| Title: | Plasma metabolomic signature of frailty and risk of late-onset schizophrenia: A prospective cohort study |
| Journal: | Schizophrenia Research |
| Published: | 19 May 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42155165/ |
| DOI: | https://doi.org/10.1016/j.schres.2026.05.011 |
Publication 19996
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Abstract
BACKGROUND: With population aging, late-onset schizophrenia is attracting increasing attention. The prospective association between frailty and late-onset schizophrenia, along with its underlying mechanisms, remains unclear. This study aimed to investigate the relationship between frailty and late-onset schizophrenia, and assess the potential role of metabolic mechanisms on this association.</p>
METHODS: A total of 489,302 participants without late-onset schizophrenia at baseline were included from UK biobank. Cox proportional hazard regression model was utilized to investigate the association between frailty and late-onset schizophrenia. Elastic net regression was used to determine the metabolic signature associated with frailty. Mediation analysis was employed to assess the mediating role of metabolic signature and specific metabolites on the relationship between frailty and late-onset schizophrenia.</p>
RESULTS: During a median follow-up of 13.49 years, 705 late-onset schizophrenia cases were identified. Compared to individuals with nonfrailty, the risk of late-onset schizophrenia was increased in those with prefrailty (HR: 1.82, 95% CI: 1.52, 2.19) and frailty (HR: 3.10, 95% CI: 2.44, 3.95). Eighty-three metabolites were identified as being related to frailty (38 positively, 45 negatively). The metabolic signature mediated the association between frailty and late-onset schizophrenia (proportion of mediation effects (PM%): 4.57, 95% CI: 2.22, 7.36). The mediation effect of metabolites from fatty acids, inflammation and lipid metabolism on the relationship between frailty and late-onset schizophrenia was significant, with PM% ranging from 2.41 to 5.93.</p>
CONCLUSIONS: Physical frailty was associated with an increased risk of late-onset schizophrenia, partly by disrupting metabolic signatures (fatty acids, inflammation, and lipid metabolism).</p>
12 Authors
- Liuqiao Sun
- Yacong Bo
- Doudou Li
- Pang Yao
- Ziyan Sun
- Qiaozhen Cai
- Hui Chang
- Meiying Cheng
- Mingyi Xue
- Zengli Yu
- Yongjian Zhu
- Xin Zhao
1 Application
| Application ID | Title |
|---|---|
| 93398 | Investigating the risk factors of non-communicable chronic disease using biomarkers, lifestyle factors, and environmental factors |
Enabling scientific discoveries that improve human health