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AGE levels significantly elevated in schizophrenia-spectrum disorders, meta-analysis findsHigher Levels of AGEs Linked to Schizophrenia Spectrum Disorders
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological PsychiatryPublished September 1, 2026Study authors: Ramdani Youssouf, Leemans Chloe, Point Camille, Oswald PierrePubMed ↗DOI ↗Editorial oversight: Dr. Ji-eun Park, MD · Brain, Mind & Pain
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Key Takeaway
Consider AGE elevation as an associated metabolic finding in schizophrenia, but interpret with caution due to heterogeneity.
This meta-analysis synthesized evidence on advanced glycation end products (AGEs) in schizophrenia-spectrum disorders, including 584 patients and 630 controls (N=1,214). The primary outcome was blood-based and skin AGE levels, with measurement modality examined as a secondary moderator. The analysis found that patients exhibited significantly higher AGE levels than healthy controls (SMD = 0.63, 95% CI 0.26-1.00, p = 0.0008).
Subgroup analyses revealed significant elevations in both blood-based measurements (SMD = 0.47, n = 6) and skin measurements (SMD = 0.87, n = 4). The association remained significant in a subset of high-quality studies (SMD = 0.70, n = 5). However, measurement modality was not a significant moderator (p = 0.20), suggesting that the elevation is consistent across methods.
The authors noted substantial heterogeneity (I² = 88.4%) across studies, indicating considerable variability in effect sizes. They also highlighted the need for longitudinal studies that control for metabolic and geographic factors, as these may influence AGE levels. The analysis is observational in nature, so causality cannot be inferred.
Clinically, these findings suggest that AGE levels are elevated in schizophrenia-spectrum disorders, but the heterogeneity and cross-sectional design limit definitive conclusions. The results may inform future research on metabolic pathways in schizophrenia, but they do not yet support routine clinical measurement of AGEs.
How this fits prior evidence
This meta-analysis extends prior coverage on schizophrenia by identifying a novel biomarker, advanced glycation end products (AGEs), as significantly elevated in schizophrenia-spectrum disorders (SMD = 0.63). It complements earlier findings on paliperidone formulations and 5-HTR antagonists by focusing on a metabolic pathway rather than treatment response. The substantial heterogeneity (I² = 88.4%) echoes the cautious interpretation advised for the dementia prevalence finding in psychotic disorders, and the need for longitudinal studies aligns with the call for definitive trials in the 5-HTR antagonist meta-analysis.
Researchers looked at a large group of 1,214 people to see if there was a link between certain compounds called advanced glycation end products (AGEs) and schizophrenia. This study included 584 patients with schizophrenia-spectrum disorders and 630 healthy individuals. The researchers measured AGE levels in both the blood and the skin of all participants.
The results showed that patients with schizophrenia-spectrum disorders had significantly higher levels of these compounds compared to the healthy group. These higher levels were found in both blood and skin measurements. The link remained strong even when looking only at the highest-quality studies in the report.
It is important to note that this study shows a link, not a cause. Because the data comes from a meta-analysis with many different types of studies, there is a lot of variation in the results. More long-term research is needed to see how factors like location or metabolism affect these levels. This finding helps researchers better understand the biological markers associated with schizophrenia.
What this means for you:
Patients with schizophrenia-spectrum disorders show significantly higher levels of AGEs in their blood and skin.
Common questions
What are AGEs and why do they matter in this study?
AGEs stand for advanced glycation end products. This study found that these specific compounds are significantly higher in people with schizophrenia-spectrum disorders. The researchers found higher levels in both blood and skin measurements, which helps identify biological markers associated with the condition.
How many people were included in this research?
The study included a large group of 1,214 people in total. This group consisted of 584 patients with schizophrenia-spectrum disorders and 630 healthy controls. These numbers allowed researchers to compare AGE levels across a large and diverse population.
Does this mean AGEs cause schizophrenia?
The study shows a link between higher AGE levels and schizophrenia-spectrum disorders, but it does not prove that one causes the other. Because the study is a meta-analysis with high variation, more research is needed to understand the exact role of these compounds.
BACKGROUND & OBJECTIVE: Elevated advanced glycation end products (AGEs) are linked to metabolic dysfunction in schizophrenia-spectrum disorders, but previous studies have shown methodological heterogeneity and overlapping cohorts. We systematically reviewed and quantified differences in blood-based and skin AGE levels between patients and healthy controls.
METHODS: Following PRISMA 2020, databases were searched up to January 2025. Independent case-control studies with quantitative AGE measurements were analysed using random-effects models, strictly excluding overlapping cohorts.
RESULTS: Nine independent studies (584 patients, 630 controls; = 1,214) were included. Patients exhibited significantly higher AGE levels than controls (SMD = 0.63, 95% CI 0.26-1.00; = 0.0008), with substantial heterogeneity (I = 88.4%). Subgroup analyses showed significant elevations in both blood-based measurements ( = 6, SMD = 0.47) and skin ( = 4, SMD = 0.87). Measurement modality was not a significant moderator ( = 0.20). The association remained significant in high-quality studies ( = 5, SMD = 0.70).
CONCLUSIONS: AGE levels are significantly elevated in schizophrenia-spectrum disorders, although substantial heterogeneity remains. Further longitudinal studies controlling for metabolic and geographic factors are needed.
