LC-HRMS Identifies Potential Mental Health Biomarkers in Adolescents

Although an increasing number of teenagers around the world are struggling with their mental health, it is still hard to tell who is most at risk. If straightforward tests—like a simple blood test—could be developed, healthcare personnel could identify vulnerable teens could be identified earlier and get them the help they need could be gotten to them before things get worse.

In response to this need, a multinational group of investigators (whose research was published in Comprehensive Psychoneuroendocrinology¹) explored plasma metabolites associated with overall psychosocial difficulties in 197 adolescents aged 11-16 from the WALNUTS study (a six-month multi-school-based randomized controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioral development of adolescents)². Plasma metabolomics data were generated by untargeted liquid chromatography-high-resolution mass spectrometry (LC-HRMS) using cross-sectional plasma samples.¹

Why is Mental Health an Issue Among Adolescents?

The mental health of children and teens is a growing global concern. In fact, over 15% of young people struggled with their mental health in 2021. Specifically, conditions like depression and anxiety are now among the top health challenges worldwide, significantly impacting young people's daily lives and overall well-being.^3-5

Catching mental health struggles early is critical. Because these issues often begin in the teenage years, they can deeply affect a person's emotional growth and cause long-term problems into adulthood. Right now, doctors mostly rely on conversations and surveys to figure out if a teen needs help. Seeing that what is missing is a clear, objective test that can spot at-risk youth much earlier, before their problems get worse, inspired this study.^1,6,7

How Did the Researchers Conduct this Study?

Psychosocial difficulties of the pool of adolescents tested were assessed using self-reported Strengths and Difficulties Questionnaire (SDQ) scores. Linear regression modelling was performed to identify associations between plasma metabolites and the total SDQ score. Logistic regression and Precision-Recall curves were used to evaluate the classification performance of candidate metabolites in distinguishing the SDQ groups (low: 0-14; raised: 15-25). Additionally, pre-existing red blood cell fatty acid profile data were analyzed to detect differences between the low and the raised SDQ score groups.¹

The team found that three metabolites (isoleucine, pregnenolone sulfate, and lysophosphatidylcholine 20:1) were significantly associated with the SDQ score, and are involved in energy metabolism, neuronal functions and phospholipid-related signaling. In addition, a trend towards lower proportions of red blood cell n-3 polyunsaturated fatty acids was observed in individuals with the raised SDQ score.¹

“Altogether,” write the authors of the study,¹ “our results represent a set of metabolites previously linked to mental health or brain functions. Alterations observed in plasma metabolites suggest possible biological changes related to lipid-mediated signaling and energy metabolism. While our findings provide insights into potential metabolic pathways involved in adolescent mental health, the cross-sectional design limits causal inference. Longitudinal studies incorporating repeated metabolomic assessments and intervention trials are necessary to confirm these findings and elucidate potential metabolic mechanisms underlying adolescent psychopathology.”

“In conclusion,” the authors state,¹ “our findings display biological pathways potentially implicated in youth mental health. By employing a global metabolomics approach, this exploratory study contributes to the growing body of evidence and provides hypotheses for future research on adolescent psychopathology. Validation of the identified candidate metabolites in adolescent mental health will require longitudinal studies that integrate additional omics layers and relevant environmental risk factors.”

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References

1. Piironen, A. K.; Afonin, A. M.; Zarei, I. et al. Plasma Metabolomics and Red Blood Cell Fatty Acid Profiles in Adolescent Mental Health. Compr Psychoneuroendocrinol. 2026, 26, 100347. DOI: 10.1016/j.cpnec.2026.100347
2. 2.Pinar-Martí, A.; Gignac, F.; Fernández-Barrés, S. et al. Effect of Walnut Consumption on Neuropsychological Development in Healthy Adolescents: A Multi-School Randomised Controlled Trial. EClinicalMedicine 2023, 59, 101954. DOI: 10.1016/j.eclinm.2023.101954
3. OECD/European Union; Health at a Glance: Europe 2022: State of Health in the EU Cycle; OECD Publishing, 2022. DOI: 10.1787/507433b0-en
4. GBD 2019 Mental Disorders Collaborators. Global, Regional, and National Burden of 12 Mental Disorders in 204 Countries and Territories, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry 2022, 9 (2), 137-150. DOI: 10.1016/S2215-0366(21)00395-3
5. Global Burden of Disease Collaborative Network; Global Burden of Disease Study 2021 (GBD 2021); Institute for Health Metrics and Evaluation (IHME), 2024.
6. Fusar-Poli, P.; Correll, C. U.; Arango, C. et al. Preventive Psychiatry: A Blueprint for Improving the Mental Health of Young People. World Psychiatry 2021, 20 (2), 200-221. DOI: 10.1002/wps.20869
7. American Psychiatric Association; Diagnostic and Statistical Manual of Mental Disorders, 5^th Ed.; American Psychiatric Publishing, 2013.