New study reveals innovative method to identify adolescents at highest risk of developing 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 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 from moderate to substantial when biological markers were added to the established sociodemographic risk score (IDEA‑RS). The newly developed biological risk score (IDEA‑BIO‑RS) identified previously undetected high‑risk adolescents, offering the possibility of improved targeted preventive support.

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.

Dr Zuzanna Zajkowska, Research Associate, The Maurice Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology & Neuroscience and lead author from King’s College London said:

“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. 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 IDEA‑BIO‑RS includes:

• Four markers in the blood linked to inflammation (IL‑2, IL‑6, IL‑12p70, TNF‑α)
• 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.

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 said: 

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

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.

Zajkowska, Z., Nikkheslat, N., Manfro, P.H. et al. Combining neurobiological markers and a sociodemographic risk score to predict adolescent depression – An IDEA RiSCo prospective cohort study. Mol Psychiatry (2026). Combining neurobiological markers and a sociodemographic risk score to predict adolescent depression – An IDEA RiSCo prospective cohort study | Molecular Psychiatry