'Depression blood test' still at lab stage

Today the Metro has boldly claimed that a “blood test diagnoses depressed teenagers”, while the Daily Mail says that a new blood test “is first to diagnose depression in teenagers”.

Currently, depression is diagnosed by a doctor using validated diagnostic methods. A doctor will question how a person is feeling and ask about their general health and wellbeing, rather than using a blood test. These headlines are based on a small study looking at whether analysing blood samples could provide a means to test for early-onset major depressive disorder (MDD), defined in the study as a serious psychiatric condition occurring in people under 25 years of age. In clinical practice, MDD is often just referred to as “depression”. The study tested blood samples from people with and without MDD and found 11 genetic markers that differed between the two, indicating that those genetic markers were potentially linked to the condition.

However, only limited conclusions can be drawn from this study as it was very small, looking at just 28 teenagers in total. Much larger studies are, therefore, needed to prove that these differences can be detected in more people of different ages.

Despite the implications of the media headlines, a blood test to diagnose depression in teenagers is not ready to use in clinical practice. This type of test will only become available if larger studies show that it is effective in a more diverse group of patients, and if it demonstrates any additional value alongside traditional diagnostic methods.

Where did the story come from?

The study was carried out by US researchers from Northwestern University in Chicago, and was funded by grants from the Research Institute of the Nationwide Children’s Hospital in Columbus, Ohio.

The study was published in the peer-reviewed medical journal Translational Psychiatry.

The media coverage of the study was balanced, but the significant limitations of the study, such as its small size, were not emphasised.

What kind of research was this?

The research investigated early-onset major depressive disorder (MDD), which this study defines as a serious psychiatric condition occurring in people under 25 years of age. Often, major depressive disorder is simply referred to in clinical practice as “depression”, with the severity of depression classed as subthreshold, mild, moderate or severe. This is estimated based on the number of symptoms and the extent to which it is affecting a person’s everyday life and functioning.

The researchers of this study say that approximately 1% of people under 12 years old have MDD and rates increase later in adolescence and young adulthood. They go on to state that MDD in teenagers can derail normal development during this crucial stage of their early adulthood, and can lead to an increase in substance misuse, physical illness, social maladjustment and suicidal tendencies.

Current diagnosis of MDD relies on the patient self-reporting symptoms to a doctor and the doctor’s ability to interpret the symptoms to make the correct diagnosis. Hence, MDD is perceived to be difficult to differentiate from the normal mood changes often seen in teenagers. The goal of this research was to identify genetic variations that differentiated people with MDD from those without, and to use this knowledge to develop a blood test to diagnose the condition objectively. This would provide an objective measure for use alongside traditional subjective assessments of psychology, and would improve existing methods of diagnosis.

What did the research involve?

This research featured two broad stages of study. In the first the researchers used blood samples from both rats and humans to identify specific genetic markers (sections of DNA) that could distinguish those with MDD from those without. The second involved looking at whether these markers could also differentiate people who had MDD and anxiety disorder from those with MDD only.

The study authors first took blood samples from rats bred to exhibit symptoms of MDD and analysed the genetic material they contained. During this analysis they tried to identify genetic markers that differed between animals with MDD and those without, and which might, therefore, be associated with the condition. The researchers put forward the theory that these markers may also be useful in humans, as rats and humans share many genetic similarities.

During these rat studies the researchers found 26 candidate genetic markers. They then tested for various combinations of them in human blood to see whether they could be used to distinguish between people with MDD and those without. To do so, blood samples were taken from a small group of 14 people with MDD. These were compared with blood samples from a group of 14 similarly-aged people without the disorder. Both groups were a mix of males and females aged between 15 and 19 years old.

The blood samples were tested in the laboratory to analyse differences in the way the genetic markers were "expressed". "Expressed" describes the way the body uses specific sections of genetic code as instructions for producing specific proteins. The researchers ultimately wanted to see if a combination of the genetic markers could be used to identify the presence or absence of MDD.

Participants and their parents were also interviewed separately about the teenager’s lifetime psychiatric symptoms and medical history. This included assessing levels of anxiety, mood disorders, disruptive behaviour disorders, schizophrenia, miscellaneous disorders (for example, eating disorders) and substance-use disorders.

Only people aged between 15 and 19 were recruited to the study. Other ages were excluded. Participants were excluded if they had major medical illness, had used antidepressants in the past three months, were pregnant, had MDD together with psychosis or had a history of mental retardation.

The analysis of this study was restricted to reporting effect sizes because it was so small. Effect sizes are the relative difference in genetic expression between those with MDD and those without. The study did not assess whether these differences were statistically significant because the study size was too small.

What were the basic results?

When comparing the genetic expression of people with MDD with those without, the researchers say that “medium to large differences” were found in 11 of the 26 genetic markers identified. Medium-to-large differences were not explicitly defined in this study, but are likely to mean those genetic markers showing the greatest difference in expression in people with MDD compared with those without.

A set of 18 of the 26 genetic markers reportedly showed medium-to-large differences between those with MDD only and those with MDD with anxiety disorders.

How did the researchers interpret the results?

The researchers concluded that they had discovered a panel of 11 genetic markers from human blood samples that could successfully distinguish subjects with early-onset MDD from those without. Similarly, they say that a set of 18 genetic markers identified youths with MDD only from those with MDD with anxiety disorders.

As the function of many of the genetic markers used in the panel was known, the researchers were able to suggest various biological mechanisms by which the genetic differences may be linked to MDD, both with and without anxiety disorder.

Conclusion

This small, early-stage research has examined the presence of certain genetic markers in blood samples taken from 14 people with MDD and 14 people without. It found that 11 independent genetic markers differed between the two groups, and also that 18 genetic markers “expressed” themselves differently in people with MDD only, compared with people with both MDD and anxiety disorders. “Genetic expression” is the way that the body uses the coded information contained within the DNA as the blueprint for creating proteins.

This research specified that it looked at major depressive disorder in teenagers aged 15 to 19. In clinical practice, MDD is commonly just referred to as depression. The severity of depression may be determined using recognised diagnostic criteria to identify the number of symptoms that are met and the extent to which it is affecting a person’s everyday life and functioning. Clinical guidance on depression from the National Institute for Health and Clinical Excellence (NICE) defines these levels of depression as subthreshold, mild, moderate or severe.

While this study does provide new information on what genetic markers may be important in early-onset MDD, it is difficult to see how these markers may be applied to the different severities of depression, or to other age groups. Likewise, results cannot be generalised to depression as part of bipolar disorder, or depression in conjunction with other psychiatric disorders. Similarly, the study excluded those receiving antidepressant medications, and so the results are not directly applicable to this important group either.

Overall, this research on its own can tell us little about the nature or origins of depression, or even the genetic basis for the condition. This is primarily due to the study being very small, comparing just 14 people with MDD to 14 people without. Much larger studies are needed to prove that these genetic markers are clinically useful in detecting MDD in a more diverse group of teenagers.

Despite the implications of the media headlines, a blood test to diagnose depression in teenagers has not yet been developed and is certainly not close to being used in routine clinical practice. Currently, depression is diagnosed by a doctor questioning how a person is feeling and asking about their general health and wellbeing. An accurate diagnosis of depression can be given if a person meets validated diagnostic criteria, but there is no clinical test that directly supports the diagnosis of MDD (aside from tests to help rule out other conditions that can be associated with depression, such as underactive thyroid). The type of test studied here will only become available if larger studies show that it is effective in a more diverse group of teenagers, and if its use could be demonstrated to give any additional value alongside standard diagnostic methods.