A groundbreaking study published in Translational Psychiatry explores the metabolic alterations associated with psychotic-like experiences (PLE) in adolescents. Conducted by Karoliina Kurkinen and colleagues, this research investigates the relationship between metabolomic changes and PLE in 76 depressed adolescents aged 14-20. The study not only delves into the metabolic markers that might predict psychosis but also examines how cannabis use alters the metabolome in relation to PLE, offering a fresh perspective on potential predictors of psychosis onset in youth.
What Are Psychotic-Like Experiences in Adolescence?
In adolescents, PLE such as hallucinations, paranoia, delusions, and thought disorders may be early indicators of psychosis, often marking the prodromal stage before the full onset of conditions like schizophrenia. While these experiences can vary widely in severity, they are concerning enough to merit closer attention from clinicians and researchers. The relationship between these experiences and underlying biological changes has been a topic of increasing interest, particularly the potential role of metabolomics— the study of metabolites in the body—as a diagnostic tool.
How the Study Was Conducted
This study focused on adolescents who were diagnosed with depression, a group already at risk for experiencing mental health disorders, including psychosis. Researchers analyzed the serum concentrations of 92 metabolites using liquid chromatography–mass spectrometry, a highly sensitive technique. The PLE were assessed using the Youth Experiences and Health (YEAH) questionnaire, which measures different dimensions of psychotic-like experiences, such as delusions, paranoia, hallucinations, negative symptoms, thought disorder, and dissociation.
Using linear regression models, the researchers assessed the correlation between various PLE symptoms and specific metabolites, adjusting for various covariates, including cannabis use.
Key Findings: Hallucinations and Cannabis Use
One of the most striking results of the study is the link between hallucinations and a wide range of metabolites. Initially, 13 metabolites were significantly associated with hallucinations, including acetoacetic acid, allantoin, and leucine. These metabolites are involved in processes like energy metabolism, inflammation, and neurotransmitter function—key areas that could explain the development of psychotic symptoms.
However, when the model was adjusted for cannabis use—an important factor given the growing concern about the relationship between cannabis use and mental health in adolescents—the number of associated metabolites dropped to eight. These metabolites included adenine, AMP, chenodeoxycholic acid, and L-kynurenine, which are involved in metabolic pathways related to inflammation, energy production, and neurochemical balance.
Inflammation and Energy Demand: Two Key Mechanisms
The study’s findings suggest that PLE in adolescence may involve diverse biological mechanisms. Hallucinations, in particular, seem to be linked to inflammatory processes in the body, which have been implicated in various mental health disorders. On the other hand, cannabis use appears to engage an alternative metabolic pathway. Specifically, the metabolites associated with cannabis use point to increased energy demand and ketogenesis—processes that could exacerbate PLE in adolescents already at risk for psychotic disorders.
The Limitations and Next Steps
While these findings are compelling, there are limitations to the study. The sample size, particularly of depressed adolescents, is relatively small, which may restrict the generalizability of the results. Additionally, the cross-sectional nature of the study means that it cannot definitively establish causality—whether metabolic changes directly contribute to the onset of psychosis, or if they are merely a response to other underlying factors.
The authors suggest that future research should focus on a larger and more diverse sample of adolescents, including those without depression, to better understand the role of metabolites in the onset of psychotic disorders. Furthermore, the relationship between cannabis use and PLE warrants further investigation, particularly in terms of how it interacts with metabolic and neuroinflammatory processes.
The Potential of Metabolomics in Predicting Psychosis
This study adds to the growing body of evidence suggesting that metabolomic changes could be an effective way to predict psychosis, potentially even before clinical symptoms fully manifest. By identifying specific metabolic biomarkers associated with PLE, researchers hope to develop more precise tools for early diagnosis and intervention. These tools could be crucial for improving outcomes in adolescents at risk for psychosis and related mental health disorders.
