Teenage Depression Can Be Detected in Blood

Scientists have discovered that adolescents with depression have altered levels of small molecules called microRNAs in their blood, which help control how genes function. Some of these microRNAs are linked to the severity of symptoms and even to changes in areas of the brain. These findings suggest that in the future, a simple blood test could help identify young people at higher risk of depression before their symptoms worsen.

Depression, also called major depressive disorder (MDD), is a very common and disabling condition that affects millions of people worldwide. It can cause a major decline in quality of life, harming work, relationships and overall health.

An important fact is that, throughout life, adolescence is the period when depression most often appears for the first time. This is worrying because when depression begins in youth, it tends to be more severe, lasts longer, responds less well to treatment and leaves lasting effects on the person’s life.

Despite this importance, we still know little about the genetic and biological causes of depression that begins in adolescence. Scientists believe it may be different from depression that begins in adulthood because adolescent brains are still undergoing important developmental changes.

This can cause the systems involved in controlling emotions and behavior to function differently at this stage of life. That’s why researchers are looking for ways to study depression in light of these age differences. One of the most promising avenues is to focus on biological markers specific to adolescents.

Scientists are currently very interested in a part of our DNA called “non-coding” regions. Unlike genes that produce proteins, these regions do not produce proteins directly, but they still control how genes function.

One example is microRNAs (or miRNAs), small molecules that help regulate which genes are turned on or off. Interestingly, miRNAs can be detected in the blood and are stable, which means they can be good indicators of what’s going on in the brain without the need for invasive tests.

In previous studies with rodents, scientists had seen that when the levels of certain miRNAs in the animals’ brains changed, the same miRNAs in their blood also changed.

In addition, the levels of these miRNAs in the blood during adolescence were able to predict the extent to which these animals would develop depression-like behaviors as adults, especially after experiencing stress. This raised the hypothesis that miRNAs in the blood of human adolescents could help identify those at greatest risk of developing depression.

To test this idea, researchers at McGill University in Canada analyzed the blood of adolescents with and without depression. Instead of using liquid samples, they adopted a technique that collects only small drops of dried blood (like those used in newborn screening), which makes the procedure less invasive.

With these samples, they used a modern technique called small-RNA sequencing, which allows them to identify all types of miRNAs present, without focusing on just a few.

The results showed that nine miRNAs were significantly higher in adolescents with depression. Three of them, called miR-3613-5p, miR-30c-2 and miR-942-5p, were strongly linked to the severity of depression symptoms, but not to anxiety symptoms. This suggests that they may be more specific markers of depression, rather than general emotional problems.

Another miRNA, miR-32-5p, was linked to the volume of the hippocampus, a part of the brain important for memory and stress management, suggesting that these markers may also be associated with physical changes in the brain.

Finally, scientists have identified that the genes affected by these miRNAs are involved in processes such as brain development, the way we think and learn, and also depressive disorders. This reinforces the idea that these miRNAs not only reflect the presence of depression, but may also be linked to the biological causes of the disease.

These findings are important because they pave the way for the future development of blood tests capable of identifying adolescents at increased risk of depression. This could allow for earlier, more effective and personalized interventions, before symptoms worsen.

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Peripheral microRNA signatures in adolescent depression

Alice Morgunova, Nicholas O’Toole, Fatme Abboud, Saché Coury, Gary Gang Chen, Maxime Teixeira, Eamon Fitzgerald, Gustavo Turecki, Anthony J. Gifuni, Ian H. Gotlib, Corina Nagy, Michael J. Meaney, Tiffany C. Ho, and Cecilia Flores 

Biological Psychiatry Global Open Science. 14 April 2025, 100505

https://doi.org/10.1016/j.bpsgos.2025.100505

Abstract:

Adolescent depression is linked to enduring maladaptive outcomes, chronic severity of symptoms, and poor treatment response. Identifying epigenetic signatures of adolescent depression is urgently needed to improve early prevention and intervention strategies. MicroRNAs are epigenetic regulators of adolescent neurodevelopmental processes, but their role as markers and mediators of adolescent depression is unknown. Here we examined microRNA profiles from dried blood spot samples of clinically depressed and psychiatrically healthy male and female adolescents. We processed and sequenced these samples using a small RNA protocol tailored for microRNA identification. We identified nine differentially expressed (DE) microRNAs (adjusted p-value < 0.05), all of which upregulated in adolescents with depression. At future follow-ups post blood collection, expression of miR-3613-5p, mir-30c-2 and miR-942-5p positively associated with depression severity but not anxiety, suggesting a stronger link to persistent depression symptoms. Expression of miR-32-5p correlated inversely with hippocampal volume, highlighting a potential neurobiological basis. Common predicted gene targets of the DE microRNAs are involved in neurodevelopment, cognitive processing, and depressive disorders. These findings lay the groundwork for identifying adolescent peripheral microRNA markers that reflect neurodevelopmental pathways shaping lifelong psychopathology risk.