Phenytoin is a well known antiepileptic agent widely used throughout the world. Recent clinical studies in patients with bipolar disorder have suggested that, as for other anticonvulsant drugs commonly used in the treatment of bipolar patients including valproate and carbamazepine, phenytoin may have mood-stabilizing effects in addition to its well-known anticonvulsant properties. In a study published in the March 2010 issue of Experimental Biology and Medicine Veronica Mariotti and colleagues utilized DNA microarrays to investigate the molecular underpinnings of the potential mood-stabilizing action of phenytoin by looking at its effect on gene expression in the rat brain.
As compared with untreated animals, rats treated for a month with phenytoin had 508 differentially expressed genes in the hippocampus and 62 in the frontal cortex, including genes involved in GABAergic and glutamatergic neurotransmission, neuroprotection and other genes thought to be crucial for mood regulation. Furthermore, some of these same genes have been shown to be modulated by classical mood-stabilizer agents, like lithium and valproate.
Thus, the findings of this study indicate that chronic phenytoin administration modulates the expression of genes involved in mood regulation and genes that are targets of established mood stabilizers. Dr Mariotti noted that "The results of this study provide preliminary insights into possible molecular mechanisms of action of phenytoin as a potential mood stabilizer and, more in general, the pathophysiology of bipolar disorders".
The study is the product of a fruitful collaboration between the Molecular Biology Laboratory of Dr. Silvia Pellegrini at the Department of Experimental Pathology, University of Pisa Medical School, Pisa, Italy and the Laboratory of Professors Galila Agam and R.H. Belmaker at the Psychiatry Research Unit at the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said "Mariotti and colleagues have provided very interesting results on the changes in gene expression in rats treated with phenytoin. There findings shed significant light on the mood altering effects of this antiepileptic drug".
Source:
Dr. Silvia Pellegrini
Society for Experimental Biology and Medicine
Friday, 30 April 2010
Thursday, 29 April 2010
Alaska Northern Lights Offers Bright Light Therapy To Combat Common Health Problems
Alaska Northern Lights manufactures a bright light therapy box that aids in treating chronic health problems such as seasonal affective disorder (SAD), depression, bipolar disorder and sleep problems. Sufferers of SAD, a form of clinical depression, include up to 25 percent of those living in northern latitudes who experience varying degrees of SAD during winter months when there is less natural light. Night shift workers are also susceptible to SAD which affects over one third of the population, or about 10.8 million Americans.
"Our bright light box treatment affects the pineal gland's production of melatonin, a hormone that is believed to help prevent and relieve symptoms of depression," says Alaska Northern Lights President Cort Christie. "We find that our bright light box treatment, prescribed by physicians for SAD, also works extremely well for insomnia and other health problems." Christie says that daily use can reduce time lost from work and reduced productivity.
"Many people subscribe to 'I'll just deal with it' thinking when it comes to SAD, depression or insomnia," said Christie. "But these illnesses may lead to more serious health problems and put a tremendous strain on relationships." The bright light therapy box is a healthy and inexpensive alternative to prescription drugs which can make users groggy and lead to bizarre side effects such as sleep eating and sleep driving. We believe that people should try a safe, non-prescription treatment first to alleviate problems."
Source
Alaska Northern Lights
"Our bright light box treatment affects the pineal gland's production of melatonin, a hormone that is believed to help prevent and relieve symptoms of depression," says Alaska Northern Lights President Cort Christie. "We find that our bright light box treatment, prescribed by physicians for SAD, also works extremely well for insomnia and other health problems." Christie says that daily use can reduce time lost from work and reduced productivity.
"Many people subscribe to 'I'll just deal with it' thinking when it comes to SAD, depression or insomnia," said Christie. "But these illnesses may lead to more serious health problems and put a tremendous strain on relationships." The bright light therapy box is a healthy and inexpensive alternative to prescription drugs which can make users groggy and lead to bizarre side effects such as sleep eating and sleep driving. We believe that people should try a safe, non-prescription treatment first to alleviate problems."
Source
Alaska Northern Lights
Common Copy Number Variations In Genes Unlikely To Contribute Significantly Toward Common Diseases
In 2007, the Wellcome Trust Case Control Consortium (WTCCC) published the results of the largest ever study of the genetics of common diseases, revealing for the first time a number of genes which were found to increase the risk of developing certain diseases. Since then, dozens more genes have been found.
Despite the large numbers of genes discovered, scientists are still some way off explaining all of the heritability of the diseases. For example, for type 2 diabetes, there are now around thirty genetic variants known to influence susceptibility to the disease, but these only account for about 10 per cent of the known inherited risk of developing these conditions.
One theory for this so-called 'missing heritability' was that it may have been caused by copy number variations (CNVs). These mainly occur when copies of the genome are passed down from parent to child. Just as mutations in the genome can give rise to different forms of genes, so whole segments of the genome may end up being duplicated or deleted - these are known as CNVs. CNVs have already been found to cause disease in rare cases, however. For example, deletions of part of chromosome 16 have previously been shown to lead to severe obesity from a young age.
Researchers from the WTCCC analysed common CNVs in DNA samples from 3,000 healthy volunteers and compared them to 16,000 patients - 2,000 each with bipolar disorder, breast cancer, coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, type 1 diabetes and type 2 diabetes respectively.
The team identified and confirmed three loci (genetic regions) that contained a commonly occurring CNV and were also associated with common disease. However, all three loci had been identified previously by searching for changes in single letters of the DNA code (known as single nucleotide polymorphisms, or 'SNPs'); by comparison, this technique, used in the original WTCCC study, identified twenty-four genetic loci. None of the three CNV loci is believed to be a 'functional variant' - in other words, it is unlikely that they contribute to disease.
"It seems unlikely that common CNVs play a major role in the genetic basis of common diseases, either through particular CNVs having a strong effect or through a large number of CNVs each contributing a small effect," concludes Dr Matt Hurles from Wellcome Trust Sanger Institute. "This is certainly the case for the diseases that we studied, but is likely to be the case for other common diseases, too."
"There was a strong view that CNVs would be important for common disease, and that they would explain much of the missing heritability," says Professor Peter Donnelly from the University of Oxford, who chairs the WTCCC. "We now believe this is not the case. Our results will be surprising and disappointing for some parts of the community."
Professor Donnelly believes that the estimates of heritability may have been overstated, and there is consequently less missing than was previously thought. The remaining genetic contribution to disease will likely comprise rare CNVs and rare SNPs, and epigenetic factors, as well as many more common gene variants and, to a lesser extent, common CNVs.
"Understanding bipolar disorder and other complex diseases is as much about ruling out possible suspects as it is about identifying new ones," says Nick Craddock, Professor of Psychiatry at Cardiff University and a study author. "We now know that we can likely focus our attention away from common CNVs and focus on other common and rare genetic variations, which we hope will provide biological insights that will lead to important advances in human physical and mental health."
Researchers involved in the WTCCC will now try to better understand the collective role of both rarer SNPs and rarer CNVs. A study funded recently by the National Institutes of Health in the US and by the Wellcome Trust, and led by Professor Mark McCarthy from the University of Oxford, will search for a contribution of rarer SNPs towards type 2 diabetes.
Source:
Craig Brierley
Wellcome Trust
Despite the large numbers of genes discovered, scientists are still some way off explaining all of the heritability of the diseases. For example, for type 2 diabetes, there are now around thirty genetic variants known to influence susceptibility to the disease, but these only account for about 10 per cent of the known inherited risk of developing these conditions.
One theory for this so-called 'missing heritability' was that it may have been caused by copy number variations (CNVs). These mainly occur when copies of the genome are passed down from parent to child. Just as mutations in the genome can give rise to different forms of genes, so whole segments of the genome may end up being duplicated or deleted - these are known as CNVs. CNVs have already been found to cause disease in rare cases, however. For example, deletions of part of chromosome 16 have previously been shown to lead to severe obesity from a young age.
Researchers from the WTCCC analysed common CNVs in DNA samples from 3,000 healthy volunteers and compared them to 16,000 patients - 2,000 each with bipolar disorder, breast cancer, coronary artery disease, Crohn's disease, hypertension, rheumatoid arthritis, type 1 diabetes and type 2 diabetes respectively.
The team identified and confirmed three loci (genetic regions) that contained a commonly occurring CNV and were also associated with common disease. However, all three loci had been identified previously by searching for changes in single letters of the DNA code (known as single nucleotide polymorphisms, or 'SNPs'); by comparison, this technique, used in the original WTCCC study, identified twenty-four genetic loci. None of the three CNV loci is believed to be a 'functional variant' - in other words, it is unlikely that they contribute to disease.
"It seems unlikely that common CNVs play a major role in the genetic basis of common diseases, either through particular CNVs having a strong effect or through a large number of CNVs each contributing a small effect," concludes Dr Matt Hurles from Wellcome Trust Sanger Institute. "This is certainly the case for the diseases that we studied, but is likely to be the case for other common diseases, too."
"There was a strong view that CNVs would be important for common disease, and that they would explain much of the missing heritability," says Professor Peter Donnelly from the University of Oxford, who chairs the WTCCC. "We now believe this is not the case. Our results will be surprising and disappointing for some parts of the community."
Professor Donnelly believes that the estimates of heritability may have been overstated, and there is consequently less missing than was previously thought. The remaining genetic contribution to disease will likely comprise rare CNVs and rare SNPs, and epigenetic factors, as well as many more common gene variants and, to a lesser extent, common CNVs.
"Understanding bipolar disorder and other complex diseases is as much about ruling out possible suspects as it is about identifying new ones," says Nick Craddock, Professor of Psychiatry at Cardiff University and a study author. "We now know that we can likely focus our attention away from common CNVs and focus on other common and rare genetic variations, which we hope will provide biological insights that will lead to important advances in human physical and mental health."
Researchers involved in the WTCCC will now try to better understand the collective role of both rarer SNPs and rarer CNVs. A study funded recently by the National Institutes of Health in the US and by the Wellcome Trust, and led by Professor Mark McCarthy from the University of Oxford, will search for a contribution of rarer SNPs towards type 2 diabetes.
Source:
Craig Brierley
Wellcome Trust
Researchers Refine DNA Testing For Predisposition To Bipolar Disorder
Genetic testing may rise to a new level with the findings of Indiana University School of Medicine researchers whose "prototype" for laboratory testing for bipolar disorder appears today in the online edition of the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics.
"This is an important advance in the development of a prototype for lab tests for bipolar disorder, and can serve as a model for developing tests in other complex disorders," said lead author Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and director of INBRAIN at the IU Institute of Psychiatric Research.
Dr. Niculescu and colleagues used two different populations from large scale genetic studies and compared those individuals' genes to a small panel of 56 genes implicated in bipolar disorder by their work, to predict who has a predisposition to the disease.
The analysis resulted in a genetic risk prediction score that indicates high or low potential for developing bipolar disorder. "The coupling of a high score with certain environmental factors may be a predictor, not a certainty, that the individual will develop bipolar disorder" said Dr. Niculescu, who also is a staff psychiatrist at the Indianapolis Roudebush VA Medical Center.
"Genes explain a small portion of the risk of developing the illness," said Dr. Niculescu. "Unlike some genetic predisposition to diseases like Huntington's or cystic fibrosis, the variances in genes that can predispose people to mood disorders are found in all of us. What we are learning is that it may take a combination of factors - too many gene variances in the wrong environment and you are at higher risk."
The predictive value of the genetic risk factors could be useful in screening before the disorder manifests itself clinically, and the implementation of interventions to lower stress, adjust regular sleep hours and other life style factors that could serve as an environmental deterrent for developing bipolar disorder. Closer follow-up and earlier therapeutic intervention may be useful for individuals who are at higher risk.
Authors on the study include Sagar D. Patel, Dr. Helen Le-Niculescu, Dr. Daniel Koller, Stephen D. Green, Dr. Debomoy K. Lahiri, Dr. Francis J. McMahon and Dr. John I. Nurnberger, Jr.
The research was funded by the Veterans Administration as well as the National Institute of Mental Health.
In a corresponding editorial in the American Journal of Medical Genetics, Dr. Alexander B. Niculescu and Dr. Helen Le-Niculescu advocate for a more efficient way to identify genes involved with mental disorders.
"Coming to Grips With Complex Disorders: Genetic Risk Prediction in Bipolar Disorder Using Panels of Genes Identified Through Convergent Functional Genomics," by Patel SD, Le-Niculescu H, Koller DL, Green SD, Lahiri DK, McMahon FJ, Nurnberger JI, and Niculescu AB. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010. Epub April 9.
Source
Indiana University
"This is an important advance in the development of a prototype for lab tests for bipolar disorder, and can serve as a model for developing tests in other complex disorders," said lead author Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and director of INBRAIN at the IU Institute of Psychiatric Research.
Dr. Niculescu and colleagues used two different populations from large scale genetic studies and compared those individuals' genes to a small panel of 56 genes implicated in bipolar disorder by their work, to predict who has a predisposition to the disease.
The analysis resulted in a genetic risk prediction score that indicates high or low potential for developing bipolar disorder. "The coupling of a high score with certain environmental factors may be a predictor, not a certainty, that the individual will develop bipolar disorder" said Dr. Niculescu, who also is a staff psychiatrist at the Indianapolis Roudebush VA Medical Center.
"Genes explain a small portion of the risk of developing the illness," said Dr. Niculescu. "Unlike some genetic predisposition to diseases like Huntington's or cystic fibrosis, the variances in genes that can predispose people to mood disorders are found in all of us. What we are learning is that it may take a combination of factors - too many gene variances in the wrong environment and you are at higher risk."
The predictive value of the genetic risk factors could be useful in screening before the disorder manifests itself clinically, and the implementation of interventions to lower stress, adjust regular sleep hours and other life style factors that could serve as an environmental deterrent for developing bipolar disorder. Closer follow-up and earlier therapeutic intervention may be useful for individuals who are at higher risk.
Authors on the study include Sagar D. Patel, Dr. Helen Le-Niculescu, Dr. Daniel Koller, Stephen D. Green, Dr. Debomoy K. Lahiri, Dr. Francis J. McMahon and Dr. John I. Nurnberger, Jr.
The research was funded by the Veterans Administration as well as the National Institute of Mental Health.
In a corresponding editorial in the American Journal of Medical Genetics, Dr. Alexander B. Niculescu and Dr. Helen Le-Niculescu advocate for a more efficient way to identify genes involved with mental disorders.
"Coming to Grips With Complex Disorders: Genetic Risk Prediction in Bipolar Disorder Using Panels of Genes Identified Through Convergent Functional Genomics," by Patel SD, Le-Niculescu H, Koller DL, Green SD, Lahiri DK, McMahon FJ, Nurnberger JI, and Niculescu AB. American Journal of Medical Genetics Part B (Neuropsychiatric Genetics). 2010. Epub April 9.
Source
Indiana University
Wednesday, 28 April 2010
Psychiatry Symposium To Address Collaborations In Mood Disorder Research
The Johns Hopkins University School of Medicine will hold its 24th Annual Mood Disorders Research and Education Symposium on April 20, focusing on joint efforts between researchers and clinicians to study and treat depression and bipolar disease.
Speakers on these topics from Hopkins and elsewhere will give talks from 12:45 p.m. to 6 p.m. in Turner Auditorium on Johns Hopkins Medicine's East Baltimore campus.
Among the presenters:
- Col. Elspeth Cameron Ritchie, M.D., adult and forensic psychiatrist and medical director of the Army Medical Department's Office of Strategic Communications. An internationally recognized expert, she brings a public health approach to the management of disaster- and combat-related mental health issues. She will address the challenges of recognizing and treating mood disorders and posttraumatic stress disorder in the military communit
- Kay Redfield Jamison, Ph.D., professor of psychiatry and behavioral sciences, co-director of the Johns Hopkins Mood Disorders Center, and an internationally recognized author. She will offer a historical perspective on mood disorders focusing on the biography of 19th century poet Nathaniel Hawthorne.
- James Potash, M.D., M.P.H., associate professor of psychiatry at the Johns Hopkins University School of Medicine, will describe current collaborative efforts to understand the underlying causes of mood disorders through genetic research. His recent research includes the identification of a novel genetic component in major depression, found by analyzing data from three major genetic studies of mood disorders.
Other speakers include Karen Swartz, M.D., director of the Mood Disorders Clinical Programs at the Johns Hopkins University School of Medicine; John Greden, M.D., former chair of psychiatry at the University of Michigan, founder of the Michigan Depression Center, and founding chair of the National Network of Depression Centers; Frank DeGruy, M.D., M.S.F.M., professor and chair of the Department of Family Medicine and director of primary care outreach and research at the University of Colorado Denver School of Medicine; and David A. Axelson, M.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine and director of the Child and Adolescent Bipolar Services Program at the Western Psychiatric Institute and Clinic.
Mood disorders are among the most common illnesses in the world. An estimated 20 percent of adults suffer from depression or bipolar disorder.
Intended for psychiatrists, social workers, psychologists and counselors, the symposium is also open to patients, family members and anyone who has an interest in learning more about bipolar disorders and recurrent depression.
The symposium is presented by the Johns Hopkins Department of Psychiatry and Behavioral Sciences, the Johns Hopkins Mood Disorders Center and the Institute for Johns Hopkins Nursing.
Source
Johns Hopkins Medicine
Speakers on these topics from Hopkins and elsewhere will give talks from 12:45 p.m. to 6 p.m. in Turner Auditorium on Johns Hopkins Medicine's East Baltimore campus.
Among the presenters:
- Col. Elspeth Cameron Ritchie, M.D., adult and forensic psychiatrist and medical director of the Army Medical Department's Office of Strategic Communications. An internationally recognized expert, she brings a public health approach to the management of disaster- and combat-related mental health issues. She will address the challenges of recognizing and treating mood disorders and posttraumatic stress disorder in the military communit
- Kay Redfield Jamison, Ph.D., professor of psychiatry and behavioral sciences, co-director of the Johns Hopkins Mood Disorders Center, and an internationally recognized author. She will offer a historical perspective on mood disorders focusing on the biography of 19th century poet Nathaniel Hawthorne.
- James Potash, M.D., M.P.H., associate professor of psychiatry at the Johns Hopkins University School of Medicine, will describe current collaborative efforts to understand the underlying causes of mood disorders through genetic research. His recent research includes the identification of a novel genetic component in major depression, found by analyzing data from three major genetic studies of mood disorders.
Other speakers include Karen Swartz, M.D., director of the Mood Disorders Clinical Programs at the Johns Hopkins University School of Medicine; John Greden, M.D., former chair of psychiatry at the University of Michigan, founder of the Michigan Depression Center, and founding chair of the National Network of Depression Centers; Frank DeGruy, M.D., M.S.F.M., professor and chair of the Department of Family Medicine and director of primary care outreach and research at the University of Colorado Denver School of Medicine; and David A. Axelson, M.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine and director of the Child and Adolescent Bipolar Services Program at the Western Psychiatric Institute and Clinic.
Mood disorders are among the most common illnesses in the world. An estimated 20 percent of adults suffer from depression or bipolar disorder.
Intended for psychiatrists, social workers, psychologists and counselors, the symposium is also open to patients, family members and anyone who has an interest in learning more about bipolar disorders and recurrent depression.
The symposium is presented by the Johns Hopkins Department of Psychiatry and Behavioral Sciences, the Johns Hopkins Mood Disorders Center and the Institute for Johns Hopkins Nursing.
Source
Johns Hopkins Medicine
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