracked the eye movements of two-year-olds with and without the disorder while they looked at cartoon animations on split-screen displays.
The researchers borrowed a technique from the video game industry, called motion capture. They then reduced the movements to only points of light at each joint in the body, like animated constellations. These cartoons played normally - upright and forward - on one half of the screen, but upside-down and in reverse on the other half. The inverted presentation engages different brain circuits and is known to disrupt perception of biological motion in young children. The normal soundtrack of the actor's voice, recorded when the animations were made, accompanied the presentations.
Eye-tracking data initially showed that 21 toddlers with ASD had no preference for the upright animations, looking back and forth between the two. By contrast, 39 typically-developing toddlers and 16 developmentally delayed but non-autistic toddlers clearly preferred the upright animations.
However, responses to one animation didn't fit the pattern. The toddlers with ASD changed their behavior and shifted their attention to the upright figure as it played a game of pat-a-cake, where the figure claps his hands repeatedly. In this animation (see movie below), unlike the others, the movements of the points of light actually cause the clapping sound. This physical synchrony - dots colliding to produce a clapping sound - only existed on the upright side of the screen, because the inverted figure played in reverse and its motions weren't in sync with the soundtrack. The children with ASD chose the upright figure 66 percent of the time, a strong preference.
This clue led the researchers to suspect that what initially appeared to be random viewing by the ASD toddlers might actually reflect preference for audiovisual synchronies that were less obvious than the clapping. So they re-analyzed the data, factoring in more subtle synchronous changes in motion and sound.
"Audio-visual synchronies accounted for about 90 percent of the preferred viewing patterns of toddlers with ASD and none of unaffected toddlers," said Jones. "Typically-developing children focused instead on the most socially relevant information."
A follow-up experiment using new animations optimized for audiovisual synchrony confirmed these results.
Klin, Jones, and colleagues also recently reported that children with autism look more at peoples' mouths than eyes as early as age 2. Since the mouth is the facial feature with most audiovisual synchrony - lip motion with speech sound - the researchers propose that their new findings offer a likely explanation for this phenomenon.
"Our results suggest that, in autism, genetic predispositions are exacerbated by atypical experience from a very early age, altering brain development," said Klin. "Attention to biological motion is a fundamental mechanism of social engagement, and in the future, we need to understand how this process is derailed in autism, starting still earlier, in the first weeks and months of life."
Notes:
NIMH is funding a related research project of Klin and Jones' that explores related behaviors in infants who have older siblings already diagnosed with ASD and who, because of the genetic heritability risk in autism, have greater risk of also developing the condition.
Also participating in the research were: David Lin, now at Harvard Medical School; Phillip Gorrindo, now at Vanderbilt University; Gordon Ramsay, Ph.D., Haskins Laboratories. The study was funded through the NIH's STAART Program (Studies To Advance Autism Research & Treatment).
Reference:
Two-year-olds with autism fail to orient toward human biological motion but attend instead to non-social physical contingencies. Klin A, Lin DJ, Gorrindo P, Ramsay G, Jones W. Nature. 2009 Mar 29 [Epub ahead of print]
The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.
Source:
Jules Asher
NIH/National Institute of Mental Health
"Typically developing children pay special attention to human movement from very early in life, within days of being born. But in children with autism, even as old as two years, we saw no evidence of this," explained Ami Klin, Ph.D., of the Yale Child Study Center, who led the research. "Toddlers with autism are missing rich social information imparted by these cues, and this is likely to adversely affect the course of their development."
Klin, Warren Jones, Ph.D., and colleagues at Yale, report the findings of their study, funded in part by the National Institute of Health's National Institute of Mental Health, online March 29, 2009 in the journal Nature.
For the first time, this study has pinpointed what grabs the attention of toddlers with ASDs," said NIMH Director Thomas R. Insel, M.D. "In addition to potential uses in screening for early diagnosis, this line of research holds promise for development of new therapies based on redirecting visual attention in children with these disorders."
A eureka moment in the research came when researchers followed up on a clue from children's responses to audiovisual synchrony embedded in a nursery rhyme cartoon.
While it was known that people with autism do not spontaneously orient to social signals, it was unclear what early-emerging mechanism may contribute to that. Nor was it clear exactly what they were attending to instead. To find out, Klin, Jones and colleagues tracked the eye movements of two-year-olds with and without the disorder while they looked at cartoon animations on split-screen displays.
The researchers borrowed a technique from the video game industry, called motion capture. They then reduced the movements to only points of light at each joint in the body, like animated constellations. These cartoons played normally - upright and forward - on one half of the screen, but upside-down and in reverse on the other half. The inverted presentation engages different brain circuits and is known to disrupt perception of biological motion in young children. The normal soundtrack of the actor's voice, recorded when the animations were made, accompanied the presentations.
Eye-tracking data initially showed that 21 toddlers with ASD had no preference for the upright animations, looking back and forth between the two. By contrast, 39 typically-developing toddlers and 16 developmentally delayed but non-autistic toddlers clearly preferred the upright animations.
However, responses to one animation didn't fit the pattern. The toddlers with ASD changed their behavior and shifted their attention to the upright figure as it played a game of pat-a-cake, where the figure claps his hands repeatedly. In this animation (see movie below), unlike the others, the movements of the points of light actually cause the clapping sound. This physical synchrony - dots colliding to produce a clapping sound - only existed on the upright side of the screen, because the inverted figure played in reverse and its motions weren't in sync with the soundtrack. The children with ASD chose the upright figure 66 percent of the time, a strong preference.
This clue led the researchers to suspect that what initially appeared to be random viewing by the ASD toddlers might actually reflect preference for audiovisual synchronies that were less obvious than the clapping. So they re-analyzed the data, factoring in more subtle synchronous changes in motion and sound.
"Audio-visual synchronies accounted for about 90 percent of the preferred viewing patterns of toddlers with ASD and none of unaffected toddlers," said Jones. "Typically-developing children focused instead on the most socially relevant information."
A follow-up experiment using new animations optimized for audiovisual synchrony confirmed these results.
Klin, Jones, and colleagues also recently reported that children with autism look more at peoples' mouths than eyes as early as age 2. Since the mouth is the facial feature with most audiovisual synchrony - lip motion with speech sound - the researchers propose that their new findings offer a likely explanation for this phenomenon.
"Our results suggest that, in autism, genetic predispositions are exacerbated by atypical experience from a very early age, altering brain development," said Klin. "Attention to biological motion is a fundamental mechanism of social engagement, and in the future, we need to understand how this process is derailed in autism, starting still earlier, in the first weeks and months of life."
Notes:
NIMH is funding a related research project of Klin and Jones' that explores related behaviors in infants who have older siblings already diagnosed with ASD and who, because of the genetic heritability risk in autism, have greater risk of also developing the condition.
Also participating in the research were: David Lin, now at Harvard Medical School; Phillip Gorrindo, now at Vanderbilt University; Gordon Ramsay, Ph.D., Haskins Laboratories. The study was funded through the NIH's STAART Program (Studies To Advance Autism Research & Treatment).
Reference:
Two-year-olds with autism fail to orient toward human biological motion but attend instead to non-social physical contingencies. Klin A, Lin DJ, Gorrindo P, Ramsay G, Jones W. Nature. 2009 Mar 29 [Epub ahead of print]
The mission of the NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure.
The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.
Source:
Jules Asher
NIH/National Institute of Mental Health
пятница, 22 июля 2011 г.
MIT Study Shows Genetic Link For Schizophrenia
Gene mutations governing a key brain enzyme make people susceptible to schizophrenia and may be targeted in future treatments for the psychiatric illness, according to MIT and Japanese researchers.
The work, by scientists from MIT's Picower Institute for Learning and Memory and Japan's RIKEN Brain Science Institute, will be reported in the early online edition of the Proceedings of the National Academy of Sciences on Feb. 20.
According to the National Institute for Mental Health, an estimated 51 million people worldwide suffer from schizophrenia. Although 80 percent of schizophrenia cases appear to be inherited, the specific genetic components underlying individuals' susceptibility and pathology are largely unknown.
By studying genetically engineered mice and the genetic makeup of schizophrenic individuals, the MIT and Japanese scientists pinpointed the PPP3CC gene and other genes in the early growth response (EGR) gene family (specifically, EGR3) as likely suspects for causing the disease.
These genes are critical in the signaling pathway for the brain enzyme calcineurin. Calcineurin is prevalent in the central nervous system, where it plays a role in many neuronal functions whose disturbances would play into the disorganized thinking, attention deficits, memory and language problems that characterize schizophrenia.
The researchers confirmed that the PPP3CC gene is involved in diagnosed schizophrenia in Caucasian, African-American and Japanese individuals. EGR3 involvement was confirmed through a separate test.
"These data suggest that the brain signals governed by calcineurin stand at a convergent point of the molecular disease pathology of schizophrenia, and the involvement of the EGR genes reinforces this," said co-author Takeo Yoshikawa of the RIKEN Brain Science Institute. This knowledge could lead to new schizophrenia therapeutics targeting the calcineurin system, he said.
"This study provides genetic and biological evidence that PPP3CC and EGR3, both constituents of the calcineurin signaling pathway, may independently elicit increased risk for schizophrenia," said co-author Susumu Tonegawa, Picower Professor of Biology and Neuroscience at MIT. "These findings raised a novel and potentially important role for EGR genes in schizophrenia pathogenesis."
In addition to Yoshikawa and Tonegawa, authors are Kazuo Yamada, Yoshimi Iwayama, Tetsuo Ohnishi, Hisako Ohba, Tomoko Toyota and Jun Aruga of RIKEN Brain Sciences Institute; David J. Gerber of the Howard Hughes Medical Institute and the RIKEN-MIT Neuroscience Research Center; and Yoshio Minabe of Kanazawa University School of Medicine in Japan.
This work is supported by the RIKEN Brain Science Institute and other agencies and institutes.
For further information please go to:
Massachusetts Institute of Technology
The work, by scientists from MIT's Picower Institute for Learning and Memory and Japan's RIKEN Brain Science Institute, will be reported in the early online edition of the Proceedings of the National Academy of Sciences on Feb. 20.
According to the National Institute for Mental Health, an estimated 51 million people worldwide suffer from schizophrenia. Although 80 percent of schizophrenia cases appear to be inherited, the specific genetic components underlying individuals' susceptibility and pathology are largely unknown.
By studying genetically engineered mice and the genetic makeup of schizophrenic individuals, the MIT and Japanese scientists pinpointed the PPP3CC gene and other genes in the early growth response (EGR) gene family (specifically, EGR3) as likely suspects for causing the disease.
These genes are critical in the signaling pathway for the brain enzyme calcineurin. Calcineurin is prevalent in the central nervous system, where it plays a role in many neuronal functions whose disturbances would play into the disorganized thinking, attention deficits, memory and language problems that characterize schizophrenia.
The researchers confirmed that the PPP3CC gene is involved in diagnosed schizophrenia in Caucasian, African-American and Japanese individuals. EGR3 involvement was confirmed through a separate test.
"These data suggest that the brain signals governed by calcineurin stand at a convergent point of the molecular disease pathology of schizophrenia, and the involvement of the EGR genes reinforces this," said co-author Takeo Yoshikawa of the RIKEN Brain Science Institute. This knowledge could lead to new schizophrenia therapeutics targeting the calcineurin system, he said.
"This study provides genetic and biological evidence that PPP3CC and EGR3, both constituents of the calcineurin signaling pathway, may independently elicit increased risk for schizophrenia," said co-author Susumu Tonegawa, Picower Professor of Biology and Neuroscience at MIT. "These findings raised a novel and potentially important role for EGR genes in schizophrenia pathogenesis."
In addition to Yoshikawa and Tonegawa, authors are Kazuo Yamada, Yoshimi Iwayama, Tetsuo Ohnishi, Hisako Ohba, Tomoko Toyota and Jun Aruga of RIKEN Brain Sciences Institute; David J. Gerber of the Howard Hughes Medical Institute and the RIKEN-MIT Neuroscience Research Center; and Yoshio Minabe of Kanazawa University School of Medicine in Japan.
This work is supported by the RIKEN Brain Science Institute and other agencies and institutes.
For further information please go to:
Massachusetts Institute of Technology
вторник, 19 июля 2011 г.
Alzheimer's Cognitive Decline Studied In Genetically Engineered Mice
In experiments with mice, researchers have discovered a mechanism by which the toxic brain protein produced in Alzheimer's disease (AD) could contribute to the cognitive deficits that are its hallmark. They found evidence that the toxic protein, called A?? peptide, triggers overexcitation of neurons in the brain's learning centers, inducing compensatory rewiring of brain circuitry in the centers--all of which could cause deterioration of neural function.
The researcher wrote that their results showed the need for studies to explore whether blocking that overexcitation might prevent such neurological deficits in AD.
Lennart Mucke and colleagues published their findings in the journal Neuron, published by Cell Press.
For their experiments, the researchers used mice genetically engineered to produce the human version of the protein that gives rise to A?? peptide in people with AD. Such mice show neurological abnormalities in learning regions of the brain that parallel those of people with AD.
EEG studies in the mice showed increased seizure activity indicative of neuronal overexcitation--especially significant because people with AD are more prone to seizures. Studies of the neuronal circuitry in learning centers of the animals' brains showed a rewiring that indicated an imbalance between the normal excitatory and inhibitory neuronal activity. The studies also indicated that the circuitry was remodeling itself to increase inhibitory circuit function.
Significantly, the researchers could induce in normal mice the same molecular and anatomical alterations found in the genetically altered mice by giving them a drug that induces neuronal overexcitation.
What's more, their studies revealed genetic and biochemical changes in the brains of the engineered mice that indicated abnormal overexcitation of neurons, as well as impaired "plasticity"--the adaptability of neuronal connections that is central to learning.
The researchers wrote that their findings indicated that "cognitive deficits in [the genetically altered] mice, and perhaps also in humans with AD, may result from the combination of neuronal overexcitation and the subsequent development of compensatory inhibitory mechanisms that reduce overexcitation but end up constraining the functional agility of specific excitatory circuits.
They wrote that "Studies are needed to determine whether blocking A??-induced neuronal overexcitation can prevent the activation of inhibitory pathways as well as the development of AD-related neurological deficits."
The researchers include Jorge J. Palop, Jeannie Chin, Erik D. Roberson, Jun Wang, Myo T. Thwin, and Nga Bien-Ly of the Gladstone Institutes and the University of California, San Francisco in San Francisco; Jong Yoo of Baylor College of Medicine in Houston; Kaitlyn O. Ho, Gui-Qiu Yu, Anatol Kreitzer, Steven Finkbeiner of the Gladstone Institutes and the University of California, San Francisco in San Francisco; Jeffrey L. Noebels of Baylor College of Medicine in Houston; and Lennart Mucke of the Gladstone Institutes and the University of California, San Francisco in San Francisco.
This work was supported in part by a fellowship from the McBean Foundation (J.J.P.) and by National Institutes of Health Grants AG023501, AG011385, and NS041787 to L.M., NS29709 and HD24064 to J.L.N., NS39074 and AG022074 to S.F., NS54811 to E.D.R., and a facilities grant (RR 018928) from the National Center for Research Resources.
Palop et al.: "Aberrant Excitatory Neuronal Activity and Compensatory Remodeling of Inhibitory Hippocampal Circuits in Mouse Models of Alzheimer's Disease." Publishing in Neuron 55, 697-711, September 6, 2007. DOI 10.1016/j.neuron.2007.07.025. neuron/
Source: Nancy Wampler
Cell Press
The researcher wrote that their results showed the need for studies to explore whether blocking that overexcitation might prevent such neurological deficits in AD.
Lennart Mucke and colleagues published their findings in the journal Neuron, published by Cell Press.
For their experiments, the researchers used mice genetically engineered to produce the human version of the protein that gives rise to A?? peptide in people with AD. Such mice show neurological abnormalities in learning regions of the brain that parallel those of people with AD.
EEG studies in the mice showed increased seizure activity indicative of neuronal overexcitation--especially significant because people with AD are more prone to seizures. Studies of the neuronal circuitry in learning centers of the animals' brains showed a rewiring that indicated an imbalance between the normal excitatory and inhibitory neuronal activity. The studies also indicated that the circuitry was remodeling itself to increase inhibitory circuit function.
Significantly, the researchers could induce in normal mice the same molecular and anatomical alterations found in the genetically altered mice by giving them a drug that induces neuronal overexcitation.
What's more, their studies revealed genetic and biochemical changes in the brains of the engineered mice that indicated abnormal overexcitation of neurons, as well as impaired "plasticity"--the adaptability of neuronal connections that is central to learning.
The researchers wrote that their findings indicated that "cognitive deficits in [the genetically altered] mice, and perhaps also in humans with AD, may result from the combination of neuronal overexcitation and the subsequent development of compensatory inhibitory mechanisms that reduce overexcitation but end up constraining the functional agility of specific excitatory circuits.
They wrote that "Studies are needed to determine whether blocking A??-induced neuronal overexcitation can prevent the activation of inhibitory pathways as well as the development of AD-related neurological deficits."
The researchers include Jorge J. Palop, Jeannie Chin, Erik D. Roberson, Jun Wang, Myo T. Thwin, and Nga Bien-Ly of the Gladstone Institutes and the University of California, San Francisco in San Francisco; Jong Yoo of Baylor College of Medicine in Houston; Kaitlyn O. Ho, Gui-Qiu Yu, Anatol Kreitzer, Steven Finkbeiner of the Gladstone Institutes and the University of California, San Francisco in San Francisco; Jeffrey L. Noebels of Baylor College of Medicine in Houston; and Lennart Mucke of the Gladstone Institutes and the University of California, San Francisco in San Francisco.
This work was supported in part by a fellowship from the McBean Foundation (J.J.P.) and by National Institutes of Health Grants AG023501, AG011385, and NS041787 to L.M., NS29709 and HD24064 to J.L.N., NS39074 and AG022074 to S.F., NS54811 to E.D.R., and a facilities grant (RR 018928) from the National Center for Research Resources.
Palop et al.: "Aberrant Excitatory Neuronal Activity and Compensatory Remodeling of Inhibitory Hippocampal Circuits in Mouse Models of Alzheimer's Disease." Publishing in Neuron 55, 697-711, September 6, 2007. DOI 10.1016/j.neuron.2007.07.025. neuron/
Source: Nancy Wampler
Cell Press
суббота, 16 июля 2011 г.
Brain Tumors Paralyze The Immune System - First Preclinical Trails With RNA-Interference To Lift Blockage
Gliomas are extremely malignant and fast growing tumors. Not only do
they secrete molecules to secure their blood supply by generating new
blood vessels, they are also able to secrete messenger molecules to
protect themselves against attacks by the immune system.
Professor Michael Weller, Medical Director of the General Neurology at
the University Clinic in T?bingen, applied the RNA-interference
technique to block the gene of one important representative of this
group of messengers, the Transforming Growth Factor-beta (TGF-
beta). When the TGF-beta gene is switched off and the blockage of the
immune system lifted, brain tumors can be attacked by the immune
system.
In all of the mice in which the researchers had switched off the TGF-
beta gene, the tumors were completely decomposed. "These results
could open the way for vaccinations against brain tumors, because
only an immune system which is working faultlessly is able to react to a
vaccination with an adequate immune response, Professor Weller said
at the Brain Tumor Conference 2006 held by the Max Delbr?ck Center
for Molecular Medicine (MDC) and the Helios Klinikum in Berlin-Buch,
Germany.
Tumors in the brain are attacked less often by the immune system
than tumors in other parts of the body. The reason for this is, amongst
others, that the blood-brain barrier protects the brain from the
pathogens transported in the blood vessels. However, this also means
that the brain is simultaneously less accessible to the immune system
than are other parts of the body. Therefore, researchers thought for a
long time that the immune system was not active in the brain at all.
Yet, in recent years, researchers were able to demonstrate immune
reactions in the brain. Multiple sclerosis, for example, is caused by an
extreme immune reaction likewise in the brain. Furthermore,
researchers could show that the brain tumor cells indeed defend
themselves against attacks by the immune system. These cells
produce messenger molecules that block the immune system of the
patient. A multitude of such molecules had already been identified by
scientists. For example, substances with complicated names such as
Transforming Growth Factor-beta (TGF-beta), Regeneration and
Tolerance Factor (RTF), and the soluble surface antigen HLA-G.
Since 1994, Professor Weller has been working on a mechanism to
switch off the messenger TGF-beta directly so that the immune system
will be able to recognize and attack tumor cells. In experiments with
mice and rats, he blocked the gene for TGF-beta with the help of the
so called RNA interference (RNAi) method. RNA stands for
"ribonucleic acid", a molecule which translates the genetic code found
in the DNA into the language of proteins (amino acids). The RNAi is a
strand of antisense RNA that binds and blocks the RNA strand of the
TGF-beta gene switched on in the tumor. Thus, the RNAi prevents the
translation of the TGF-beta gene into its corresponding protein. In
other words, the gene is quasi silenced and no TGF-beta protein is
produced.
Furthermore, Professor Weller could show that certain cells of the
immune system, like lymphocytes and natural killer cells, are able to
recognize and destroy the tumor. To prevent a recurrence of the tumor,
the researchers additionally vaccinated the mice with dead tumor cells.
"These dead cells cannot proliferate anymore. Therefore, they are not
dangerous for the organism", Professor Weller pointed out. But their
cell surface characteristics are the same as "regular" tumor cells and,
therefore, they can stimulate the immune system. Only when the
immune system is no longer blocked by TGF-beta can an effective
immune response be provoked by these vaccinations. "At this time,
such strategies are merely experimental as we did all our research on
animals. These methods cannot yet be transferred to human patients",
Professor Weller emphasized.
Max Delbr?ck Center for Molecular Medicine (MDC) Berlin-Buch
they secrete molecules to secure their blood supply by generating new
blood vessels, they are also able to secrete messenger molecules to
protect themselves against attacks by the immune system.
Professor Michael Weller, Medical Director of the General Neurology at
the University Clinic in T?bingen, applied the RNA-interference
technique to block the gene of one important representative of this
group of messengers, the Transforming Growth Factor-beta (TGF-
beta). When the TGF-beta gene is switched off and the blockage of the
immune system lifted, brain tumors can be attacked by the immune
system.
In all of the mice in which the researchers had switched off the TGF-
beta gene, the tumors were completely decomposed. "These results
could open the way for vaccinations against brain tumors, because
only an immune system which is working faultlessly is able to react to a
vaccination with an adequate immune response, Professor Weller said
at the Brain Tumor Conference 2006 held by the Max Delbr?ck Center
for Molecular Medicine (MDC) and the Helios Klinikum in Berlin-Buch,
Germany.
Tumors in the brain are attacked less often by the immune system
than tumors in other parts of the body. The reason for this is, amongst
others, that the blood-brain barrier protects the brain from the
pathogens transported in the blood vessels. However, this also means
that the brain is simultaneously less accessible to the immune system
than are other parts of the body. Therefore, researchers thought for a
long time that the immune system was not active in the brain at all.
Yet, in recent years, researchers were able to demonstrate immune
reactions in the brain. Multiple sclerosis, for example, is caused by an
extreme immune reaction likewise in the brain. Furthermore,
researchers could show that the brain tumor cells indeed defend
themselves against attacks by the immune system. These cells
produce messenger molecules that block the immune system of the
patient. A multitude of such molecules had already been identified by
scientists. For example, substances with complicated names such as
Transforming Growth Factor-beta (TGF-beta), Regeneration and
Tolerance Factor (RTF), and the soluble surface antigen HLA-G.
Since 1994, Professor Weller has been working on a mechanism to
switch off the messenger TGF-beta directly so that the immune system
will be able to recognize and attack tumor cells. In experiments with
mice and rats, he blocked the gene for TGF-beta with the help of the
so called RNA interference (RNAi) method. RNA stands for
"ribonucleic acid", a molecule which translates the genetic code found
in the DNA into the language of proteins (amino acids). The RNAi is a
strand of antisense RNA that binds and blocks the RNA strand of the
TGF-beta gene switched on in the tumor. Thus, the RNAi prevents the
translation of the TGF-beta gene into its corresponding protein. In
other words, the gene is quasi silenced and no TGF-beta protein is
produced.
Furthermore, Professor Weller could show that certain cells of the
immune system, like lymphocytes and natural killer cells, are able to
recognize and destroy the tumor. To prevent a recurrence of the tumor,
the researchers additionally vaccinated the mice with dead tumor cells.
"These dead cells cannot proliferate anymore. Therefore, they are not
dangerous for the organism", Professor Weller pointed out. But their
cell surface characteristics are the same as "regular" tumor cells and,
therefore, they can stimulate the immune system. Only when the
immune system is no longer blocked by TGF-beta can an effective
immune response be provoked by these vaccinations. "At this time,
such strategies are merely experimental as we did all our research on
animals. These methods cannot yet be transferred to human patients",
Professor Weller emphasized.
Max Delbr?ck Center for Molecular Medicine (MDC) Berlin-Buch
пятница, 15 июля 2011 г.
This Month's Family Murder-Suicides Only "The Tip Of The Iceberg" Sociologist Says
A family sociologist at the University at Buffalo says this month's murder-suicides involving a family of four in Ohio and a family of five in California may be "just the tip of the iceberg."
Sampson Blair, Ph.D., associate professor of sociology at UB, says, "Family murder-suicide is still relatively uncommon, but I expect an increase in such incidents over the next few years because economic strain on families provokes depression and desperation."
He adds that family researchers have long pointed to how financial and occupational stressors can negatively impact the quality of family relationships.
"The economic situation also portends a significant increase in other forms of family violence, including spousal and child abuse, child neglect and other forms of dysfunctional behavior like substance abuse," Blair explains.
"What makes this situation even worse -- and yes, it can get worse -- is that there is also a clear association between suicide rates and the state of the larger economy. Generally, in periods of economic depression, there is a slight increase in the overall suicide rate and job loss produces a two- to three-fold increase in that risk.
"Such tragedies don't occur just because one or more breadwinners have lost their jobs," he says. "High levels of stress arising from job loss are compounded by the level of responsibility that goes along with being a spouse and/or being a parent," Blair says.
"So, from the individual's point of view, the loss of a job is certainly bad, but it can become much, much worse when it coincides with a loss of savings and investments, the loss of the family home (through foreclosure, for instance), and dismal prospects for finding another job soon.
"Understandably, when you put all of those factors together, and consider the current conditions for families here in the U.S., it's a rather bleak forecast," Blair says.
He says the incidence of suicide, or worse, murder-suicide, hasn't received a lot of attention among family researchers because it is a relatively uncommon occurrence, but some basic patterns have been recognized.
"It isn't the loss of a job per se that causes this," he says, "but the level of fear and worry that accompanies it that takes its toll on people. Financial stressors are among the greatest risk factors for emotional disturbance and such physiological reactions as insomnia and high blood pressure."
Blair conducts research in the sociology of the family, child and adolescent development, gender and ethnicity. He directs the undergraduate program in sociology at UB and is the former senior editor of Sociological Inquiry, and the former associate editor of the journals Social Justice Research, Journal of Family Values and Marriage and Family Review.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Sampson Blair, Ph.D., associate professor of sociology at UB, says, "Family murder-suicide is still relatively uncommon, but I expect an increase in such incidents over the next few years because economic strain on families provokes depression and desperation."
He adds that family researchers have long pointed to how financial and occupational stressors can negatively impact the quality of family relationships.
"The economic situation also portends a significant increase in other forms of family violence, including spousal and child abuse, child neglect and other forms of dysfunctional behavior like substance abuse," Blair explains.
"What makes this situation even worse -- and yes, it can get worse -- is that there is also a clear association between suicide rates and the state of the larger economy. Generally, in periods of economic depression, there is a slight increase in the overall suicide rate and job loss produces a two- to three-fold increase in that risk.
"Such tragedies don't occur just because one or more breadwinners have lost their jobs," he says. "High levels of stress arising from job loss are compounded by the level of responsibility that goes along with being a spouse and/or being a parent," Blair says.
"So, from the individual's point of view, the loss of a job is certainly bad, but it can become much, much worse when it coincides with a loss of savings and investments, the loss of the family home (through foreclosure, for instance), and dismal prospects for finding another job soon.
"Understandably, when you put all of those factors together, and consider the current conditions for families here in the U.S., it's a rather bleak forecast," Blair says.
He says the incidence of suicide, or worse, murder-suicide, hasn't received a lot of attention among family researchers because it is a relatively uncommon occurrence, but some basic patterns have been recognized.
"It isn't the loss of a job per se that causes this," he says, "but the level of fear and worry that accompanies it that takes its toll on people. Financial stressors are among the greatest risk factors for emotional disturbance and such physiological reactions as insomnia and high blood pressure."
Blair conducts research in the sociology of the family, child and adolescent development, gender and ethnicity. He directs the undergraduate program in sociology at UB and is the former senior editor of Sociological Inquiry, and the former associate editor of the journals Social Justice Research, Journal of Family Values and Marriage and Family Review.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
четверг, 14 июля 2011 г.
Study Shows That Parents Can Play Valuable Role In Helping Young Children Succeed Despite Stressful Circumstances
Researchers at the NYU Child Study Center demonstrated that a brief program for families of Pre-Kindergarten students attending schools in disadvantaged urban communities improved children's behavior at school. The study, called "Promoting effective parenting practices and preventing child behavior problems in school among ethnically diverse families from underserved, urban communities," was published in the February 2011 issue of Child Development.
Dr. Laurie Miller Brotman and her colleagues spent several years developing ParentCorps, a program for families of young children as they transition to school. ParentCorps includes a series of 13 group sessions for parents and children held at the school during early evening hours, facilitated by trained school staff and mental health professionals. The program is unique by reaching parents through public schools in underserved communities to help them learn a set of parenting strategies. For example, parents can learn ways to establish routines and rules for the family, reinforce positive behavior and provide effective consequences for misbehavior. ParentCorps helps each parent to select from a portfolio of scientifically-proven strategies that will work for them based on their own family goals, values and culture. By bringing families and early childhood educators together to support and learn from each other, the ParentCorps program helps young children succeed.
"Rich or poor, urban or rural, every parent wants their child to succeed " said Laurie Miller Brotman, PhD, the Corzine Family Professor of Child and Adolescent Psychiatry, Department Child and Adolescent Psychiatry, NYU Child Study Center. "There are hundreds of studies that show that parenting under stress can lead to negative outcomes for children. Parents who are struggling to make ends meet, parents who experience depression, parents who are raising children on their own - all need extra support in their important role as parent."
Using a rigorous experimental design, where some schools were assigned to receive ParentCorps and some receive school services as usual, the study examined the impact of ParentCorps among 171 children enrolled in Pre-Kindergarten across eight public elementary schools in a large NYC school district, representing an ethnically diverse population.
Despite multiple demands and stressors, parents made the time to come to the 13-session family series to share with and learn from other parents. "We saw great enthusiasm for and commitment to a program that helps young children do well in school, and this was true for parents and teachers from all different backgrounds," said Dr. Esther Calzada, one of the study co-authors.
In schools that offered ParentCorps, parents had improved knowledge of evidence-based parenting strategies, reported using more effective discipline strategies and were observed in the home to be more responsive to their children during play interactions. Most importantly, by the end of the Pre-Kindergarten year, relative to control schools, children in schools with ParentCorps, were rated by their teachers to be better behaved in the classroom and to show more social and emotional competencies, foundational skills for learning.
Based on the very promising findings from this study, Brotman and her team are conducting a second study that examines the long-term benefits on classroom behavior and academic achievement in over 1000 children. "All families deserve to have access to resources and services that will help their children succeed," Brotman said.
Dr. Laurie Miller Brotman and her colleagues spent several years developing ParentCorps, a program for families of young children as they transition to school. ParentCorps includes a series of 13 group sessions for parents and children held at the school during early evening hours, facilitated by trained school staff and mental health professionals. The program is unique by reaching parents through public schools in underserved communities to help them learn a set of parenting strategies. For example, parents can learn ways to establish routines and rules for the family, reinforce positive behavior and provide effective consequences for misbehavior. ParentCorps helps each parent to select from a portfolio of scientifically-proven strategies that will work for them based on their own family goals, values and culture. By bringing families and early childhood educators together to support and learn from each other, the ParentCorps program helps young children succeed.
"Rich or poor, urban or rural, every parent wants their child to succeed " said Laurie Miller Brotman, PhD, the Corzine Family Professor of Child and Adolescent Psychiatry, Department Child and Adolescent Psychiatry, NYU Child Study Center. "There are hundreds of studies that show that parenting under stress can lead to negative outcomes for children. Parents who are struggling to make ends meet, parents who experience depression, parents who are raising children on their own - all need extra support in their important role as parent."
Using a rigorous experimental design, where some schools were assigned to receive ParentCorps and some receive school services as usual, the study examined the impact of ParentCorps among 171 children enrolled in Pre-Kindergarten across eight public elementary schools in a large NYC school district, representing an ethnically diverse population.
Despite multiple demands and stressors, parents made the time to come to the 13-session family series to share with and learn from other parents. "We saw great enthusiasm for and commitment to a program that helps young children do well in school, and this was true for parents and teachers from all different backgrounds," said Dr. Esther Calzada, one of the study co-authors.
In schools that offered ParentCorps, parents had improved knowledge of evidence-based parenting strategies, reported using more effective discipline strategies and were observed in the home to be more responsive to their children during play interactions. Most importantly, by the end of the Pre-Kindergarten year, relative to control schools, children in schools with ParentCorps, were rated by their teachers to be better behaved in the classroom and to show more social and emotional competencies, foundational skills for learning.
Based on the very promising findings from this study, Brotman and her team are conducting a second study that examines the long-term benefits on classroom behavior and academic achievement in over 1000 children. "All families deserve to have access to resources and services that will help their children succeed," Brotman said.
среда, 13 июля 2011 г.
Three UCSF Faculty Elected To Institute Of Medicine
Three UCSF faculty scientists are among the 65 new members elected to the Institute of Medicine, part of the National Academy of Sciences, the Institute announced today.
The new UCSF members are:
* Kathleen Giacomini, PhD, professor and chair of biopharmaceutical sciences.
* James Marks, MD, PhD, professor of anesthesia and pharmaceutical chemistry at UCSF and chief of anesthesia at San Francisco General Hospital Medical Center.
* John L.R. Rubenstein, MD, PhD, the Nina Ireland Distinguished Professor in Child Psychiatry and a basic science researcher in the Department of Psychiatry.
The election brings to 72 the number of UCSF faculty who are members of the prestigious Institute. Election to the Institute recognizes those who have made major contributions to the advancement of the medical sciences, health care, and public health. It is considered one of the highest honors in these fields.
Kathleen Giacomini, PhD, professor and chair of biopharmaceutical sciences, is an expert on membrane transporters, proteins that control the movement of drugs and natural compounds into and out of cells. Her research focuses on the role of transporters in drug disposition. Giacomini is a leader in the new field of pharmacogenetics, which seeks to identify the genetic basis of response to drugs. She is the principal investigator of a multi-disciplinary project funded by the National Institutes of Health to determine if variations in the genes of people's membrane transporters affects their sensitivity or resistance to drugs used to treat a variety of diseases, including cancer and depression. The aim is improved drug design, drug selection for patients and more effective treatment, with quicker drug response and fewer side effects.
James D. Marks, MD, PhD, professor of anesthesia and pharmaceutical chemistry at UCSF and chief of anesthesia at San Francisco General Hospital Medical Center, is a world-recognized pioneer in the field of antibody engineering. He developed widely used technologies employing antibody gene diversity libraries and display technologies that can be used to generate and optimize human therapeutic antibodies. Marks has employed these technologies to better understand the relationship between antibody structure and function and to develop antibody based diagnostics and therapeutics. In the field of oncology, his research has elucidated the impact of antibody biophysical properties on tumor targeting. Working with UCSF Breast SPORE colleagues, his laboratory has generated an antibody against HER2, an oncogene product produced at high levels in breast cancer, and used the antibody to engineer a novel antibody targeted drug. In the field of infectious disease, he has defined how combinations of antibodies can synergize to potently neutralize bacterial toxins. Marks has utilized this approach to generate a combination of three monoclonal antibodies that potently neutralize type A botulinum neurotoxins and which can be mass produced to prevent or treat botulism.
John L.R. Rubenstein, MD, PhD, is the Nina Ireland Distinguished Professor in Child Psychiatry and a basic science researcher in the Department of Psychiatry at UCSF. His research focuses on the regulatory genes that orchestrate development of the forebrain. In the mammalian embryo, the forebrain is the portion of the neural tube where primitive cells are organized to form the cerebral cortex, the basal ganglia and other components of the adult brain -- the structures of the human brain most involved in key functions such as speech, language, cognition and fine motor skills. Rubenstein's lab has demonstrated the role of specific genes in regulating neuronal specification, differentiation, migration and axon growth during embryonic development and on through adult life. His work may help to explain some of the mechanisms underlying human neurodevelopmental disorders such as autism.
Established in 1970 by the National Academy of Sciences, the Institute of Medicine is a national resource for independent, scientifically informed analysis and recommendations on issues related to human health. With their election, members make a commitment to devote a significant amount of volunteer time as members of IOM study committees.
Current active members elect new members from among candidates nominated for their professional achievement and commitment to service. The Institute's charter stipulates that at least one-quarter of the membership be selected from outside the health professions, from such fields as the natural, social, and behavioral sciences, as well as law, administration, engineering, and the humanities.
The Institute of Medicine's total active membership is now 1,501. In addition, the Institute has elected five new individuals to foreign associate membership, bringing the total members in that category to 82. With another 68 members holding emeritus status, the total IOM membership is now 1,651.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the health professions and life sciences, and providing complex patient care.
Contact: Jennifer O'Brien
University of California - San Francisco
The new UCSF members are:
* Kathleen Giacomini, PhD, professor and chair of biopharmaceutical sciences.
* James Marks, MD, PhD, professor of anesthesia and pharmaceutical chemistry at UCSF and chief of anesthesia at San Francisco General Hospital Medical Center.
* John L.R. Rubenstein, MD, PhD, the Nina Ireland Distinguished Professor in Child Psychiatry and a basic science researcher in the Department of Psychiatry.
The election brings to 72 the number of UCSF faculty who are members of the prestigious Institute. Election to the Institute recognizes those who have made major contributions to the advancement of the medical sciences, health care, and public health. It is considered one of the highest honors in these fields.
Kathleen Giacomini, PhD, professor and chair of biopharmaceutical sciences, is an expert on membrane transporters, proteins that control the movement of drugs and natural compounds into and out of cells. Her research focuses on the role of transporters in drug disposition. Giacomini is a leader in the new field of pharmacogenetics, which seeks to identify the genetic basis of response to drugs. She is the principal investigator of a multi-disciplinary project funded by the National Institutes of Health to determine if variations in the genes of people's membrane transporters affects their sensitivity or resistance to drugs used to treat a variety of diseases, including cancer and depression. The aim is improved drug design, drug selection for patients and more effective treatment, with quicker drug response and fewer side effects.
James D. Marks, MD, PhD, professor of anesthesia and pharmaceutical chemistry at UCSF and chief of anesthesia at San Francisco General Hospital Medical Center, is a world-recognized pioneer in the field of antibody engineering. He developed widely used technologies employing antibody gene diversity libraries and display technologies that can be used to generate and optimize human therapeutic antibodies. Marks has employed these technologies to better understand the relationship between antibody structure and function and to develop antibody based diagnostics and therapeutics. In the field of oncology, his research has elucidated the impact of antibody biophysical properties on tumor targeting. Working with UCSF Breast SPORE colleagues, his laboratory has generated an antibody against HER2, an oncogene product produced at high levels in breast cancer, and used the antibody to engineer a novel antibody targeted drug. In the field of infectious disease, he has defined how combinations of antibodies can synergize to potently neutralize bacterial toxins. Marks has utilized this approach to generate a combination of three monoclonal antibodies that potently neutralize type A botulinum neurotoxins and which can be mass produced to prevent or treat botulism.
John L.R. Rubenstein, MD, PhD, is the Nina Ireland Distinguished Professor in Child Psychiatry and a basic science researcher in the Department of Psychiatry at UCSF. His research focuses on the regulatory genes that orchestrate development of the forebrain. In the mammalian embryo, the forebrain is the portion of the neural tube where primitive cells are organized to form the cerebral cortex, the basal ganglia and other components of the adult brain -- the structures of the human brain most involved in key functions such as speech, language, cognition and fine motor skills. Rubenstein's lab has demonstrated the role of specific genes in regulating neuronal specification, differentiation, migration and axon growth during embryonic development and on through adult life. His work may help to explain some of the mechanisms underlying human neurodevelopmental disorders such as autism.
Established in 1970 by the National Academy of Sciences, the Institute of Medicine is a national resource for independent, scientifically informed analysis and recommendations on issues related to human health. With their election, members make a commitment to devote a significant amount of volunteer time as members of IOM study committees.
Current active members elect new members from among candidates nominated for their professional achievement and commitment to service. The Institute's charter stipulates that at least one-quarter of the membership be selected from outside the health professions, from such fields as the natural, social, and behavioral sciences, as well as law, administration, engineering, and the humanities.
The Institute of Medicine's total active membership is now 1,501. In addition, the Institute has elected five new individuals to foreign associate membership, bringing the total members in that category to 82. With another 68 members holding emeritus status, the total IOM membership is now 1,651.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the health professions and life sciences, and providing complex patient care.
Contact: Jennifer O'Brien
University of California - San Francisco
Effects Of Depression And Pain Severity On Satisfaction In Medical Outpatients: Analysis Of The Medical Outcomes Study
Patient satisfaction is a critical measure of healthcare quality. We performed this study to see how depression and pain severity affected patient satisfaction in medical outpatients. We analyzed data from the Medical Outcomes Study and found that pain was very common and patients with depression and pain were much more likely to be dissatisfied with their healthcare. These findings may also have care-delivery implications, should dissatisfaction indicate poorer quality of care. Further study is needed to determine the reasons for dissatisfaction with care in patients with depression and pain.
The Journal of Rehabilitation Research and Development (JRRD) has been a leading research journal in the field of rehabilitation medicine and technology for over 40 years. Formerly the Bulletin of Prosthetics Research, JRRD debuted in 1983 to include cross-disciplinary findings in rehabilitation. JRRD, a scientifically indexed journal, publishes original research papers, review articles, as well as clinical and technical commentary from U.S. and international researchers on all rehabilitation research disciplines.
JRRD publishes in both print and electronic formats, increasing the journal's dissemination from a hard copy circulation of 8,000 to 2.3 million Web downloads in 2005. Currently, there are over 1,000 peer-reviewed articles available in electronic format and free for downloading. JRRD will initiate an archiving program in 2005 to make all issues of JRRD and the Bulletin of Prosthetics Research available online.
Journal of Rehabilitation Research and Development
Now Available Online and in Print: rehab.research.va
The Journal of Rehabilitation Research and Development (JRRD) has been a leading research journal in the field of rehabilitation medicine and technology for over 40 years. Formerly the Bulletin of Prosthetics Research, JRRD debuted in 1983 to include cross-disciplinary findings in rehabilitation. JRRD, a scientifically indexed journal, publishes original research papers, review articles, as well as clinical and technical commentary from U.S. and international researchers on all rehabilitation research disciplines.
JRRD publishes in both print and electronic formats, increasing the journal's dissemination from a hard copy circulation of 8,000 to 2.3 million Web downloads in 2005. Currently, there are over 1,000 peer-reviewed articles available in electronic format and free for downloading. JRRD will initiate an archiving program in 2005 to make all issues of JRRD and the Bulletin of Prosthetics Research available online.
Journal of Rehabilitation Research and Development
Now Available Online and in Print: rehab.research.va
вторник, 12 июля 2011 г.
JAMA Study: Effectively Managing Pain With Depression
Pain, the most common reason for adults to visit a primary care physician, and depression, the most frequent mental complaint requiring a doctor's appointment, occur together as often as half the time.
Researchers from the Indiana University School of Medicine and the Regenstrief Institute report in the May 27 issue of the Journal of the American Medical Association (JAMA) that a strategy they developed of closely monitored antidepressant therapy coupled with pain self-management can produce substantial improvements in both depression and pain.
"Treating depression these days is like treating high blood pressure. There are many effective drugs out there. To control high blood pressure, the physician closely monitors the patient to determine the most appropriate drug and the proper dosage. Often with depression treatment, the patient is prescribed one of the many effective antidepressants but is not closely followed to see if it's the best choice and the proper dosage, which means the patient's depression is not being effectively managed," said the study's principal investigator, Kurt Kroenke, M.D., professor of medicine at the IU School of Medicine and a Regenstrief investigator.
"There are more significant challenges in treating patients with persistent pain. Ironically research on effective pain treatment has lagged a couple of decades behind work on depression and the drug choices are not as good. More study on the basic science and clinical levels needs to be done on both pain and the link between pain and depression, which may share common biological pathways, to develop better options," said Dr. Kroenke, an Indiana University-Purdue University Indianapolis Chancellor's Professor.
The 250 individuals in the JAMA study had low back, hip, or knee pain for three months or longer and at least moderate depression. They were randomized into two groups. The control group of 127 received usual care from their internists for both depression and pain. The other 123 received careful monitoring of the medications prescribed for their depression plus 12 weeks of pain self-management training. This training included muscle relaxation and deep breathing exercises as well as coping, distraction and other tactics.
Those whose depression medications were closely monitored and who were trained in pain self- management were two to three times more likely to have decreased depression than those in the control group. Pain severity and disability also lessened. These benefits continued for the six months after optimizing antidepressant therapy and pain self-management had been completed.
"We were pleased to see the patients whose anti-depressants were closely monitored and who practiced self-management improved, but we think we can lessen pain and depression even more. In our next studies we plan to investigate cognitive behavioral therapy as well as optimizing pain medications to see if even greater improvements in pain can be achieved. Because pain and depression are among the leading causes of decreased work productivity, a strategy that is effective for both should be attractive not only to patients and their physicians. Health insurers and the business community will be interested as well," said Dr. Kroenke, an internist who is a former president of the Society of General Internal Medicine.
In addition to Dr. Kroenke, co-authors of "Optimized Antidepressant Therapy and Pain Self-management in Primary Care Patients with Depression and Musculoskeletal Pain A Randomized Controlled Trial" are Matthew J. Bair, M.D., Teresa M. Damush, Ph.D., and Wanzhu Tu, Ph.D., of the IU School of Medicine and the Regenstrief Institute; Jingwei Wu, M.S., of the IU School of Medicine; Shawn Hoke, B.A. of the Regenstrief Institute; and Jason Sutherland, Ph.D., formerly of the Regenstrief Institute. Dr. Bair and Dr. Damush also are affiliated with the Richard Roudebush Veterans Affairs Medical Center.
The study was funded by the National Institute of Mental Health.
Source
Indiana University School of Medicine
Researchers from the Indiana University School of Medicine and the Regenstrief Institute report in the May 27 issue of the Journal of the American Medical Association (JAMA) that a strategy they developed of closely monitored antidepressant therapy coupled with pain self-management can produce substantial improvements in both depression and pain.
"Treating depression these days is like treating high blood pressure. There are many effective drugs out there. To control high blood pressure, the physician closely monitors the patient to determine the most appropriate drug and the proper dosage. Often with depression treatment, the patient is prescribed one of the many effective antidepressants but is not closely followed to see if it's the best choice and the proper dosage, which means the patient's depression is not being effectively managed," said the study's principal investigator, Kurt Kroenke, M.D., professor of medicine at the IU School of Medicine and a Regenstrief investigator.
"There are more significant challenges in treating patients with persistent pain. Ironically research on effective pain treatment has lagged a couple of decades behind work on depression and the drug choices are not as good. More study on the basic science and clinical levels needs to be done on both pain and the link between pain and depression, which may share common biological pathways, to develop better options," said Dr. Kroenke, an Indiana University-Purdue University Indianapolis Chancellor's Professor.
The 250 individuals in the JAMA study had low back, hip, or knee pain for three months or longer and at least moderate depression. They were randomized into two groups. The control group of 127 received usual care from their internists for both depression and pain. The other 123 received careful monitoring of the medications prescribed for their depression plus 12 weeks of pain self-management training. This training included muscle relaxation and deep breathing exercises as well as coping, distraction and other tactics.
Those whose depression medications were closely monitored and who were trained in pain self- management were two to three times more likely to have decreased depression than those in the control group. Pain severity and disability also lessened. These benefits continued for the six months after optimizing antidepressant therapy and pain self-management had been completed.
"We were pleased to see the patients whose anti-depressants were closely monitored and who practiced self-management improved, but we think we can lessen pain and depression even more. In our next studies we plan to investigate cognitive behavioral therapy as well as optimizing pain medications to see if even greater improvements in pain can be achieved. Because pain and depression are among the leading causes of decreased work productivity, a strategy that is effective for both should be attractive not only to patients and their physicians. Health insurers and the business community will be interested as well," said Dr. Kroenke, an internist who is a former president of the Society of General Internal Medicine.
In addition to Dr. Kroenke, co-authors of "Optimized Antidepressant Therapy and Pain Self-management in Primary Care Patients with Depression and Musculoskeletal Pain A Randomized Controlled Trial" are Matthew J. Bair, M.D., Teresa M. Damush, Ph.D., and Wanzhu Tu, Ph.D., of the IU School of Medicine and the Regenstrief Institute; Jingwei Wu, M.S., of the IU School of Medicine; Shawn Hoke, B.A. of the Regenstrief Institute; and Jason Sutherland, Ph.D., formerly of the Regenstrief Institute. Dr. Bair and Dr. Damush also are affiliated with the Richard Roudebush Veterans Affairs Medical Center.
The study was funded by the National Institute of Mental Health.
Source
Indiana University School of Medicine
понедельник, 11 июля 2011 г.
Recovery For Elderly With Depression Improves With Medication, Says Pitt School Of Medicine Study
Adding a medication to a standard treatment regimen for major depressive disorder in the elderly improves chances of recovery in those who do not adequately respond to the first-course therapy or who relapse from it, finds a University of Pittsburgh School of Medicine study published in the June issue of the American Journal of Psychiatry, the official journal of the American Psychiatric Association. Up to 84 percent of the elderly who experience depression either fail to respond to first-course treatment or relapse during the first six to 12 weeks of treatment.
The study found that adding a second drug to the treatment of depressed participants over the age of 70 who either did not respond to initial treatment with the antidepressant paroxetine and interpersonal psychotherapy, or to those who responded to the initial treatment but quickly relapsed, caused the likelihood of recovery to rise from 40 percent to 60 percent. Recovery was slower in those who did not respond to the original treatment.
"Depression should not be considered a normal part of aging. The scientific evidence is growing that there are a number of effective treatment options available for people of all ages," said Mary Amanda Dew, Ph.D., professor of psychiatry, psychology and epidemiology at the University of Pittsburgh and lead author of the study.
The University of Pittsburgh researchers followed 105 adults aged 70 or older who had major depressive disorder and who did not respond to standardized treatment of paroxetine and interpersonal psychotherapy or who did respond but experienced an early recurrence of depressive symptoms. Participants were given one of three augmenting agents: sustained-release bupropion, nortriptyline or lithium. Researchers selected the additional agent that each participant received based on individual medical status and history. Thirty-six participants either declined new medicine or did not receive augmentation because of accompanying medical conditions.
Half of the patients who did not respond to the initial treatment responded to the augmentation therapy. It took a median 28 weeks for the participants to achieve recovery. Of the patients who relapsed after the initial therapy, 67 percent recovered after augmentation over a median recovery time of 24 weeks. Of the patients who responded to the first-course therapy of paroxetine and psychotherapy, 87 percent achieved recovery.
"While the recovery rates of those receiving augmentation are not as high as in those who responded to first-line therapy, the recovery rates are still high enough to suggest that augmentation should be tried when older adults' depression is not improving," said Dr. Dew.
The study was funded by the National Institute of Mental Health, one of the National Institutes of Health.
Co-authors include: Ellen M. Whyte, M.D., Eric J. Lenze, M.D., Patricia R. Houck, M.S., Benoit H. Mulsant, M.D., Bruce G. Pollock, M.D., Ph.D., Jacqueline A. Stack, M.S.N., Salem Benassi, B.S., and Charles F. Reynolds III, M.D., of the University of Pittsburgh. Drs. Mulsant and Pollock also have appointments at the University of Toronto.
Financial Disclosures: Dr. Dew has received research support from Astellas Pharma Inc. Dr. Whyte has received research support in the form of pharmaceutical supplies from Pfizer. Dr. Lenze has received research support from Pfizer, Johnson & Johnson and Forest Laboratories. Dr. Mulsant has received research and educational support from Eli Lilly, Jannsen Pharmaceuticals and Pfizer; speaker's bureau honoraria from Astra Zeneca and Pfizer; and honoraria for other consulting from Lundbeck and Pfizer. Dr. Pollock received research support from Jannsen Pharmaceuticals and honoraria for consulting from Forest Laboratories and Lundbeck. Dr. Reynolds has received research support in the form of pharmaceutical supplies from GlaxoSmithKline, Pfizer, Forest Laboratories, Eli Lilly and Bristol-Myers Squibb.
Contact: Jocelyn Uhl Duffy
University of Pittsburgh Schools of the Health Sciences
The study found that adding a second drug to the treatment of depressed participants over the age of 70 who either did not respond to initial treatment with the antidepressant paroxetine and interpersonal psychotherapy, or to those who responded to the initial treatment but quickly relapsed, caused the likelihood of recovery to rise from 40 percent to 60 percent. Recovery was slower in those who did not respond to the original treatment.
"Depression should not be considered a normal part of aging. The scientific evidence is growing that there are a number of effective treatment options available for people of all ages," said Mary Amanda Dew, Ph.D., professor of psychiatry, psychology and epidemiology at the University of Pittsburgh and lead author of the study.
The University of Pittsburgh researchers followed 105 adults aged 70 or older who had major depressive disorder and who did not respond to standardized treatment of paroxetine and interpersonal psychotherapy or who did respond but experienced an early recurrence of depressive symptoms. Participants were given one of three augmenting agents: sustained-release bupropion, nortriptyline or lithium. Researchers selected the additional agent that each participant received based on individual medical status and history. Thirty-six participants either declined new medicine or did not receive augmentation because of accompanying medical conditions.
Half of the patients who did not respond to the initial treatment responded to the augmentation therapy. It took a median 28 weeks for the participants to achieve recovery. Of the patients who relapsed after the initial therapy, 67 percent recovered after augmentation over a median recovery time of 24 weeks. Of the patients who responded to the first-course therapy of paroxetine and psychotherapy, 87 percent achieved recovery.
"While the recovery rates of those receiving augmentation are not as high as in those who responded to first-line therapy, the recovery rates are still high enough to suggest that augmentation should be tried when older adults' depression is not improving," said Dr. Dew.
The study was funded by the National Institute of Mental Health, one of the National Institutes of Health.
Co-authors include: Ellen M. Whyte, M.D., Eric J. Lenze, M.D., Patricia R. Houck, M.S., Benoit H. Mulsant, M.D., Bruce G. Pollock, M.D., Ph.D., Jacqueline A. Stack, M.S.N., Salem Benassi, B.S., and Charles F. Reynolds III, M.D., of the University of Pittsburgh. Drs. Mulsant and Pollock also have appointments at the University of Toronto.
Financial Disclosures: Dr. Dew has received research support from Astellas Pharma Inc. Dr. Whyte has received research support in the form of pharmaceutical supplies from Pfizer. Dr. Lenze has received research support from Pfizer, Johnson & Johnson and Forest Laboratories. Dr. Mulsant has received research and educational support from Eli Lilly, Jannsen Pharmaceuticals and Pfizer; speaker's bureau honoraria from Astra Zeneca and Pfizer; and honoraria for other consulting from Lundbeck and Pfizer. Dr. Pollock received research support from Jannsen Pharmaceuticals and honoraria for consulting from Forest Laboratories and Lundbeck. Dr. Reynolds has received research support in the form of pharmaceutical supplies from GlaxoSmithKline, Pfizer, Forest Laboratories, Eli Lilly and Bristol-Myers Squibb.
Contact: Jocelyn Uhl Duffy
University of Pittsburgh Schools of the Health Sciences
воскресенье, 10 июля 2011 г.
Genome-Driven Diagnoses And Treatments May Be Accelerated By Electronic Medical Records
A new study reveals an exciting potential benefit of the rapidly accumulating databases of health care information, the ability to make unprecedented links between genomic data and clinical medicine. The research, published by Cell Press in the April issue of the American Journal of Human Genetics, supports the idea that large scale DNA databanks linked to electronic medical record (EMR) systems provide a valuable platform for discovering, assessing and validating associations between genes and diseases.
"The deployment of EMRs offers the hope of improving routine care, not only by enhancing individual practitioner access to patient information but also by aggregating information for clinical research," explains senior study author Dr. Dan M. Roden from Vanderbilt University School of Medicine in Nashville Tennessee. "EMRs contain large populations with diverse diseases and have the potential to act as platforms for rapid and inexpensive creation of large inclusive patient sets."
Dr. Roden and colleagues in informatics and in genome science were interested in examining whether large biorepositories containing DNA samples linked to EMRs might be useful for discovering and incorporating new genotype-phenotype associations. "Implementing such a vision requires that major obstacles be overcome, including technological, computational, ethical, and financial issues and determining whether genomic information will meaningfully inform clinical decision making and health care outcomes," says Dr. Roden.
The researchers used BioVU, the Vanderbilt DNA databank, to detect known common genetic variants associated with five diseases: atrial fibrillation, Crohn's disease, multiple sclerosis, rheumatoid arthritis and type 2 diabetes. It took only four months to generate a set of nearly 10,000 records from which the cases and controls were identified. Although the process of accessing and defining the samples was technically complex, for each of the five phenotypes, at least one previously reported genetic association was replicated.
These results support the use DNA resources coupled to EMR systems as a valuable tool for clinical research. "Our data demonstrate that phenotypes representing clinical diagnoses can be extracted from EMR systems, and support the use of DNA resources coupled to EMR systems as tools for rapid generation of large datasets required for replication of associations found in research and for discovery in genome science," concludes Dr. Roden.
The researchers include Marylyn D. Ritchie, Joshua C. Denny, Dana C. Crawford, Andrea H. Ramirez, Justin B. Weiner, Jill M. Pulley, Melissa A. Basford, Kristin Brown-Gentry, Jeffrey R. Balser, Daniel R. Masys, Jonathan L. Haines, Dan M. Roden, of Vanderbilt University School of Medicine, Nashville, TN.
Source:
Cathleen Genova
Cell Press
"The deployment of EMRs offers the hope of improving routine care, not only by enhancing individual practitioner access to patient information but also by aggregating information for clinical research," explains senior study author Dr. Dan M. Roden from Vanderbilt University School of Medicine in Nashville Tennessee. "EMRs contain large populations with diverse diseases and have the potential to act as platforms for rapid and inexpensive creation of large inclusive patient sets."
Dr. Roden and colleagues in informatics and in genome science were interested in examining whether large biorepositories containing DNA samples linked to EMRs might be useful for discovering and incorporating new genotype-phenotype associations. "Implementing such a vision requires that major obstacles be overcome, including technological, computational, ethical, and financial issues and determining whether genomic information will meaningfully inform clinical decision making and health care outcomes," says Dr. Roden.
The researchers used BioVU, the Vanderbilt DNA databank, to detect known common genetic variants associated with five diseases: atrial fibrillation, Crohn's disease, multiple sclerosis, rheumatoid arthritis and type 2 diabetes. It took only four months to generate a set of nearly 10,000 records from which the cases and controls were identified. Although the process of accessing and defining the samples was technically complex, for each of the five phenotypes, at least one previously reported genetic association was replicated.
These results support the use DNA resources coupled to EMR systems as a valuable tool for clinical research. "Our data demonstrate that phenotypes representing clinical diagnoses can be extracted from EMR systems, and support the use of DNA resources coupled to EMR systems as tools for rapid generation of large datasets required for replication of associations found in research and for discovery in genome science," concludes Dr. Roden.
The researchers include Marylyn D. Ritchie, Joshua C. Denny, Dana C. Crawford, Andrea H. Ramirez, Justin B. Weiner, Jill M. Pulley, Melissa A. Basford, Kristin Brown-Gentry, Jeffrey R. Balser, Daniel R. Masys, Jonathan L. Haines, Dan M. Roden, of Vanderbilt University School of Medicine, Nashville, TN.
Source:
Cathleen Genova
Cell Press
Targeting Of 5-HT1A Receptors, Journal Of Neuroscience
Depression is associated with decreased binding of serotonin 5 HT1A receptors. Receptors must be targeted to the appropriate membrane domain function properly, and although trafficking mechanisms have been elucidated for some receptors, little is known about how serotonin receptors are targeted to dendrites.
Because the C terminus of 5 HT1A receptors is required for targeting, Carrel et al. screened for proteins that directly interact with this domain in rat hippocampus. They identified Yif1B, a homolog of a yeast protein involved in transport between the endoplasmic reticulum (ER) and Golgi apparatus.
Yif1B colocalized with 5 HT1A receptor in vesicle-like puncta in the soma and proximal dendrites of hippocampal neurons, and colocalized with ER markers in transfected cell lines. The authors report that knockdown of Yif1B by RNA inhibition in cultured neurons prevented expression of 5 HT1A receptors in distal dendrites, but did not alter the expression pattern of other receptors, suggesting a specific role in targeting 5 HT1A receptors.
Journal of Neuroscience
The Journal of Neuroscience is the official journal of the Society for Neuroscience. The Journal publishes papers on a broad range of topics of general interest to those working on the nervous system.
Journal of Neuroscience
Because the C terminus of 5 HT1A receptors is required for targeting, Carrel et al. screened for proteins that directly interact with this domain in rat hippocampus. They identified Yif1B, a homolog of a yeast protein involved in transport between the endoplasmic reticulum (ER) and Golgi apparatus.
Yif1B colocalized with 5 HT1A receptor in vesicle-like puncta in the soma and proximal dendrites of hippocampal neurons, and colocalized with ER markers in transfected cell lines. The authors report that knockdown of Yif1B by RNA inhibition in cultured neurons prevented expression of 5 HT1A receptors in distal dendrites, but did not alter the expression pattern of other receptors, suggesting a specific role in targeting 5 HT1A receptors.
Journal of Neuroscience
The Journal of Neuroscience is the official journal of the Society for Neuroscience. The Journal publishes papers on a broad range of topics of general interest to those working on the nervous system.
Journal of Neuroscience
суббота, 9 июля 2011 г.
Young Adolescent Girls' Depression Is Tied To More Stressful Life Events
Children's conduct problems--skipping school, sneaking out of the house, lying to parents, shoplifting, or bullying other children--are a major source of concern for parents and teachers. As a potential cause of these problems, parents' marital conflict has received a lot of research attention. Now a new study finds that parents' fighting may not be to blame but rather that parents who argue a lot may pass on genes for disruptive behavior to their children.
The findings are published in the journal Child Development.
A group of researchers from the University of Virginia and several other universities looked at this question, studying 1,045 twins and their 2,051 children. Some of the parents were identical twins and shared all of their genes and some were fraternal and shared only half of their genes.
The study found that parents' fighting is not likely a cause of children's conduct problems. On the other hand, parents' genes influenced how often they argued with their spouses and these same genes, when passed to their children, caused more conduct problems.
"This study suggests that marital conflict is not a major culprit, but genes are," said K. Paige Harden, the lead researcher and professor of psychology at the University of Virginia. "Our findings have potential implications for treating conduct problems: Focusing on a child's parents, as is common in family therapy, may not be as effective as focusing on the child."
The study was supported, in part, by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Alliance for Research on Schizophrenia and Depression.
Summarized from Child Development, Vol. 78, Issue 1, Marital Conflict and Conduct Problems in Children-of-Twins, by Harden, KP, Turkheimer, E, and Emery, RE (University of Virginia), D'Onofrio, BM (Indiana University), Slutske, WS (University of Missouri), Heath, AC (Washington University, St. Louis), and Martin, NG (Queensland Institute of Medical Research). Copyright 2007 The Society for Research in Child Development, Inc. All rights reserved.
Contact: Andrea Browning
Society for Research in Child Development
The findings are published in the journal Child Development.
A group of researchers from the University of Virginia and several other universities looked at this question, studying 1,045 twins and their 2,051 children. Some of the parents were identical twins and shared all of their genes and some were fraternal and shared only half of their genes.
The study found that parents' fighting is not likely a cause of children's conduct problems. On the other hand, parents' genes influenced how often they argued with their spouses and these same genes, when passed to their children, caused more conduct problems.
"This study suggests that marital conflict is not a major culprit, but genes are," said K. Paige Harden, the lead researcher and professor of psychology at the University of Virginia. "Our findings have potential implications for treating conduct problems: Focusing on a child's parents, as is common in family therapy, may not be as effective as focusing on the child."
The study was supported, in part, by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Alliance for Research on Schizophrenia and Depression.
Summarized from Child Development, Vol. 78, Issue 1, Marital Conflict and Conduct Problems in Children-of-Twins, by Harden, KP, Turkheimer, E, and Emery, RE (University of Virginia), D'Onofrio, BM (Indiana University), Slutske, WS (University of Missouri), Heath, AC (Washington University, St. Louis), and Martin, NG (Queensland Institute of Medical Research). Copyright 2007 The Society for Research in Child Development, Inc. All rights reserved.
Contact: Andrea Browning
Society for Research in Child Development
пятница, 8 июля 2011 г.
Seniors' Communication Skills Adversely Affected By Hearing, Voice Problems
Hearing and vocal problems go hand-in-hand among the elderly more frequently than previously thought, according to researchers at Duke University Medical Center. Together, they pack a devastating double punch on communication skills and overall well-being.
"It's important to realize these disabilities often occur concurrently," says Seth Cohen, MD, an otolaryngologist at the Duke Voice Care Center. "And when they do, they can increase the likelihood of depression and social isolation."
Nearly half of people age 65 and older have some degree of hearing loss, according to previously published reports, and about one-third of elderly adults have vocal problems including dysphonia, more commonly known as hoarseness. Taken apart, the disabilities have been linked in the elderly to increased depression, anxiety and social isolation.
In a study presented at the American Laryngological, Rhinological and Otological Society, (aka the Triological Society) in Phoenix, Cohen found that nearly 11 percent of the 248 participants with a median age of 82.4 had both disabilities. And, those respondents had greater depression scores.
While Cohen's study did not prove a direct cause and effect link between hearing loss and dysphonia, he says there appears to be a causal relationship.
"When people have trouble hearing, they strain their voices to hear themselves. Likewise, people may strain their voices if their communication partners can't hear." Because there is effective treatment for both hearing loss and dysphonia, he says it's important that people with one disability be evaluated for the other.
"We need to take a more global view of communication function in the elderly," he stresses.
"It's important to realize these disabilities often occur concurrently," says Seth Cohen, MD, an otolaryngologist at the Duke Voice Care Center. "And when they do, they can increase the likelihood of depression and social isolation."
Nearly half of people age 65 and older have some degree of hearing loss, according to previously published reports, and about one-third of elderly adults have vocal problems including dysphonia, more commonly known as hoarseness. Taken apart, the disabilities have been linked in the elderly to increased depression, anxiety and social isolation.
In a study presented at the American Laryngological, Rhinological and Otological Society, (aka the Triological Society) in Phoenix, Cohen found that nearly 11 percent of the 248 participants with a median age of 82.4 had both disabilities. And, those respondents had greater depression scores.
While Cohen's study did not prove a direct cause and effect link between hearing loss and dysphonia, he says there appears to be a causal relationship.
"When people have trouble hearing, they strain their voices to hear themselves. Likewise, people may strain their voices if their communication partners can't hear." Because there is effective treatment for both hearing loss and dysphonia, he says it's important that people with one disability be evaluated for the other.
"We need to take a more global view of communication function in the elderly," he stresses.
четверг, 7 июля 2011 г.
Genome Of The Parasite Behind Trichomoniasis Decoded By Team Of International Scientists - Could Offer Clues To Better Treatments
A team of international scientists has decoded the genome of the parasite behind trichomoniasis, a sexually transmitted infection (STI) that each year affects about 170 million people worldwide.
Trichomonas vaginalis colonises the urogenital tract and causes the infection also known as "trick", the most common non-viral STI.
University of Queensland PhD scholar Rebecca Dunne was one of a team of 65 scientists that worked on the project to sequence the genome, which could offer clues to better treatments for both men and women.
Ms Dunne said the results would allow researchers to hone in on genes and gene families of interest, particularly those involved in drug resistance.
"The completion of the genome sequence by The Institute for Genomic Research (TIGR) and subsequent annotation of the genome database has opened many avenues of research by providing a searchable data set," Ms Dunne said.
"Drug resistance in many human pathogens is increasing. T. vaginalis is among these, with no alternative drugs approved to treat resistant infections.
"This is particularly an issue in developing countries, where the number of infected individuals is high and the access to public health services is low.
"Now that researchers have access to a complete genome dataset the search for alternative drug targets can really take-off."
Amazingly, the pesky parasite was found to have an exceptionally large collection of DNA, with the possibility of having more genes than humans.
But Ms Dunne said while the sequencing of the genome project has largely elevated awareness of T. vaginalis among researchers, public awareness remains low, especially in developing countries where it has the most impact.
"This is a problem as infection with T. vaginalis increases the transmission and acquisition of many other serious STIs, including HIV.
"Furthermore, prolonged infection with T. vaginalis associates with pre-term birth, low infant birth weight and some cervical cancers.
"Alarmingly, trichomoniasis is not considered a notifiable disease."
Routine gynaecological check-ups do not test for this particular STI and the infection does not require public health notification.
Because of this, and also due to the broad and non-specific nature of symptoms, which can range from severe to negligible depending on the individual, some people pass it on without knowing.
"Furthermore, the non-specific nature (or in some cases, absence) of trichomoniasis symptoms often confuses it with other STIs, making the process of diagnosis itself, difficult," Ms Dunne said.
"Many infections remain undiagnosed as a result."
It is hoped that the results of the project will help research and improve treatments, in turn sponsoring awareness.
Ms Dunne's contribution to the project involved the identification and annotation of several large families of genes related to those involved in various mechanisms of antimicrobial resistance.
As a result of the genome being sequenced, she has since been able to localise specific genes of interest to the whole chromosome and begin the mapping process.
"Mapping the genome is the next step in the genome sequencing of T. vaginalis and will create a visual blueprint of the parasite, allowing researchers to see where their genes fit in to the big picture."
The results of the collaborative project have been published in the prestigious international journal SCIENCE.
For further information please go to:
The University of Queensland, Brisbane Australia
Source:
UQ News Online
Trichomonas vaginalis colonises the urogenital tract and causes the infection also known as "trick", the most common non-viral STI.
University of Queensland PhD scholar Rebecca Dunne was one of a team of 65 scientists that worked on the project to sequence the genome, which could offer clues to better treatments for both men and women.
Ms Dunne said the results would allow researchers to hone in on genes and gene families of interest, particularly those involved in drug resistance.
"The completion of the genome sequence by The Institute for Genomic Research (TIGR) and subsequent annotation of the genome database has opened many avenues of research by providing a searchable data set," Ms Dunne said.
"Drug resistance in many human pathogens is increasing. T. vaginalis is among these, with no alternative drugs approved to treat resistant infections.
"This is particularly an issue in developing countries, where the number of infected individuals is high and the access to public health services is low.
"Now that researchers have access to a complete genome dataset the search for alternative drug targets can really take-off."
Amazingly, the pesky parasite was found to have an exceptionally large collection of DNA, with the possibility of having more genes than humans.
But Ms Dunne said while the sequencing of the genome project has largely elevated awareness of T. vaginalis among researchers, public awareness remains low, especially in developing countries where it has the most impact.
"This is a problem as infection with T. vaginalis increases the transmission and acquisition of many other serious STIs, including HIV.
"Furthermore, prolonged infection with T. vaginalis associates with pre-term birth, low infant birth weight and some cervical cancers.
"Alarmingly, trichomoniasis is not considered a notifiable disease."
Routine gynaecological check-ups do not test for this particular STI and the infection does not require public health notification.
Because of this, and also due to the broad and non-specific nature of symptoms, which can range from severe to negligible depending on the individual, some people pass it on without knowing.
"Furthermore, the non-specific nature (or in some cases, absence) of trichomoniasis symptoms often confuses it with other STIs, making the process of diagnosis itself, difficult," Ms Dunne said.
"Many infections remain undiagnosed as a result."
It is hoped that the results of the project will help research and improve treatments, in turn sponsoring awareness.
Ms Dunne's contribution to the project involved the identification and annotation of several large families of genes related to those involved in various mechanisms of antimicrobial resistance.
As a result of the genome being sequenced, she has since been able to localise specific genes of interest to the whole chromosome and begin the mapping process.
"Mapping the genome is the next step in the genome sequencing of T. vaginalis and will create a visual blueprint of the parasite, allowing researchers to see where their genes fit in to the big picture."
The results of the collaborative project have been published in the prestigious international journal SCIENCE.
For further information please go to:
The University of Queensland, Brisbane Australia
Source:
UQ News Online
Can Omega 3 Fatty Acids Prevent Depression In Coronary Heart Disease?
Depression is an established risk factor for the development of coronary heart disease (CHD) in healthy patients and for adverse cardiovascular outcomes in patients with existing CHD. Dietary factors resulting in lower levels of omega 3 fatty acids not only increase CHD risk, but may also be involved in the pathophysiology of depression. The investigators measured red blood cell levels of two omega 3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and assessed depressive symptoms in a cross-sectional study of 987 adults with CHD. Omega 3 fatty acids were blindly measured in fasting venous blood samples using capillary gas chromatography to measure the fatty acid composition of red blood cell membranes. Red blood cell levels of EPA and DHA are presented as a percentage composition of total fatty acid methyl esters. The investigators assessed current depression using the 9-item Patient Health Questionnaire. They evaluated the association between omega 3 fatty acid levels and depressive symptoms as continuous variables using linear regression.
The investigators also examined the association of omeg 3 fatty acid tertiles with depression as a dichotomous variable using X2 analysis and logistic regression. All statistical tests were two-sided, and p4.3% of total blood fatty acids; p for trend = 0.004). Each unit decrease in EPA + DHA was inversely associated with depressive symptoms as a continuous variable, and these associations persisted after adjustment for age, sex and race. Similarly, each SD decrease in EPA + DHA was associated with significantly greater odds of depression as a dichotomous variable (Patient Health Questionnaire score >10). However, in both analyses, omega 3 fatty acid levels were no longer associated with depression after adjustment for education and household income level. This study extends this existing literature by finding a strong association between low omeg 3 fatty acids and depression in outpatients with stable CHD, a population distinct from sicker, hospitalized patients with acute coronary syndrome. In addition, the investigators examined the role of several important potential confounders and measured erythrocyte membrane levels of fatty acids rather than using less accurate serum measurements or dietary questionnaires. However, the cross-sectional nature of this study precluded the investigators from making any definitive comments on causality. Additionally, the cohort participants were mostly older, urban men and thus are not entirely reflective of the general population. To better understand the potential efficacy of omeg 3 fatty acid supplementation for improving depressive symptoms in patients with CHD, future studies should carefully consider the role of socioeconomic status (SES) in this association.
The investigators also examined the association of omeg 3 fatty acid tertiles with depression as a dichotomous variable using X2 analysis and logistic regression. All statistical tests were two-sided, and p4.3% of total blood fatty acids; p for trend = 0.004). Each unit decrease in EPA + DHA was inversely associated with depressive symptoms as a continuous variable, and these associations persisted after adjustment for age, sex and race. Similarly, each SD decrease in EPA + DHA was associated with significantly greater odds of depression as a dichotomous variable (Patient Health Questionnaire score >10). However, in both analyses, omega 3 fatty acid levels were no longer associated with depression after adjustment for education and household income level. This study extends this existing literature by finding a strong association between low omeg 3 fatty acids and depression in outpatients with stable CHD, a population distinct from sicker, hospitalized patients with acute coronary syndrome. In addition, the investigators examined the role of several important potential confounders and measured erythrocyte membrane levels of fatty acids rather than using less accurate serum measurements or dietary questionnaires. However, the cross-sectional nature of this study precluded the investigators from making any definitive comments on causality. Additionally, the cohort participants were mostly older, urban men and thus are not entirely reflective of the general population. To better understand the potential efficacy of omeg 3 fatty acid supplementation for improving depressive symptoms in patients with CHD, future studies should carefully consider the role of socioeconomic status (SES) in this association.
среда, 6 июля 2011 г.
Behavioral Problems Linked To Cortisol Levels
Cortisol, the so-called stress hormone, seems to behave in contradictory ways in children. Some youngsters with behavioral problems have abnormally high levels of cortisol, while others with identical problems have abnormally low levels. What's going on?
Researchers at Concordia University and the Centre for Research in Human Development may have resolved the cortisol paradox. In a groundbreaking study published in the journal Hormones and Behavior, they link cortisol levels not simply to behavior problems, but to the length of time individuals have experienced behavior problems.
"We studied the relationship between cortisol levels in young people with problematic behaviour such as aggression or depression, and the length of time since the onset of these behaviours," explains Paula Ruttle, lead author and PhD candidate at Concordia's Department of Psychology. "Cortisol levels were abnormally high around the time problem behaviours began, but abnormally low when they had been present for a long time."
To obtain subjects' cortisol levels, researchers analyzed saliva samples taken from 96 young people during early adolescence. They then matched cortisol levels to behavioral assessments taken in childhood and again during adolescence. Problem behaviours were classified as either "internalizing" (depression and anxiety) or "externalizing" (aggression, attentional problems).
Riding the cortisol roller coaster
Youngsters who developed depression-like symptoms or anxiety problems in adolescence had high levels of cortisol. However, those who developed symptoms earlier had abnormally low cortisol levels. The conclusion? Cortisol levels go up when individuals are first stressed by depression or anxiety, but then decline again if they experience stress for an extended period.
"It seems the body adapts to long-term stress, such as depression, by blunting its normal response," says coauthor Lisa Serbin, a psychology professor who is Ruttle's PhD supervisor and Concordia University Research Chair in Human Development.
"To take an extreme example, if someone sees a bear in the yard, that person experiences a 'flight or fight' reaction," continues Serbin, a member of the Centre for Research in Human Development. "Stress levels and therefore cortisol levels go up. However, if the same person sees bears in the yard every day for a year, the stress response is blunted. Eventually, cortisol levels become abnormally low."
Aggressive behavior in early childhood
At first glance, study results from children with aggressive behavior and attentional problems seem to contradict this theory. In this group they found that low levels of cortisol were related to aggressive behavior both during childhood and adolescence. However, the authors contend that since aggressive behavior often begins in the second year of life or earlier, subjects may have been stressed for years before entering the study, resulting in abnormally low cortisol levels.
"This blunted response makes sense from a physiological point of view," says Ruttle. "In the short term, high levels of cortisol help the body respond to stress. However, in the long term, excessive levels of cortisol are linked to a range of physical and mental health problems. So, to protect itself, the body shuts down the cortisol system - but research shows that's not good either."
What, me worry?
Individuals with a blunted response to stress may not respond to things that would - and should - make other people nervous. For example, children with long-term behaviour problems perform poorly in school. Because of their blunted stress response, these youngsters may not be worried about exams, so they don't bother to prepare as much as their peers.
The study has many significant implications, according to Serbin. "This research suggests interventions should begin as soon as a behavioural problem appears," she says. "For children with severe externalizing problems, this may be very early, perhaps even when they are preschoolers or toddlers.
"We now have evidence that behavioural problems in children are linked to mental and physical health. Taking a 'wait-and-see' attitude may not be the right approach."
Partners in research:
This research was funded by the Social Sciences and Humanities Research Council of Canada and the Canadian Institutes of Health Research
About the study:
The paper, "Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: Longitudinal and concurrent associations with cortisol," published Hormones and Behavior, was coauthored by Paula L. Ruttle, Lisa A. Serbin, Dahlia Ben-Dat Fisher, Dale M. Stack and Alex E. Schwartzman of Concordia University and the Centre for Research in Human Development as well as Elizabeth A. Shirtcliff of the University of New Orleans.
Researchers at Concordia University and the Centre for Research in Human Development may have resolved the cortisol paradox. In a groundbreaking study published in the journal Hormones and Behavior, they link cortisol levels not simply to behavior problems, but to the length of time individuals have experienced behavior problems.
"We studied the relationship between cortisol levels in young people with problematic behaviour such as aggression or depression, and the length of time since the onset of these behaviours," explains Paula Ruttle, lead author and PhD candidate at Concordia's Department of Psychology. "Cortisol levels were abnormally high around the time problem behaviours began, but abnormally low when they had been present for a long time."
To obtain subjects' cortisol levels, researchers analyzed saliva samples taken from 96 young people during early adolescence. They then matched cortisol levels to behavioral assessments taken in childhood and again during adolescence. Problem behaviours were classified as either "internalizing" (depression and anxiety) or "externalizing" (aggression, attentional problems).
Riding the cortisol roller coaster
Youngsters who developed depression-like symptoms or anxiety problems in adolescence had high levels of cortisol. However, those who developed symptoms earlier had abnormally low cortisol levels. The conclusion? Cortisol levels go up when individuals are first stressed by depression or anxiety, but then decline again if they experience stress for an extended period.
"It seems the body adapts to long-term stress, such as depression, by blunting its normal response," says coauthor Lisa Serbin, a psychology professor who is Ruttle's PhD supervisor and Concordia University Research Chair in Human Development.
"To take an extreme example, if someone sees a bear in the yard, that person experiences a 'flight or fight' reaction," continues Serbin, a member of the Centre for Research in Human Development. "Stress levels and therefore cortisol levels go up. However, if the same person sees bears in the yard every day for a year, the stress response is blunted. Eventually, cortisol levels become abnormally low."
Aggressive behavior in early childhood
At first glance, study results from children with aggressive behavior and attentional problems seem to contradict this theory. In this group they found that low levels of cortisol were related to aggressive behavior both during childhood and adolescence. However, the authors contend that since aggressive behavior often begins in the second year of life or earlier, subjects may have been stressed for years before entering the study, resulting in abnormally low cortisol levels.
"This blunted response makes sense from a physiological point of view," says Ruttle. "In the short term, high levels of cortisol help the body respond to stress. However, in the long term, excessive levels of cortisol are linked to a range of physical and mental health problems. So, to protect itself, the body shuts down the cortisol system - but research shows that's not good either."
What, me worry?
Individuals with a blunted response to stress may not respond to things that would - and should - make other people nervous. For example, children with long-term behaviour problems perform poorly in school. Because of their blunted stress response, these youngsters may not be worried about exams, so they don't bother to prepare as much as their peers.
The study has many significant implications, according to Serbin. "This research suggests interventions should begin as soon as a behavioural problem appears," she says. "For children with severe externalizing problems, this may be very early, perhaps even when they are preschoolers or toddlers.
"We now have evidence that behavioural problems in children are linked to mental and physical health. Taking a 'wait-and-see' attitude may not be the right approach."
Partners in research:
This research was funded by the Social Sciences and Humanities Research Council of Canada and the Canadian Institutes of Health Research
About the study:
The paper, "Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: Longitudinal and concurrent associations with cortisol," published Hormones and Behavior, was coauthored by Paula L. Ruttle, Lisa A. Serbin, Dahlia Ben-Dat Fisher, Dale M. Stack and Alex E. Schwartzman of Concordia University and the Centre for Research in Human Development as well as Elizabeth A. Shirtcliff of the University of New Orleans.
вторник, 5 июля 2011 г.
St. Jude Medical Announces First Patient Implants In Clinical Study Evaluating Deep Brain Stimulation For Depression
St. Jude Medical, Inc. (NYSE:STJ) announced the first patient implants in a clinical study that is investigating whether deep brain stimulation (DBS) therapy will help people who suffer from major depressive disorder, a severe form of depression. The patients, a 59-year-old woman and a 42-year-old man, were implanted at Alexian Brothers Behavioral Health Hospital in Chicago, with the St. Jude Medical Libra® Deep Brain Stimulation System, an investigational device.
The study, called BROADEN™ (BROdmann Area 25 DEep brain Neuromodulation), is a controlled, multi-site, blinded study that is evaluating the safety and effectiveness of DBS in patients with depression for whom currently available treatments are not effective.
"We are excited to be part of the first double-blind study of Deep Brain Stimulation for depression and remain hopeful that this therapy may prove beneficial for this seriously ill patient population," said Anthony D'Agostino, M.D., medical director of Alexian Brothers Behavioral Health Hospital and the principal investigator at the study site. "The study is an important contribution to the advancement of treatment options for severely depressed patients."
This study is researching a specific area in the brain called Brodmann Area 25 that is thought to be involved in depression. The first research of DBS for depression was conducted in Toronto, Canada, by neurologist Helen S. Mayberg, M.D., and neurosurgeon Andres Lozano, M.D., in 2003. They published their findings in Neuron in March 2005, reporting that brain imaging studies indicate that Brodmann Area 25 appears to be overactive in profoundly sad and depressed people.
St. Jude Medical owns the intellectual property rights, and has various patents issued and pending, for the use of neurostimulation at Brodmann Area 25. The Libra Deep Brain Stimulation System provides mild pulses of current from a device implanted near the collarbone and connected to small electrical leads placed at specific targets in the brain.
"This depression study represents a continuation of our commitment to provide solutions for those who are suffering and in need of additional therapy options," said Chris Chavez, president of the St. Jude Medical ANS Division. "The Brodmann Area 25 study is an important step in bringing physicians and their patients a neuromodulation therapy that, if successful, will treat this debilitating form of depression."
The National Institute of Mental Health estimates that more than 21 million U.S. adults suffer from some kind of depressive disorder. Current therapies are effective for about 80 percent of this patient population according to the National Advisory Mental Health Council. That means approximately 4 million adult Americans live with depression that doesn't respond to medications, psychotherapy or electroconvulsive therapy.
To be eligible for this study, participants must:
- Currently be diagnosed with major depressive disorder
- Be between 21 and 70 years old, with onset of first episode before age 45
- Have tried at least four treatments in their current episode, such as different medications, various combinations of medications or electroconvulsive therapy
- Have been depressed for at least one year
For more information about this study, call toll-free at 866-787-4332, visit BROADENstudy.
Sponsored by St. Jude Medical, the BROADEN study is being conducted under a U.S. Food and Drug Administration (FDA) investigational device exemption (IDE). Initial study centers are located in Chicago, Dallas and New York City. This clinical study was preceded by a smaller pilot study of 20 patients at three sites in Canada which found that six months after the procedure, 56 percent of the patients experienced at least a 40 percent decrease in depressive symptoms. At last follow-up, 78 percent of the patients were responders, and eight of the patients have re-engaged in life activities such as work, school, travel and relationships, and three of the study patients are considered to be in remission. Patients' symptoms were measured using the Hamilton Rating Scale for Depression.
About St. Jude Medical
St. Jude Medical develops medical technology and services that focus on putting more control into the hands of those who treat cardiac, neurological and chronic pain patients worldwide. The company is dedicated to advancing the practice of medicine by reducing risk wherever possible and contributing to successful outcomes for every patient. Headquartered in St. Paul, Minn., St. Jude Medical employs more than 12,000 people worldwide and has five major focus areas that include: cardiac rhythm management, atrial fibrillation, cardiac surgery, cardiology and neuromodulation. For more information, please visit sjm.
About the ANS Division of St. Jude Medical
The ANS Division (Advanced Neuromodulation Systems) became a part of St. Jude Medical in 2005. The ANS Division is an innovative technology leader dedicated to the design, development, manufacturing and marketing of implantable neuromodulation systems to improve the quality of life for people suffering from disabling chronic pain and other nervous system disorders (ans-medical).
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. Such forward-looking statements include the expectations, plans and prospects for the Company, including potential clinical successes, anticipated regulatory approvals and future product launches, and projected revenues, margins, earnings, and market shares. The statements made by the Company are based upon management's current expectations and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include market conditions and other factors beyond the Company's control and the risk factors and other cautionary statements described in the Company's filings with the SEC, including those described in the Risk Factors and Cautionary Statements sections of the Company's Annual Report on Form 10-K filed on February 27, 2008. The Company does not intend to update these statements and undertakes no duty to any person to provide any such update under any circumstance.
ANS Division of St. Jude Medical
The study, called BROADEN™ (BROdmann Area 25 DEep brain Neuromodulation), is a controlled, multi-site, blinded study that is evaluating the safety and effectiveness of DBS in patients with depression for whom currently available treatments are not effective.
"We are excited to be part of the first double-blind study of Deep Brain Stimulation for depression and remain hopeful that this therapy may prove beneficial for this seriously ill patient population," said Anthony D'Agostino, M.D., medical director of Alexian Brothers Behavioral Health Hospital and the principal investigator at the study site. "The study is an important contribution to the advancement of treatment options for severely depressed patients."
This study is researching a specific area in the brain called Brodmann Area 25 that is thought to be involved in depression. The first research of DBS for depression was conducted in Toronto, Canada, by neurologist Helen S. Mayberg, M.D., and neurosurgeon Andres Lozano, M.D., in 2003. They published their findings in Neuron in March 2005, reporting that brain imaging studies indicate that Brodmann Area 25 appears to be overactive in profoundly sad and depressed people.
St. Jude Medical owns the intellectual property rights, and has various patents issued and pending, for the use of neurostimulation at Brodmann Area 25. The Libra Deep Brain Stimulation System provides mild pulses of current from a device implanted near the collarbone and connected to small electrical leads placed at specific targets in the brain.
"This depression study represents a continuation of our commitment to provide solutions for those who are suffering and in need of additional therapy options," said Chris Chavez, president of the St. Jude Medical ANS Division. "The Brodmann Area 25 study is an important step in bringing physicians and their patients a neuromodulation therapy that, if successful, will treat this debilitating form of depression."
The National Institute of Mental Health estimates that more than 21 million U.S. adults suffer from some kind of depressive disorder. Current therapies are effective for about 80 percent of this patient population according to the National Advisory Mental Health Council. That means approximately 4 million adult Americans live with depression that doesn't respond to medications, psychotherapy or electroconvulsive therapy.
To be eligible for this study, participants must:
- Currently be diagnosed with major depressive disorder
- Be between 21 and 70 years old, with onset of first episode before age 45
- Have tried at least four treatments in their current episode, such as different medications, various combinations of medications or electroconvulsive therapy
- Have been depressed for at least one year
For more information about this study, call toll-free at 866-787-4332, visit BROADENstudy.
Sponsored by St. Jude Medical, the BROADEN study is being conducted under a U.S. Food and Drug Administration (FDA) investigational device exemption (IDE). Initial study centers are located in Chicago, Dallas and New York City. This clinical study was preceded by a smaller pilot study of 20 patients at three sites in Canada which found that six months after the procedure, 56 percent of the patients experienced at least a 40 percent decrease in depressive symptoms. At last follow-up, 78 percent of the patients were responders, and eight of the patients have re-engaged in life activities such as work, school, travel and relationships, and three of the study patients are considered to be in remission. Patients' symptoms were measured using the Hamilton Rating Scale for Depression.
About St. Jude Medical
St. Jude Medical develops medical technology and services that focus on putting more control into the hands of those who treat cardiac, neurological and chronic pain patients worldwide. The company is dedicated to advancing the practice of medicine by reducing risk wherever possible and contributing to successful outcomes for every patient. Headquartered in St. Paul, Minn., St. Jude Medical employs more than 12,000 people worldwide and has five major focus areas that include: cardiac rhythm management, atrial fibrillation, cardiac surgery, cardiology and neuromodulation. For more information, please visit sjm.
About the ANS Division of St. Jude Medical
The ANS Division (Advanced Neuromodulation Systems) became a part of St. Jude Medical in 2005. The ANS Division is an innovative technology leader dedicated to the design, development, manufacturing and marketing of implantable neuromodulation systems to improve the quality of life for people suffering from disabling chronic pain and other nervous system disorders (ans-medical).
Forward-Looking Statements
This news release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that involve risks and uncertainties. Such forward-looking statements include the expectations, plans and prospects for the Company, including potential clinical successes, anticipated regulatory approvals and future product launches, and projected revenues, margins, earnings, and market shares. The statements made by the Company are based upon management's current expectations and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. These risks and uncertainties include market conditions and other factors beyond the Company's control and the risk factors and other cautionary statements described in the Company's filings with the SEC, including those described in the Risk Factors and Cautionary Statements sections of the Company's Annual Report on Form 10-K filed on February 27, 2008. The Company does not intend to update these statements and undertakes no duty to any person to provide any such update under any circumstance.
ANS Division of St. Jude Medical
понедельник, 4 июля 2011 г.
Researchers feed tiny pills of RNA to planarians to identify genes essential for regeneration
University of Utah researchers-feeding microscopic pills of RNA to quarter-inch long worms called planarians-have
identified many genes essential to understanding a biological mystery that has captivated scientists for hundreds of years:
regeneration.
In pinpointing the genes, the U School of Medicine researchers have established the planarian as a genetically sound model
for human biology, to take its place alongside Drosophila (fruit flies), C.elegans (another worm), zebrafish, and mice.
The study, to be published in the May issue of Developmental Cell, employed the first large-scale use of RNA interference
(RNAi) to silence planarian genes to identify their role in the worm's biology, according to Alejandro S?nchez Alvarado,
Ph.D., principal investigator and U medical school associate professor of neurobiology and anatomy. The U team's work shows
that planarian genes can be selectively manipulated to study some of the most basic and important areas of biological
research: stem cells, homeostasis (tissue loss and replacement), regeneration, and disease.
"Planarian biology has much in common to the biology that you and I share," said S?nchez Alvarado, who last month was
appointed a Howard Hughes Medical Institute investigator. "This work opens a whole new window to study aspects of human
biology that are barely accessible today."
The planarians used in these studies, also called flatworms, live in fresh water and have a singular ability to regenerate.
Chop one in half, and two new worms grow. Their ability to regenerate is so prolific that a tissue fragment only 1/279th of
the worm's length can grow into a new planarian. Researchers know that planarian stem cells, called neoblasts, play a central
role in both regeneration and homeostasis. But how they do that has remained shrouded in mystery.
S?nchez Alvarado and his research associates used bacteria to synthesize double-stranded RNA that silences planarian genes.
The bacteria effectively become tiny pills-five to 10 microns across-that now can be mixed into planarian food. When S?nchez
Alvarado and his associates fed the worms dinner, the RNA diffused throughout their bodies.
S?nchez Alvarado and Helen Hay Whitney Foundation postdoctoral fellow Peter W. Reddien, Ph.D., silenced and screened 1,065
planarian genes with RNAi. Specific defects were associated with 240 of the genes that were silenced. About 85 percent (204)
of the 240 genes are shared by the genomes of other species, including humans, according to S?nchez Alvarado.
The researchers found that 145 of the silenced genes affect both regeneration and tissue loss and replacement. Some of the
genes were essential to homeostasis, but not regeneration, and 35 genes were found to be essential to regeneration, but not
homeostasis.
"This tells us that separate genetic pathways for regeneration and homeostasis must exist," S?nchez Alvarado said. "It's a
huge step forward for us and opens the possibility of systematic molecular studies to find the genetic cause of regenerative
processes in animals."
Silencing planarian genes may also help in studying human disease. Thirty-eight of the genes S?nchez Alvarado and his team
silenced are related to human genes associated with diseases, such as ataxia (inability to coordinate muscular movements),
bradyopsia (slow vision), and cancer. Only eight of those genes have a corresponding knockout gene in mice. This means
researchers may be able to use planarians to learn about human diseases that can't be studied in other animal models.
Another 35 of the silenced genes may shed light on the parasitic platyhelminthes, such as Schitosoma mansoni, which cause
disease in millions of people. The genes identified by the U researchers may be required for the survival of the parasites.
"Considering such pathogens are estimated to cause disease in nearly 300 million people throughout the world, these genes
might make attractive drug targets," S?nchez Alvarado and his fellow researchers wrote in the study.
The planarian makes an ideal biological model for three important reasons, according to S?nchez Alvarado.
-- It is amenable to genetic manipulation.
-- It is an extremely simple organism with little redundancy in its genes, meaning it has fewer genes to carry out specific
functions. This makes it easier to identify a gene's function by silencing it and will help how researchers target their
efforts on equivalent genes in mice or zebrafish, for example.
-- It is inexpensive to study.
Now that S?nchez Alvarado and his colleagues have opened the door to understanding regeneration by identifying key genes in
the process, the U researcher predicts, with aid of the planarian, more discoveries are on the way.
"Our limitations right now are how many experiments we can do in a day," he said. "The mystery of what makes regeneration
possible, particularly in these animals, is on its way to finally being resolved."
Other authors of the study include Peter W. Reddien, Ph.D, Helen Hay Whitney Foundation postdoctoral fellow, Kenneth J.
Murfitt, and Joya R. Jennings, all of the University of Utah Department of Neurobiology and Anatomy in the School of
Medicine; and Adam L. Bermange, currently at the London Research Institute.
This news release and a downloadable, high-resolution photograph will be available at this Web site at noon (EST) on Monday,
May 2. utah.edu/unews/releases/05/may/planaria.html
Contact: Phil Sahm, Office of Public Affairs
Phil.Sahmhsc.utah.edu
801-581-2517
University of Utah Health Sciences Center
uuhsc.utah.edu
identified many genes essential to understanding a biological mystery that has captivated scientists for hundreds of years:
regeneration.
In pinpointing the genes, the U School of Medicine researchers have established the planarian as a genetically sound model
for human biology, to take its place alongside Drosophila (fruit flies), C.elegans (another worm), zebrafish, and mice.
The study, to be published in the May issue of Developmental Cell, employed the first large-scale use of RNA interference
(RNAi) to silence planarian genes to identify their role in the worm's biology, according to Alejandro S?nchez Alvarado,
Ph.D., principal investigator and U medical school associate professor of neurobiology and anatomy. The U team's work shows
that planarian genes can be selectively manipulated to study some of the most basic and important areas of biological
research: stem cells, homeostasis (tissue loss and replacement), regeneration, and disease.
"Planarian biology has much in common to the biology that you and I share," said S?nchez Alvarado, who last month was
appointed a Howard Hughes Medical Institute investigator. "This work opens a whole new window to study aspects of human
biology that are barely accessible today."
The planarians used in these studies, also called flatworms, live in fresh water and have a singular ability to regenerate.
Chop one in half, and two new worms grow. Their ability to regenerate is so prolific that a tissue fragment only 1/279th of
the worm's length can grow into a new planarian. Researchers know that planarian stem cells, called neoblasts, play a central
role in both regeneration and homeostasis. But how they do that has remained shrouded in mystery.
S?nchez Alvarado and his research associates used bacteria to synthesize double-stranded RNA that silences planarian genes.
The bacteria effectively become tiny pills-five to 10 microns across-that now can be mixed into planarian food. When S?nchez
Alvarado and his associates fed the worms dinner, the RNA diffused throughout their bodies.
S?nchez Alvarado and Helen Hay Whitney Foundation postdoctoral fellow Peter W. Reddien, Ph.D., silenced and screened 1,065
planarian genes with RNAi. Specific defects were associated with 240 of the genes that were silenced. About 85 percent (204)
of the 240 genes are shared by the genomes of other species, including humans, according to S?nchez Alvarado.
The researchers found that 145 of the silenced genes affect both regeneration and tissue loss and replacement. Some of the
genes were essential to homeostasis, but not regeneration, and 35 genes were found to be essential to regeneration, but not
homeostasis.
"This tells us that separate genetic pathways for regeneration and homeostasis must exist," S?nchez Alvarado said. "It's a
huge step forward for us and opens the possibility of systematic molecular studies to find the genetic cause of regenerative
processes in animals."
Silencing planarian genes may also help in studying human disease. Thirty-eight of the genes S?nchez Alvarado and his team
silenced are related to human genes associated with diseases, such as ataxia (inability to coordinate muscular movements),
bradyopsia (slow vision), and cancer. Only eight of those genes have a corresponding knockout gene in mice. This means
researchers may be able to use planarians to learn about human diseases that can't be studied in other animal models.
Another 35 of the silenced genes may shed light on the parasitic platyhelminthes, such as Schitosoma mansoni, which cause
disease in millions of people. The genes identified by the U researchers may be required for the survival of the parasites.
"Considering such pathogens are estimated to cause disease in nearly 300 million people throughout the world, these genes
might make attractive drug targets," S?nchez Alvarado and his fellow researchers wrote in the study.
The planarian makes an ideal biological model for three important reasons, according to S?nchez Alvarado.
-- It is amenable to genetic manipulation.
-- It is an extremely simple organism with little redundancy in its genes, meaning it has fewer genes to carry out specific
functions. This makes it easier to identify a gene's function by silencing it and will help how researchers target their
efforts on equivalent genes in mice or zebrafish, for example.
-- It is inexpensive to study.
Now that S?nchez Alvarado and his colleagues have opened the door to understanding regeneration by identifying key genes in
the process, the U researcher predicts, with aid of the planarian, more discoveries are on the way.
"Our limitations right now are how many experiments we can do in a day," he said. "The mystery of what makes regeneration
possible, particularly in these animals, is on its way to finally being resolved."
Other authors of the study include Peter W. Reddien, Ph.D, Helen Hay Whitney Foundation postdoctoral fellow, Kenneth J.
Murfitt, and Joya R. Jennings, all of the University of Utah Department of Neurobiology and Anatomy in the School of
Medicine; and Adam L. Bermange, currently at the London Research Institute.
This news release and a downloadable, high-resolution photograph will be available at this Web site at noon (EST) on Monday,
May 2. utah.edu/unews/releases/05/may/planaria.html
Contact: Phil Sahm, Office of Public Affairs
Phil.Sahmhsc.utah.edu
801-581-2517
University of Utah Health Sciences Center
uuhsc.utah.edu
Sleep Treatment Often Denied To Insomnia Patients When They Have Mental Health Conditions
Patients with insomnia who are diagnosed with accompanying mental health ailments often are not prescribed medication that will help them sleep - which could then make related anxiety or depression worse, new research suggests.
Scientists examining treatment patterns for insomniacs say that their findings suggest that many doctors appear to be reluctant to prescribe sleep aids, even those that pose no risk of dependence, if patients also have depression, anxiety or mood disorders. An exception is psychiatrists, who were found to be twice as likely as primary care physicians to prescribe medication for insomnia.
"Insomnia can cause you to have anxiety and depression, and depression and anxiety can cause you to have insomnia. It's a chicken-and-egg type of story. But research has shown that if one of the conditions is left untreated it can exacerbate the other condition," said senior study author Rajesh Balkrishnan, the Merrell Dow professor of pharmacy at Ohio State University.
"What this calls for is specific guidelines related to the treatment of insomnia that takes into consideration these different types of patients, because insomnia has become such a big public health problem."
An estimated 20 percent of Americans have occasional sleep problems, with about one in 10 suffering from chronic insomnia.
Balkrishnan acknowledges concerns that physicians might have about prescribing certain medications that can cause dependence, especially to patients with mental health disorders. Older sleep aids, a class of drugs called benzodiazepines, are muscle relaxants with addictive properties and high potential for abuse. However, since the early 1990s, a new class of drugs for insomnia called non-benzodiazepines has been on the market. They are effective sleep aids that don't carry the risk of addiction, Balkrishnan said, and for that reason, patients should have ready access to these medications.
"This research highlights the need to take into account that many patients who see their doctors with complaints of insomnia also have a psychiatric condition. But the presence of those mental conditions should not preclude them from being appropriately treated for their insomnia," he said.
The study is published in the January issue of the Journal of Medical Economics.
Balkrishnan and colleagues collected data from the National Ambulatory Medical Care Survey, which tracks Americans' annual outpatient medical visits. The researchers identified 5,487 physician visits by patients with insomnia between 1995 and 2004, which was calculated to represent about 161 million U.S. patients over that 10-year period.
According to the analysis, an estimated 6.5 million Americans who saw a doctor for insomnia also were diagnosed with a mental health disorder. Of the visits examined, 38 percent of patients with insomnia were diagnosed with at least one other condition, and at least four of every 10 of those accompanying conditions related to mental health. The most common additional condition was anxiety (15.6 percent), followed by episodic mood disorders (14.9 percent), high blood pressure (10.1 percent), depression (7 percent) and diabetes (3.5 percent).
The study showed that insomnia patients with mental health disorders were 36 percent less likely to receive medication for their sleeping problems than were patients without the mental health diagnosis. Those with anxiety were the least likely to receive a sleep aid, with a 45 percent decreased likelihood of receiving medication for insomnia compared to patients without anxiety.
Balkrishnan said that with generic forms of nonaddictive insomnia medication available by prescription, even patients taking antidepressants and anti-anxiety drugs can safely - and affordably - add a sleep aid to their regimen. The most common forms of antidepressants prescribed in the United States are a class of drugs called selective serotonin reuptake inhibitors (SSRIs).
"Physicians might perceive that drowsiness is induced by medications such as SSRIs so there might be a general fear about combining them with insomnia medications," Balkrishnan said. "But I think those fears are somewhat unfounded because we found that psychiatrists don't have any problems prescribing sleep medications in patients who have accompanying mental conditions; they know there is no danger of a drug-to-drug interaction."
According to the analysis, patients visiting psychiatrists had two times higher odds of receiving medication for insomnia than patients visiting family practice or internal medicine physicians. The study showed that 33 percent of patients with insomnia saw family practice or internal medicine physicians, 30 percent visited psychiatrists and 9 percent went to neurologists.
The study identified other factors associated with insomnia medication prescribing patterns - for example, older and established patients were more likely to receive insomnia medications than were younger patients or those seeing the doctor for the first time. But Balkrishnan said a clear theme emerged from the analysis.
"There is a divide in who gets appropriate medication and who is not appropriately medicated," he said. "It might not be happening willfully, but it points to a knowledge gap between different types of physicians and the need to develop widely accepted treatment guidelines. And the guidelines should be ratified by essentially all physicians treating the condition."
This research was funded by a grant from Sanofi-Aventis, a sleep-aid manufacturer based in Bridgewater, N.J. The study does not discuss any specific products of the sponsor company. Balkrishnan is a paid consultant for the company.
Co-authors on the study were Manjiri Pawaskar of Ohio State's College of Pharmacy, Vijay Joish of Sanofi-Aventis, Fabian Camacho of Wake Forest University School of Medicine, and Rafia Rasu of the University of Missouri-Kansas City.
Written by Emily Caldwell
Scientists examining treatment patterns for insomniacs say that their findings suggest that many doctors appear to be reluctant to prescribe sleep aids, even those that pose no risk of dependence, if patients also have depression, anxiety or mood disorders. An exception is psychiatrists, who were found to be twice as likely as primary care physicians to prescribe medication for insomnia.
"Insomnia can cause you to have anxiety and depression, and depression and anxiety can cause you to have insomnia. It's a chicken-and-egg type of story. But research has shown that if one of the conditions is left untreated it can exacerbate the other condition," said senior study author Rajesh Balkrishnan, the Merrell Dow professor of pharmacy at Ohio State University.
"What this calls for is specific guidelines related to the treatment of insomnia that takes into consideration these different types of patients, because insomnia has become such a big public health problem."
An estimated 20 percent of Americans have occasional sleep problems, with about one in 10 suffering from chronic insomnia.
Balkrishnan acknowledges concerns that physicians might have about prescribing certain medications that can cause dependence, especially to patients with mental health disorders. Older sleep aids, a class of drugs called benzodiazepines, are muscle relaxants with addictive properties and high potential for abuse. However, since the early 1990s, a new class of drugs for insomnia called non-benzodiazepines has been on the market. They are effective sleep aids that don't carry the risk of addiction, Balkrishnan said, and for that reason, patients should have ready access to these medications.
"This research highlights the need to take into account that many patients who see their doctors with complaints of insomnia also have a psychiatric condition. But the presence of those mental conditions should not preclude them from being appropriately treated for their insomnia," he said.
The study is published in the January issue of the Journal of Medical Economics.
Balkrishnan and colleagues collected data from the National Ambulatory Medical Care Survey, which tracks Americans' annual outpatient medical visits. The researchers identified 5,487 physician visits by patients with insomnia between 1995 and 2004, which was calculated to represent about 161 million U.S. patients over that 10-year period.
According to the analysis, an estimated 6.5 million Americans who saw a doctor for insomnia also were diagnosed with a mental health disorder. Of the visits examined, 38 percent of patients with insomnia were diagnosed with at least one other condition, and at least four of every 10 of those accompanying conditions related to mental health. The most common additional condition was anxiety (15.6 percent), followed by episodic mood disorders (14.9 percent), high blood pressure (10.1 percent), depression (7 percent) and diabetes (3.5 percent).
The study showed that insomnia patients with mental health disorders were 36 percent less likely to receive medication for their sleeping problems than were patients without the mental health diagnosis. Those with anxiety were the least likely to receive a sleep aid, with a 45 percent decreased likelihood of receiving medication for insomnia compared to patients without anxiety.
Balkrishnan said that with generic forms of nonaddictive insomnia medication available by prescription, even patients taking antidepressants and anti-anxiety drugs can safely - and affordably - add a sleep aid to their regimen. The most common forms of antidepressants prescribed in the United States are a class of drugs called selective serotonin reuptake inhibitors (SSRIs).
"Physicians might perceive that drowsiness is induced by medications such as SSRIs so there might be a general fear about combining them with insomnia medications," Balkrishnan said. "But I think those fears are somewhat unfounded because we found that psychiatrists don't have any problems prescribing sleep medications in patients who have accompanying mental conditions; they know there is no danger of a drug-to-drug interaction."
According to the analysis, patients visiting psychiatrists had two times higher odds of receiving medication for insomnia than patients visiting family practice or internal medicine physicians. The study showed that 33 percent of patients with insomnia saw family practice or internal medicine physicians, 30 percent visited psychiatrists and 9 percent went to neurologists.
The study identified other factors associated with insomnia medication prescribing patterns - for example, older and established patients were more likely to receive insomnia medications than were younger patients or those seeing the doctor for the first time. But Balkrishnan said a clear theme emerged from the analysis.
"There is a divide in who gets appropriate medication and who is not appropriately medicated," he said. "It might not be happening willfully, but it points to a knowledge gap between different types of physicians and the need to develop widely accepted treatment guidelines. And the guidelines should be ratified by essentially all physicians treating the condition."
This research was funded by a grant from Sanofi-Aventis, a sleep-aid manufacturer based in Bridgewater, N.J. The study does not discuss any specific products of the sponsor company. Balkrishnan is a paid consultant for the company.
Co-authors on the study were Manjiri Pawaskar of Ohio State's College of Pharmacy, Vijay Joish of Sanofi-Aventis, Fabian Camacho of Wake Forest University School of Medicine, and Rafia Rasu of the University of Missouri-Kansas City.
Written by Emily Caldwell
воскресенье, 3 июля 2011 г.
Researchers Lift A Corner Of The Veil Of Depression
Antwerp, Belgium and Ume??, Sweden ??' About 1 in 10 Europeans has to contend with some form of depression during his or her life. But how people become depressed is still largely a mystery. With their recent research, scientists from the Flanders Interuniversity Institute for Biotechnology (VIB) connected to the University of Antwerp in collaboration with scientists of the University of Ume?? in Sweden, are lifting a corner of the veil. Their studies indicate that the TPH2 protein is involved in the development of depression and manic depression.
Depression and manic depression
Depression is one of the most prevalent disorders in the Western world, and, according to the World Health Organization, it will even be the No. 1 disorder in 2020. Ten to 15 per cent of the population ??' from all levels of society ??' experience depression during their lifetime; and about 5% has to contend with manic depression. Despite the high socio-economic costs and mortality rate, the causes of these psychiatric disorders are not yet known. However, scientists are in agreement that the origin of depression can be attributed to a combination of hereditary and environmental factors such as stress.
The role of serotonin
The hormone serotonin plays an important role in our brain chemistry. The amount of serotonin in the brain has a large influence on our thinking, emotions and behavior. Because antidepressants affect the level of serotonin in the brain, it has long been suspected that serotonin plays a role in the development of psychiatric disorders. So, the amount of serotonin that you produce and keep under control appears to be crucial in the fight against (manic) depression. Because the TPH2 protein is instrumental in regulating the serotonin level, scientists suspect that TPH2 plays a role in the development of psychiatric disorders.
Genetic study
Ann Van Den Bogaert and her colleagues from the research group of Jurgen Del-Favero have also been studying the role of TPH2 in the development of depression and manic depression. They have conducted a genetic study in which they compared the variation in the TPH2 gene between patients with depression and healthy individuals. The DNA of two random individuals are 99.9% identical ??' the 0.1% that is different contains the genetic variation that can originate disorders.
In collaboration with the Swedish research group under the direction of Rolf Adolfsson and Karl-Fredrik Norrback, the researchers studied the DNA of hundreds of Swedish patients with depression and manic depression and that of healthy control subjects. By comparing the genetic variations between the patients and healthy individuals, they have shown that in this Swedish population TPH2 is involved in the development of depression and manic depression.
Thus, their research brings us a step closer to a better understanding of these psychiatric disorders.
Contact: Sooike Stoops
infovib.be
VIB, Flanders Interuniversity Institute of Biotechnology
Depression and manic depression
Depression is one of the most prevalent disorders in the Western world, and, according to the World Health Organization, it will even be the No. 1 disorder in 2020. Ten to 15 per cent of the population ??' from all levels of society ??' experience depression during their lifetime; and about 5% has to contend with manic depression. Despite the high socio-economic costs and mortality rate, the causes of these psychiatric disorders are not yet known. However, scientists are in agreement that the origin of depression can be attributed to a combination of hereditary and environmental factors such as stress.
The role of serotonin
The hormone serotonin plays an important role in our brain chemistry. The amount of serotonin in the brain has a large influence on our thinking, emotions and behavior. Because antidepressants affect the level of serotonin in the brain, it has long been suspected that serotonin plays a role in the development of psychiatric disorders. So, the amount of serotonin that you produce and keep under control appears to be crucial in the fight against (manic) depression. Because the TPH2 protein is instrumental in regulating the serotonin level, scientists suspect that TPH2 plays a role in the development of psychiatric disorders.
Genetic study
Ann Van Den Bogaert and her colleagues from the research group of Jurgen Del-Favero have also been studying the role of TPH2 in the development of depression and manic depression. They have conducted a genetic study in which they compared the variation in the TPH2 gene between patients with depression and healthy individuals. The DNA of two random individuals are 99.9% identical ??' the 0.1% that is different contains the genetic variation that can originate disorders.
In collaboration with the Swedish research group under the direction of Rolf Adolfsson and Karl-Fredrik Norrback, the researchers studied the DNA of hundreds of Swedish patients with depression and manic depression and that of healthy control subjects. By comparing the genetic variations between the patients and healthy individuals, they have shown that in this Swedish population TPH2 is involved in the development of depression and manic depression.
Thus, their research brings us a step closer to a better understanding of these psychiatric disorders.
Contact: Sooike Stoops
infovib.be
VIB, Flanders Interuniversity Institute of Biotechnology
суббота, 2 июля 2011 г.
Psychotherapy Combined With Antidepressant Medication Most Effective In Depressed Adolescents
A combination of psychotherapy and antidepressant medication appears to be the most effective treatment for adolescents with major depressive disorder -- more than medication alone or psychotherapy alone, according to results from a major clinical trial funded by the National Institutes of Health's National Institute of Mental Health (NIMH). The study was published in the October 2007 issue of the Archives of General Psychiatry.
The long-term results of the Treatment for Adolescents with Depression Study (TADS) found that when adolescents received fluoxetine (Prozac) alone or in combination with cognitive behavioral therapy (CBT) over the course of 36 weeks, they recovered faster than those who were receiving CBT alone.
However, taking fluoxetine alone appeared to pose some safety concerns for the teens. During treatment, those taking fluoxetine alone had higher rates of suicidal thinking (15 percent) than those in combination treatment (8 percent) and those in CBT alone (6 percent), particularly in the early stages of treatment. This suggests that while treatment with fluoxetine may speed recovery, adding CBT provides additional safeguards for those vulnerable to suicide, according to the researchers.
"Depression in teens is a serious illness that can and should be treated aggressively," said NIMH Director Thomas R. Insel, M.D. "TADS provides compelling evidence for families and clinicians that the most effective way to treat depression in teens is with a two-pronged approach. It reassures us that antidepressant medication combined with psychotherapy is an effective and safe way to help teens recover from this disabling illness."
Results at 36 weeks of treatment were consistent with those found at 12 weeks in the 439-person study, when NIMH reported that combination treatment produced the greatest improvement in teenagers with major depression. At 18 weeks (results not previously reported), combination treatment still outpaced the other treatments with an 85 percent response rate, compared to 69 percent for fluoxetine alone and 65 percent for CBT alone. By 36 weeks, the response rate to combination treatment still remained the highest (86 percent), while response rates to fluoxetine and CBT essentially caught up, at 81 percent each.
"In the combination approach, the two treatments complemented each other," said John March, M.D, MPH, of Duke University and lead author of the study. "The fluoxetine can help dissipate the physical symptoms of major depression relatively quickly, and CBT can help patients develop new skills to contend with difficult, negative emotions."
Because the trial sample included a mix of younger and older teens, both genders, substantial minority representation and variable socioeconomic status, the TADS results can be applied broadly to the adolescent population.
The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, nimh.nih/.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
Reference: The TADS Team. The Treatment for Adolescents with Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Archives of General Psychiatry. Oct 2007; VOL 64(10).
The long-term results of the Treatment for Adolescents with Depression Study (TADS) found that when adolescents received fluoxetine (Prozac) alone or in combination with cognitive behavioral therapy (CBT) over the course of 36 weeks, they recovered faster than those who were receiving CBT alone.
However, taking fluoxetine alone appeared to pose some safety concerns for the teens. During treatment, those taking fluoxetine alone had higher rates of suicidal thinking (15 percent) than those in combination treatment (8 percent) and those in CBT alone (6 percent), particularly in the early stages of treatment. This suggests that while treatment with fluoxetine may speed recovery, adding CBT provides additional safeguards for those vulnerable to suicide, according to the researchers.
"Depression in teens is a serious illness that can and should be treated aggressively," said NIMH Director Thomas R. Insel, M.D. "TADS provides compelling evidence for families and clinicians that the most effective way to treat depression in teens is with a two-pronged approach. It reassures us that antidepressant medication combined with psychotherapy is an effective and safe way to help teens recover from this disabling illness."
Results at 36 weeks of treatment were consistent with those found at 12 weeks in the 439-person study, when NIMH reported that combination treatment produced the greatest improvement in teenagers with major depression. At 18 weeks (results not previously reported), combination treatment still outpaced the other treatments with an 85 percent response rate, compared to 69 percent for fluoxetine alone and 65 percent for CBT alone. By 36 weeks, the response rate to combination treatment still remained the highest (86 percent), while response rates to fluoxetine and CBT essentially caught up, at 81 percent each.
"In the combination approach, the two treatments complemented each other," said John March, M.D, MPH, of Duke University and lead author of the study. "The fluoxetine can help dissipate the physical symptoms of major depression relatively quickly, and CBT can help patients develop new skills to contend with difficult, negative emotions."
Because the trial sample included a mix of younger and older teens, both genders, substantial minority representation and variable socioeconomic status, the TADS results can be applied broadly to the adolescent population.
The National Institute of Mental Health (NIMH) mission is to reduce the burden of mental and behavioral disorders through research on mind, brain, and behavior. More information is available at the NIMH website, nimh.nih/.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
Reference: The TADS Team. The Treatment for Adolescents with Depression Study (TADS): Long-term Effectiveness and Safety Outcomes. Archives of General Psychiatry. Oct 2007; VOL 64(10).
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