What are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimise the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. ‘The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,’ states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. ‘The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.’ Dr. Osuch explains, ‘This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.’
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients.
Lawson Health Research Institute
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Washington University researchers have found that some of the same genes likely are involved in alcohol dependence and eating disorders.
Part of the risk for alcohol dependence is genetic, and the same is true for eating disorders. Now, researchers at Washington University School of Medicine in St. Louis have found it’s likely some of the same genes are involved in both.
The researchers report that people with alcohol dependence may be more genetically susceptible to certain types of eating disorders and vice versa.
‘In clinical practice, it’s been observed that individuals with eating disorders also have high rates of alcohol abuse and dependence,’ said Melissa A. Munn-Chernoff, PhD, the study’s first author. ‘Other studies have focused on the genetic connections between alcohol dependence and eating disorders, but all of those studies looked only at women. Ours was the first to include men as well.’
According to Munn-Chernoff, a postdoctoral research scholar in psychiatry, that’s important because although eating disorders tend to be thought of as a female problem, they affect men, too.
Studying data gathered from nearly 6,000 adult twins in Australia, Munn-Chernoff and her colleagues found that common genetic factors underlie alcoholism and certain eating-disorder symptoms, such as binge eating and purging habits that include self-induced vomiting and the abuse of laxatives.
By studying twins, the researchers used statistical methods to determine the odds that certain traits result from the same genes. Those statistical insights are based on the fact that identical twins share 100 percent of their genetic makeup while fraternal twins share about half.
‘By comparing the findings in identical and fraternal twins, we can develop estimates of how much of the difference in particular traits is due to genes or environment,’ Munn-Chernoff explained. ‘We found that some of the genes that influence alcohol dependence also influence binge eating in men and women.’
Even with the growing awareness and more frequent diagnoses of problems such as anorexia nervosa and bulimia nervosa, rates of the full-blown forms of these disorders are relatively low, and they’re rare in populations of twins. So the researchers surveyed study subjects about whether they suffered from eating-disorder symptoms.
‘The symptoms can cut across multiple eating disorder diagnoses,’ said Munn-Chernoff. ‘And several past studies have suggested that the particular behaviour of binge eating, as well as purging and other practices that we call compensatory behaviours, may be closely associated with alcohol dependence, which is why we focused on those symptoms.’
All of the men and women in the study were surveyed about their alcohol use and binge eating, but because the researchers were analysing data that had been gathered previously for a different study, not everyone was asked about compensatory behaviours, such as purging or using laxatives and diuretics. Only the female twins were asked about those symptoms.
In all, nearly 25 percent of the men and 6 percent of women had been alcohol dependent at some point. Almost 11 percent of these same men and 13 percent of the women had experienced problems with binge eating. In addition, about 14 percent of the women had engaged in purging or abuse of laxatives or diuretics.
On a statistical scale that runs from zero (no shared genes) to 1 (all genes shared), the researchers found that the genetic correlation between binge eating and alcohol dependence was statistically significant at .26.
Among women in the study, the genetic correlation between compensatory behaviours and alcohol dependence was significant at .32.
‘Those numbers suggest that there are shared genetic risk factors for these behaviours, such as purging and fasting,’ said Munn-Chernoff. ‘It appears that some genes that influence alcohol dependence also influence binge eating in men and women, and compensatory behaviours in women.’
Washington University School of Medicine
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A recent study by members of the Children’s Oncology Group reports results of a large trial showing that children whose leukaemia cells have amplification of a portion of chromosome 21 may require more aggressive treatment for Acute Lymphoblastic Leukaemia (ALL) than children without this gene amplification.
‘This helps identify patients who need more therapy than they may otherwise get,’ says Stephen Hunger, MD, investigator at the University of Colorado Cancer Center, professor of paediatrics at the University of Colorado School of Medicine, and director of the Center for Cancer and Blood Disorders at Children’s Hospital Colorado.
Hunger notes that this genetic abnormality was first described in 2003 and has subsequently been found in about 2 percent of pediatric ALL patients. Initial reports described poor outcomes for small groups of children with this abnormality, but the current study is by far the largest and shows the importance of this genetic abnormality even with modern treatments. The study documents the treatments and outcomes of more than 8,000 cases of pediatric ALL.
‘What we found is that when this genetic abnormality is present in children with good risk features who get a standard level of treatment, there is more treatment failure than with similar, low-risk kids who don’t have this genetic marker. But with kids whose risk features already dictate more aggressive treatment, this genetic abnormality doesn’t seem to be associated with a worse outcome, because kids are already getting the appropriate treatment. Recognising this abnormality could help us treat even otherwise low-risk kids more aggressively up front leading to improved cure rates,’ Hunger says.
Specifically, the genetic abnormality is defined as four or more copies of the gene RUNX1, located on an abnormal chromosome 21. And this amplification is already detected as a by-product of another genetic test standard in pediatric ALL, namely a test for fusion of this RUNX1 gene with the gene ETV6.
‘In a sense, the testing comes for free with other testing you’re already doing,’ Hunger says.
A study published by the same group in 2012 showed that pediatric ALL cure rates are at or above 90.4 percent.
‘In early 1960s this disease was incurable,’ Hunger says. ‘Then in the late 1960s, the cure rate was 10 percent. Now 90 percent of children and adolescents diagnosed with ALL will be cured. Still, a 90-percent survival rate is little consolation to the 10 percent of families whose child doesn’t survive. There’s still more work to be done.’
University of Colorado Cancer Center
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Alzheimer’s disease has proven to be a difficult enemy to defeat. After all, ageing is the No. 1 risk factor for the disorder, and there’s no stopping that. Most researchers believe the disease is caused by one of two proteins, one called tau, the other beta-amyloid. As we age, most scientists say, these proteins either disrupt signalling between neurons or simply kill them.
Now, a new UCLA study suggests a third possible cause: iron accumulation. Dr. George Bartzokis, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and senior author of the study, and his colleagues looked at two areas of the brain in patients with Alzheimer’s. They compared the hippocampus, which is known to be damaged early in the disease, and the thalamus, an area that is generally not affected until the late stages. Using sophisticated brain-imaging techniques, they found that iron is increased in the hippocampus and is associated with tissue damage in that area. But increased iron was not found in the thalamus.
While most Alzheimer’s researchers focus on the build-up of tau or beta-amyloid that results in the signature plaques associated with the disease, Bartzokis has long argued that the breakdown begins much further ‘upstream.’ The destruction of myelin, the fatty tissue that coats nerve fibres in the brain, he says, disrupts communication between neurons and promotes the build-up of the plaques. These amyloid plaques in turn destroy more and more myelin, disrupting brain signalling and leading to cell death and the classic clinical signs of Alzheimer’s.
Myelin is produced by cells called oligodendrocytes. These cells, along with myelin, have the highest levels of iron of any cells in the brain, Bartzokis says, and circumstantial evidence has long supported the possibility that brain iron levels might be a risk factor for age-related diseases like Alzheimer’s. Although iron is essential for cell function, too much of it can promote oxidative damage, to which the brain is especially vulnerable.
In the current study, Bartzokis and his colleagues tested their hypothesis that elevated tissue iron caused the tissue breakdown associated with Alzheimer’s disease. They targeted the vulnerable hippocampus, a key area of the brain involved in the formation of memories, and compared it to the thalamus, which is relatively spared by Alzheimer’s until the very late stages of disease.
The researchers used an MRI technique that can measure the amount of brain iron in ferritin, a protein that stores iron, in 31 patients with Alzheimer’s and 68 healthy control subjects.
In the presence of diseases like Alzheimer’s, as the structure of cells breaks down, the amount of water increases in the brain, which can mask the detection of iron, according to Bartzokis.
‘It is difficult to measure iron in tissue when the tissue is already damaged,’ he said. ‘But the MRI technology we used in this study allowed us to determine that the increase in iron is occurring together with the tissue damage. We found that the amount of iron is increased in the hippocampus and is associated with tissue damage in patients with Alzheimer’s but not in the healthy older individuals — or in the thalamus. So the results suggest that iron accumulation may indeed contribute to the cause of Alzheimer’s disease.’
But it’s not all bad news from this study, Bartzokis noted.
‘The accumulation of iron in the brain may be influenced by modifying environmental factors, such as how much red meat and iron dietary supplements we consume and, in women, having hysterectomies before menopause,’ he said.
In addition, he noted, medications that chelate and remove iron from tissue are being developed by several pharmaceutical companies as treatments for the disorder. This MRI technology may allow doctors to determine who is most in need of such treatments.
University of California – Los Angeles
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An international consortium has shown for the first time evidence of substantial overlap of genetic risk factors shared between bipolar disorder, major depressive disorder and schizophrenia and less overlap between those conditions and autism and attention deficit-hyperactivity disorder (ADHD), according to a study.
The root cause of psychiatric illnesses such as bipolar disorder, major depressive disorder schizophrenia, autism and ADHD is not fully understood. For more than 125 years, clinicians have based diagnosis on a collection of symptoms observed in patients.
But, scientists have since identified that the five psychiatric disorders share a common genetic link and are now moving toward understanding the molecular underpinnings of psychiatric illness. The precise degree to which these disorders share common ground has remained unknown, until now.
The project is led by the Cross-Disorder Group of the Psychiatric Genomics Consortium and is the largest genetic study of psychiatric illness to date.
The findings provide insight into the biological pathways that may predispose an individual to disease and could ultimately lead to the development of new therapeutic avenues to treat the five major psychiatric illnesses.
‘This is a very large scale study using a new, innovative statistical method,’ said study co-senior author Kenneth S. Kendler, M.D., professor of psychiatry, and human and molecular genetics in the Virginia Commonwealth University School of Medicine, and an internationally recognised psychiatric geneticist.
‘Prior to this model, we have not been able to address these questions. These results give us by far the clearest picture available to date of the degree of genetic similarity between these key psychiatric disorders. We hope that this will help us both in developing a more scientifically based diagnostic system and understanding the degree of sharing of the biological foundation these illnesses,’ he said.
The study builds on findings published earlier this year in The Lancet, which reported that specific single nucleotide polymorphisms, or SNPs, are associated with a range of psychiatric disorders that can occur during childhood or adulthood.
Next, the group will examine other disorders for which molecular genetic data is accumulating including eating disorders, obsessive compulsive disorder and drug use disorders.
Since 2007, the Cross-Disorder Group of the Psychiatric Genomics Consortium has reviewed scientific literature of genome-wide association studies, or GWAS, on psychiatric disorders. To date, GWAS data from more than 19 countries has been gathered by the consortium.
Virginia Commonwealth University
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One night when she was trying to fall asleep, a 60-year-old woman suddenly began hearing music, as if a radio were playing at the back of her head.
The songs were popular tunes her husband recognised when she sang or hummed them. But she herself could not identify them.
This is the first known case of a patient hallucinating music that was familiar to people around her, but that she herself did not recognise, according to Dr. Danilo Vitorovic and Dr. José Biller of Loyola University Medical Center.
The case raises ‘intriguing questions regarding memory, forgetting and access to lost memories,’ the authors write.
Musical hallucinations are a form of auditory hallucinations, in which patients hear songs, instrumental music or tunes, even though no such music is actually playing. Most patients realise they are hallucinating, and find the music intrusive and occasionally unpleasant. There is no cure.
Musical hallucinations usually occur in older people. Several conditions are possible causes or predisposing factors, including hearing impairment, brain damage, epilepsy, intoxications and psychiatric disorders such as depression, schizophrenia and obsessive-compulsive disorder. Hearing impairment is the most common predisposing condition, but is not by itself sufficient to cause hallucinations.
Vitorovic and Biller describe a hearing-impaired patient who initially hallucinated music when she was trying to fall asleep. Within four months, she was hearing music all the time. For example, she would hear one song over and over for three weeks, then another song would begin playing. The volume never changed, and she was able to hear and follow conversations while hallucinating the music.
The patient was treated with carbamazepine, an anti-seizure drug, and experienced some improvement in her symptoms.
The unique feature of the patient was her ability to hum parts of some tunes and recall bits of lyrics from some songs that she did not even recognise. This raises the possibility that the songs were buried in her memory, but she could not access them except when she was hallucinating.
‘Further research is necessary on the mechanisms of forgetfulness,’ Vitorovic and Biller write. ‘In other words, is forgotten information lost, or just not accessible?’
Vitorovic is a former chief neurology resident and Biller is a professor and chair in the Department of Neurology of Loyola University Chicago Stritch School of Medicine.
Loyola University Health System
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Indiana University School of Medicine researchers have found a series of RNA biomarkers in blood that may help identify who is at risk for committing suicide.
The researchers said the biomarkers were found at significantly higher levels in the blood of both bipolar disorder patients with thoughts of suicide as well in a group of people who had committed suicide.
Principal investigator Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and attending psychiatrist and research and development investigator at the Richard L. Roudebush Veterans Affairs Medical Center in Indianapolis, said he believes the results provide a first ‘proof of principle’ for a test that could provide an early warning of somebody being at higher risk for an impulsive suicide act.
‘Suicide is a big problem in psychiatry. It’s a big problem in the civilian realm, it’s a big problem in the military realm and there are no objective markers,’ said Dr. Niculescu, director of the Laboratory of Neurophenomics at the Institute of Psychiatric Research at the IU School of Medicine.
‘There are people who will not reveal they are having suicidal thoughts when you ask them, who then commit it and there’s nothing you can do about it. We need better ways to identify, intervene and prevent these tragic cases,’ he said.
Over a three-year period, Niculescu and his colleagues followed a large group of patients diagnosed with bipolar disorder, completing interviews and taking blood samples every three to six months. The researchers conducted a variety of analyses of the blood of a subset of participants who reported a dramatic shift from no suicidal thoughts to strong suicidal ideation. They identified differences in gene expression between the ‘low’ and ‘high’ states of suicidal thoughts and subjected those findings to a system of genetic and genomic analysis called Convergent Functional Genomics that identified and prioritized the best markers by cross-validation with other lines of evidence.
The researchers found that the marker SAT1 and a series of other markers provided the strongest biological ‘signal’ associated with suicidal thoughts.
Next, to validate their findings, working with the local coroner’s office, they analysed blood samples from suicide victims and found that some of same top markers were significantly elevated.
Finally, the researchers analysed blood test results from two additional groups of patients and found that high blood levels of the biomarkers were correlated with future suicide-related hospitalisations, as well as hospitalisations that had occurred before the blood tests.
‘This suggests that these markers reflect more than just a current state of high risk, but could be trait markers that correlate with long term risk,’ said Dr. Niculescu.
Although confident in the biomarkers validity, Dr. Niculescu noted that a limitation is that the research subjects were all male.
‘There could be gender differences,’ he said. ‘We would also like to conduct more extensive, normative studies, in the population at large.’
In addition to extending the research to females to see if the same or other markers come into play, Dr. Niculescu and colleagues plan to conduct research among other groups, such as persons who have less impulsive, more deliberate and planned subtypes of suicide.
Indiana University School of Medicine
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A new way of screening for ovarian cancer is showing ‘potential’, according to researchers in the US. Tumours in the ovaries are hard to detect in the earliest stages meaning it can be too late to treat them effectively by the time they are found. A trial of 4,051 women showed the method could identify those needing treatment. But a huge study taking place in the UK will give a final verdict on the test when it is completed in 2015.
There is a survival rate of up to 90% when ovarian cancer is caught early, compared with less than 30% if it is discovered in the later stages. Unlike other cancers, the symptoms, such as pelvic and abdominal pain or persistent bloating, are often put down to other common ailments and the tumour can be missed. There is no mass screening programme to detect the cancer either.
Scientists already know that levels of a protein in the blood, called CA125, are often higher with ovarian cancer. However, it is too unreliable on its own. It misses some patients and tells others they have the cancer when they are actually healthy.
Researchers are now testing the idea of using the blood test to sort patients in risk groups based on levels of CA125. Instead of going straight for surgery, low-risk patients are tested again in a year, medium-risk ones after three months and high-risk patients have an ultrasound scan to hunt for tumours.
The US study, at the University of Texas, followed post-menopausal women for 11 years on average. Ten women had surgery based on their ultrasound scan and all the cancers detected were at an early stage.
Researcher Dr Karen Lu told the BBC: ‘Clinical practice definitely should not change from our study, but it gives us an insight – we didn’t get a lot of false positives.’
She said the UK study of 50,000 people would give definitive results: ‘There are two big questions – do we see cancers at an earlier stage and do we decrease the number of deaths.’
Dr Sarah Blagden, from the Ovarian Cancer Action research centre, said: ‘Relative to the trial under way in the in the UK , this is a small study, but it does show that effective ovarian screening is possible.
‘In 2015 the results of the UKCTOCs study will become available and the results are eagerly anticipated, more so now that this American study has produced such encouraging results.’
BBC
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Reversing inflammation in the fluid surrounding the brain’s cortex may provide a solution to the complex riddle of Parkinson’s, according to researchers who have found a link between pro-inflammatory biomarkers and the severity of symptoms such as fatigue, depression and anxiety in patients with the chronic disease.
Lena Brundin of Michigan State University’s College of Human Medicine was part of a research team that measured inflammatory markers found in cerebrospinal fluid samples of Parkinson’s patients and members of a control group.
‘The degree of neuroinflammation was significantly associated with more severe depression, fatigue, and cognitive impairment even after controlling for factors such as age, gender and disease duration,’ said Brundin, an associate professor in the college and a researcher with the Van Andel Institute.
‘By investigating associations between inflammatory markers and non-motor symptoms we hope to gain further insight into this area, which in turn could lead to new treatment options.’
Inflammation in the brain long has been suspected to be involved in the development of Parkinson’s disease, specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. Recent research suggests inflammation could drive cell death and that developing new drugs that target this inflammation might slow disease progression.
Parkinson´s disease is the second most common degenerative disorder of the central nervous system; the causes of the disease and its development are not yet fully understood.
‘The few previous studies investigating inflammatory markers in the cerebrospinal fluid of Parkinson’s patients have been conducted on comparatively small numbers of subjects, and often without a healthy control group for comparison,’ Brundin said.
In the study, 87 Parkinson’s patients were enrolled between 2008 and 2012. For the control group, 37 individuals were recruited. Participants underwent a general physical exam and routine blood screening. Researchers looked at the following markers: C-reactive protein, interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 and macrophage inflammatory protein 1-β.
The study was carried out in collaboration with researchers from Lund University in Sweden, Skåne University Hospital in Sweden and the Mayo Clinic College of Medicine in Florida.
Michigan State University
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Researchers have tied mutations in a gene that causes amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders to the toxic build-up of certain proteins and related molecules in cells, including neurons. The research offers a new approach for developing treatments against these devastating diseases.
Scientists at St. Jude Children’s Research Hospital and the University of Colorado, Boulder, led the work.
The findings provide the first evidence that a gene named VCP plays a role in the break-up and clearance of protein and RNA molecules that accumulate in temporary structures called RNA granules. RNAs perform a variety of vital cell functions, including protein production. RNA granules support proper functioning of RNA.
In ALS and related degenerative diseases, the process of assembling and clearing RNA granules is impaired. The proteins and RNAs associated with the granules often build up in nerve cells of patients. This study shows how mutations in VCP might contribute to that process and neurodegenerative disease.
‘The results go a long way to explaining the process that links a variety of neurodegenerative diseases, including ALS, frontotemporal dementia and related diseases of the brain, muscle and bone known as multisystem proteinopathies,’ said the study’s co-corresponding author, J. Paul Taylor, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. Roy Parker, Ph.D., of the University of Colorado’s Department of Chemistry and Biochemistry and the Howard Hughes Medical Institute (HHMI), is the other corresponding author.
St Jude Children’s Research Hospital
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Imaging in mental health and improving the diagnostic process
, /in E-News /by 3wmediaWhat are some of the most troubling numbers in mental health? Six to 10 — the number of years it can take to properly diagnose a mental health condition. Dr. Elizabeth Osuch, a Researcher at Lawson Health Research Institute and a Psychiatrist at London Health Sciences Centre and the Department of Psychiatry at Western University, is helping to end misdiagnosis by looking for a ‘biomarker’ in the brain that will help diagnose and treat two commonly misdiagnosed disorders.
Major Depressive Disorder (MDD), otherwise known as Unipolar Disorder, and Bipolar Disorder (BD) are two common disorders. Currently, diagnosis is made by patient observation and verbal history. Mistakes are not uncommon, and patients can find themselves going from doctor to doctor receiving improper diagnoses and prescribed medications to little effect.
Dr. Osuch looked to identify a ‘biomarker’ in the brain which could help optimise the diagnostic process. She examined youth who were diagnosed with either MDD or BD (15 patients in each group) and imaged their brains with an MRI to see if there was a region of the brain which corresponded with the bipolarity index (BI). The BI is a diagnostic tool which encompasses varying degrees of bipolar disorder, identifying symptoms and behavior in order to place a patient on the spectrum.
What she found was the activation of the putamen correlated positively with BD. This is the region of the brain that controls motor skills, and has a strong link to reinforcement and reward. This speaks directly to the symptoms of bipolar disorder. ‘The identification of the putamen in our positive correlation may indicate a potential trait marker for the symptoms of mania in bipolar disorder,’ states Dr. Osuch.
In order to reach this conclusion, the study approached mental health research from a different angle. ‘The unique aspect of this research is that, instead of dividing the patients by psychiatric diagnoses of bipolar disorder and unipolar depression, we correlated their functional brain images with a measure of bipolarity which spans across a spectrum of diagnoses.’ Dr. Osuch explains, ‘This approach can help to uncover a ‘biomarker’ for bipolarity, independent of the current mood symptoms or mood state of the patient.’
Moving forward Dr. Osuch will repeat the study with more patients, seeking to prove that the activation of the putamen is the start of a trend in large numbers of patients. Lawson Health Research Institute
Alcohol abuse, eating disorders share genetic link
, /in E-News /by 3wmediaWashington University researchers have found that some of the same genes likely are involved in alcohol dependence and eating disorders.
Part of the risk for alcohol dependence is genetic, and the same is true for eating disorders. Now, researchers at Washington University School of Medicine in St. Louis have found it’s likely some of the same genes are involved in both.
The researchers report that people with alcohol dependence may be more genetically susceptible to certain types of eating disorders and vice versa.
‘In clinical practice, it’s been observed that individuals with eating disorders also have high rates of alcohol abuse and dependence,’ said Melissa A. Munn-Chernoff, PhD, the study’s first author. ‘Other studies have focused on the genetic connections between alcohol dependence and eating disorders, but all of those studies looked only at women. Ours was the first to include men as well.’
According to Munn-Chernoff, a postdoctoral research scholar in psychiatry, that’s important because although eating disorders tend to be thought of as a female problem, they affect men, too.
Studying data gathered from nearly 6,000 adult twins in Australia, Munn-Chernoff and her colleagues found that common genetic factors underlie alcoholism and certain eating-disorder symptoms, such as binge eating and purging habits that include self-induced vomiting and the abuse of laxatives.
By studying twins, the researchers used statistical methods to determine the odds that certain traits result from the same genes. Those statistical insights are based on the fact that identical twins share 100 percent of their genetic makeup while fraternal twins share about half.
‘By comparing the findings in identical and fraternal twins, we can develop estimates of how much of the difference in particular traits is due to genes or environment,’ Munn-Chernoff explained. ‘We found that some of the genes that influence alcohol dependence also influence binge eating in men and women.’
Even with the growing awareness and more frequent diagnoses of problems such as anorexia nervosa and bulimia nervosa, rates of the full-blown forms of these disorders are relatively low, and they’re rare in populations of twins. So the researchers surveyed study subjects about whether they suffered from eating-disorder symptoms.
‘The symptoms can cut across multiple eating disorder diagnoses,’ said Munn-Chernoff. ‘And several past studies have suggested that the particular behaviour of binge eating, as well as purging and other practices that we call compensatory behaviours, may be closely associated with alcohol dependence, which is why we focused on those symptoms.’
All of the men and women in the study were surveyed about their alcohol use and binge eating, but because the researchers were analysing data that had been gathered previously for a different study, not everyone was asked about compensatory behaviours, such as purging or using laxatives and diuretics. Only the female twins were asked about those symptoms.
In all, nearly 25 percent of the men and 6 percent of women had been alcohol dependent at some point. Almost 11 percent of these same men and 13 percent of the women had experienced problems with binge eating. In addition, about 14 percent of the women had engaged in purging or abuse of laxatives or diuretics.
On a statistical scale that runs from zero (no shared genes) to 1 (all genes shared), the researchers found that the genetic correlation between binge eating and alcohol dependence was statistically significant at .26.
Among women in the study, the genetic correlation between compensatory behaviours and alcohol dependence was significant at .32.
‘Those numbers suggest that there are shared genetic risk factors for these behaviours, such as purging and fasting,’ said Munn-Chernoff. ‘It appears that some genes that influence alcohol dependence also influence binge eating in men and women, and compensatory behaviours in women.’ Washington University School of Medicine
Chromosome 21 abnormality tells oncologists to treat pediatric ALL more aggressively
, /in E-News /by 3wmediaA recent study by members of the Children’s Oncology Group reports results of a large trial showing that children whose leukaemia cells have amplification of a portion of chromosome 21 may require more aggressive treatment for Acute Lymphoblastic Leukaemia (ALL) than children without this gene amplification.
‘This helps identify patients who need more therapy than they may otherwise get,’ says Stephen Hunger, MD, investigator at the University of Colorado Cancer Center, professor of paediatrics at the University of Colorado School of Medicine, and director of the Center for Cancer and Blood Disorders at Children’s Hospital Colorado.
Hunger notes that this genetic abnormality was first described in 2003 and has subsequently been found in about 2 percent of pediatric ALL patients. Initial reports described poor outcomes for small groups of children with this abnormality, but the current study is by far the largest and shows the importance of this genetic abnormality even with modern treatments. The study documents the treatments and outcomes of more than 8,000 cases of pediatric ALL.
‘What we found is that when this genetic abnormality is present in children with good risk features who get a standard level of treatment, there is more treatment failure than with similar, low-risk kids who don’t have this genetic marker. But with kids whose risk features already dictate more aggressive treatment, this genetic abnormality doesn’t seem to be associated with a worse outcome, because kids are already getting the appropriate treatment. Recognising this abnormality could help us treat even otherwise low-risk kids more aggressively up front leading to improved cure rates,’ Hunger says.
Specifically, the genetic abnormality is defined as four or more copies of the gene RUNX1, located on an abnormal chromosome 21. And this amplification is already detected as a by-product of another genetic test standard in pediatric ALL, namely a test for fusion of this RUNX1 gene with the gene ETV6.
‘In a sense, the testing comes for free with other testing you’re already doing,’ Hunger says.
A study published by the same group in 2012 showed that pediatric ALL cure rates are at or above 90.4 percent.
‘In early 1960s this disease was incurable,’ Hunger says. ‘Then in the late 1960s, the cure rate was 10 percent. Now 90 percent of children and adolescents diagnosed with ALL will be cured. Still, a 90-percent survival rate is little consolation to the 10 percent of families whose child doesn’t survive. There’s still more work to be done.’ University of Colorado Cancer Center
Study suggests iron is at core of Alzheimer’s disease
, /in E-News /by 3wmediaAlzheimer’s disease has proven to be a difficult enemy to defeat. After all, ageing is the No. 1 risk factor for the disorder, and there’s no stopping that. Most researchers believe the disease is caused by one of two proteins, one called tau, the other beta-amyloid. As we age, most scientists say, these proteins either disrupt signalling between neurons or simply kill them.
Now, a new UCLA study suggests a third possible cause: iron accumulation. Dr. George Bartzokis, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and senior author of the study, and his colleagues looked at two areas of the brain in patients with Alzheimer’s. They compared the hippocampus, which is known to be damaged early in the disease, and the thalamus, an area that is generally not affected until the late stages. Using sophisticated brain-imaging techniques, they found that iron is increased in the hippocampus and is associated with tissue damage in that area. But increased iron was not found in the thalamus.
While most Alzheimer’s researchers focus on the build-up of tau or beta-amyloid that results in the signature plaques associated with the disease, Bartzokis has long argued that the breakdown begins much further ‘upstream.’ The destruction of myelin, the fatty tissue that coats nerve fibres in the brain, he says, disrupts communication between neurons and promotes the build-up of the plaques. These amyloid plaques in turn destroy more and more myelin, disrupting brain signalling and leading to cell death and the classic clinical signs of Alzheimer’s.
Myelin is produced by cells called oligodendrocytes. These cells, along with myelin, have the highest levels of iron of any cells in the brain, Bartzokis says, and circumstantial evidence has long supported the possibility that brain iron levels might be a risk factor for age-related diseases like Alzheimer’s. Although iron is essential for cell function, too much of it can promote oxidative damage, to which the brain is especially vulnerable.
In the current study, Bartzokis and his colleagues tested their hypothesis that elevated tissue iron caused the tissue breakdown associated with Alzheimer’s disease. They targeted the vulnerable hippocampus, a key area of the brain involved in the formation of memories, and compared it to the thalamus, which is relatively spared by Alzheimer’s until the very late stages of disease.
The researchers used an MRI technique that can measure the amount of brain iron in ferritin, a protein that stores iron, in 31 patients with Alzheimer’s and 68 healthy control subjects.
In the presence of diseases like Alzheimer’s, as the structure of cells breaks down, the amount of water increases in the brain, which can mask the detection of iron, according to Bartzokis.
‘It is difficult to measure iron in tissue when the tissue is already damaged,’ he said. ‘But the MRI technology we used in this study allowed us to determine that the increase in iron is occurring together with the tissue damage. We found that the amount of iron is increased in the hippocampus and is associated with tissue damage in patients with Alzheimer’s but not in the healthy older individuals — or in the thalamus. So the results suggest that iron accumulation may indeed contribute to the cause of Alzheimer’s disease.’
But it’s not all bad news from this study, Bartzokis noted.
‘The accumulation of iron in the brain may be influenced by modifying environmental factors, such as how much red meat and iron dietary supplements we consume and, in women, having hysterectomies before menopause,’ he said.
In addition, he noted, medications that chelate and remove iron from tissue are being developed by several pharmaceutical companies as treatments for the disorder. This MRI technology may allow doctors to determine who is most in need of such treatments. University of California – Los Angeles
New patterns found in the genetic relationship of five major psychiatric disorders
, /in E-News /by 3wmediaAn international consortium has shown for the first time evidence of substantial overlap of genetic risk factors shared between bipolar disorder, major depressive disorder and schizophrenia and less overlap between those conditions and autism and attention deficit-hyperactivity disorder (ADHD), according to a study.
The root cause of psychiatric illnesses such as bipolar disorder, major depressive disorder schizophrenia, autism and ADHD is not fully understood. For more than 125 years, clinicians have based diagnosis on a collection of symptoms observed in patients.
But, scientists have since identified that the five psychiatric disorders share a common genetic link and are now moving toward understanding the molecular underpinnings of psychiatric illness. The precise degree to which these disorders share common ground has remained unknown, until now.
The project is led by the Cross-Disorder Group of the Psychiatric Genomics Consortium and is the largest genetic study of psychiatric illness to date.
The findings provide insight into the biological pathways that may predispose an individual to disease and could ultimately lead to the development of new therapeutic avenues to treat the five major psychiatric illnesses.
‘This is a very large scale study using a new, innovative statistical method,’ said study co-senior author Kenneth S. Kendler, M.D., professor of psychiatry, and human and molecular genetics in the Virginia Commonwealth University School of Medicine, and an internationally recognised psychiatric geneticist.
‘Prior to this model, we have not been able to address these questions. These results give us by far the clearest picture available to date of the degree of genetic similarity between these key psychiatric disorders. We hope that this will help us both in developing a more scientifically based diagnostic system and understanding the degree of sharing of the biological foundation these illnesses,’ he said.
The study builds on findings published earlier this year in The Lancet, which reported that specific single nucleotide polymorphisms, or SNPs, are associated with a range of psychiatric disorders that can occur during childhood or adulthood.
Next, the group will examine other disorders for which molecular genetic data is accumulating including eating disorders, obsessive compulsive disorder and drug use disorders.
Since 2007, the Cross-Disorder Group of the Psychiatric Genomics Consortium has reviewed scientific literature of genome-wide association studies, or GWAS, on psychiatric disorders. To date, GWAS data from more than 19 countries has been gathered by the consortium. Virginia Commonwealth University
Unique form of musical hallucinations
, /in E-News /by 3wmediaOne night when she was trying to fall asleep, a 60-year-old woman suddenly began hearing music, as if a radio were playing at the back of her head.
The songs were popular tunes her husband recognised when she sang or hummed them. But she herself could not identify them.
This is the first known case of a patient hallucinating music that was familiar to people around her, but that she herself did not recognise, according to Dr. Danilo Vitorovic and Dr. José Biller of Loyola University Medical Center.
The case raises ‘intriguing questions regarding memory, forgetting and access to lost memories,’ the authors write.
Musical hallucinations are a form of auditory hallucinations, in which patients hear songs, instrumental music or tunes, even though no such music is actually playing. Most patients realise they are hallucinating, and find the music intrusive and occasionally unpleasant. There is no cure.
Musical hallucinations usually occur in older people. Several conditions are possible causes or predisposing factors, including hearing impairment, brain damage, epilepsy, intoxications and psychiatric disorders such as depression, schizophrenia and obsessive-compulsive disorder. Hearing impairment is the most common predisposing condition, but is not by itself sufficient to cause hallucinations.
Vitorovic and Biller describe a hearing-impaired patient who initially hallucinated music when she was trying to fall asleep. Within four months, she was hearing music all the time. For example, she would hear one song over and over for three weeks, then another song would begin playing. The volume never changed, and she was able to hear and follow conversations while hallucinating the music.
The patient was treated with carbamazepine, an anti-seizure drug, and experienced some improvement in her symptoms.
The unique feature of the patient was her ability to hum parts of some tunes and recall bits of lyrics from some songs that she did not even recognise. This raises the possibility that the songs were buried in her memory, but she could not access them except when she was hallucinating.
‘Further research is necessary on the mechanisms of forgetfulness,’ Vitorovic and Biller write. ‘In other words, is forgotten information lost, or just not accessible?’
Vitorovic is a former chief neurology resident and Biller is a professor and chair in the Department of Neurology of Loyola University Chicago Stritch School of Medicine. Loyola University Health System
Researchers identify biomarkers for possible blood test to predict suicide risk
, /in E-News /by 3wmediaIndiana University School of Medicine researchers have found a series of RNA biomarkers in blood that may help identify who is at risk for committing suicide.
The researchers said the biomarkers were found at significantly higher levels in the blood of both bipolar disorder patients with thoughts of suicide as well in a group of people who had committed suicide.
Principal investigator Alexander B. Niculescu III, M.D., Ph.D., associate professor of psychiatry and medical neuroscience at the IU School of Medicine and attending psychiatrist and research and development investigator at the Richard L. Roudebush Veterans Affairs Medical Center in Indianapolis, said he believes the results provide a first ‘proof of principle’ for a test that could provide an early warning of somebody being at higher risk for an impulsive suicide act.
‘Suicide is a big problem in psychiatry. It’s a big problem in the civilian realm, it’s a big problem in the military realm and there are no objective markers,’ said Dr. Niculescu, director of the Laboratory of Neurophenomics at the Institute of Psychiatric Research at the IU School of Medicine.
‘There are people who will not reveal they are having suicidal thoughts when you ask them, who then commit it and there’s nothing you can do about it. We need better ways to identify, intervene and prevent these tragic cases,’ he said.
Over a three-year period, Niculescu and his colleagues followed a large group of patients diagnosed with bipolar disorder, completing interviews and taking blood samples every three to six months. The researchers conducted a variety of analyses of the blood of a subset of participants who reported a dramatic shift from no suicidal thoughts to strong suicidal ideation. They identified differences in gene expression between the ‘low’ and ‘high’ states of suicidal thoughts and subjected those findings to a system of genetic and genomic analysis called Convergent Functional Genomics that identified and prioritized the best markers by cross-validation with other lines of evidence.
The researchers found that the marker SAT1 and a series of other markers provided the strongest biological ‘signal’ associated with suicidal thoughts.
Next, to validate their findings, working with the local coroner’s office, they analysed blood samples from suicide victims and found that some of same top markers were significantly elevated.
Finally, the researchers analysed blood test results from two additional groups of patients and found that high blood levels of the biomarkers were correlated with future suicide-related hospitalisations, as well as hospitalisations that had occurred before the blood tests.
‘This suggests that these markers reflect more than just a current state of high risk, but could be trait markers that correlate with long term risk,’ said Dr. Niculescu.
Although confident in the biomarkers validity, Dr. Niculescu noted that a limitation is that the research subjects were all male.
‘There could be gender differences,’ he said. ‘We would also like to conduct more extensive, normative studies, in the population at large.’
In addition to extending the research to females to see if the same or other markers come into play, Dr. Niculescu and colleagues plan to conduct research among other groups, such as persons who have less impulsive, more deliberate and planned subtypes of suicide. Indiana University School of Medicine
Ovarian cancer screening ‘has potential’
, /in E-News /by 3wmediaA new way of screening for ovarian cancer is showing ‘potential’, according to researchers in the US. Tumours in the ovaries are hard to detect in the earliest stages meaning it can be too late to treat them effectively by the time they are found. A trial of 4,051 women showed the method could identify those needing treatment. But a huge study taking place in the UK will give a final verdict on the test when it is completed in 2015.
There is a survival rate of up to 90% when ovarian cancer is caught early, compared with less than 30% if it is discovered in the later stages. Unlike other cancers, the symptoms, such as pelvic and abdominal pain or persistent bloating, are often put down to other common ailments and the tumour can be missed. There is no mass screening programme to detect the cancer either.
Scientists already know that levels of a protein in the blood, called CA125, are often higher with ovarian cancer. However, it is too unreliable on its own. It misses some patients and tells others they have the cancer when they are actually healthy.
Researchers are now testing the idea of using the blood test to sort patients in risk groups based on levels of CA125. Instead of going straight for surgery, low-risk patients are tested again in a year, medium-risk ones after three months and high-risk patients have an ultrasound scan to hunt for tumours.
The US study, at the University of Texas, followed post-menopausal women for 11 years on average. Ten women had surgery based on their ultrasound scan and all the cancers detected were at an early stage.
Researcher Dr Karen Lu told the BBC: ‘Clinical practice definitely should not change from our study, but it gives us an insight – we didn’t get a lot of false positives.’
She said the UK study of 50,000 people would give definitive results: ‘There are two big questions – do we see cancers at an earlier stage and do we decrease the number of deaths.’
Dr Sarah Blagden, from the Ovarian Cancer Action research centre, said: ‘Relative to the trial under way in the in the UK , this is a small study, but it does show that effective ovarian screening is possible.
‘In 2015 the results of the UKCTOCs study will become available and the results are eagerly anticipated, more so now that this American study has produced such encouraging results.’ BBC
Brain inflammation linked to more severe Parkinson’s symptoms
, /in E-News /by 3wmediaReversing inflammation in the fluid surrounding the brain’s cortex may provide a solution to the complex riddle of Parkinson’s, according to researchers who have found a link between pro-inflammatory biomarkers and the severity of symptoms such as fatigue, depression and anxiety in patients with the chronic disease.
Lena Brundin of Michigan State University’s College of Human Medicine was part of a research team that measured inflammatory markers found in cerebrospinal fluid samples of Parkinson’s patients and members of a control group.
‘The degree of neuroinflammation was significantly associated with more severe depression, fatigue, and cognitive impairment even after controlling for factors such as age, gender and disease duration,’ said Brundin, an associate professor in the college and a researcher with the Van Andel Institute.
‘By investigating associations between inflammatory markers and non-motor symptoms we hope to gain further insight into this area, which in turn could lead to new treatment options.’
Inflammation in the brain long has been suspected to be involved in the development of Parkinson’s disease, specifically in non-motor symptoms such as depression, fatigue and cognitive impairment. Recent research suggests inflammation could drive cell death and that developing new drugs that target this inflammation might slow disease progression.
Parkinson´s disease is the second most common degenerative disorder of the central nervous system; the causes of the disease and its development are not yet fully understood.
‘The few previous studies investigating inflammatory markers in the cerebrospinal fluid of Parkinson’s patients have been conducted on comparatively small numbers of subjects, and often without a healthy control group for comparison,’ Brundin said.
In the study, 87 Parkinson’s patients were enrolled between 2008 and 2012. For the control group, 37 individuals were recruited. Participants underwent a general physical exam and routine blood screening. Researchers looked at the following markers: C-reactive protein, interleukin-6, tumor necrosis factor-alpha, eotaxin, interferon gamma-induced protein-10, monocyte chemotactic protein-1 and macrophage inflammatory protein 1-β.
The study was carried out in collaboration with researchers from Lund University in Sweden, Skåne University Hospital in Sweden and the Mayo Clinic College of Medicine in Florida. Michigan State University
Scientists identify ALS disease mechanism
, /in E-News /by 3wmediaResearchers have tied mutations in a gene that causes amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders to the toxic build-up of certain proteins and related molecules in cells, including neurons. The research offers a new approach for developing treatments against these devastating diseases.
Scientists at St. Jude Children’s Research Hospital and the University of Colorado, Boulder, led the work.
The findings provide the first evidence that a gene named VCP plays a role in the break-up and clearance of protein and RNA molecules that accumulate in temporary structures called RNA granules. RNAs perform a variety of vital cell functions, including protein production. RNA granules support proper functioning of RNA.
In ALS and related degenerative diseases, the process of assembling and clearing RNA granules is impaired. The proteins and RNAs associated with the granules often build up in nerve cells of patients. This study shows how mutations in VCP might contribute to that process and neurodegenerative disease.
‘The results go a long way to explaining the process that links a variety of neurodegenerative diseases, including ALS, frontotemporal dementia and related diseases of the brain, muscle and bone known as multisystem proteinopathies,’ said the study’s co-corresponding author, J. Paul Taylor, M.D., Ph.D., a member of the St. Jude Department of Developmental Neurobiology. Roy Parker, Ph.D., of the University of Colorado’s Department of Chemistry and Biochemistry and the Howard Hughes Medical Institute (HHMI), is the other corresponding author. St Jude Children’s Research Hospital