Posts tagged biomarker
Articles and news from the latest research reports.
Study Identifies Possible Biomarker for Parkinson’s Disease
Researchers discover that an important clue to diagnosing Parkinson’s disease may lie just beneath the skin
Although Parkinson’s disease is the second most prevalent neurodegenerative disorder in the U.S., there are no standard clinical tests available to identify this widespread condition. As a result, Parkinson’s disease often goes unrecognized until late in its progression, when the brain’s affected neurons have already been destroyed and telltale motor symptoms such as tremor and rigidity have already appeared.
Now researchers from Beth Israel Deaconess Medical Center (BIDMC) have discovered that an important clue to diagnosing Parkinson’s may lie just beneath the skin.
In a study scheduled to appear in the October 29 print issue of the journal Neurology and currently published on-line, the investigators report that elevated levels of a protein called alpha-synuclein can be detected in the skin of Parkinson’s patients, findings that offer a possible biomarker to enable clinicians to identify and diagnose PD before the disease has reached an advanced stage.
Parkinson’s disease affects more than 1 million individuals throughout the U.S. Diagnosis is currently made through neurological history and examination, often by a patient’s primary care physician.
“Even the experts are wrong in diagnosing Parkinson’s disease a large percentage of the time,” says senior author Roy Freeman, MD, Director of the Autonomic and Peripheral Nerve Laboratory at BIDMC and Professor of Neurology at Harvard Medical School. “A reliable biomarker could help doctors in more accurately diagnosing Parkinson’s disease at an earlier stage and thereby offer patients therapies before the disease has progressed.”
Alpha-synuclein is a protein found throughout the nervous system. Although its function is unknown, it is the primary component of protein clumps known as Lewy bodies, which are considered the hallmark of Parkinson’s disease. There is accumulating evidence that the protein plays a role in Parkinson’s disease development.
“Alpha-synuclein deposition occurs early in the course of Parkinson’s disease and precedes the onset of clinical symptoms,” explains Freeman, who with his coauthors suspected that the protein was elevated in the skin’s structures with autonomic innervation.
“Symptoms related to the autonomic nervous system, including changes in bowel function, temperature regulation, and blood pressure control may antedate motor symptoms in Parkinson’s patients,” he explains. “Skin-related autonomic manifestations, including excessive and diminished sweating and changes in skin color and temperature, occur in almost two-thirds of patients with Parkinson’s disease. The skin can provide an accessible window to the nervous system and based on these clinical observations, we decided to test whether examination of the nerves in a skin biopsy could be used to identify a PD biomarker.”
To test this hypothesis, the research team enrolled 20 patients with Parkinson’s disease and 14 control subjects of similar age and gender. The participants underwent examinations, autonomic testing and skin biopsies in three locations on the leg. Alpha-synuclein deposition and density of cutaneous sensory, sudomotor and pilomotor nerve fibers were measured.
As predicted, their results showed that alpha-synuclein was increased in the cutaneous nerves supplying the sweat glands and pilomotor muscles in the Parkinson’s patients. Higher alpha-synuclein deposition in the nerves supplying the skin’s autonomic structures was associated with more advanced Parkinson’s disease and worsening autonomic function.
“There is a strong and unmet need for a biomarker for Parkinson’s disease,” says Freeman. “Alpha-synuclein deposition within the skin has the potential to provide a safe, accessible and repeatable biomarker. Our next steps will be to test whether this protein is present in the cutaneous nerves of individuals at risk for Parkinson’s disease, and whether measurement of alpha-synuclein deposition in the skin can differentiate Parkinson’s disease from other neurodegenerative disorders.”
(Source: newswise.com)
A New Method Will Enable the Early Detection of Parkinson’s Disease Through Handwriting
Today’s primary tool for diagnosing Parkinson’s disease is the diagnostic ability of the physician, who can generally identify the clinical symptoms only when the disease is at a relatively advanced stage. A new joint study by researchers at the University of Haifa and Rambam Hospital that compared the handwriting of 40 sick and healthy subjects suggests an innovative and noninvasive method of diagnosing Parkinson’s at a fairly early stage.
“Identifying the changes in handwriting could lead to an early diagnosis of the illness and neurological intervention at a critical moment,” explains Prof. Sara Rosenblum, of the University of Haifa’s Department of Occupational Therapy, who initiated the study.
The methods for diagnosing Parkinson’s today are a physician evaluation or a test called SPECT, which uses radioactive material to image the brain. The latter, however, is no more effective in diagnosing the illness than an expert doctor and it exposes the patient to unnecessary radiation.
Studies from recent years show that there are unique and distinctive differences between the handwriting of patients with Parkinson’s disease and that of healthy people. However, most studies that to date have focused on handwriting focused on motor skills (such as the drawing of spirals) and not on writing that involves cognitive abilities, such as signing a check, copying addresses, etc.
According to Prof. Rosenblum, Parkinson’s patients report feeling a change in their cognitive abilities before detecting a change in their motor abilities and therefore a test of cognitive impairment like the one performed in this study could attest to the presence of the disease and offer a way to diagnose it earlier.
This research was conducted in cooperation with Dr. Ilana Schlesinger, head of the Center for Movement Disorders and Parkinson’s Disease at Haifa’s Rambam Medical Center and occupational therapists working in the hospital. In the study, the researchers asked the subjects to write their names and gave them addresses to copy, two everyday tasks that require cognitive abilities. Participants were 40 adults with at least 12 years of schooling, half healthy and half known to be in the early stages of Parkinson’s disease (before obvious motor signs are visible).
The writing was done on a regular piece of paper that was placed on electronic tablet, using a special pen with pressure-sensitive sensors operated by the pen when it hit the writing surface. A computerized analysis of the results compared a number of parameters: writing form (length, width and height of the letters), time required, and the pressure exerted on the surface while performing the assignment.
Analysis of the results showed significant differences between the patients and the healthy group, and all subjects, except one, had their status correctly diagnosed (97.5% accuracy). The Parkinson’s disease patients wrote smaller letters (“micrograph”), exerted less pressure on the writing surface, and took more time to complete the task. According to Prof. Rosenblum a particularly noticeable difference was the length of time the pen was in the air between the writing of each letter and each word.
“This finding is particularly important because while the patient holds the pen in the air, his mind is planning his next action in the writing process, and the need for more time reflects the subject’s reduced cognitive ability. Changes in handwriting can occur years before a clinical diagnosis and therefore can be an early signal of the approaching disease,” Prof. Rosenblum said.
According to Dr. Schlesinger, validating these findings in a broader study would allow this method to be used for a preliminary diagnosis of the disease in a safe and non-invasive fashion. “This study is a breakthrough toward an objective diagnosis of the disease,” said Dr. Schlesinger, adding, “Publication of the study in the journal of the European Neurological Society aroused great interest at the International Congress of Parkinson’s Disease and Movement held last week in Sydney, Australia.”
The researchers note that this diagnostic method has the added benefit of reducing the load on the health system, because the test can be performed by a professional other than a doctor. After the results are in, patients can be referred to a doctor for further treatment and testing if necessary. The researchers are currently using the method in a new experiment, in which they use handwriting analysis to evaluate the degree of Parkinson’s patients’ improved functioning after they have brain pacemakers implanted.
(Source: newswise.com)
Imaging in mental health and improving the diagnostic process
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 optimize 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. The hope is that one day there could be a definitive biological marker which could help differentiate the two disorders, leading to a faster diagnosis and optimal care.
In using a co-relative approach, a novel method in the field, Dr. Osuch uncovered results in patients that extend beyond verbal history and observation. These results may go on to change the way mental health is diagnosed, and subsequently treated, worldwide.
New Effort to Identify Parkinson’s Biomarkers
Last month, the National Institutes of Health announced a new collaborative initiative that aims to accelerate the search for biomarkers — changes in the body that can be used to predict, diagnose or monitor a disease — in Parkinson’s disease, in part by improving collaboration among researchers and helping patients get involved in clinical studies. As part of this program, launched by the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH, Clemens Scherzer, MD, a neurologist and researcher at Brigham and Women’s Hospital (BWH), was awarded $2.6 million over five years to work on the development of biomarkers and facilitate NINDS-wide access to one of the largest data and biospecimens bank in the world for Parkinson’s available at BWH. This NINIDS initiative is highlighted in an editorial in the March issue of Lancet Neurology.
"There is a critical gap in the research that leads to lack of treatment for diseases like Parkinson’s," said Scherzer. "Biomarkers are desperately needed to make clinical trials more efficient, less expensive and to monitor disease and treatment response. We are hopeful that this initiative will fast track new discoveries in this area."
According to Scherzer, most of our knowledge of the human brain is based on the analysis of just 1.5 percent of the human genome that encodes proteins. The first part of Scherzer’s project will examine the function of the remaining 98.5 percent of the genome that, so far, has been unexplored in the human brain. While this remainder had been previously dismissed as “junk”, it is now becoming clearer that parts of it actively regulate cell biology. Scherzer and colleagues believe that “dark matter” RNA transcribed from stretches of so called “junk” DNA is active in brain cells and contributes to the complexity of normal dopamine neurons and, when corrupted, Parkinson’s disease.
"This offers a potentially ground breaking opportunity for biomarker development. Initially, the team will search for these RNAs associated in brain tissue of individuals at earliest stages of the disease. Then, this team will look for related biomarkers in the bloodstream and cerebrospinal fluid in both healthy brains and those with Parkinson’s," Scherzer said.
Scherzer’s lab has been spearheading biomarker research in this field since 2004 and the team already has 2,000 patients enrolled and being followed in a longitudinal study with rich clinical data and one of the largest biobanks in the world for Parkinson’s tissue with support from the Harvard NeuroDiscovery Center. The biobank was designed as an incubator for Parkinson’s research and until now was chiefly available for research collaborations within the Harvard-affiliated community. As part of this new project, this vast resource will be open to all NIH-funded investigators.
"Our ultimate goal is to personalize treatment for our patients with Parkinson’s." said Scherzer. "By opening up this vast collection of specimens, we are exploding the resources that are available to NIH-funded investigators looking at this disease. We hope to harness the power of collaboration to speed up biomarkers discovery."
(Source: brighamandwomens.org)
Mom’s Placenta Reflects Her Exposure to Stress
The mammalian placenta is more than just a filter through which nutrition and oxygen are passed from a mother to her unborn child. According to a new study by a research group from the University of Pennsylvania School of Veterinary Medicine, if a mother is exposed to stress during pregnancy, her placenta translates that experience to her fetus by altering levels of a protein that affects the developing brains of male and female offspring differently.
These findings suggest one way in which maternal-stress exposure may be linked to neurodevelopmental diseases such as autism and schizophrenia, which affect males more frequently or more severely than females.
“Most everything experienced by a woman during a pregnancy has to interact with the placenta in order to transmit to the fetus,” said Tracy L. Bale, senior author on the paper and an associate professor in the Department of Animal Biology at Penn Vet. “Now we have a marker that appears to signal to the fetus that its mother has experienced stress.”
Bale also holds an appointment in the Department of Psychiatry in Penn’s Perelman School of Medicine. Her coauthors include lead author and postdoctoral researcher Christopher L. Howerton, graduate student Christopher Morgan and former technician David B. Fischer, all of Penn Vet.
Published in the Proceedings of the National Academy of Sciences, the study builds on previous work by Bale and her colleagues which found that female mice exposed to stress during pregnancy gave birth to males who had heightened reactions to stress. Further research showed that the effect extended to the second generation: The sons of those male mice also had abnormal stress reactions.
Meanwhile, human studies conducted by other researchers have shown that males born to women who experience stress in the first trimester of pregnancy are at an increased risk of developing schizophrenia.
The Penn team hoped to find a biomarker that could account for these changes and risk factors. To be an effective signal of maternal stress, the researchers reasoned, a biomarker would need to show differences in expression between male and female offspring and would need to be different between stressed and unstressed mothers. They also wanted to find a marker that behaved similarly in humans.
Study Seeks Biomarkers for Invisible War Scars
Over the past decade, about half a million veterans have received diagnoses of or . Thousands have received both. Yet underlying the growing numbers lies a disconcerting question: How many of those diagnoses are definitive? And how many more have been missed?
Imaging Biomarker Predicts Response to Rapid Antidepressant
A telltale boost of activity at the back of the brain while processing emotional information predicted whether depressed patients would respond to an experimental rapid-acting antidepressant, a National Institutes of Health study has found.
“We have discovered a potential neuroimaging biomarker that may eventually help to personalize treatment selection by revealing brain-based differences between patients,” explained Maura Furey, Ph.D., of NIH’s National Institute of Mental Health (NIMH).
Furey, NIMH’s Carlos Zarate, M.D., and colleagues, reported on their functional magnetic resonance imaging (fMRI) study of a pre-treatment biomarker for the antidepressant response to scopolamine, Jan. 30, 2013, online in JAMA Psychiatry.
Scopolamine, better known as a treatment for motion sickness, has been under study since Furey and colleagues discovered its fast-acting antidepressant properties in 2006. Unlike ketamine, scopolamine works through the brain’s acetylcholine chemical messenger system. The NIMH team’s research has demonstrated that by blocking receptors for acetylcholine on neurons, scopolamine can lift depression in many patients within a few days; conventional antidepressants typically take weeks to work. But not all patients respond, spurring interest in a predictive biomarker.
The acetylcholine system plays a pivotal role in working memory, holding information in mind temporarily, but appears to act by influencing the processing of information rather than through memory. Imaging studies suggest that visual working memory performance can be enhanced by modulating acetylcholine-induced activity in the brain’s visual processing area, called the visual cortex, when processing information that is important to the task. Since working memory performance can predict response to conventional antidepressants and ketamine, Furey and colleagues turned to a working memory task and imaging visual cortex activity as potential tools to identify a biomarker for scopolamine response.
Depressed patients have a well-known tendency to process and remember negative emotional information. The researchers propose that this bias stems from dysregulated acetylcholine systems in some patients. They reasoned that such patients would show aberrant visual cortex activity in response to negative emotional features of a working memory task. They also expected to find that patients with more dysfunctional acetylcholine systems would respond better to scopolamine treatment.
Researcher uncovers potential cause, biomarker for autism and proposes study to investigate theory
A New York-based physician-researcher from Touro College of Osteopathic Medicine, best known for his research into fertility and twinning, has uncovered a potential connection between autism and a specific growth protein that could eventually be used as a way to predict an infant’s propensity to later develop the disease. The protein, called insulin-like growth factor (IGF), is especially involved in the normal growth and development of babies’ brain cells. Based on findings of prior published studies, Touro researcher Gary Steinman, MD, PhD, proposes that depressed levels of this protein in the blood of newborns could potentially serve as a biomarker for the later development of autism. However, this connection, described below in greater detail, has never been directly studied. Steinman presents his exciting theory in the journal Medical Hypotheses.
IGF stimulates special cells in the brain to provide an essential insulating material, called myelin, around the developing nerves that is needed to efficiently transmit important messages about everything the brain controls — from physical functions such as movement to mental functions such as sensory perception, thinking and emotions. In the developing fetal and pediatric brain, myelin is also important for nerve fibers in one area of the brain to form proper pathways to other regions, allowing the body to hone functions over time. Insufficient IGF results in insufficient insulating material, as has been seen in brain biopsies of autistic individuals, and may impede proper pathway development. Steinman is proposing that this potential relationship between neonatal IGF levels and autism be directly studied.
"Autism is on the rise, especially in the last two decades — either because of environmental factors, expanded diagnostic criteria, or both. Yet almost nothing is currently known about the predisposing molecular and histological changes that differentiate a newborn destined to be neurologically normal from an autistic one," said Steinman.
Because no effective treatment or prevention for autism exists, research examining Steinman’s idea is critical, as it may hold the key to understanding the cause of this often devastating illness. In his article, Steinman proposes a study to investigate this hypothesis, and if this study supports his theory that identification of reduced IGF at birth is later followed by the appearance of autistic characteristics, then the subsequent development of a simple biomarker blood test is equally critical.
Scientists identify depression and anxiety biomarker in youths
Scientists have discovered a cognitive biomarker – a biological indicator of a disease – for young adolescents who are at high risk of developing depression and anxiety. Their findings were published in the journal PLOS ONE.
The test for the unique cognitive biomarker, which can be done on a computer, could be used as an inexpensive tool to screen adolescents for common emotional mental illnesses. As the cognitive biomarker may appear prior to the symptoms of depression and anxiety, early intervention (which has proven to be one of the most effective ways of combatting mental illness) could then be initiated.
For the study, 15-18 year old participants underwent genetic testing and environmental assessment, an exercise which would currently be too expensive and take too long to use as a widespread method of screening. The adolescents were then given a computer test to gauge how they process emotional information. The test had the participants evaluate whether words were positive, negative or neutral (examples included ‘joyful’ for positive, ‘failure’ for negative, and ‘range’ for neutral).
Those adolescents with a variation of one gene (the short form of the serotonin transporter) as well as exposure to intermittent family arguments for longer than six months and violence between parents before the age of six were shown to have marked difficulty in evaluating the emotion within the words, indicating an inability to process emotional information. Previous research associated a maladjusted perception and response to emotions, as seen here, with a significantly increased risk of depression and anxiety.
Professor Ian Goodyer, Principal Investigator on the study from the University of Cambridge, said: “Whether we succumb to anxiety and depression depends in part on our tendencies to think well or poorly of ourselves at troubled times. How it comes about that some people see the ‘glass half full’ and think positively whereas other see the ‘glass half empty’ and think negatively about themselves at times of stress is not known.
The evidence is that both our genes and our early childhood experiences contribute to such personal thinking styles. Before there are any clinical symptoms of depression or anxiety, this test reveals a deficient ability to efficiently and effectively perceive emotion processes in some teenagers – a biomarker for low resilience which may lead to mental illnesses.”
Wandering Minds Associated With Aging Cells
Scientific studies have suggested that a wandering mind indicates unhappiness, whereas a mind that is present in the moment indicates well-being. Now a preliminary UCSF study suggests a possible link between mind wandering and aging, by looking at a biological measure of longevity.
In the study, telomere length, an emerging biomarker for cellular and general bodily aging, was assessed in association with the tendency to be present in the moment versus the tendency to mind wander, in research on 239 healthy, midlife women ranging in age from 50 to 65 years.
Being present in the moment was defined as an inclination to be focused on current tasks, while mind wandering was defined as the inclination to have thoughts about things other than the present or being elsewhere.
According to the findings, published online on Nov. 15 in the new Association for Psychological Science journal Clinical Psychological Science, those who reported more mind wandering had shorter telomeres, while those who reported more presence in the moment, or having a greater focus and engagement with their current activities, had longer telomeres, even after adjusting for current stress.