A New Method to Identify Adolescents At Highest Risk of Developing Depression

A major new MQ funded study has found that combining specific biological markers with sociodemographic factors dramatically improves the ability to predict which adolescents will go on to develop depression. 

The research, led by scientists at King’s College London and the Universidade Federal do Rio Grande do Sul in Brazil, followed 100 adolescents based in Brazil over three years as part of the Identifying Depression Early in Adolescence Risk‑Stratified Cohort (IDEA‑RiSCo). It is funded by MQ Mental Health Research, the Royal Academy of Engineering, the UK Medical Research Council, the National Institute of Mental Health (USA), and partners in Brazil.

It builds on earlier IDEA project research from the IoPPN. One paper published last year, that showed that a biological brain mechanism called the ‘kynurenine pathway’ is imbalanced in adolescents with depression, and this imbalance is more pronounced in teenage girls than boys; and in 2020 the development a predictive tool that can recognise adolescents who are at high or low risk of depression in young adulthood.

The study is the first to put together different biological factors including information about the immune system, neurotoxic substances, brain images and socioenvironmental factors to help predict who might develop depression in adolescence.

The researchers found that prediction accuracy increased substantially when biological markers were added to the established sociodemographic risk score. The newly developed biological risk score identified previously undetected high‑risk adolescents, meaning they could be offered more preventative support.

Nearly half of adolescents rated high‑risk on both biological and sociodemographic factors developed depression within three years whilst none of the adolescents rated low‑risk on both measures developed depression. This shows the increased accuracy of using the combined method. This may pave the way for the first clinically feasible early‑warning system for one of the world’s most common and disabling mental health conditions.

This research demonstrates the value of investing in innovative, cross-disciplinary, international collaboration in mental health. It marks an important step forward in how we identify young people most at risk of developing depression. By bringing together social factors with biological and cognitive markers, the team has significantly strengthened our ability to predict risk earlier and more accurately. What’s particularly exciting is that this approach moves us closer to providing targeted support at a stage where intervention can make the greatest difference.

 

Hala Rachidi. Research grants lead at MQ.

A simple, scalable early‑detection tool

Depression rates among adolescents have risen sharply worldwide.  With one in five children and adolescents worldwide experiencing a depressive episode or have depressive symptoms. Early prevention is key, but identifying who is  at risk has remained a challenge, especially in low‑ and middle‑income countries where resources are limited.

Using sociodemographic information alone, the model had only moderate success in predicting which teenagers would later develop depression. But when biological markers were added, prediction became much stronger. The difference in outcomes was striking. None of the young people identified as low risk on both measures developed depression over the next three years, while nearly half (44%) of those identified as high risk on both did. Those who were high risk on just one measure fell somewhere in between, showing that combining life circumstances with biological information gives a much clearer picture of who may need support. It was published today (Monday 2 March) in Molecular Psychiatry.

“This is the first time we’ve been able to show that integrating biological markers with social and environmental factors can meaningfully improve the prediction of adolescent depression,” said Dr Zuzanna Zajkowska, Research Associate, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience and lead author from King’s College London. 

“It brings us a step closer to a practical screening tool that could help implement more targeted and effective prevention strategies before symptoms even begin.”

The new combined testing method, called IDEA‑BIO‑RS includes:

• Four markers in the blood linked to inflammation

• Kynurevnic acid/quinolinic acid ratio(KA/QA) - a measure of how the brain balances protective versus harmful chemical processes

• Brain activity in a region (amygdala) involved in processing emotional experiences such as sadness, fear or anger.  These biomarkers reflect processes known to influence vulnerability to depression, including inflammation, neural sensitivity to negative emotions, and biochemical pathways linked to stress.

Potential for global impact

The study’s set‑up was intentionally designed for global scalability, with blood‑based markers offering a more practical option for most countries compared to neuroimaging. The authors suggest a stepwise screening approach, beginning with the low‑cost IDEA‑RS, and then applying the biological score to adolescents flagged as higher risk.

“Most young people developing depression never access mental health support,” 

Said Professor Valeria Mondelli, senior author, co-lead of the Psychosis and Mood Disorders Theme at the NIHR Maudsley Biomedical Research Centre and Professor of Psychoneuroimmunology at the Institute of Psychiatry, Psychology & Neuroscience, King’s College London. “A tool like this could transform prevention strategies worldwide, especially in low‑resource settings where the need is greatest. A stepwise screening approach could offer a pragmatic solution, whereby low-cost, accessible indicators are used initially, and more resource-intensive biological assessments are reserved for individuals at higher risk. Blood-based biomarkers appear relatively feasible given their established clinical utility and modest cost”, she adds.

Researchers emphasise the need to validate the IDEA‑BIO‑RS in larger and more diverse populations and explore how biological markers may operate differently across sexes and sociocultural contexts.

If confirmed, this combined biological–sociodemographic approach could form the basis of the first clinically actionable screening method for depression risk in young people.

The Identifying Depression Early in Adolescence (IDEA) project is a global initiative involving researchers across five continents, aiming to transform early detection and prevention of youth depression.

The researchers are extremely grateful to the schools and individuals who participated in this study.

Read more about the IDEA project