News blog

‘Unwarranted’ hype surrounds new blood test for depression

Posted on behalf of Leila Haghighat.

A paper published this Tuesday in Translational Psychiatry prompted media claims about the development of the “first blood test to diagnose depression in teenagers.” But psychiatrists say that much more data are needed about the reproducibility and accuracy of the test before it ends up in the clinic.

In the paper, scientists at Northwestern University in Chicago, Illinois, were looking to identify blood biomarkers for early-onset major depression disorder (MDD) in teenagers aged 15–19. They identified a set of 11 genes whose proteins are expressed at low levels in the blood of adolescents with MDD. The genes are involved mostly in neurodevelopment and neurodegeneration.

The scientists, led by psychiatrist Eva Redei, picked candidate biomarkers using two separate rat models that accounted for both the genetic and environmental causes of depression. The genetic profile of their brain and blood samples pointed to 26 candidate biomarkers, which they tested in 28 adolescents, 14 with MDD and 14 controls.

The study is not the first to identify blood biomarkers for MDD. A study published last December developed a diagnostic blood test specifically for MDD. It provided a correct diagnosis 90% of the time using just nine proteins already associated with MDD as biomarkers.

Redei says that her team’s approach with the genomic profiling of rats is part of what makes their study novel. They are the first to find blood biomarkers for MDD using gene expression, rather than proteins, and the first to explore for such biomarkers by looking beyond what is already known about MDD.

“I don’t argue which approach is better,” says Redei. She says that a diagnostic test developed from this study would be only supplementary to the standard means of diagnosis. MDD is now diagnosed by patients reporting their own symptoms.

A blood test would be more objective. It could potentially have less bias than current practice, and provide comfort to adolescents teased by their peers. “Everything is going against this group of adolescents to get better, but if you measure something objectively, someone is less likely to tell you to get yourself together,” says Redei.

Alexander Niculescu, a psychiatrist at the Indiana University School of Medicine in Indianapolis, cautions that “more work needs to be done, and the current level of hype for this study is unwarranted”.

“What is important is to show reproducibility and predictive ability for such tests in independent cohorts of patients, with solid numbers for sensitivity and specificity of the tests. That is the gold standard,” Niculescu says.

The scientists plan to increase the numbers of patients in their future studies, including patients with other psychiatric disorders. They will also compare the results of the blood test before and after treatment to assess whether it can predict response to treatment.

Image of blood tests courtesy of Neeta Lind via Flickr under Creative Commons.

Comments

  1. Report this comment

    Alexander Niculescu said:

    In addition to being a small study, with no reproducibility, sensitivity and specificity data provided, it is not the first to report data on depression biomarkers, as noted in the commentary above, and it is also not the first to use animal model gene expression data integrated with human data to find biomarkers. My group has pioneered that approach over the last decade, publishing several papers, including two papers in Molecular Psychiatry on gene expression blood biomarkers- one in 2008 on mood (depression, mania) biomarkers in bipolar patients, and one in 2009 on psychosis (hallucinations, delusions) biomarkers in schizophrenia patients. Ours and others previously published studies have taken the correct approach of looking at reproducibility, sensitivity and specificity in independent cohorts before publishing the data. Human genetic variability is such that the data is not credible without such validations. I share Dr. Redei’s stated noble goals of helping patients, but unlike her I am also a practicing psychiatrist, and perhaps more aware how much people suffer and how desperate patients and families are for any new hope. We should be mindful of that, and it is best to underpromise and overdeliver with our science. On a positive note, I do thing that genetic and blood biomarker tests will transform psychiatry, we just have to do the comprehensive and exacting scientific work first.

  2. Report this comment

    William Gardner said:

    In response to Dr. Niculescu:

    We are puzzled by the tone of Dr. Niculescu’s response and some of the content. While we agree with some of the concerns raised, there are others that are difficult to reconcile with the current state of research on this topic. We have replied to each of the comments below.

    “more work needs to be done, and the current level of hype for this study is unwarranted”

    — We agree that some of the press coverage of our article overstated the significance of our results. For example, the Daily Mail’s report that the study was able to diagnose depression is inaccurate. We wish to make clear that this claim was not in our article.

    “What is important is to show reproducibility and predictive ability for such tests in independent cohorts of patients, with solid numbers for sensitivity and specificity of the tests. That is the gold standard…”

    — We agree that sensitivity and specificity are the gold standard for diagnostic tests. If we were claiming that our biomarkers were ready for diagnostic use, we would have calculated these statistics and reported them. However, we made no such claim. An actual diagnostic procedure would entail a sufficiently large sample to estimate statistical weights for the individual biomarkers. Conceivably, it would also integrate data derived from psychiatric interviews and patient histories. This is the long-term goal of our research, as we made clear in our article. It is not accomplished by this study, as we state.

    Similarly, Niculescu’s work is promising but is preliminary work, which does not yet meet the gold standard. The Le-Niculescu paper on mood disorders reports sensitivity and specificity for mood disorders, but in quite an odd way. Our study contrasted children with depression to non-affected controls. In his study, all subjects were patients with mood disorders, and there were no controls. We are unable to see how he is able to make inferences about sensitivity and specificity for mood disorders in a study that does not include controls.

    “In addition to being a small study, with no reproducibility, sensitivity and specificity data provided, it is not the first to report data on depression biomarkers,… and it is also not the first to use animal model gene expression data integrated with human data to find biomarkers. My group has pioneered that approach over the last decade, publishing several papers,… Ours and others previously published studies have taken the correct approach of looking at reproducibility, sensitivity and specificity in independent cohorts before publishing the data. Human genetic variability is such that the data is not credible without such validations.”

    — We have great respect for Dr. Niculescu’s work, which significantly informed our work; we cited it very positively in our paper. However, our method is different and this was a pilot test of our method in humans – as our title states. Our study was nevertheless novel in that we were the first to study early onset mood disorders.

    Morevover, we agree that our work needs to be replicated in larger samples, and we stated this in our limitations. So our results are preliminary, as is clearly implied our article’s title and conclusion. What we do not understand is why Dr. Niculescu views his work as definitive. His mood disorders paper, for example, involved one cohort of 30 patients, and one cohort of 19 patients, although he followed small sub-groups of each of these longitudinally. Work in this area is at a very early stage of development. But this is true for Dr. Niculescu’s group as well as ours.

    “I share Dr. Redei’s stated noble goals of helping patients, but unlike her I am also a practicing psychiatrist, and perhaps more aware how much people suffer and how desperate patients and families are for any new hope.”

    — The patients that Dr. Niculescu treats are, presumably, already diagnosed, so it is unclear how a report of progress toward a diagnostic procedure could bring them false hope. For future reference, we too have first hand experience with families and their suffering. Dr. Pajer is a clinical psychiatrist, a Professor of Psychiatry at Dalhousie University, and Head of the Division of Child and Adolescent Psychiatry. Dr. Strange is an Assistant Professor of Psychiatry at The Ohio State University and a practicing child and adolescent psychiatrist. Dr. Campo is a child and adolescent psychiatrist, Professor of Psychiatry, and Chairman of the Department of Psychiatry at The Ohio State University. As seasoned clinicians and researchers, we are working to help patients, as is Dr. Niculescu. We are all working to help patients – and the patients would fare better if we worked together towards our common goal with open minds.

    — Kathleen Pajer, MD MPH & William Gardner, PhD

Comments are closed.