Summary: Researchers have identified nine blood-based microRNAs that are elevated in teens diagnosed with depression, offering a potential biomarker for early detection. These molecules, absent in adult depression, may signal unique biological processes in adolescents.
The study used a minimally invasive method involving dried blood spots, making it practical for broader screening applications. This breakthrough could lead to more objective, early diagnosis of teen depression, before symptoms become severe or treatment-resistant.
Using a novel lab method they developed, McGill University researchers have identified nine molecules in the blood that were elevated in teens diagnosed with depression. These molecules also predicted how symptoms might progress over time.
The findings of the clinical study could pave the way for earlier detection, before symptoms worsen and become hard to treat.
"Alarmingly, more and more adolescents are being diagnosed with depression, and when it starts early, the effects can be long-lasting and severe," said senior author Cecilia Flores, James McGill Professor in McGill's Department of Psychiatry, a researcher at the Douglas Research Centre and a principal investigator at the Ludmer Centre.
"Teens with depression are more likely to struggle with substance use, social isolation and experience symptoms that often don't respond well to treatment."
Notably, the nine molecules - known as microRNAs - have not been linked to adult depression, suggesting they reflect biological processes unique to teens.
The study, conducted in collaboration with colleagues at the University of California, Los Angeles and Stanford University, focused on 62 teenagers: 34 with depression and 28 without.
Researchers collected small volumes of blood samples, let them dry, and then froze the samples to preserve molecular integrity over time. Such samples are taken with a simple finger prick and are easy to store and transport, making the approach practical and scalable for broader use.
The McGill team developed the lab method used to extract and analyze microRNAs from the samples.
"Our findings pave the way for using dried blood spots as a practical tool in psychiatric research, allowing us to track early biological changes linked to mental health using a minimally invasive method," said first author Alice Morgunova, postdoctoral fellow at McGill.
Diagnosing depression mostly relies on self-reported symptoms. The authors say this could delay care, especially if teens don't recognize the signs or aren't ready to talk about them. A blood-based screening tool could provide an additional and more objective metric to identify teens at risk.
The researchers plan to validate their findings in larger groups of adolescents and to study how these microRNAs interact with genetic and environmental risk factors.
About the study
"Peripheral microRNA signatures in adolescent depression" by Alice Morgunova and Cecilia Flores et al., was published in Biological Psychiatry Global Open Science.
Funding: The study was funded by the Douglas Foundation and Bombardier Fund grant, the National Institute on Drug Abuse of NIH, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, a Healthy Brains for Healthy Lives Graduate Student Fellowship, an Integrated Program in Neuroscience Internal Award, and Postdoctoral Fellowship from the McGill-Douglas Max Planck Institute of Psychiatry International Collaborative Initiative in Adversity and Mental Health, an international partnership funded by the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative.
Peripheral microRNA signatures in adolescent depression
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.