Blood test may help determine who is at risk for psychosis

A study led by University of North Carolina at Chapel Hill researchers represents an important step forward in the accurate diagnosis of people who are experiencing the earliest stages of psychosis.

Psychosis includes hallucinations or delusions that define the development of severe mental disorders such as schizophrenia. Schizophrenia emerges in late adolescence and early adulthood and affects about 1 in every 100 people. In severe cases, the impact on a young person can be a life compromised, and the burden on family members can be almost as severe.

The study published in the journal Schizophrenia Bulletin reports preliminary results showing that a blood test, when used in psychiatric patients experiencing symptoms that are considered to be indicators of a high risk for psychosis, identifies those who later went on to develop psychosis.

“The blood test included a selection of 15 measures of immune and hormonal system imbalances as well as evidence of oxidative stress,” said Diana O. Perkins, MD, MPH, professor of psychiatry in the UNC School of Medicine and corresponding author of the study. She is also medical director of UNC’s Outreach and Support Intervention Services (OASIS) program for schizophrenia.

“While further research is required before this blood test could be clinically available, these results provide evidence regarding the fundamental nature of schizophrenia, and point towards novel pathways that could be targets for preventative interventions,” Perkins said.

Clark D. Jeffries, PhD, bioinformatics scientist at the UNC-based Renaissance Computing Institute (RENCI), is a co-author of the study, which was conducted as part of the North American Prodrome Longitudinal Study (NAPLS), an international effort to understand risk factors and mechanisms for development of psychotic disorders. 

“Modern, computer-based methods can readily discover seemingly clear patterns from nonsensical data,” said Jeffries. “Added to that, scientific results from studies of complex disorders like schizophrenia can be confounded by many hidden dependencies. Thus, stringent testing is necessary to build a useful classifier. We did that.”

The study concludes that the multiplex blood assay, if independently replicated and if integrated with studies of other classes of biomarkers, has the potential to be of high value in the clinical setting.

(Image: Shutterstock)

Depression is detectable in the blood

Researchers at the MedUni Vienna have demonstrated the possibility of using a blood test to detect depression. While blood tests for mental illnesses have until recently been regarded as impossible, a recent study clearly indicates that, in principle, depression can in fact be diagnosed in this way and this could become reality in the not too distant future.

Serotonin transporter (SERT) is a protein in the cell membrane that facilitates the transport of the neurotransmitter serotonin (popularly known as the “happiness hormone”) into the cell. In the brain, serotonin transporter regulates neural depression networks. Depressive conditions can frequently be caused by a lack of serotonin. As a result, the serotonin transporter is also the point of action for the major antidepressant drugs.

The serotonin transporter, however, also occurs in large quantities in numerous other organs such as the intestines or blood. Recent studies have shown that the serotonin transporter in the blood works in exactly the same way as in the brain. In the blood, it ensures that blood platelets maintain the appropriate concentration of serotonin in the blood plasma.

Researchers at the MedUni Vienna have now used functional magnetic resonance imaging of the brain and pharmacological investigations to demonstrate that there is a close relationship between the speed of the serotonin uptake in blood platelets and the function of a depression network in the brain.

This network is termed the “default mode network” because it is primarily active at rest and processes content with strong self-reference. Findings from recent years have also demonstrated that it is actively suppressed during complex thought processes, which is essential for adequate levels of concentration. Interestingly, patients with depression find it difficult to suppress this network during thought processes, leading to negative thoughts and ruminations as well as poor concentration.

“This is the first study that has been able to predict the activity of a major depression network in the brain using a blood test. While blood tests for mental illnesses have until recently been regarded as impossible, this study clearly shows that a blood test is possible in principle for diagnosing depression and could become reality in the not too distant future,” explains study leader Lukas Pezawas from the Department of Biological Psychiatry at the University Department of Psychiatry and Psychotherapy within the MedUni Vienna. This result means that the diagnosis of depression through blood tests could become reality in the not too distant future.

Blood Test Identifies Those At-Risk for Cognitive Decline, Alzheimer’s Within 3 Years

Researchers have discovered and validated a blood test that can predict with greater than 90 percent accuracy if a healthy person will develop mild cognitive impairment or Alzheimer’s disease within three years.

Described in the April issue of Nature Medicine, the study heralds the potential for developing treatment strategies for Alzheimer’s at an earlier stage, when therapy would be more effective at slowing or preventing onset of symptoms. It is the first known published report of blood-based biomarkers for preclinical Alzheimer’s.

The test identifies 10 lipids, or fats, in the blood that predict disease onset. It could be ready for use in clinical studies in as few as two years and, researchers say, other diagnostic uses are possible.

“Our novel blood test offers the potential to identify people at risk for progressive cognitive decline and can change how patients, their families and treating physicians plan for and manage the disorder,” says the study’s corresponding author Howard J. Federoff, MD, PhD, professor of neurology and executive vice president for health sciences at Georgetown University Medical Center.

There is no cure or effective treatment for Alzheimer’s. Worldwide, about 35.6 million individuals have the disease and, according to the World Health Organization, the number will double every 20 years to 115.4 million people with Alzheimer’s by 2050.

Federoff explains there have been many efforts to develop drugs to slow or reverse the progression of Alzheimer’s disease, but all of them have failed. He says one reason may be the drugs were evaluated too late in the disease process.

“The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention,” Federoff says. “Biomarkers such as ours that define this asymptomatic period are critical for successful development and application of these therapeutics.”

The study included 525 healthy participants aged 70 and older who gave blood samples upon enrolling and at various points in the study. Over the course of the five-year study, 74 participants met the criteria for either mild Alzheimer’s disease (AD) or a condition known as amnestic mild cognitive impairment (aMCI), in which memory loss is prominent. Of these, 46 were diagnosed upon enrollment and 28 developed aMCI or mild AD during the study (the latter group called converters).

In the study’s third year, the researchers selected 53 participants who developed aMCI/AD (including 18 converters) and 53 cognitively normal matched controls for the lipid biomarker discovery phase of the study. The lipids were not targeted before the start of the study, but rather, were an outcome of the study.

A panel of 10 lipids was discovered, which researchers say appears to reveal the breakdown of neural cell membranes in participants who develop symptoms of cognitive impairment or AD. The panel was subsequently validated using the remaining 21 aMCI/AD participants (including 10 converters), and 20 controls. Blinded data were analyzed to determine if the subjects could be characterized into the correct diagnostic categories based solely on the 10 lipids identified in the discovery phase.

“The lipid panel was able to distinguish with 90 percent accuracy these two distinct groups: cognitively normal participants who would progress to MCI or AD within two to three years, and those who would remain normal in the near future,” Federoff says.

The researchers examined if the presence of the APOE4 gene, a known risk factor for developing AD, would contribute to accurate classification of the groups, but found it was not a significant predictive factor in this study.

“We consider our results a major step toward the commercialization of a preclinical disease biomarker test that could be useful for large-scale screening to identify at-risk individuals,” Federoff says. “We’re designing a clinical trial where we’ll use this panel to identify people at high risk for Alzheimer’s to test a therapeutic agent that might delay or prevent the emergence of the disease.”

A possible blood test for Alzheimer’s disease?

A new blood test can be used to discriminate between people with Alzheimer’s disease and healthy controls. It’s hoped the test, described in the open access journal Genome Biology, could one day be used to help diagnose the disease and other degenerative disorders.

Alzheimer’s disease, the most common form of dementia, can only be diagnosed with certainty at autopsy, so the hunt is on to find reliable, non-invasive biomarkers for diagnosis in the living. Andreas Keller and colleagues focused on microRNAs (miRNAs), small non-coding RNA molecules known to influence the way genes are expressed, and which can be found circulating in bodily fluids including blood.

The team, from Saarland University and Siemens Healthcare highlighted and tested a panel of 12 miRNAs, levels of which were found to be different amongst a small sample of Alzheimer’s patients and healthy controls. In a much bigger sample, the test reliably distinguished between the two groups.

Decent biomarkers need to be accurate, sensitive (able to correctly identify people with the disease) and specific (able to correctly pinpoint people without the disease). The new test scores over 90% on all three measures. But whilst the test shows obvious promise, it still needs to be validated for clinical use, and may eventually work best when combined with other standard diagnostic tools, such as imaging, the authors say.

As people with other brain disorders can sometimes show Alzheimer’s-like symptoms, the team also looked for the miRNA signature in other patient groups. The test distinguished controls from people with various psychological disorders, such as schizophrenia and depression, with over 95% accuracy, and from patients with other neurodegenerative disorders, such as mild cognitive impairment and Parkinson’s disease, with lower accuracy. It also discriminated between  Alzheimer’s patients and patients with other neurodegenerative disorders, with an accuracy of around 75%. But by tweaking the miRNAs used in the test, accuracy could be improved.

The work builds on previous studies highlighting the potential of miRNAs as blood-based biomarkers for many diseases, including numerous cancers, and suggests that miRNAs could yield useful biomarkers for various brain disorders. But it also sheds light on the mechanisms underpinning Alzheimer’s disease. Two of the miRNAs are known involved in amyloid precursor protein processing, which itself is involved in the formation of plaques, a classic hallmark of Alzheimer’s disease.  And many of the miRNAs are believed to influence the growth and shape of neurons in the developing brain.

(Image: Reuters)

One step closer to a blood test for Alzheimer’s

Australian scientists are much closer to developing a screening test for the early detection of Alzheimer’s disease, the leading cause of dementia.

A quarter of a million Australians currently suffer from dementia and given our ageing population, this is predicted to increase to one million by 2050.

Researchers identified blood-based biological markers that are associated with the build up of amyloid beta, a toxic protein in the brain, which occurs years before symptoms appear and irreversible brain damage has occurred.

“Early detection is critical, giving those at risk a much better chance of receiving treatment earlier, before it’s too late to do much about it,” said Dr Samantha Burnham from CSIRO’s Preventative Health Flagship.

This research is just one part of the Australian Imaging and Biomarkers Lifestyle Study of Aging (AIBL), a longitudinal study in conjunction with research partners from Austin Health, Edith Cowan University, the Florey Institute of Neurosciences and Mental Health and the National Aging Research Institute. The AIBL study aims to discover which biomarkers, cognitive characteristics and health and lifestyle factors are linked with the development of Alzheimer’s disease.

“Another recent study from the AIBL team showed that amyloid beta levels become abnormal about 17 years before dementia symptoms appear,” said Dr Burnham. “This gives us a much longer time to intervene to try to slow disease progression if we are able to detect cases early.

“We hope our continued research will lead to the development of a low cost, minimally invasive population based screening test for Alzheimer’s in the next five to ten years. A blood test would be the ideal first stage to help identify many more people at risk before a diagnosis is confirmed more specialised testing.”

The results have been published today in the journal Molecular Psychiatry.

Autism Blood Test Shows Promise

Diagnosing autism could soon be much simpler, with researchers saying this week that they’ve developed a blood test that appears to identify those with the disorder even before symptoms are apparent.

The early-stage test developed at Boston Children’s Hospital may be able to flag about two-thirds of those with autism, researchers reported in the journal PLOS ONE.

Currently, clinicians rely on observation to screen children for autism. Most kids are not diagnosed until after age 4, according to the U.S. Centers for Disease Control and Prevention.

But a blood test offers the promise of flagging kids and potentially enrolling them in early intervention programs even before symptoms appear.

In order to develop the test, researchers analyzed blood samples from 66 boys with autism and 33 without the developmental disorder in an effort to establish patterns. Ultimately, the scientists were able to focus on a group of 55 genes that they used to successfully identify autism with 68 percent accuracy in a second test group made up of 104 people with autism and 82 controls.

“It’s clear that no single mutation or even a single pathway is responsible for all cases,” said Isaac Kohane of Boston Children’s Hospital who worked on the research. “By looking at this 55-gene signature, which can capture disruptions in multiple pathways at once, we can say with about 70 percent accuracy, ‘this child does not have autism,’ or ‘this child could be at risk,’ putting him at the head of the queue for early intervention and evaluation. And we can do it relatively inexpensively and quickly.”

The blood test is not yet ready for prime time, researchers said, but it has been licensed to the company SynapDx for further exploration and potential commercialization.

A simple blood test for Creutzfeldt-Jakob Disease and Mad Cow disease is a step closer, following a breakthrough by medical researchers at the University of Melbourne.

Using newly available genetic sequencing scientists discovered cells infected with prions (the infectious agent responsible for these diseases) release particles which contain easily recognized ‘signature genes’.

Associate Professor Andrew Hill — from the Department of Biochemistry and Molecular Biology at the Bio21 Institute — said these particles travel in the blood stream, making a diagnostic blood test a possibility.

“This might provide a way to screen people who have spent time in the UK, who currently face restrictions on their ability to donate blood,” he said.

“With a simple blood test nurses could deem a prospective donor’s blood as healthy, with the potential to significantly boost critical blood stocks.”

Mad Cow disease was linked to the deaths of nearly 200 people in Great Britain who consumed meat from infected animals in the late 1980s.

Since 2000, the Australia Red Cross Blood Service has not accepted blood from anybody who lived in the UK for more than six months between 1980 and 1996, or who received a blood transfusion in the UK after 1980.

(Photo by Peter Cade via Getty Images)

Blood Test for Alzheimer’s Gaining Ground

Hu and his collaborators at the University of Pennsylvania and Washington University, St. Louis, measured the levels of 190 proteins in the blood of 600 study participants at those institutions. Study participants included healthy volunteers and those who had been diagnosed with Alzheimer’s disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer’s disease, causes a slight but measurable decline in cognitive abilities.

A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer’s. When those markers were checked against data from 566 people participating in the multicenter Alzheimer’s Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide.

Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer’s. The analysis grouped together people with MCI, who are at high risk of developing Alzheimer’s, and full Alzheimer’s.

“We were looking for a sensitive signal,” says Hu. “MCI has been hypothesized to be an early phase of AD, and sensitive markers that capture the physiological changes in both MCI and AD would be most helpful clinically.”