3.25 (4 votes)
Andy Irons' autopsy results have finally been released and his family posted a lengthy statement regarding the tragedy that took place last November when Irons, a three-time world surfing champion from Hawaii, to a combination of a heart attack and drugs in his system. Heart attack was ruled cause of death, but the family was open about Irons' battle with bipolarism and medications. Andy Irons was 32 years old.
Dr. Vincent Di Maio, a prominent forensic pathologist in San Antonio, TX was asked to review and explain the autopsy results to the family. He stated:
"This is a very straightforward case. Mr. Irons died of a heart attack due to focal severe coronary atherosclerosis, i.e., 'hardening of the arteries.' He had an atherosclerotic plaque producing 70%-80% narrowing of his anterior descending coronary artery. This is very severe narrowing. A plaque of this severity, located in the anterior descending coronary artery, is commonly associated with sudden death. The only unusual aspect of the case is Mr. Irons' age, 32 years old. Deaths due to coronary atherosclerosis usually begin to appear in the late 40's. Individuals such as Mr. Irons have a genetic predisposition to early development of coronary artery disease. In about 25% of the population, the first symptom of severe coronary atherosclerosis is sudden death. There were no other factors contributing to the death."
Irons was found in his hotel room in Texas. In the room, the police discovered prescription bottles for Alprazolam, used to treat anxiety, and Zolpidem, a sleep aid, along with tablets containing methadone, a narcotic used to treat pain and opiate addiction. Toxicology tests showed Irons also had cocaine and methamphetamine in his system.
Andy had a grandmother, 77, and a grand-uncle, 51, both on his father's side, who died of congestive heart failure. The family mentioned that Andy complained of chest pains and occasional intense heartburn for the first time last year and also recalls a holistic health practitioner, whom he sought out in Australia for vitamin therapy offhandedly mentioning he "had the heart of a 50-year-old." In addition, Andy contracted Typhoid Fever five years ago, which can result in damage to the heart muscle. Andy shrugged it all off and led no one to believe he was in ill health.
After winning championships from 2002 through 2004, and cementing his reputation as one of the greatest competitive surfers, Irons baffled the surfing world with erratic behavior. He abruptly quit the 2008 tour, and sat out the 2009 season before making a comeback in 2010.
The family's statement continues:
"Andy was prescribed Xanax and Zolpidem (Ambien) to treat anxiety and occasional insomnia, a result of a bipolar disorder diagnosed by his family doctor at age 18. This is when Andy first began experiencing episodes of manic highs and depressive lows. The family believes Andy was in some denial about the severity of his chemical imbalance and tended to blame his mood swings on himself and his own weaknesses, choosing to self-medicate with recreational drugs. Members of his family, close friends, and an industry sponsor intervened over the years to help Andy get clean, but the effort to find balance in his life was certainly complicated by his chemical makeup."
In December, Irons' widow, Lyndie, received a six-month injunction from releasing the autopsy report from a Texas judge. On May 20, she received another 30-day injunction. This week the results were finally made public.
Source: SURFER Magazine
Written by Sy Kraft
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Monday, June 13, 2011
Saturday, May 28, 2011
Case Western Reserve Receives $7.8M To Study Mania In Children
4 (1 votes)
The Department of Psychiatry at Case Western Reserve University School of Medicine has received a $7.8 million renewal grant from the National Institute of Mental Health (NIMH) for the long-term study of manic symptoms in children.
The grant from the NIMH, one of the National Institutes of Health (NIH), funds the continuation of a study launched five years ago in which 707 children between the ages of six and 12 years were screened and evaluated for elevated symptoms of mania (ESM), a common indicator of bipolar disease and other childhood psychiatric disorders.
By studying the course of a child's ESM over time, which can include periods of rapid mood swings and intense irritability, researchers hope to learn more about what factors make children with ESM more likely to develop a bipolar spectrum disorder.
"We want to develop the means by which to more accurately diagnose bipolar disease in children," says Robert L. Findling, MD, the Rocco L Motto, M.D. Professor of Child & Adolescent Psychiatry at the School of Medicine, and director of the Division of Child and Adolescent Psychiatry at University Hospitals (UH) Case Medical Center. He is the study's coordinating principal investigator.
From the point of enrollment, children participating in the study's initial phase have been evaluated every six months for their psychiatric diagnoses, symptoms, use of mental health services and medication, and psychosocial function. The NIMH renewal grant allows researchers to continue these six-month evaluations among participants, who will now be between eight and 17 years of age. This will enable the collection of data during a period when study participants are at greater risk of developing a bipolar spectrum disorder, Dr. Findling says.
Researchers will also incorporate both neurocognitive testing (evaluations that assess how well a person processes new data, as well as their ability to process information and pay attention) and neuroimaging. The aim is to identify possible biomarkers that signal or reflect underlying biological mechanisms that predispose individuals to bipolar disease, a type of mood disorder that affects an estimated 5.7 million Americans who often report symptoms that can be traced back to their childhood.
"We're particularly excited about adding neuroimaging to this next phase of the study to examine brain functioning in these children," Dr. Findling says. "This research component is very innovative and will lay the groundwork for future studies between the child and adolescent psychiatry and radiology departments through collaborations involving neuroimaging in children." Neuroimaging involves the use of functional magnetic resonance imaging (MRI), a type of brain scan that maps brains activity. In this area, Dr. Findling is collaborating with neuroradiologist Jeffrey Sunshine, MD, PhD, associate professor and vice chair of the Department of Radiology at the School of Medicine and UH Case Medical Center.
The continued research will further document the trajectories of children with ESM and related psychiatric disorders to better determine the most appropriate points for intervention. Study goals include assessing the nature of manic symptoms over time in relation to changes in mood. Researchers hope to enhance their understanding of the predictive value of manic symptoms, alone and in combination with other symptoms, developing evidence-based criteria for diagnosing the spectrum of bipolar disorders in children; and identifying risk factors associated with poor functional outcomes among youth with manic symptoms.
The investigators will examine the relationships between mood episodes and clinical outcomes over time. They will also evaluate neurocognitive performance, together with functional abnormalities, to better understand how these relate to ESM and the development of bipolar disorder in childhood through early adulthood.
In addition to the School of Medicine and UH Case Medical Center, children enrolled in the study have been recruited from three other collaborating sites: University of Pittsburgh Medical Center, The Ohio State University Medical Center, and Cincinnati Children's Hospital.
Source:
Case Western Reserve University
The Department of Psychiatry at Case Western Reserve University School of Medicine has received a $7.8 million renewal grant from the National Institute of Mental Health (NIMH) for the long-term study of manic symptoms in children.
The grant from the NIMH, one of the National Institutes of Health (NIH), funds the continuation of a study launched five years ago in which 707 children between the ages of six and 12 years were screened and evaluated for elevated symptoms of mania (ESM), a common indicator of bipolar disease and other childhood psychiatric disorders.
By studying the course of a child's ESM over time, which can include periods of rapid mood swings and intense irritability, researchers hope to learn more about what factors make children with ESM more likely to develop a bipolar spectrum disorder.
"We want to develop the means by which to more accurately diagnose bipolar disease in children," says Robert L. Findling, MD, the Rocco L Motto, M.D. Professor of Child & Adolescent Psychiatry at the School of Medicine, and director of the Division of Child and Adolescent Psychiatry at University Hospitals (UH) Case Medical Center. He is the study's coordinating principal investigator.
From the point of enrollment, children participating in the study's initial phase have been evaluated every six months for their psychiatric diagnoses, symptoms, use of mental health services and medication, and psychosocial function. The NIMH renewal grant allows researchers to continue these six-month evaluations among participants, who will now be between eight and 17 years of age. This will enable the collection of data during a period when study participants are at greater risk of developing a bipolar spectrum disorder, Dr. Findling says.
Researchers will also incorporate both neurocognitive testing (evaluations that assess how well a person processes new data, as well as their ability to process information and pay attention) and neuroimaging. The aim is to identify possible biomarkers that signal or reflect underlying biological mechanisms that predispose individuals to bipolar disease, a type of mood disorder that affects an estimated 5.7 million Americans who often report symptoms that can be traced back to their childhood.
"We're particularly excited about adding neuroimaging to this next phase of the study to examine brain functioning in these children," Dr. Findling says. "This research component is very innovative and will lay the groundwork for future studies between the child and adolescent psychiatry and radiology departments through collaborations involving neuroimaging in children." Neuroimaging involves the use of functional magnetic resonance imaging (MRI), a type of brain scan that maps brains activity. In this area, Dr. Findling is collaborating with neuroradiologist Jeffrey Sunshine, MD, PhD, associate professor and vice chair of the Department of Radiology at the School of Medicine and UH Case Medical Center.
The continued research will further document the trajectories of children with ESM and related psychiatric disorders to better determine the most appropriate points for intervention. Study goals include assessing the nature of manic symptoms over time in relation to changes in mood. Researchers hope to enhance their understanding of the predictive value of manic symptoms, alone and in combination with other symptoms, developing evidence-based criteria for diagnosing the spectrum of bipolar disorders in children; and identifying risk factors associated with poor functional outcomes among youth with manic symptoms.
The investigators will examine the relationships between mood episodes and clinical outcomes over time. They will also evaluate neurocognitive performance, together with functional abnormalities, to better understand how these relate to ESM and the development of bipolar disorder in childhood through early adulthood.
In addition to the School of Medicine and UH Case Medical Center, children enrolled in the study have been recruited from three other collaborating sites: University of Pittsburgh Medical Center, The Ohio State University Medical Center, and Cincinnati Children's Hospital.
Source:
Case Western Reserve University
Friday, May 27, 2011
Study: Premenstrual Mood Changes Predictive Of Greater Bipolar Disorder Severity
4 (2 votes)Article Opinions: 4 posts
A study of nearly 300 women with bipolar disorder showed that those reporting flare-ups of mood symptoms before menstruation had more depressive episodes and more severe symptoms during the following year, compared with bipolar women without premenstrual mood changes.
The study was part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and was conducted by Rodrigo Dias, M.D., and colleagues at Massachusetts General Hospital in Boston. The report will be published online at AJP in Advance, the online advance edition of The American Journal of Psychiatry, the official journal of the American Psychiatric Association.
The study results provide evidence that premenstrual mood exacerbation may be a clinical marker predicting a worse presentation and course of bipolar disorder in reproductive-age women. The authors note that estrogen and other reproductive hormones influence mood symptoms through their action in the central nervous system. In women with bipolar disorder, the time following childbirth and the menopause transition are also periods of increased vulnerability to illness relapse. The susceptibility of mood to fluctuating hormone levels may result in greater mood instability in general.
The number of diagnosed illness episodes differed only for depressive episodes, not those characterized by mania or hypomania. Also, the women with premenstrual exacerbations were no more likely to have the extreme form of bipolar disorder known as rapid cycling (defined as four or more episodes per year). They did, however, have shorter gaps between symptomatic intervals.
Dr. Dias pointed out the implications for clinical practice: "The results reinforce the importance of identifying mood fluctuations across the menstrual cycle in women with bipolar disorder. The women with premenstrual mood changes may benefit from more intensive monitoring. The value of antidepressants isn't clear, since on the one hand, these women were less likely to be taking antidepressants and might have benefited from them, but on the other hand, antidepressants can trigger manic symptoms in bipolar patients." The article will appear on Feb. 15 at AJP in Advance. STEP-BD is funded by the National Institute of Mental Health; this study was funded in part by a donation from the Thompson Motta Family to the Bipolar Research Program, Institute of Psychiatry of the Hospital das Clinicas, University São Paulo Medical School. Financial support received by the individual authors is reported in the article.
Source: American Psychiatric Association
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
A study of nearly 300 women with bipolar disorder showed that those reporting flare-ups of mood symptoms before menstruation had more depressive episodes and more severe symptoms during the following year, compared with bipolar women without premenstrual mood changes.
The study was part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) and was conducted by Rodrigo Dias, M.D., and colleagues at Massachusetts General Hospital in Boston. The report will be published online at AJP in Advance, the online advance edition of The American Journal of Psychiatry, the official journal of the American Psychiatric Association.
The study results provide evidence that premenstrual mood exacerbation may be a clinical marker predicting a worse presentation and course of bipolar disorder in reproductive-age women. The authors note that estrogen and other reproductive hormones influence mood symptoms through their action in the central nervous system. In women with bipolar disorder, the time following childbirth and the menopause transition are also periods of increased vulnerability to illness relapse. The susceptibility of mood to fluctuating hormone levels may result in greater mood instability in general.
The number of diagnosed illness episodes differed only for depressive episodes, not those characterized by mania or hypomania. Also, the women with premenstrual exacerbations were no more likely to have the extreme form of bipolar disorder known as rapid cycling (defined as four or more episodes per year). They did, however, have shorter gaps between symptomatic intervals.
Dr. Dias pointed out the implications for clinical practice: "The results reinforce the importance of identifying mood fluctuations across the menstrual cycle in women with bipolar disorder. The women with premenstrual mood changes may benefit from more intensive monitoring. The value of antidepressants isn't clear, since on the one hand, these women were less likely to be taking antidepressants and might have benefited from them, but on the other hand, antidepressants can trigger manic symptoms in bipolar patients." The article will appear on Feb. 15 at AJP in Advance. STEP-BD is funded by the National Institute of Mental Health; this study was funded in part by a donation from the Thompson Motta Family to the Bipolar Research Program, Institute of Psychiatry of the Hospital das Clinicas, University São Paulo Medical School. Financial support received by the individual authors is reported in the article.
Source: American Psychiatric Association
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
A New Clue To The Genetics Of Bipolar Disorder
3.88 (8 votes)Article Opinions: 2 posts
Understanding the genetics of bipolar disorder could lead to new treatments, but identifying specific genetic variations associated with this disorder has been challenging.
A new study in Biological Psychiatry implicates a brain protein called Piccolo in the risk for inheriting bipolar disorder. In the orchestra of neuronal proteins, Piccolo is a member of a protein family that includes another protein called Bassoon. Piccolo is located at the endings of nerve cells, where it contributes to the ability of nerve cells to release their chemical messengers.
Choi and colleagues conducted a creative study to implicate the gene coding for Piccolo (PCLO) in the heritable risk for bipolar disorder.
They compared gene expression patterns in postmortem cortical tissue from people who were diagnosed with bipolar disorder to tissue from people who did not have psychiatric illnesses prior to their death. This analysis identified 45 genes and genetic variations that had significantly altered mRNA levels, and they used this information to narrow the part of the genome that they explored in their genetics study.
They then tested genetic markers (small DNA sequence variations called single nucleotide polymorphisms or SNPs) that are close to the genes that had altered expression levels in the postmortem tissue. A marker for PCLO, SNP rs13438494, emerged as significant in this analysis, suggesting that variation in PCLO contributes to the risk for bipolar disorder.
"We have taken an innovative approach in correlating gene expression with genetic variation data from well-characterized postmortem brains and then combining with a large scale meta-analysis of genome-wide association studies," explained Dr. Kwang Choi. "If replicated, this study could finally forge a link between gene expression and genome-wide association studies in a complex genetic disorder."
"This study is an example of how better knowledge of brain biology may help to guide our genetics studies," added Dr. John Krystal, Editor of Biological Psychiatry.
Sources: Elsevier, AlphaGalileo Foundation.
Understanding the genetics of bipolar disorder could lead to new treatments, but identifying specific genetic variations associated with this disorder has been challenging.
A new study in Biological Psychiatry implicates a brain protein called Piccolo in the risk for inheriting bipolar disorder. In the orchestra of neuronal proteins, Piccolo is a member of a protein family that includes another protein called Bassoon. Piccolo is located at the endings of nerve cells, where it contributes to the ability of nerve cells to release their chemical messengers.
Choi and colleagues conducted a creative study to implicate the gene coding for Piccolo (PCLO) in the heritable risk for bipolar disorder.
They compared gene expression patterns in postmortem cortical tissue from people who were diagnosed with bipolar disorder to tissue from people who did not have psychiatric illnesses prior to their death. This analysis identified 45 genes and genetic variations that had significantly altered mRNA levels, and they used this information to narrow the part of the genome that they explored in their genetics study.
They then tested genetic markers (small DNA sequence variations called single nucleotide polymorphisms or SNPs) that are close to the genes that had altered expression levels in the postmortem tissue. A marker for PCLO, SNP rs13438494, emerged as significant in this analysis, suggesting that variation in PCLO contributes to the risk for bipolar disorder.
"We have taken an innovative approach in correlating gene expression with genetic variation data from well-characterized postmortem brains and then combining with a large scale meta-analysis of genome-wide association studies," explained Dr. Kwang Choi. "If replicated, this study could finally forge a link between gene expression and genome-wide association studies in a complex genetic disorder."
"This study is an example of how better knowledge of brain biology may help to guide our genetics studies," added Dr. John Krystal, Editor of Biological Psychiatry.
Sources: Elsevier, AlphaGalileo Foundation.
Study Examines Prevalence And Severity Of Bipolar Disorder Worldwide
Despite international variation in prevalence rates of bipolar spectrum disorder, the severity and associated disorders are similar and treatment needs are often unmet, especially in low-income countries, according to a report in the March issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
"Bipolar disorder (BP) is responsible for the loss of more disability-adjusted life-years than all forms of cancer or major neurologic conditions such as epilepsy and Alzheimer disease, primarily because of its early onset and chronicity across the life span," the authors write as background information in the article. "Few prior international studies of BP have included information on severity or disability associated with this condition."
Kathleen R. Merikangas, Ph.D., of the National Institute of Mental Health, Genetic Epidemiology Research Branch, Bethesda, Md., and colleagues conducted cross-sectional, face-to-face, household surveys to describe the prevalence, symptom severity, patterns of co-existing illnesses, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. Surveys of 61,392 community adults were carried out in the United States, Mexico, Brazil, Colombia, Bulgaria, Romania, China, India, Japan, Lebanon, and New Zealand.
"In a combined sample of 61,392 adults from 11 countries, the total lifetime prevalences were 0.6 percent for BP-I, 0.4 percent for BP-II, and 1.4 percent for sub-threshold BP, yielding a total BPS prevalence estimate of 2.4 percent worldwide," the authors report.
The severity of symptoms was greater for depressive than manic episodes. Approximately 74.0 percent of respondents with depression and 50.9 percent of respondents with mania reported severe role impairment.
Three-quarters of those with BPS also met criteria for at least one other disorder. Anxiety disorders, especially panic attacks, were the most common comorbid condition.
The surveys found that treatment needs for BPS are often unmet. "Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2 percent reported contact with the mental health system," the authors write.
The authors believe their findings document the magnitude and major impact of BP worldwide and underscore the urgent need for increased recognition and treatment facilitation.
Arch Gen Psychiatry, 2011;68
Americans More Likely To Have Bipolar Disorder Than Anybody Else In The World
3.88 (8 votes)Article Opinions: 11 posts
Approximately 4.4% of Americans have had a diagnosis of bipolar disorder at some time during their lives, compared to a global average of 2.4%, and just 0.1% in India, researchers have revealed in Archives of General Psychiatry. The authors add that even though prevalence rates for bipolar spectrum disorder vary considerably around the globe, the associated disorders and their severities are not significantly different.
Unfortunately, a considerable number of bipolar disorder sufferers do not receive proper treatment, especially in low-income nations.
The authors wrote:
"Bipolar disorder (BP) is responsible for the loss of more disability-adjusted life-years than all forms of cancer or major neurologic conditions such as epilepsy and Alzheimer disease, primarily because of its early onset and chronicity across the life span. Few prior international studies of BP have included information on severity or disability associated with this condition."
Kathleen R. Merikangas, Ph.D., of the National Institute of Mental Health, Genetic Epidemiology Research Branch, Bethesda, Md., and team sought to find out what the prevalence of the disorder might be worldwide. They also aimed to describe its symptom severity, patterns of co-existing illnesses, and service utilization patterns for BPS (bipolar spectrum disorder) in the World Health Organization World Mental Health Survey Initiative. The survey included 61,392 adults from New Zealand, the Lebanon, Japan, India, China, Romania, Bulgaria, Columbia, Brazil, Mexico, and the USA.
The authors wrote:
"In a combined sample of 61,392 adults from 11 countries, the total lifetime prevalences were 0.6 percent for BP-I, 0.4 percent for BP-II, and 1.4 percent for sub-threshold BP, yielding a total BPS prevalence estimate of 2.4 percent worldwide."
They found that depressive episodes were linked to more severe symptoms than manic ones. About 74% of those with depression and 50.9% of those with mania reported severe role impairment.
Approximately three-quarters of respondents with a bipolar spectrum disorder appeared to have at least another disorder as well - they met the criteria for it (them). The most common comorbid conditions were anxiety disorders, particularly panic attacks.
A significant proportion of people worldwide with a BPS do not receive the treatment they need.
The authors wrote:
"Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2 percent reported contact with the mental health system."
Experts from the National Institute of Mental Health, Bethesda, USA, who contributed to this study, say more research is required to define the thresholds and boundaries of bipolar symptoms more clearly and accurately. We also need to improve our understanding of why and how BP tends to start during adolescence and persists into adulthood, and how it intersects with comorbid mental disorders.
The researchers stressed that there is an urgent need for access to proper treatment and better recognition of BPS.
They concluded:
"Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries."What is bipolar disorder?Bipolar disorder, also known as BP, manic-depressive illness or manic depression is a mental illness. The patient experiences instability in mood which is typically serious and disabling. An individual with BP has abnormal shifts in mood, energy, and their ability to function properly is affected - these shifts can go on for weeks, sometimes even months. The general "ups" and "downs" we experience in everyday life have nothing to do with BP. BP symptoms are severe and can destroy relationships, job prospects, and academic performance - put simply, they can ruin a person's life. Symptoms may become so severe that some patients either attempt to or manage to commit suicide.
Fortunately, bipolar disorder is treatable. Millions of patients worldwide manage to lead full and productive lives thanks to effective therapy.
The signs and symptoms of bipolar disorder vary, depending on whether the patient is on a high (mania) or low (depression).
Manic (mania) episodes signs and symptoms can include:ElationAggressive and intrusive behavior Agitation and extreme irritabilityReduced need for sleep Refusing to accept that anything is wrongDrug abuse, particularly cocaine, alcohol, and sleep aidesExtremely "high," overly good mood Increased drive to perform or achieve goals Increased energy, activity, and restlessness Increased sexual drive Exaggerated self-esteem lack of proper judgment Rapid speechRacing thoughtsRisky behavior Spending sprees Tendency to be easily distracted and difficulty concentratingUnrealistic beliefs in one's abilities and powers Depressive (depression) episodes signs and symptoms can include:Anxiety, overly worriedAppetite problems Concentration problemsDifficulty making decisionsGuilt, worthlessness, and helplessnessHopelessnessIrritability Loss of interest in daily activities Low libidoPessimism Reduced energySadness, gloomSensation of emptinessSleeping difficultiesSuicidal thoughts or behavior Tiredness Unexplained chronic painUnintended weight gain or loss"Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative"
Kathleen R. Merikangas, PhD; Robert Jin, MA; Jian-Ping He, MD; Ronald C. Kessler, PhD; Sing Lee, MB, BS, FRCPsych; Nancy A. Sampson, BA; Maria Carmen Viana, MD, PhD; Laura Helena Andrade, MD, PhD; Chiyi Hu, MD, PhD; Elie G. Karam, MD; Maria Ladea, MD, PhD; Maria Elena Medina-Mora, PhD; Yutaka Ono, MD; Jose Posada-Villa, MD; Rajesh Sagar, MD; J. Elisabeth Wells, PhD; Zahari Zarkov, MD
Arch Gen Psychiatry. 2011;68(3):241-251. doi:10.1001/archgenpsychiatry.2011.12
Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Approximately 4.4% of Americans have had a diagnosis of bipolar disorder at some time during their lives, compared to a global average of 2.4%, and just 0.1% in India, researchers have revealed in Archives of General Psychiatry. The authors add that even though prevalence rates for bipolar spectrum disorder vary considerably around the globe, the associated disorders and their severities are not significantly different.
Unfortunately, a considerable number of bipolar disorder sufferers do not receive proper treatment, especially in low-income nations.
The authors wrote:
"Bipolar disorder (BP) is responsible for the loss of more disability-adjusted life-years than all forms of cancer or major neurologic conditions such as epilepsy and Alzheimer disease, primarily because of its early onset and chronicity across the life span. Few prior international studies of BP have included information on severity or disability associated with this condition."
Kathleen R. Merikangas, Ph.D., of the National Institute of Mental Health, Genetic Epidemiology Research Branch, Bethesda, Md., and team sought to find out what the prevalence of the disorder might be worldwide. They also aimed to describe its symptom severity, patterns of co-existing illnesses, and service utilization patterns for BPS (bipolar spectrum disorder) in the World Health Organization World Mental Health Survey Initiative. The survey included 61,392 adults from New Zealand, the Lebanon, Japan, India, China, Romania, Bulgaria, Columbia, Brazil, Mexico, and the USA.
The authors wrote:
"In a combined sample of 61,392 adults from 11 countries, the total lifetime prevalences were 0.6 percent for BP-I, 0.4 percent for BP-II, and 1.4 percent for sub-threshold BP, yielding a total BPS prevalence estimate of 2.4 percent worldwide."
They found that depressive episodes were linked to more severe symptoms than manic ones. About 74% of those with depression and 50.9% of those with mania reported severe role impairment.
Approximately three-quarters of respondents with a bipolar spectrum disorder appeared to have at least another disorder as well - they met the criteria for it (them). The most common comorbid conditions were anxiety disorders, particularly panic attacks.
A significant proportion of people worldwide with a BPS do not receive the treatment they need.
The authors wrote:
"Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2 percent reported contact with the mental health system."
Experts from the National Institute of Mental Health, Bethesda, USA, who contributed to this study, say more research is required to define the thresholds and boundaries of bipolar symptoms more clearly and accurately. We also need to improve our understanding of why and how BP tends to start during adolescence and persists into adulthood, and how it intersects with comorbid mental disorders.
The researchers stressed that there is an urgent need for access to proper treatment and better recognition of BPS.
They concluded:
"Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries."What is bipolar disorder?Bipolar disorder, also known as BP, manic-depressive illness or manic depression is a mental illness. The patient experiences instability in mood which is typically serious and disabling. An individual with BP has abnormal shifts in mood, energy, and their ability to function properly is affected - these shifts can go on for weeks, sometimes even months. The general "ups" and "downs" we experience in everyday life have nothing to do with BP. BP symptoms are severe and can destroy relationships, job prospects, and academic performance - put simply, they can ruin a person's life. Symptoms may become so severe that some patients either attempt to or manage to commit suicide.
Fortunately, bipolar disorder is treatable. Millions of patients worldwide manage to lead full and productive lives thanks to effective therapy.
The signs and symptoms of bipolar disorder vary, depending on whether the patient is on a high (mania) or low (depression).
Manic (mania) episodes signs and symptoms can include:ElationAggressive and intrusive behavior Agitation and extreme irritabilityReduced need for sleep Refusing to accept that anything is wrongDrug abuse, particularly cocaine, alcohol, and sleep aidesExtremely "high," overly good mood Increased drive to perform or achieve goals Increased energy, activity, and restlessness Increased sexual drive Exaggerated self-esteem lack of proper judgment Rapid speechRacing thoughtsRisky behavior Spending sprees Tendency to be easily distracted and difficulty concentratingUnrealistic beliefs in one's abilities and powers Depressive (depression) episodes signs and symptoms can include:Anxiety, overly worriedAppetite problems Concentration problemsDifficulty making decisionsGuilt, worthlessness, and helplessnessHopelessnessIrritability Loss of interest in daily activities Low libidoPessimism Reduced energySadness, gloomSensation of emptinessSleeping difficultiesSuicidal thoughts or behavior Tiredness Unexplained chronic painUnintended weight gain or loss"Prevalence and Correlates of Bipolar Spectrum Disorder in the World Mental Health Survey Initiative"
Kathleen R. Merikangas, PhD; Robert Jin, MA; Jian-Ping He, MD; Ronald C. Kessler, PhD; Sing Lee, MB, BS, FRCPsych; Nancy A. Sampson, BA; Maria Carmen Viana, MD, PhD; Laura Helena Andrade, MD, PhD; Chiyi Hu, MD, PhD; Elie G. Karam, MD; Maria Ladea, MD, PhD; Maria Elena Medina-Mora, PhD; Yutaka Ono, MD; Jose Posada-Villa, MD; Rajesh Sagar, MD; J. Elisabeth Wells, PhD; Zahari Zarkov, MD
Arch Gen Psychiatry. 2011;68(3):241-251. doi:10.1001/archgenpsychiatry.2011.12
Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
Depression Needs A Second Opinion
4 (3 votes)Article Opinions: 1 posts
As he struggled for decades with a depression that often left him despondent, Eric Wilson never thought to get a second opinion.
"This might be true of many of us," he said. "We feel we have more ownership of what we see as our body and physical health so, if a doctor gives me a diagnosis I don't like, I'm likely to get a second opinion. It just wasn't the same for mental health."
After decades of broken relationships, multiple flirtations with suicide, and manic highs and lows, he received his final and accurate diagnosis of bipolar II mixed. This form of bipolar disorder is difficult to diagnose because its sufferers often are highly functioning and extremely productive. The highs can masquerade as general happiness. The difficulty is when the mood swings drastically and uncontrollably.
Researchers have found that as many as 69 percent of initial diagnoses of people with bipolar disorder were incorrect, underlining the importance of seeking a second opinion. With bipolar, the wrong medication can have devastating effects, plunging a patient into a deeper depression or into rapid cycles of highs and lows.
Wilson describes his journey from a dangerously moody teen to happily married father in "The Mercy of Eternity." He credits the loving persistence of his wife and the wonder of his daughter for pushing him beyond that first incorrect diagnosis of his disease.
He is sure he would never have sought additional help on his own.
"The idea that I had mental illness scared me," he said. "So I felt that any therapist I was seeing had a mastery of this strange, mysterious world of mental health, and I'd do whatever this person told me to do. I struggled with medications for a long time that simply were not working.
"It was a very long process that required a lot of patience and a lot of flexibility, but it's paid off beautifully."
Source: Wake Forest University
As he struggled for decades with a depression that often left him despondent, Eric Wilson never thought to get a second opinion.
"This might be true of many of us," he said. "We feel we have more ownership of what we see as our body and physical health so, if a doctor gives me a diagnosis I don't like, I'm likely to get a second opinion. It just wasn't the same for mental health."
After decades of broken relationships, multiple flirtations with suicide, and manic highs and lows, he received his final and accurate diagnosis of bipolar II mixed. This form of bipolar disorder is difficult to diagnose because its sufferers often are highly functioning and extremely productive. The highs can masquerade as general happiness. The difficulty is when the mood swings drastically and uncontrollably.
Researchers have found that as many as 69 percent of initial diagnoses of people with bipolar disorder were incorrect, underlining the importance of seeking a second opinion. With bipolar, the wrong medication can have devastating effects, plunging a patient into a deeper depression or into rapid cycles of highs and lows.
Wilson describes his journey from a dangerously moody teen to happily married father in "The Mercy of Eternity." He credits the loving persistence of his wife and the wonder of his daughter for pushing him beyond that first incorrect diagnosis of his disease.
He is sure he would never have sought additional help on his own.
"The idea that I had mental illness scared me," he said. "So I felt that any therapist I was seeing had a mastery of this strange, mysterious world of mental health, and I'd do whatever this person told me to do. I struggled with medications for a long time that simply were not working.
"It was a very long process that required a lot of patience and a lot of flexibility, but it's paid off beautifully."
Source: Wake Forest University
Thursday, May 26, 2011
Award In Excellence For Clinical Pharmacology Honours Bryan Roth
Article Opinions: 1 posts
Bryan L. Roth, PhD, the Michael J. Hooker Distinguished Professor of Pharmacology in the University of North Carolina at Chapel Hill School of Medicine, has received the PhRMA Foundation Award in Excellence in Pharmacology/Toxicology.
Roth is also professor in the departments of pharmacology, medicinal chemistry and natural products and he holds the Michael Hooker Chair of Protein Therapeutics and Translational Proteomics.
His work in pharmacology and drug discovery has earned him numerous patents and he has published nearly 300 articles in, among many other publications, Science, Nature, Cell and the New England Journal of Medicine. He has also trained dozens of doctoral and post-doctoral students who have also become leaders in their field.
Much of Roth's research focuses on trying to understand how central nervous system drugs affect the brain's neurons. The goal is to investigate existing treatments in order to find new treatments and mitigate side effects, particularly for such problems as schizophrenia, depression, bipolar disorder and eating disorders.
"We really don't understand how most drugs currently used in brain disorders work," he explained. "If we can uncover how they exert their therapeutic actions, we hope to find drugs that are more effective. Additionally, if we can understand the side effects of current drugs, we'll know what molecular targets we have to avoid in making new drugs so they don't have the side effects."
Essentially, the work identifies both good targets for drug development, and bad targets to be avoided. In one application of the technique, Roth's lab identified potentially safe and effective compounds for treating obesity. Those compounds have been out-licensed to biotech companies for commercial development.
And In one of his most important research projects, Dr. Roth and his team at UNC, along with scientists at the University of California, San Francisco, developed and validated a computer model that can allow researchers to predict likely side effects before a drug is even put into clinical testing. The method compares the structures of all known drugs for various disease targets to their naturally-occurring binding partners. That comparison has revealed interactions between drugs and their targets that could not be predicted simply by studying their chemical structures.
A native of Butte, Montana, Roth graduated from Carroll College in Helena in 1977 with a degree in biology and chemistry. He subsequently earned his combined MD/PhD in Biochemistry in 1983 from St. Louis University School of Medicine.
He completed an internship in psychiatry at the National Naval Medical Center in Bethesda, Md. in 1984, and from 1983-1986 worked at the National Institute of Mental Health. During much of that period, he also worked at the Naval Medical Research Institute in Bethesda, first as a principal investigator and later as assistant division head of the institute's surgical research division.
In 1991 Dr. Roth concluded his residency in psychiatry at Stanford University Medical School, where he was also a Dana Foundation Fellow in Neurosciences in the Nancy Pritzker Laboratory of Molecular and Developmental Neurobiology. That year, he also received his first PhRMA Foundation grant.
After completing his studies at Stanford he held appointments at Case Western Reserve University School of Medicine for more than a decade in Departments of Psychiatry, and Biochemistry, ultimately becoming a Full Professor of Biochemistry in 2003. During much of that time he was on the faculty of Case Western Reserve University, where he specialized in the treatment of schizophrenia and, for a time, directed the Schizophrenia Research Ward at University Hospitals of Cleveland.
The annual Award in Excellence honors researchers who received PhRMA Foundation grants early in their careers and then distinguished themselves through outstanding scientific and/or academic achievements.
"This award is wonderful for me and for my lab. Essentially, the PhRMA Foundation makes a bet on young investigators, and no one knows for years whether it was a good bet or not. I am happy I was able to find success and, hopefully, will continue to find it for many years."
The Award in Excellence will be presented April 9 at a meeting of the American Society for Pharmacology and Experimental Therapeutics.
Source:
Les Lang
University of North Carolina School of Medicine
Bryan L. Roth, PhD, the Michael J. Hooker Distinguished Professor of Pharmacology in the University of North Carolina at Chapel Hill School of Medicine, has received the PhRMA Foundation Award in Excellence in Pharmacology/Toxicology.
Roth is also professor in the departments of pharmacology, medicinal chemistry and natural products and he holds the Michael Hooker Chair of Protein Therapeutics and Translational Proteomics.
His work in pharmacology and drug discovery has earned him numerous patents and he has published nearly 300 articles in, among many other publications, Science, Nature, Cell and the New England Journal of Medicine. He has also trained dozens of doctoral and post-doctoral students who have also become leaders in their field.
Much of Roth's research focuses on trying to understand how central nervous system drugs affect the brain's neurons. The goal is to investigate existing treatments in order to find new treatments and mitigate side effects, particularly for such problems as schizophrenia, depression, bipolar disorder and eating disorders.
"We really don't understand how most drugs currently used in brain disorders work," he explained. "If we can uncover how they exert their therapeutic actions, we hope to find drugs that are more effective. Additionally, if we can understand the side effects of current drugs, we'll know what molecular targets we have to avoid in making new drugs so they don't have the side effects."
Essentially, the work identifies both good targets for drug development, and bad targets to be avoided. In one application of the technique, Roth's lab identified potentially safe and effective compounds for treating obesity. Those compounds have been out-licensed to biotech companies for commercial development.
And In one of his most important research projects, Dr. Roth and his team at UNC, along with scientists at the University of California, San Francisco, developed and validated a computer model that can allow researchers to predict likely side effects before a drug is even put into clinical testing. The method compares the structures of all known drugs for various disease targets to their naturally-occurring binding partners. That comparison has revealed interactions between drugs and their targets that could not be predicted simply by studying their chemical structures.
A native of Butte, Montana, Roth graduated from Carroll College in Helena in 1977 with a degree in biology and chemistry. He subsequently earned his combined MD/PhD in Biochemistry in 1983 from St. Louis University School of Medicine.
He completed an internship in psychiatry at the National Naval Medical Center in Bethesda, Md. in 1984, and from 1983-1986 worked at the National Institute of Mental Health. During much of that period, he also worked at the Naval Medical Research Institute in Bethesda, first as a principal investigator and later as assistant division head of the institute's surgical research division.
In 1991 Dr. Roth concluded his residency in psychiatry at Stanford University Medical School, where he was also a Dana Foundation Fellow in Neurosciences in the Nancy Pritzker Laboratory of Molecular and Developmental Neurobiology. That year, he also received his first PhRMA Foundation grant.
After completing his studies at Stanford he held appointments at Case Western Reserve University School of Medicine for more than a decade in Departments of Psychiatry, and Biochemistry, ultimately becoming a Full Professor of Biochemistry in 2003. During much of that time he was on the faculty of Case Western Reserve University, where he specialized in the treatment of schizophrenia and, for a time, directed the Schizophrenia Research Ward at University Hospitals of Cleveland.
The annual Award in Excellence honors researchers who received PhRMA Foundation grants early in their careers and then distinguished themselves through outstanding scientific and/or academic achievements.
"This award is wonderful for me and for my lab. Essentially, the PhRMA Foundation makes a bet on young investigators, and no one knows for years whether it was a good bet or not. I am happy I was able to find success and, hopefully, will continue to find it for many years."
The Award in Excellence will be presented April 9 at a meeting of the American Society for Pharmacology and Experimental Therapeutics.
Source:
Les Lang
University of North Carolina School of Medicine
Genetic Link To Attempted Suicide Identified: Findings Could Lead To New Avenues Of Treatment Research
4 (1 votes)
A study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide.
Johns Hopkins scientists, reporting in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found more than normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior.
The researchers say the findings could lead to better suicide prevention efforts by providing new directions for research and drug development.
"We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," says study leader Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost three times as likely.
Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder. By using only DNA from people with bipolar disorder, the researchers say they were able to control for mental illness and narrow in on what may cause one group to attempt suicide and another to control those urges.
Suicide is estimated to kill 1.4 percent of the U.S. population, and roughly 4.6 percent of the population has attempted suicide at least once, Willour says. Among people with bipolar disorder, 47 percent think about killing themselves while 25 percent actually try to do it, she says.
Willour says the next steps are to replicate these findings and to determine the exact biological mechanisms through which these genetic risk factors increase the risk for suicidal behavior.
"What's promising are the implications of this work for learning more about the biology of suicide and the medications used to treat patients who may be at risk," Willour says. "Not everyone with bipolar disorder can take lithium because of its side effects. If we could give them another option, that would be fantastic."
Notes:
The study was funded by grants from the National Institute of Mental Health and the American Foundation for Suicide Prevention.
Other Hopkins researchers who participated in the study are Fayaz Seifuddin, M.S.; Pamela B. Mahon, Ph.D.; Dubravka Jancic, Ph.D.; Mehdi Pirooznia, M.D., Ph.D.; Barbara Schweizer, R.N., B.S.; Fernando S. Goes, M.D.; Francis Mondimore, M.D.; Dean F. MacKinnon, M.D.; J. Raymond DePaulo Jr., M.D.; Peter P. Zandi, Ph.D.; and James B. Potash, M.D., M.P.H.
Source:
Stephanie Desmon
Johns Hopkins Medical Institutions
A study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide.
Johns Hopkins scientists, reporting in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found more than normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior.
The researchers say the findings could lead to better suicide prevention efforts by providing new directions for research and drug development.
"We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," says study leader Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.
Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost three times as likely.
Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder. By using only DNA from people with bipolar disorder, the researchers say they were able to control for mental illness and narrow in on what may cause one group to attempt suicide and another to control those urges.
Suicide is estimated to kill 1.4 percent of the U.S. population, and roughly 4.6 percent of the population has attempted suicide at least once, Willour says. Among people with bipolar disorder, 47 percent think about killing themselves while 25 percent actually try to do it, she says.
Willour says the next steps are to replicate these findings and to determine the exact biological mechanisms through which these genetic risk factors increase the risk for suicidal behavior.
"What's promising are the implications of this work for learning more about the biology of suicide and the medications used to treat patients who may be at risk," Willour says. "Not everyone with bipolar disorder can take lithium because of its side effects. If we could give them another option, that would be fantastic."
Notes:
The study was funded by grants from the National Institute of Mental Health and the American Foundation for Suicide Prevention.
Other Hopkins researchers who participated in the study are Fayaz Seifuddin, M.S.; Pamela B. Mahon, Ph.D.; Dubravka Jancic, Ph.D.; Mehdi Pirooznia, M.D., Ph.D.; Barbara Schweizer, R.N., B.S.; Fernando S. Goes, M.D.; Francis Mondimore, M.D.; Dean F. MacKinnon, M.D.; J. Raymond DePaulo Jr., M.D.; Peter P. Zandi, Ph.D.; and James B. Potash, M.D., M.P.H.
Source:
Stephanie Desmon
Johns Hopkins Medical Institutions
Brain Cells Recreated From Skin Cells To Study Schizophrenia Safely
A team of scientists at Penn State University, the Salk Institute for Biological Studies, and other institutions have developed a method for recreating a schizophrenic patient's own brain cells, which then can be studied safely and effectively in a Petri dish. The method brings researchers a step closer to understanding the biological underpinnings of schizophrenia. The method also is expected to be used to study other mysterious diseases such as autism and bipolar disorder, and the researchers hope that it will open the door to personalized medicine - customized treatments for individual sufferers of a disease based on genetic and cellular information. The study will be published in a future edition of the journal Nature and will be posted on the journal's advance online website on 13 April 2011.
Gong Chen, an associate professor of biology at Penn State and one of the study's authors, explained that the team first took samples of skin cells from schizophrenic patients. Then, using molecular-biology techniques, they reprogrammed these original skin cells to become unspecialized or undifferentiated stem cells called induced pluripotent stem cells (iPSCs). "A pluripotent stem cell is a kind of blank slate," Chen explained. "During development, such stem cells differentiate into many diverse, specialized cell types, such as a muscle cell, a brain cell, or a blood cell."
After generating iPSCs from skin cells, the authors cultured them to become brain cells, or neurons. They then compared the neurons derived from schizophrenic patients to the neurons created from the iPSCs of healthy individuals. They found that the neurons generated from schizophrenic patients were, in fact, distinct: compared with healthy neurons, they made fewer connections with each other. Kristen Brennand, a Salk researcher and one of the study's authors, then administered a number of frequently prescribed antipsychotic medications to test the drugs' ability to improve how neurons communicate with neighboring cells. "Now, for the very first time, we have a model system that allows us to study how antipsychotic drugs work in live, genetically identical neurons from patients with known clinical outcomes, and we can start correlating pharmacological effects with symptoms," Brennand said.
Chen, who contributed to the study by using electrophysiology techniques to test the function of the iPSC-derived neurons, described the new method as "patient specific," offering a step toward personalized medicine for sufferers of schizophrenia and potentially other diseases. "What's so exciting about this approach is that we can examine patient-derived neurons that are perhaps equivalent to a particular patient's own neural cells," Chen said. "Obviously, we don't want to remove someone's brain cells to experiment on, so recreating the patient's brain cells in a Petri dish is the next best thing for research purposes. Using this method, we can figure out how a particular drug will affect that particular patient's brain cells, without needing the patient to try the drug, and potentially, to suffer the side effects. The patient can be his or her own guinea pig for the design of his or her own treatment, without having to be experimented on directly."
Lead author Fred Gage, a professor at Salk's Laboratory of Genetics and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases, explained that schizophrenia exemplifies many of the research challenges posed by complex psychiatric disorders. "This model not only affords us the opportunity to look at live neurons from schizophrenia patients and healthy individuals to understand more about the disease mechanism, but also it allows us to screen for drugs that may be effective in reversing it," Gage said.
Schizophrenia, which is defined by a combination of paranoid delusions, auditory hallucinations, and diminished cognitive function, afflicts one percent of the population worldwide, corresponding to nearly three million people in the United States alone. Genetic evidence indicates that many different combinations of genetic lesions - some of them affecting the susceptibility to environmental influences - may lead to a variety of signs and symptoms collectively labeled schizophrenia.
"Nobody knows how much the environment contributes to the disease," said Brennand. "By growing neurons in a dish, we can take the environment out of the equation and start focusing on the underlying biological problems." In another part of the study, Brennand used a modified rabies virus, developed by Salk professors Edward Callaway and John Young, to highlight the connections between neurons. The viral tracer made it apparent that the schizophrenic neurons connected less frequently with each other and had fewer projections growing out from their cell bodies. In addition, gene-expression profiles identified almost 600 genes whose activity was misregulated in these neurons; 25 percent of those genes had been implicated in schizophrenia before.
Gage added that, for many years, mental illness has been thought of as a strictly social or environmental disease. "Many people believed that if affected individuals just worked through their problems, they could overcome them," he said. "But we are showing real biological dysfunctions in neurons that are independent of the environment."
Notes:
In addition to Gage, Brennand, and Chen, other researchers who contributed to the study include Anthony Simone, Jessica Jou, Chelsea Gelboin-Burkhart, Ngoc Tran, Sarah Sangar, Yan Li, Yanglin Mu and Diana Yu in the Gage Laboratory; Shane McCarthy at the Cold Spring Harbor Laboratory in New York; and Jonathan Sebat at the University of California at San Diego.
The work was funded, in part, by the California Institute for Regenerative Medicine, the Lookout Foundation, the Mathers Foundation, and the Helmsley Foundation.
Source:
Barbara Kennedy
Penn State
New Approach To Bipolar Mood Swings
3.64 (11 votes)Article Opinions: 1 posts
The future mood swings of people with bipolar disorder can be predicted by their current thoughts and behaviour, a study has found.
Psychologists from the Universities of Manchester and Lancaster say their findings are important because they mean talking therapies, like cognitive behavioural therapy (CBT), could prove effective treatments for the condition.
People with bipolar are prone to extreme mood swings that take them from great emotional highs to the pits of depression; the cause of these mood swings is often put down to the patients' genes and biology rather than their own thoughts and actions.
For this latest study - published in the American Psychological Association journal Psychological Assessment - the researchers followed 50 people with bipolar disorder for a month. The team found that the patients' thinking and behaviour predicted their future mood swings even when their medical history had been accounted for.
"Individuals who believed extreme things about their moods - for example that their moods were completely out of their own control or that they had to keep active all the time to prevent becoming a failure - developed more mood problems in a month's time," said study lead Dr Warren Mansell, in Manchester's School of Psychological Sciences.
"In contrast, people with bipolar disorder who could let their moods pass as a normal reaction to stress or knew they could manage their mood, faired well a month later. These findings are encouraging for talking therapies - such as CBT - that aim to help patients to talk about their moods and change their thinking about them."
A new form of CBT, known as TEAMS (Think Effectively About Mood Swings), is being developed by Dr Mansell and colleagues, at The University of Manchester. It aims to improve on previous therapies by focusing on current problems, like depression, anxiety and irritability, and helping patients to set goals for their life as a whole.
The aim of this new approach is to encourage patients to accept and manage a range of normal emotions - like joy, anger and fear - and a controlled trial is about to start following a successful case series of the TEAMS approach.
The researchers will use the TEAMS approach to follow up their current findings with a larger study that identifies who relapses and who heads towards recovery in the long term.
The paper: 'Extreme Appraisals of Internal States and Bipolar Symptoms: The Hypomanic Attitudes and Positive Predictions Inventory,' published in the ASA's Psychological Assessment journal.
Source:
Aeron Haworth
University of Manchester
The future mood swings of people with bipolar disorder can be predicted by their current thoughts and behaviour, a study has found.
Psychologists from the Universities of Manchester and Lancaster say their findings are important because they mean talking therapies, like cognitive behavioural therapy (CBT), could prove effective treatments for the condition.
People with bipolar are prone to extreme mood swings that take them from great emotional highs to the pits of depression; the cause of these mood swings is often put down to the patients' genes and biology rather than their own thoughts and actions.
For this latest study - published in the American Psychological Association journal Psychological Assessment - the researchers followed 50 people with bipolar disorder for a month. The team found that the patients' thinking and behaviour predicted their future mood swings even when their medical history had been accounted for.
"Individuals who believed extreme things about their moods - for example that their moods were completely out of their own control or that they had to keep active all the time to prevent becoming a failure - developed more mood problems in a month's time," said study lead Dr Warren Mansell, in Manchester's School of Psychological Sciences.
"In contrast, people with bipolar disorder who could let their moods pass as a normal reaction to stress or knew they could manage their mood, faired well a month later. These findings are encouraging for talking therapies - such as CBT - that aim to help patients to talk about their moods and change their thinking about them."
A new form of CBT, known as TEAMS (Think Effectively About Mood Swings), is being developed by Dr Mansell and colleagues, at The University of Manchester. It aims to improve on previous therapies by focusing on current problems, like depression, anxiety and irritability, and helping patients to set goals for their life as a whole.
The aim of this new approach is to encourage patients to accept and manage a range of normal emotions - like joy, anger and fear - and a controlled trial is about to start following a successful case series of the TEAMS approach.
The researchers will use the TEAMS approach to follow up their current findings with a larger study that identifies who relapses and who heads towards recovery in the long term.
The paper: 'Extreme Appraisals of Internal States and Bipolar Symptoms: The Hypomanic Attitudes and Positive Predictions Inventory,' published in the ASA's Psychological Assessment journal.
Source:
Aeron Haworth
University of Manchester
Wednesday, May 25, 2011
Funding For The Broad's Stanley Center For Psychiatric Research Extended By $50M Grant
Impressed by four years of remarkable progress - including pioneering discoveries of the first genes underlying schizophrenia - the Stanley Medical Research Institute (SMRI) has announced that it will make a $50 million gift to support the Broad Institute's Stanley Center for Psychiatric Research.
Launched in 2007 with a ten-year, $100 million grant from the SMRI, the Stanley Center brings together scientists from diverse fields to unlock the genetic mysteries of schizophrenia, bipolar disorder and other mental illnesses, and translate these findings into new treatments for patients. The newly announced grant will provide $10 million per year in funding for an additional five years, making the Stanley Center a fixture in the biomedical landscape for many years to come.
"The renewed support of the Stanley Medical Research Institute underscores the remarkable progress we have made in just a few short years in unraveling the genetics of psychiatric illnesses," said Edward Scolnick, director of the Stanley Center and a core faculty member of the Broad Institute. "I am deeply grateful for their sustained support, which has catalyzed our work in countless ways."
In the United States alone, more than 8 million people suffer from schizophrenia and bipolar disorder. These illnesses tend to run in families, suggesting that they are influenced by genetic factors. Researchers in the Stanley Center are working to unearth the genetic underpinnings of psychiatric disease to pave the way toward better treatment options for patients.
"We are thrilled by the remarkable results flowing from the Stanley Center, which are laying bare the biological roots of psychiatric illnesses," said Ted Stanley, founder of the SMRI. "We are delighted that we can help enable even further progress through our continued support."
Over the last five years, researchers around the world have developed new tools and methods that have the potential to dramatically change the field of psychiatric research. With new genetic methods, tools for studying the brain's circuitry, and ways to grow cells in culture that accurately mimic living cells in the brain, the Broad's Stanley Center researchers can now bring these remarkable tools to bear on schizophrenia and bipolar disorder, as well as other psychiatric illnesses.
"It's really a new world and it's just starting," said Scolnick. "All of this has happened in the last few years. What's different in the field now is it's no longer stuck. A few years ago, no matter what you wanted to do, you didn't have a way of approaching these illnesses experimentally. And now you do."
Already, the Broad's Stanley Center and its partner institutions have uncovered several genes that confer risk of bipolar disorder or schizophrenia and have even found that these two diseases share common risk genes. Additionally, the researchers have revealed important biological pathways - or chains of molecular events - tied to the development of schizophrenia, which could lead to better treatment approaches. The new funding from the SMRI will provide sustained support for this kind of transformative research through early 2022.
"The Stanley Center brings together scientists with different areas of expertise to work together toward a common goal: uncovering the molecular mechanisms of mental illness to bring about better treatment," said Eric S. Lander, director of the Broad Institute. "Genomic tools are accelerating the pace of discovery in psychiatric disease research and the additional support of the Stanley Medical Research Institute ensures that this progress will continue for many years to come."
Source:
Nicole Davis
Broad Institute of MIT and Harvard
Tuesday, May 24, 2011
New Developments in Repeated Transcranial Magnetic Stimulation (rTMS)
At the 65th Annual Scientific Convention of the Society of Biological Psychiatry, several findings related to repeated transcranial magnetic stimulation (rTMS) were reported.
E. Baron Short reported that two weeks of 10 Hz rTMS at 120% of motor threshold (MT) was highly effective in the treatment of fibromyalgia. Pain ratings decreased 45% by day six and 80% by day 10 in this randomized sham-controlled double-blind study.
Also at the convention, Motoaki Nakamura reported that either 1 Hz or 20 Hz rTMS at 90-100% of motor threshold over left prefrontal cortex in depressed patients increased gray matter in left dorsolateral prefrontal cortex and left hippocampus in association with almost 50% reductions in Hamilton depression rating scale scores and associated increases in performance on the Wisconsin card sort test.
Editor’s note: These data are of particular interest in light of increasing evidence for prefrontal and hippocampal neurochemical and volumetric deficits in major depression and other evidence that rTMS may be capable of increasing neurotrophic and neuroprotective factors. This is the first clinical evidence suggesting that rTMS may have direct effects on brain volume as well. These data would converge with other data indicating that long-term antidepressant therapy can prevent hippocampal atrophy and short-term lithium can increases gray matter and hippocampal volume.
The first large multi-center study of rTMS, which was sponsored by industry, gained FDA approval for the apparatus. As reported in previous BNNs, Mark George and collaborators conducted a second large multi-center study sponsored by the National Institute of Mental Health (NIMH), which indicated that rTMS can produce significantly greater rates of remission than those achieved by sham rTMS, as reported in the Archives of General Psychiatry this year. Hopefully, these new efficacy data by George and colleagues will increase the ease of receiving insurance reimbursement for the expensive procedures of a full course of rTMS for the treatment of an acute depression that has been unresponsive to at least one prior clinical trial of an antidepressant.
The data of Nakamura et al. noted above are also of interest in relationship to data from a study in which this editor participated (Speer et al., 2010), which indicated that both 1 Hz and 20 Hz stimulation were more effective than sham rTMS in improving the condition of patients with highly treatment-refractory depression. Moreover, in that study, we observed that 1 Hz rTMS at 110% of a patient’s motor threshold decreased brain activity as measured with cerebral blood flow on PET scan, while 20 Hz markedly increased brain activity in a widespread fashion that remained for at least 48 hours following the last of 15 rTMS sessions spread over a period of three weeks. The Nakamura data indicating that both 1 and 20 Hz increase indices of gray matter in left dorsolateral and left hippocampus suggests that this neurotrophic effect may, in fact, occur at both high and low frequency rTMS, even though they produce opposite effects on brain activity.
--rTMS for Adolescent Depression
January 26, 2011 · Posted in Potential Treatments
In an abstract presented at the 65th Annual Scientific Convention of the Society of Biological Psychiatry, Christopher Wall reported that treatment with rTMS (10 Hz at 120% of motor threshold) was successful in the treatment of adolescent depression.
These data from an open (as opposed to blind) study deserve further and more systematic investigation. Alternatives to antidepressant drug treatment are desirable for adolescents with depression since increases in suicidal ideation are a potential side effect during the first two months after initiation of pharmacological antidepressant treatment in teens. (Suicidal ideation and actions among adolescents decrease with longer-term antidepressant treatment, especially when it is used in conjunction with cognitive/behavioral psychotherapy.) Children and adolescents treated with antidepressants may also be at higher risk for switching into mania than adults treated with antidepressants.
Editor’s Note: The rTMS parameters used in this study are the same as those used successfully in adults with depression in the two large positive multi-center sham-controlled studies (one by industry and one by the National Institute of Mental Health) mentioned in yesterday’s article.
--Monday, May 23, 2011
Early Life Stressors Linked to Persistent Inflammation and Endocrine Abnormalities
January 27, 2011 · Posted in Neurobiology, Risk Factors
Epigenetics is a relatively new area of study that examines changes in DNA regulation and structure that can come about as a result of environmental events, as opposed to the genetic inheritance (DNA sequence) people receive through their parents’ genes. Epigenetic effects occur when an environmental stressor or chemical causes methyl or acetyl groups to attach to DNA or to histones (around which DNA are wound). These epigenetic changes determine how difficult it is to turn on genes coded in the DNA (see here for more information about the way the environment produces these epigenetic effects).
After the jump: Several studies presented at the 65th Annual Scientific Convention of the Society of Biological Psychiatry earlier this year suggested a link between environmental stress and both inflammation and abnormalities in DNA.
Schizophrenia v. Bipolar Disorder: Different Risk Factors
Robin Murray gave a plenary presentation at the 65th Annual Scientific Convention of the Society of Biological Psychiatry this year, in which he indicated that the genetic risk for schizophrenia and other major mental disorders may be overestimated. He suggested that even in identical twins there are considerable differences in incidence of major psychiatric illnesses, and sharing an environment could further inflate the appearance of genetic risk.
Evidence of some genetic vulnerability factors, such as neuregulin, disbindin, DISC-1, zinc finger transcription factors, and neurexin, has been replicated. However, these genes appear to contribute only about 1% of the vulnerability to schizophrenia or bipolar illness. Copy number variations (CNVs, extra or missing copies of a gene, which may alter its activity) and gene micro-deletions (in which small bits of DNA are missing) have been found in about 5% of patients with schizophrenia, in some patients with autism and mental disabilities, but not in those with bipolar illness.
Murray emphasized the importance of psychosocial and neuromotor markers of neural development in determining risk of subsequent major psychiatric illness, rather than the relatively weak genetic effects. He cited the work of MacCabe (2009), who collected information from 907,000 individuals in Sweden. Their scholastic achievement at age 15?16 was rated, and hospitalizations for psychosis were recorded from age 17?31. Of the 315,000 followed for the long term, 493 developed schizophrenia and 208 developed bipolar disorder.
Predictors of cognitive and motor development in these two major psychiatric illnesses appeared to differ. In those who went on to develop schizophrenia, there was a slower rate of motor development, receptive language, and overall IQ in adolescence, while in those who went on to develop bipolar disorder, there was a faster rate of motor development, more language facility, and higher IQ in adolescence.
IQ-related risks were notably different for the two disorders. People who fell within the two standard deviations below the mean IQ had almost 4-fold higher rates of schizophrenia, while those who scored higher than two standard deviations above the mean were at decreased risk. In contrast, those with IQs two standard deviations above the mean were at 3-fold increased risk for bipolar disorder, with a smaller subgroup showing mildly increased risk with lower IQs as well.
These data are partially consistent with observations of increased obstetrical complications in schizophrenia, including neonatal insults to the brain (during delivery) resulting in brain damage, small growth, and a 7-fold increased incidence of neonatal hypoxia (low blood oxygen concentration). In contrast there is generally little evidence for an increase in obstetrical complications in bipolar illness. Instead, being highly creative and an exceptional, enthusiastic student appears associated with a slightly increased risk for bipolar illness. Other risk factors for schizophrenia included: living in a bigger city, experiencing childhood abuse and neglect, social isolation, adverse life events (of the intrusive variety, such as being in a car accident, and not of the loss variety, such as losing a job or significant other, which are more associated with bipolar illness).
Editor’s Note: We have postulated that the increased intelligence and creativity seen in those with bipolar disorder (or at risk for it) could be related to the findings that a common variant in the gene for brain-derived neurotrophic factor (BDNF) that functions more efficiently (val 66 val proBDNF) is a risk factor for bipolar disorder. The poorer functioning allele (val 66 met proBDNF) is a risk factor for mild cognitive dysfunction in both patients with bipolar disorder and schizophrenia, as well as in normal volunteer controls.
Murray formulated the hypothesis that environmental events could alter the dopamine system, which has been closely linked to psychosis and its treatment with dopamine antagonists (antipsychotics). He cited data indicating that dopamine synthesis, as measured by PET scan, was increased in those with prodromal psychosis. Since dopamine is associated with reward learning and the salience of ideas and objects, he reasoned that increases in dopamine could account for delusions, because the increases in dopamine might involve assigning salience to unimportant stimuli.
Murray noted that pre-term hypoxia leads to a 50% increase in the size of the ventricles and a decrease in hippocampal volume, and other investigators have shown that ventral/hippocampal lesions lead to sensitization of the dopamine systems. Tony Grace has postulated that decreased hippocampal excitatory output reverses the break on dopamine release in the n. accumbens, and increases dopamine and cell firing in the midbrain ventral tegmental dopamine neurons that synapse in the n. accumbens.
Such a model may also have relevance for the pathophysiology of bipolar disorder. Those experiencing a first psychotic episode have higher than normal levels of cortisol in their blood, and increased cortisol is associated with decreased hippocampal volume.
Editor’s note: These findings may intersect with data that show that BDNF appears decreased in the hippocampus of patients with depression, rodents subjected to defeat stress, and cocaine-sensitized animals. Increases in BDNF have been noted in the n. accumbens of depressed patients who died via suicide compared with controls (Krishnan et al. 2008). Moreover, increases in BDNF in the n. accumbens are also seen in animals experiencing defeat stress-induced depressive-like behaviors, and in cocaine sensitization paradigms.
Thus, deficient hippocampal function as marked by decreased volume in those with schizophrenia, or decreased hippocampal BDNF in those with mood disorders, could be associated with disinhibition of firing of dopamine neurons in the ventral/tegmental area and increased release of dopamine in that area of the brain along with increases in BDNF as well. This BDNF formulation is also consistent with the environmental vulnerabilities Murray describes acting to alter dopamine functioning in the psychoses. Environmental stressors and exposure to abused substances could cause hippocampal volumetric and functional deficits in concert with n. accumbens hyperactivity.
--The Role of Calcium in Genetic Vulnerability, Pathophysiology, and Treatment Of Bipolar Illness
February 1, 2011 · Posted in Neurobiology, Risk Factors
One of the most consistent findings in biological psychiatry is that levels of intracellular calcium in blood elements (platelets and white cells) are higher than normal in patients with mood disorders, particularly bipolar disorder. These data are now supported by genome-wide association studies that have identified a relationship between alterations in a calcium channel and vulnerability to bipolar illness. The specific alteration is in the alpha-IC subunit of the L-type calcium channels, otherwise referred to as CACNA1C. These findings were initially reported by one group funded by the Welcome Trust, a charitable organization that funds health research, in a series of studies that included thousands of patients and controls. Investigator Pamela Sklar later replicated these findings in another large independent sample.
Valnoctamide Effective in Mania, Maybe Without Valproate’s Side Effects
Valproate (Depakote), also known as divalproex sodium and valproic acid (VPA), is highly effective in the treatment of mania, seizures, and migraine. However, its use in pregnant mothers can cause birth defects and developmental delay. A closely related compound, valnoctamide, may not pose the same dangers, but its efficacy in mania has only recently been investigated.
Yuly Bersudsky et al. reported at the 4th Biennial Conference of the International Society for Bipolar Disorders conference in Sao Paulo, Brazil in March that valnoctamide was more effective than placebo as an add-on to risperidone for the treatment of mania.
Since there is now evidence that valnoctamide does work in mania, it is plausible that some of the shared characteristics of valproate and valnoctamide, such as increasing brain GABA and blocking sodium channels, are responsible for both drugs’ antimanic effects.
VPA is thought to cause birth defects through its epigenetic effects. The emerging field of epigenetics has shown that environmental factors can influence the structure of DNA or tightness of its packaging, and these alterations may even be passed on to the next generation.
VPA has epigenetic effects because in addition to being an anticonvulsant, it is also a potent histone deacetylase inhibitor (HDAC-I). HDAC-Is make DNA easier to transcribe by keeping acetyl from detaching from histones.
Valnoctamide, on the other hand, is an anticonvulsant that does not get converted to VPA, and is not an HDAC-I. Valnoctamide’s efficacy in mania suggests that VPA’s epigenetic effects (as an HDAC-I) do not account for its anticonvulsant or antimanic efficacy. Moreover, valnoctamide does not appear to be as terotogenic (causing birth defects) in animals as is VPA, and may ultimately be shown to be safer in pregnancy than VPA.
Editor’s Note: VPA is associated with increased risks of spina bifida and other major birth defects as well as major decreases in a child’s IQ (9 points on average). Neurologists suggest that all women of childbearing age and potential who are treated with VPA should take folic acid, B6, and B12 regularly in case they have an unplanned pregnancy. It is hoped that these vitamins might help prevent birth defects, but this has not been proven.
In any event, women of child-bearing age who are taking VPA should use reliable birth control regimens to avoid becoming pregnant. This is especially the case as mania can be associated with poor judgment and sexual indiscretions, making unplanned pregnancies more common.
--Ketamine Effective in ECT-Resistant Depression
In an abstract presented at the Society of Biological Psychiatry meeting in May, Lobna Ibrahim and Carlos Zarate of the National Institute of Mental Health reported that intravenous infusions of ketamine were effective in a majority of patients with highly treatment-resistant depression, i.e. even those who had been unresponsive to a course of electroconvulsive therapy.
Editor’s note: Few treatments have been explored for this subgroup of highly treatment-resistant patients, although some have been referred for experimental protocols with intracranial deep brain stimulation (DBS) and others have been successfully treated by Mark George and colleagues at the Medical University of South Carolina with very high intensity rTMS over the left prefrontal cortex (at 130% of motor threshold, 10 Hz stimulation). Further study is needed to determine what follow-up procedures can be used to sustain an acute response to ketamine, rTMS, or ECT for the long term.
Prudic, Sackeim and colleagues have reported that 40% of patients with a good response to three times a week ECT relapsed within a month of completing that course of treatment. This loss of effect occurred even when ECT was continued more intermittently, suggesting that other therapeutic options need to be developed for this rapidly relapsing subgroup.
Most of the data suggest that if patients fail to respond to a drug treatment regimen prior to ECT and then respond to ECT, a different or an increased intensity of the earlier drug regimen is required in order to sustain their response. Nonresponse to a drug treatment regimen prior to ECT predicts nonresponse to the same regimen following ECT. Since there are now numerous drugs for the primary and auxiliary treatment of depression, research should focus on determining optimal treatment algorithms for patients, both those who are responsive to ECT and those who are not.
Having a potential treatment such as intravenous ketamine that is rapidly effective for ECT nonresponders is a good start. However, at the present time it is not clear how the acute onset antidepressant effects of intravenous ketamine may be sustained for the long term. Since intravenous ketamine also exerts positive effects on acute suicidal ideation, it is likely that IV ketamine will develop into an emergency room procedure for patients in suicidal crisis.
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