Bipolar
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Anti-Epileptic Drugs Found Safe to Treat Bipolar Disorder WEDNESDAY, Dec. 9 (HealthDay News) -- The risk of suicidality among bipolar disorder patients treated with anti-epileptic drugs does not increase relative to those taking lithium or no drugs, according to a study published in the December issue of the Archives of General Psychiatry. Robert D. Gibbons, Ph.D., of the University of Illinois in Chicago, and colleagues analyzed data from a medical claims database on 47,918 bipolar disorder patients to ascertain suicide attempt rates among those taking any of 11 anti-epileptic drugs that were included in a U.S. Food and Drug Administration alert on increased risk of suicide, as well as rates for those taking lithium, or neither type of medication. There were 13 suicide attempts per 1,000 person-years for patients taking an anti-epileptic drug and for patients not treated with an anti-epileptic drug or lithium, but the rate for those treated with antiepileptic medications dropped from 72 per 1,000 person-years prior to treatment, the researchers found. "Drawing causal inference from observational data is complicated in general, but even more complicated for the study of suicide," the authors write. "In summary, the present analysis provides no evidence that anti-epileptic drugs increase risk of suicide attempts in patients with bipolar disorder. Most anti-epileptic drugs and lithium are associated with reduction in suicide attempt rates relative to pretreatment levels in patients who are ultimately prescribed these drugs." The lead author reported serving as an expert witness for Pfizer Pharmaceuticals, which manufactures gabapentin, one of the drugs used in the study, but Pfizer was not involved in the research data.
Faulty Body Clock May Make Kids Bipolar ScienceDaily (Nov. 13, 2009) Malfunctioning circadian clock genes may be responsible for bipolar disorder in children. Researchers writing in the open access journal BMC Psychiatry found four versions of the regulatory gene RORB that were associated with pediatric bipolar disorder. Alexander Niculescu from Indiana University School of Medicine, Indianapolis, US, worked with a team of researchers at Harvard, UC San Diego, Massachusetts General Hospital and SUNY Upstate Medical University to study the RORA and RORB genes of 152 children with the condition and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. Niculescu said, "Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder". RORB is mainly expressed in the eye, pineal gland and brain. Its expression is known to change as a function of circadian rhythm in some tissues, and mice without the gene exhibit circadian rhythm abnormalities. According to Niculescu, "Bipolar disorder is often characterized by circadian rhythm abnormalities, and this is particularly true among pediatric bipolar patients. Decreased sleep has even been noted as one of the earliest symptoms discriminating children with bipolar disorder from those with attention deficit hyperactivity disorder (ADHD). It will be necessary to verify our association results in other independent samples, and to continue to study the relationship between RORB, other clock genes, and bipolar disorder".
Pediatric bipolar disorder is a controversial diagnosis characterized by alternating bouts of depression and mania in children, although it does not affect all young people in the same way and the duration and severity of the disorder can vary enormously.
Immune System Activated in Schizophrenia ScienceDaily (Nov. 18, 2009) Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. Their findings offer hope of being able to treat schizophrenia with drugs that affect the immune system.
The causes of schizophrenia are largely unknown, and this hinders the development of effective treatments. One theory is that infections caught early on in life might increase the risk of developing schizophrenia, but to date any direct evidence of this has not been forthcoming. Scientists at Karolinska Institutet have now been able to analyse inflammatory substances in the spinal fluid of patients with schizophrenia, instead of, as in previous studies, in the blood. The results show that patients with recent-onset schizophrenia have raised levels of a signal substance called interleukin1beta, which can be released in the presence of inflammation. In the healthy control patients, this substance was barely measurable. "This suggests that the brain's immune defence system is activated in schizophrenia," says Professor Göran Engberg, who led the study. "It now remains to be seen whether there is an underlying infection or whether the immune system is triggered by some other means." According to the dominant hypothesis, schizophrenia is related to an overactive dopamine system. Previous studies have shown that interleukin-1beta can upset the dopamine system in rats in a similar way to schizophrenia in humans. "We would have made terrific progress if we were one day able to treat schizophrenia patients with immunotherapy, as it might then be possible to interrupt the course of the disease at an early stage of its development," says Professor Engberg. The group is now studying if the inflammatory process is only activated in connection with the development of schizophrenia, or whether chronic patients exhibit the same phenomenon.
Anti-Inflammatory Medications May Become A Treatment For Schizophrenia ScienceDaily (Oct. 28, 2008) Many of the structural and neurochemical features of schizophrenia are present long before the full syndrome of schizophrenia develops. What processes tip the balance between the ultra-high risk states and the development of schizophrenia? One candidate mechanism is cerebral inflammation, studied by Dr. Bart van Berckel and colleagues in the November 1st issue of Biological Psychiatry. Using positron emission tomography, or PET, imaging, the researchers provide evidence of a brain inflammatory state that may be associated with the development of schizophrenia. The authors reported increased binding levels of [11C]PK11195, a radiotracer with high affinity for the peripheral benzodiazepine receptor (PBR) in patients who had carried the diagnosis of schizophrenia for five years or less. PBR is a molecular target that is present at higher levels in activated microglia. Microglia are
activated during inflammatory states. Drs. van Berckel and Kahn further explain: It was found that microglia activation is present in schizophrenia patients early after disease onset, suggesting brain cells are damaged in schizophrenia. In addition, since microglia can have either a protective or a toxic role, activated microglia may be the result, but also the cause of damage to brain cells. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds, It will be important to understand whether this process takes place in a special way in association with the first onset of symptoms or whether inflammation is more generally a process that contributes to worsening of symptoms. Because this data suggests that inflammation may contribute to features of the early course of schizophrenia, a new potential avenue of treatment for schizophrenia may be to use anti-inflammatory agents. Although some anti-inflammatory medications have already been studied, with limited success, in schizophrenia patients, a new generation of these drugs that more specifically target activated microglia have yet to be explored.
Traffic Jam In Brain Causes Schizophrenia Symptoms; Mouse Develops Disease As Teenager, Just Like Humans ScienceDaily (Aug. 11, 2009) Schizophrenia waits silently until a seemingly normal child becomes a teenager or young adult. Then it swoops down and derails a young life. Scientists have not understood what causes the severe mental disorder, which affects up to 1 percent of the population and results in hallucinations, memory loss and social withdrawal. But new research from the Northwestern University Feinberg School of Medicine has revealed how schizophrenia works in the brain and provided a fresh opportunity for treatment. In a new, genetically engineered mouse model, scientists have discovered the disease symptoms are triggered by a low level of a brain protein necessary for neurons to talk to one another. A Traffic Jam in Brain In human and mouse brains, kalirin is the brain protein needed to build the dense network of highways, called dendritic spines, which allow information to flow from one neuron to another. Northwestern scientists have found that without adequate kalirin, the frontal cortex of the brain of a person with schizophrenia only has a few narrow roads. The information from neurons gets jammed up like rush hour traffic on an interstate highway squeezed to a single lane. "Without enough pathways, the information takes much longer to travel between neurons and much of it will never arrive," said Peter Penzes, assistant professor of physiology at the Feinberg School. He is senior author of a paper reporting the findings published in a recent issue of the Proceedings of the National Academy of Science. Michael Cahill, a Feinberg doctoral student in neuroscience, is the lead author. Mouse Model Develops Disease as a Teenager Penzes discovered the kalirin effect after he created the mouse model, which has a low level of kalirin and develops symptoms of schizophrenia as an adolescent (two months old in mouse time). This mimics the delayed onset of the disease in humans. In normal development, the brain ramps up the production of kalirin as it begins to mature in adolescence. New Direction for Treatment "This discovery opens a new direction for treating the devastating cognitive symptoms of schizophrenia," Penzes said. "There is currently no treatment for that. It suggests that if you can
stimulate and amplify the activity of the protein kalirin that remains in the brain, perhaps we can help the symptoms." Currently the only drug treatment for schizophrenia is an antipsychotic. "The drugs address the hallucinations and calm down the patient, but they don't improve their working memory (the ability of the brain to temporarily store and manage information required for complex mental tasks such as learning and reasoning) or their ability to think or their social behavior," Penzes said. "So you end up with patients who still can't integrate into society. Many attempt suicide."
Similarities Between Human and Mouse Brains A few years ago in postmortem examinations of schizophrenic human brains, other scientists had found fewer connections between the brain cells in the frontal cortex and lower levels of kalirin. But the scientists couldn't show whether one condition led to the other. With the new mouse model, Penzes was able to demonstrate that the low level of kalirin resulted in fewer dendritic spines in the frontal cortex of the brain, the part of the brain responsible for problem solving, planning and reasoning. Other areas of the brain had a normal number of the dendritic spines. Human brains and mouse brains share many similarities in the way they function, Penzes said. The new schizophrenic mouse model also exhibits more schizophrenic symptoms than other models, making these mice especially good for drug testing and development, Penzes said. The mice with low amounts of kalirin had a poor working memory, were antisocial and hyperactive. Penzes said future studies would aim at enhancing the function of kalirin in the brain in an effort to correct the cognitive symptoms of schizophrenia.
Faulty Body Clock May Make Kids Bipolar ScienceDaily (Nov. 13, 2009) Malfunctioning circadian clock genes may be responsible for bipolar disorder in children. Researchers writing in the open access journal BMC Psychiatry found four versions of the regulatory gene RORB that were associated with pediatric bipolar disorder. Alexander Niculescu from Indiana University School of Medicine, Indianapolis, US, worked with a team of researchers at Harvard, UC San Diego, Massachusetts General Hospital and SUNY Upstate Medical University to study the RORA and RORB genes of 152 children with the condition and 140 control children. They found four alterations to the RORB gene that were positively associated with being bipolar. Niculescu said, "Our findings suggest that clock genes in general and RORB in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder". RORB is mainly expressed in the eye, pineal gland and brain. Its expression is known to change as a function of circadian rhythm in some tissues, and mice without the gene exhibit circadian rhythm abnormalities. According to Niculescu, "Bipolar disorder is often characterized by circadian rhythm abnormalities, and this is particularly true among pediatric bipolar patients. Decreased sleep has even been noted as one of the earliest symptoms discriminating children with bipolar disorder from those with attention deficit hyperactivity disorder (ADHD). It will be necessary to verify our association results in other independent samples, and to continue to study the relationship between RORB, other clock genes, and bipolar disorder".
Pediatric bipolar disorder is a controversial diagnosis characterized by alternating bouts of depression and mania in children, although it does not affect all young people in the same way and the duration and severity of the disorder can vary enormously.
Immune System Activated in Schizophrenia ScienceDaily (Nov. 18, 2009) Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. Their findings offer hope of being able to treat schizophrenia with drugs that affect the immune system.
The causes of schizophrenia are largely unknown, and this hinders the development of effective treatments. One theory is that infections caught early on in life might increase the risk of developing schizophrenia, but to date any direct evidence of this has not been forthcoming. Scientists at Karolinska Institutet have now been able to analyse inflammatory substances in the spinal fluid of patients with schizophrenia, instead of, as in previous studies, in the blood. The results show that patients with recent-onset schizophrenia have raised levels of a signal substance called interleukin1beta, which can be released in the presence of inflammation. In the healthy control patients, this substance was barely measurable. "This suggests that the brain's immune defence system is activated in schizophrenia," says Professor Göran Engberg, who led the study. "It now remains to be seen whether there is an underlying infection or whether the immune system is triggered by some other means." According to the dominant hypothesis, schizophrenia is related to an overactive dopamine system. Previous studies have shown that interleukin-1beta can upset the dopamine system in rats in a similar way to schizophrenia in humans. "We would have made terrific progress if we were one day able to treat schizophrenia patients with immunotherapy, as it might then be possible to interrupt the course of the disease at an early stage of its development," says Professor Engberg. The group is now studying if the inflammatory process is only activated in connection with the development of schizophrenia, or whether chronic patients exhibit the same phenomenon.
Anti-Inflammatory Medications May Become A Treatment For Schizophrenia ScienceDaily (Oct. 28, 2008) Many of the structural and neurochemical features of schizophrenia are present long before the full syndrome of schizophrenia develops. What processes tip the balance between the ultra-high risk states and the development of schizophrenia? One candidate mechanism is cerebral inflammation, studied by Dr. Bart van Berckel and colleagues in the November 1st issue of Biological Psychiatry. Using positron emission tomography, or PET, imaging, the researchers provide evidence of a brain inflammatory state that may be associated with the development of schizophrenia. The authors reported increased binding levels of [11C]PK11195, a radiotracer with high affinity for the peripheral benzodiazepine receptor (PBR) in patients who had carried the diagnosis of schizophrenia for five years or less. PBR is a molecular target that is present at higher levels in activated microglia. Microglia are
activated during inflammatory states. Drs. van Berckel and Kahn further explain: It was found that microglia activation is present in schizophrenia patients early after disease onset, suggesting brain cells are damaged in schizophrenia. In addition, since microglia can have either a protective or a toxic role, activated microglia may be the result, but also the cause of damage to brain cells. John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds, It will be important to understand whether this process takes place in a special way in association with the first onset of symptoms or whether inflammation is more generally a process that contributes to worsening of symptoms. Because this data suggests that inflammation may contribute to features of the early course of schizophrenia, a new potential avenue of treatment for schizophrenia may be to use anti-inflammatory agents. Although some anti-inflammatory medications have already been studied, with limited success, in schizophrenia patients, a new generation of these drugs that more specifically target activated microglia have yet to be explored.
Traffic Jam In Brain Causes Schizophrenia Symptoms; Mouse Develops Disease As Teenager, Just Like Humans ScienceDaily (Aug. 11, 2009) Schizophrenia waits silently until a seemingly normal child becomes a teenager or young adult. Then it swoops down and derails a young life. Scientists have not understood what causes the severe mental disorder, which affects up to 1 percent of the population and results in hallucinations, memory loss and social withdrawal. But new research from the Northwestern University Feinberg School of Medicine has revealed how schizophrenia works in the brain and provided a fresh opportunity for treatment. In a new, genetically engineered mouse model, scientists have discovered the disease symptoms are triggered by a low level of a brain protein necessary for neurons to talk to one another. A Traffic Jam in Brain In human and mouse brains, kalirin is the brain protein needed to build the dense network of highways, called dendritic spines, which allow information to flow from one neuron to another. Northwestern scientists have found that without adequate kalirin, the frontal cortex of the brain of a person with schizophrenia only has a few narrow roads. The information from neurons gets jammed up like rush hour traffic on an interstate highway squeezed to a single lane. "Without enough pathways, the information takes much longer to travel between neurons and much of it will never arrive," said Peter Penzes, assistant professor of physiology at the Feinberg School. He is senior author of a paper reporting the findings published in a recent issue of the Proceedings of the National Academy of Science. Michael Cahill, a Feinberg doctoral student in neuroscience, is the lead author. Mouse Model Develops Disease as a Teenager Penzes discovered the kalirin effect after he created the mouse model, which has a low level of kalirin and develops symptoms of schizophrenia as an adolescent (two months old in mouse time). This mimics the delayed onset of the disease in humans. In normal development, the brain ramps up the production of kalirin as it begins to mature in adolescence. New Direction for Treatment "This discovery opens a new direction for treating the devastating cognitive symptoms of schizophrenia," Penzes said. "There is currently no treatment for that. It suggests that if you can
stimulate and amplify the activity of the protein kalirin that remains in the brain, perhaps we can help the symptoms." Currently the only drug treatment for schizophrenia is an antipsychotic. "The drugs address the hallucinations and calm down the patient, but they don't improve their working memory (the ability of the brain to temporarily store and manage information required for complex mental tasks such as learning and reasoning) or their ability to think or their social behavior," Penzes said. "So you end up with patients who still can't integrate into society. Many attempt suicide."
Similarities Between Human and Mouse Brains A few years ago in postmortem examinations of schizophrenic human brains, other scientists had found fewer connections between the brain cells in the frontal cortex and lower levels of kalirin. But the scientists couldn't show whether one condition led to the other. With the new mouse model, Penzes was able to demonstrate that the low level of kalirin resulted in fewer dendritic spines in the frontal cortex of the brain, the part of the brain responsible for problem solving, planning and reasoning. Other areas of the brain had a normal number of the dendritic spines. Human brains and mouse brains share many similarities in the way they function, Penzes said. The new schizophrenic mouse model also exhibits more schizophrenic symptoms than other models, making these mice especially good for drug testing and development, Penzes said. The mice with low amounts of kalirin had a poor working memory, were antisocial and hyperactive. Penzes said future studies would aim at enhancing the function of kalirin in the brain in an effort to correct the cognitive symptoms of schizophrenia.
