Daily Archives: September 17, 2014

Diagnosing clinical depression in adults is tricky for doctors. That's mostly because assessment is largely reliant on imperfect analysis, like patient observations and interviews. Most laboratory tests are, by and large, of little use in determining if someone is depressed or not.

That could soon change. About three years ago, a team of researchers co-led by Eva Redei, a research professor for psychiatric disease at the Northwestern University Feinberg School of Medicine, published a study finding that certain RNA markers--a short identifiable string in the DNA sequence, which can be read sort of like fingerprints--were associated with clinical depression in teenagers.

In a new study published today, that same team has identified nine RNA blood markers that, at very specific levels, could be used to diagnose major depression in adults. Furthermore, three of those genetic fingerprints could be used to determine who might be receptive to cognitive behavioral therapy as a means to get better; the researchers saw consistent patterns in patients for whom therapy was helpful.

Now, the sample size wasn't huge: The team looked at 32 depressed individual, and another 32 in a control group (the subjects varied greatly in age, from 23 to 83), and put all of them through cognitive behavioral therapy. All the while, researchers kept a close eye on their gene markers.

Of the afflicted, some 40% showed improved mental health after treatment. And after controlling for variables like gender and age, the team found a correlation between nine of the markers in people who were clinically diagnosed as depressed. In the patients who were better after treatment, the team identified three other RNA markers that could be be used for future diagnoses. "We could identify one of those nine, and two others, that were very different between those who got well and those who didnt," Redei tells Fast Company. "That shows clearly the efficacy of cognitive behavioral therapy [for certain individuals]."

The methodology wasn't perfect, but the results were strong enough that "it's very hopeful for the future," Redei says. And the team doesn't yet know how early these gene markers can be detected in, say, children--especially to determine who might be vulnerable to clinical depression as they age. "That's a huge independent study on its own," she says.

But for adults suffering from depression? If you can identify who might be receptive to psychotherapy, for example, there may be other unidentified gene markers that can identify who might be receptive to certain types of antidepressants. "What we hope to do," adds Redei, "is to have an FDA-approved test in the future that any clinical laboratory can do."

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How A Simple Blood Test Can Now Help Diagnose Depression

TORONTO Twenty-five years ago this month, the medical world was turned on its ear with the isolation of the gene that causes cystic fibrosis, a devastating inherited disease that usually killed children by their late teens.

At the helm of the research was Lap-Chee Tsui, who led the team at Torontos Hospital for Sick Children that made the seminal discovery in collaboration with scientists at the University of Michigan.

The science of human genetics was still in its infancy at that time. Pinpointing the mutated CFTR gene came about through painstaking mapping of bits of DNA to locate the root of CF symptoms thick, sticky mucus that clogs the lungs and gums up the gastrointestinal tract, requiring patients to take scores of digestive enzymes a day so they could digest food.

The cystic fibrosis defect is really a very subtle defect, Tsui (pronounced Choy), 63, said Monday during an event at Sick Kids to mark the 1989 discovery. It didnt kill the patients (right away), but the problems accumulated slowly, and at the end the patients succumbed to infection.

Using the same analogy as he used in 1989 to explain CFTRs location on chromosome 7, Tsui said researchers first narrowed it down to somewhere between Halifax and Vancouver, then further pinpointed it in Toronto, and finally zeroed in to a certain street and then the actual house that represented the defective gene.

In the ensuing years, researchers have determined there is not only one mutation in the CF gene, but about 1,900 different defects that cause greater or lesser severity of symptoms in individual patients a scientific process Tsui likened to going into the house and turning on all the lights and taps to see which ones are faulty.

The celebrated geneticist, who left Toronto 12 years ago to become vice-chancellor and president of the University of Hong Kong, from which he just retired, called progress in understanding and treating CF since the gene was isolated very exciting.

Within two years of that discovery, other Sick Kids researchers had determined that a protein that keeps epithelial cells lining the lungs, airways and digestive system nice and moist was faulty, causing the buildup of mucus that clogs the lungs and disables the digestive system.

I think the expectation when the gene was first discovered was that it would be easy to fix because the disease was caused by a single gene, and if you replaced that gene through gene therapy, then you would be able to completely reverse the consequences of the disease, said senior scientist Christine Bear, who led that team.

And it may be that gene therapy will be part of that future therapy in CF, but right now we havent developed safe ways to do that.

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Canadian researchers mark 25 years since CF gene found

PUBLIC RELEASE DATE:

16-Sep-2014

Contact: Mary Clarke press.office@sanger.ac.uk 01-223-492-368 Wellcome Trust Sanger Institute @sangerinstitute

Research using data collected from around 4,000 healthy people in the UK has enabled scientists to identify a rare genetic variant that dramatically reduces levels of certain types of lipids in the blood. The study is the first to emerge from the UK10K Project's cohort of samples from the general public and demonstrates the power of whole genome sequencing at scale.

"Until now it has only been possible to look for common variants of small effect in large genome wide association studies," says Dr Nicholas Timpson, first author from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol. "Thanks to the quantity of data available through the UK10K Project and because of the relatively large effect of this variant, we have been able to find a rare genetic variant that has clinical relevance."

By looking at whole genome sequences from 4,000 people and comparing this with data about their lipid levels, scientists spotted an association between levels of lipids called triglycerides and the presence of the APOC3 gene variant. The research suggests that people with the rare change (approximately 0.2 per cent of the population carry this) typically have lower levels of triglycerides, which (as shown elsewhere) is associated with reduced risk of cardiovascular disease.

Two studies in the New England Journal of Medicine have recently explored the role of this genetic variant through the examination of APOC3 in a targeted approach, and through coding and analysing only part of the genome. These studies give important context to this finding as they also relate this change to heart disease.

"These three studies independently reporting this finding give us confidence that it is reliable and informative for clinical understanding," says Professor Steve Humphries, a British Heart Foundation-funded senior author from University College London. "Once we can understand the mechanism of the protective function of this variant, we can try to use this information to develop novel therapies to help those at risk of cardiovascular disease."

This is the first in a series of studies that will use whole genome sequences and clinical information about physical characteristics from the UK10K project to find rare genetic variants.

"Extending genome wide association studies to include whole genome sequencing can help us to identify more clinically informative variants," says Dr Nicole Soranzo, senior author from the Wellcome Trust Sanger Institute. "Data collected as part of the UK10K project is essential to this and we are beginning to see its extraordinary value."

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Gene variant that dramatically reduces 'bad' lipids